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Everolimus for subependymal giant cell astrocytoma in patients with tuberous sclerosis complex: 2-year open-label extension of the randomised EXIST-1 study. In the EXIST-1 trial, initiated on Aug 10, 2009, more than 35% of patients with subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex had at least 50% reduction in SEGA volume after 9·6 months of treatment with everolimus. In this Article, we report interim data (up to Jan 11, 2013) to support longer-term tolerability and efficacy of everolimus from the continuing 4-year extension phase of EXIST-1. We assessed data from a prospective, open-label extension of a multicentre, phase 3, randomised, double-blind, placebo-controlled study in patients with tuberous sclerosis complex who had SEGA that was growing and needed treatment. In this extension study, we included all patients who had been assigned everolimus during the double-blind, randomised phase of the trial and those patients who crossed over from the placebo group to receive everolimus during the randomised phase or at the start of the extension phase. All patients received oral everolimus at a starting dose of 4·5 mg/m(2) per day. Everolimus dose was subsequently adjusted subject to tolerability to attain blood trough concentrations of 5-15 ng/mL. An independent central radiology review team assessed SEGA response (at least a 50% reduction from baseline in total volume of all target SEGAs; the primary endpoint) by MRI at 12, 24, and 48 weeks, then every year thereafter in all patients who received at least one dose of everolimus. This study was registered with ClinicalTrials.gov, number NCT00789828. Of the original 117 randomly assigned patients, 111 were given everolimus between Aug 20, 2009, and Jan 11, 2013 (date of data cutoff); we included these patients in our longer-term analysis. Median duration of everolimus exposure was 29·3 months (IQR 19·4-33·8). Median follow-up was 28·3 months (IQR 19·3-33·0). 54 (49%) patients had a response of 50% or greater reduction in SEGA volume (95% CI 39·0-58·3), and duration of response was between 2·1 and 31·1 months (median not reached). SEGA volume was reduced by 50% or more in 39 (37%) of 105 patients at 24 weeks, 48 (46%) of 104 patients at 48 weeks, 36 (47%) of 76 patients at 96 weeks, and 11 (38%) of 29 patients at 144 weeks. Stomatitis (48 [43%] patients) and mouth ulceration (33 [30%] patients) were the most frequent treatment-related adverse events; infections were the most commonly reported treatment-related serious adverse event, occurring in 15 (14%) patients. 35 (32%) patients reported treatment-related grade 3 or 4 adverse events, the most common of which were stomatitis (nine [8%]) and pneumonia (nine [8%]). 18 (16%) patients had treatment-related serious adverse events. Six (5%) patients withdrew because of adverse events. These results support the longer-term use of everolimus in patients who have few treatment options and who need continued treatment for tuberous sclerosis complex and its varied manifestations. Reduction or stabilisation of tumour volume with everolimus will hopefully provide long-term clinical benefit in patients with SEGA. Novartis Pharmaceuticals.

Preoperative hyperfractionated chemoradiation for locally recurrent rectal cancer in patients previously irradiated to the pelvis: A multicentric phase II study. The combination of irradiation and total mesorectal excision for rectal carcinoma has significantly lowered the incidence of local recurrence. However, a new problem is represented by the patient with locally recurrent cancer who has received previous irradiation to the pelvis. In these patients, local recurrence is very often not easily resectable and reirradiation is expected to be associated with a high risk of late toxicity. The aim of this multicenter phase II study is to evaluate the response rate, resectability rate, local control, and treatment-related toxicity of preoperative hyperfractionated chemoradiation for locally recurrent rectal cancer in patients previously irradiated to the pelvis. Patients with histologically proven pelvic recurrence of rectal carcinoma, with the absence of extrapelvic disease or bony involvement and previous pelvic irradiation with doses < or =55 Gy; age > or =18 years; performance status (PS) (Karnofsky) > or =60, and who gave institutional review board-approved written informed consent were treated by preoperative chemoradiation. Radiotherapy was delivered to a planning target volume (PTV2) including the gross tumor volume (GTV) plus a 4-cm margin, with a dose of 30 Gy (1.2 Gy twice daily with a minimum 6-h interval). A boost was delivered, with the same fractionation schedule, to a PTV1 including the GTV plus a 2-cm margin (10.8 Gy). During the radiation treatment, concurrent chemotherapy was delivered (5-fluorouracil, protracted intravenous infusion, 225 mg/m(2)/day, 7 days per week). Four to 6 weeks after the end of chemoradiation, patients were evaluated for tumor resectability, and, when feasible, surgical resection of recurrence was performed between 6-8 weeks from the end of chemoradiation. Adjuvant chemotherapy was prescribed to all patients, using Raltitrexed, 3 mg/square meter (sm), every 3 weeks, for a total of 5 cycles. Patients were staged using the computed tomography (CT)-based F-classification (F0: no side-wall involvement; F1, F2, F3: 1, 2, and 3-4 side-walls involved, respectively). Toxicity was evaluated on the basis of the Radiation Therapy Oncology Group (RTOG) criteria. Fifty-nine patients (38 male, 21 female; median age, 62 years; range, 43-77 years) were enrolled in the study, by 12 different Italian radiotherapy departments. Previous surgery was anterior resection in 45 patients (76.3%) and abdominal-perineal resection in 14 patients (23.7%); previous radiotherapy dosage ranged between 30 and 55 Gy (median, 50.4 Gy); the median interval between prior radiation therapy to the onset of reirradiation was 27 months (range, 9-106 months); 44 patients (74.6%) had received some form of previous chemotherapy (concurrent and/or adjuvant). Fifty-one of 59 patients (86.4%) completed chemoradiation without treatment interruptions: 6 patients (10.2%) had temporary treatment interruption due to toxicity or patient compliance, and 2 patients (3.4%) had definitive treatment interruption. The incidence of Grade 3 lower gastrointestinal acute toxicity was only 5.1%. No patient developed Grade 4 acute toxicity. After chemoradiation, 5 patients (8.5%) had complete response (CR), 21 patients (35.6%) had partial response (PR), 31 patients (52.6%) had no change (NC) and 2 patients (3.4%) showed progressive disease (PD). Overall, the response rate (PR + CR) was 44.1% (95% confidence interval, 29.0-58.9%). Twenty of 24 patients (83.3%) with pelvic pain before treatment had symptomatic response. Tumor resection was performed in 30 of 59 patients (50.8%) including 2 local excisions, 4 anterior resections, 18 abdominoperineal resections, and 6 other. Surgical resection resulted as R0 and R1 in 21 patients (35.6%) and 3 patients (5.1%), respectively. The possibility of radical resection was influenced by tumor response to chemoradiation (PD/NC: 7/33; PR/CR: 14/26; p = 0.009). Thirty-three patients received adjuvant chemotherapy, which was completed in 30 (50.8%). At a median follow-up of 36 months (range, 9-69 months), 28 patients (47.5%) developed local recurrence or tumor progression in the unresected pelvic disease and 18 patients (30.5%) developed distant metastasis. Seven patients showed late toxicity, including 2 skin fibrosis, 2 impotence, 2 urinary complications requiring nephrostomy, and 1 small bowel fistula requiring surgical diversion. Overall median survival was 42 months. Five-year actuarial survival was 39.3%; 66.8% in R0 resected patients and 22.3% in patients treated without surgery or undergoing subtotal tumor removal. Local control and disease-free survival were significantly correlated with the interval between surgical treatment for primary tumor and local recurrence (p = 0.028 and p = 0.003, respectively). Radical resection significantly influenced local control, disease-free survival, and overall survival (p = 0.010, p = 0.010, and p = 0.050 respectively). The multivariate analysis confirmed the impact of surgery-relapse interval on local control (p = 0.016) and disease-free survival (p = 0.002), and confirmed the correlation between R0 surgery with local control and disease-free survival (p = 0.016). Use of hyperfractionated chemoradiation was associated with a low rate of acute toxicity and an acceptable incidence of late complications. Pain control was excellent. The overall 5-year survival was 39%. Despite 87.4% of patients having F1-3 stage disease, approximately one-third (35%) achieved R0 resection, and two-thirds of patients in this cohort of patients were alive at the 5-year mark. However, further studies using innovative treatment algorithms are warranted to, hopefully, improve the local tumor response and control.

Effects of the use of a morantel sustained release bolus in first and second year grazing cattle. In an experiment carried out in 1981 and 1982, the effect of the use of a morantel sustained release bolus (Paratect bolus) on the weight gain and a number of parasitological parameters of cattle was studied. In the first year 42 calves were divided into 3 equal groups, one group was kept outside and treated with a bolus (B), the second group was kept outside and was not treated (C), while the third group remained indoors (I). Groups B and C were grazed separately on contaminated pasture. During the first months Group B had a negligible egg output. The egg output in the controls was much higher and in mid-August they had to be treated for parasitic gastroenteritis. At the end of the grazing season the advantage in weight gain of Group B was 20 kg compared with the controls. During the housing period the growth in the 3 groups was not significantly different. At the start of the second grazing season half the animals of Groups B, C and I received a bolus (Groups BB, CB and IB). The other half remained untreated (BC, CC and IC). The animals treated with a bolus in 1982 gained significantly more weight (64 g/day) than untreated animals. Heifers turned out for the first time (IB and IC) showed much less weight gain than heifers in their second grazing season. The heifers which had previously grazed in 1981 had a very low egg output compared with Groups IB and IC, although the level of egg output of the latter was also not very high (max, almost 40 (eggs per gram (EPG)). In faecal cultures of heifers of Group BC, CB and CC, no Cooperia oncophora-larvae were seen from May onwards, indicating a strong immunity against this species. In Group BB very low numbers of C. oncophora-larvae were observed. In Groups IB and IC, C. oncophora was present during the whole season. At the end of the first season the level of herbage infestation on the control pastures was much higher. In 1982 only slight differences in level of infestation between the pastures were observed. At the start of the season in 1982 serum pepsinogen levels were much higher in the groups which grazed in 1981, compared with the indoor-fed groups. Groups BC and CC had significantly higher levels than Groups BB and CB and all 4 groups always had higher levels than Groups IB and IC.(ABSTRACT TRUNCATED AT 400 WORDS)

Probing systems in solution by NMR using sulfur hexafluoride as a spy molecule. The use of SF6 as a spy molecule in solution-state NMR is investigated as an alternative to 129Xe NMR. 19F chemical shift, longitudinal relaxation time, and integral measurements, as well as intermolecular nuclear Overhauser effects, are reported for SF6 dissolved in simple deuterated solvents and/or in various solutions among which are aqueous solutions of cucurbit[6]uril (CB) and alpha-cyclodextrin (alphaCD). Both CB and alphaCD form a 1:1 inclusion complex with SF6. In a 0.2 M D2SO4-D2O solution, the affinity of CB for SF6 is 2.9x10(5) L mol(-1) at 298 K; it is the largest value ever found for the inclusion of a neutral guest into the CB cavity. It is one order of magnitude larger than in a 0.2 M Na2SO4-D2O solution, and the role of the cation is evidenced. In D2O, the affinity of alphaCD for SF6 is about 25 L mol(-1). With CB, the kinetics is slow on both the 1H and 19F chemical shift time scales, while with alphaCD fast exchange is observed. The 19F chemical shift of SF6 is much less sensitive to medium effects than the chemical shift of 129Xe. This might be a limitation if minute structural changes are to be investigated but, in the present study, turned out to be an advantage for determining the affinity of alphaCD for SF6. With CB, the 19F chemical shift of included SF6 is found to be sensitive to the nature of the cation bound at the portals. The 19F relaxation time of SF6 dissolved in deuterated solvents is dominated by the spin-rotation mechanism and is orders of magnitude shorter that the 129Xe relaxation time. It is found to be rather sensitive to the environment and was used to determine the affinity of alphaCD for SF6. The detection limit of SF6 by 19F NMR is lower than the NMR detection limit of thermally polarized 129Xe by more than three orders of magnitude. It lies in the micromolar range, and SF6 concentrations of the order of 10 microM were determined by 19F NMR signal integral measurements and used to quantify the affinity of CB for SF6. Integrals, which are usually not reliable for quantitative measurements in 129Xe NMR, were proven to be highly valuable for determining the affinity of alphaCD for SF6 as well. Most interestingly, heteronuclear Overhauser effect measurements allow to selectively highlight the 1H of a SF6 binding site according to the 19F-1H proximity and were used to characterize the inclusion complex formed with alphaCD.

FAST scan: is it worth doing in hemodynamically stable blunt trauma patients? During the last decade, focused assessment with sonography for trauma increasingly has become the initial diagnostic modality of choice in trauma patients. It is still questionable, however, whether its use results in the underdiagnosis of intra-abdominal injury. It also remains doubtful whether a positive focused assessment with sonography for trauma affects clinical decision making in hemodynamically stable blunt trauma patients as evidenced through abdominal computerized tomography use. The aim of this study was to evaluate the results of focused assessment with sonography for trauma in hemodynamically stable blunt trauma patients and to determine its role in the diagnostic evaluation of these patients. We reviewed our prospectively maintained trauma database. In trauma patients at our institute, focused assessment with sonography for trauma examinations are performed by surgery residents and are considered positive when free intra-abdominal fluid is visualized. Abdominal computerized tomography, diagnostic peritoneal lavage, or exploratory laparotomy findings were used as confirmation of intra-abdominal injury. In our 7-year study period, 2,980 trauma patients were evaluated at our institute, of which 2,130 patients underwent a focused assessment with sonography for trauma. In all, 18 patients had an inconclusive focused assessment with sonography for trauma, whereas 7 patients died on arrival, leaving 2,105 patients for our analysis. A total 88 true positive focused assessment with sonography for trauma were conducted. All hemodynamically stable blunt trauma patients who had a positive focused assessment with sonography for trauma (70/88) were confirmed by computerized tomography. Patients who underwent exploratory laparotomy directly (17/88) or diagnostic peritoneal lavage (1/88) as confirmation either had penetrating trauma or became hemodynamically unstable. A total of 1,894 true negative focused assessments with sonography for trauma scans were conducted, with 1,201 confirmed by computerized tomography and the rest by observation. In all, 118 false negative focused assessment with sonography for trauma were performed, of which 44 (37.3%) subsequently required exploratory laparotomy. Five patients had false positive focused assessment with sonography for trauma scans. Focused assessment with sonography for trauma scan had an overall sensitivity of 43%, a specificity of 99%, and positive and negative predictive values of 95% and 94%, respectively. Accuracy was 94.1%. In the hemodynamically stable blunt trauma group, there were 60 patients with true positive focused assessment with sonography for trauma examinations and 87 patients with false negative focused assessment with sonography for trauma examinations. In this group of patients, focused assessment with sonography for trauma had a sensitivity of 41%, specificity of 99%, and positive and negative predictive values of 94% and 95%, respectively. The overall accuracy was 95%. Given the low sensitivity, a negative focused assessment with sonography for trauma without confirmation by computerized tomography may result in missed intra-abdominal injuries. It is also observed in all focused assessment with sonography for trauma positive hemodynamically stable blunt trauma patients, confirmation is preferred through the use of a computerized tomography for better understanding of the intra-abdominal injuries and to decide on operative versus no-operative management. Thus, the use of focused assessment with sonography for trauma in hemodynamically stable blunt trauma patients seems not worthwhile. It should be reserved for hemodynamically unstable patients with blunt trauma.

[Neonatal meningitis. Epidemiological study of the Grupo de Hospitales Castrillo]. A prospective multicenter study was designed to assess the incidence, etiology, risk factors and outcomes of vertically transmitted and nosocomial meningitis in neonates over a two-year period. Cases of neonatal meningitis diagnosed between January 1, 1997 and December 31, 1998 in the neonatology departments of 28 acute-care hospitals in Spain ("Grupo de Hospitales Castrillo") were prospectively studied. Bacteriological meningitis was considered confirmed when cerebrospinal fluid culture (CSF) was positive for bacteria, virus or fungi, probable when CSF culture was negative but blood culture was positive, and unconfirmed when both cultures were negative. During the study period, 151 cases of meningitis were diagnosed. Transmission was vertical in 84 cases and nosocomial in 67. The incidence of vertically transmitted meningitis was 0.51 of live births, and was significantly higher in very low birth weight (VLBW) infants. Confirmed bacteriological meningitis was diagnosed in 66 patients (78.6 %). No risk factors were identified in 46.4 % of the patients. Group B Streptococcus (agalactiae) was isolated in 48.5 % of cases of confirmed meningitis and Escherichia coli was isolated in 18.2 %. In 69.7 % of cases the results of blood culture were in agreement with those of CSF culture. The overall mortality rate was 8.3 %; mortality was significantly higher in VLBW infants (33.3 % vs 4.2 % in infants weighing 1,500 g). Thirteen percent of survivors had sequelae. The incidence of meningitis of nosocomial transmission was 0.2 % of admissions and was more frequent in VLBW infants. Confirmed bacteriological meningitis was diagnosed in 49 patients (73.1 %). Two or more risk factors were present in 62.7 % of patients. E. coli was isolated in 26.5 % of cases of nosocomial meningitis and Staphylococcus epidermidis was isolated in 24.5 %. In 55 % of patients the results of blood culture agreed with those of CSF culture. The overall mortality rate was 19.4 %. Mortality was significantly higher in VLBW infants and 18.5 % of survivors showed sequelae. The incidence, mortality and sequelae of neonatal meningitis in Spain were similar to those reported in recent studies. The most commonly isolated pathogens were group B Streptococcus in vertically transmitted meningitis and E. coli and S. epidermidis in nosocomial meningitis. We believe the distinction between vertical and nosocomial meningitis to be appropriate because the epidemiology of these diseases is different, which implies a different therapeutic approach. The high percentage of positive blood cultures indicates the need to include lumbar puncture whenever systemic infection is suspected in the neonatal period.

Cytoskeleton Structure in Mouse Sperm and Testes After 30 Days of Hindlimb Unloading and 12 Hours of Recovery. Changes in the external mechanical field result in cytoskeleton reorganization and the formation of adaptive patterns in different types of cells, including somatic cells and sex cells. The aim of this research was to study the protein and mRNA content of cytoskeletal and sperm-specific genes in the sperm and testis cells of mice. Mice were subjected to 30 days of antiorthostatic suspension to simulate weightlessness, followed by 12 h of recovery, while receiving essential phospholipids at a dosage of 500 mg/kg/day (30HSE and 30HSE+12h groups) or a similar dosage of a placebo (30HS and 30HS+12h groups). Accordingly, reference groups (CE group and C group) were formed. The total number and the percentage of motile spermatozoa were calculated using a Makler chamber. To analyze the number of viable spermatozoa and the permeability of their membranes, eosin staining was used as well as Diff-Quick for a morphological evaluation. Relative protein and mRNA content was estimated in a western blot and quantitative PCR assay, respectively. The relative protein expression levels of actin (beta and gamma) and two alpha-actinin isoforms (1 and 4) remained constant in the sperm of all study groups, except for the 30HS+12h group, where the alpha-actinin-4 level was 13% higher than in the reference group (p < 0.1). In the testis cells, the relative actin isoform content was equivalent to that in the spermatozoa. However, in the testis cells, the ACTN1 mRNA content was 17% higher in the 30HS group than in the C group (p < 0.05), and decreased after 12 h of recovery. In contrast, the ACTN4 mRNA content was 20% lower in the 30HS group than in the reference group (p < 0.05) and increased after the 12-h recovery period. At the same time, in the group administered the essential phospholipids, the relative ACTN1 and ACTN4 mRNA content did not differ from those of the reference group. The relative beta-tubulin content was similar in the reference C group and the reference CE group, which was administered the essential phospholipids. In the 30HS and 30HS+12h groups, the beta-tubulin content decreased by 19% and 22% (p < 0.05), respectively, and they also decreased in the groups administered the essential phospholipids (30HSE and 30HSE+12h groups, by 27% and 33%, respectively, p < 0.05). In the testis tissue, the relative tubulin content did not change in any of the experimental groups. At the same time, the relative mRNA content of the genes encoding the studied cytoskeletal proteins increased, which may indicate the protein content was regulated mainly at the translational level. The spermogram parameters and the content of the sperm-specific proteins and the associated mRNAs revealed a decrease in the number of mature spermatozoa in mice suspended under conditions of weightlessness. Moreover, the decrease was prevented by the administration of essential phospholipids.

Quantitation of plasma apolipoproteins in the primary and secondary prevention of coronary artery disease. To review current knowledge of apolipoprotein quantitation used in the clinical management of persons with or at risk for the development of premature coronary artery disease. The English-language literature was analyzed using MEDLINE (1975 to 1993) with key words "apolipoproteins," "quantitation," and "coronary artery disease." Article bibliographies were also reviewed to obtain additional references. Published, peer-reviewed retrospective and prospective studies relevant to the association of plasma apolipoprotein levels with coronary artery disease in humans. Most studies concerned apolipoprotein A-I (apo A-I), apolipoprotein B (apo B), and lipoprotein(a) [Lp(a)]. In retrospective cross-sectional studies, apo A-l levels were not substantially more predictive of coronary artery disease than were high-density lipoprotein (HDL) cholesterol levels. In contrast, levels of apo B and Lp(a) were often more strongly associated with coronary artery disease than were traditional lipid measurements. In studies of the relation between apolipoprotein levels in children and premature coronary artery disease in their parents, Lp(a) levels, but not apo A-l and apo B levels, were consistently predictive of familial coronary artery disease. Prospective studies have yielded variable results for all three apolipoproteins. Low apo A-l levels were consistently associated with coronary artery disease in six prospective studies but were not more predictive than HDL levels. Apolipoprotein B levels were strongly associated with coronary artery disease in four of five prospective studies but were more predictive of coronary artery disease than were total cholesterol levels in only two of the four studies. Lipoprotein(a) levels were strongly associated with coronary artery disease in five of seven prospective studies but were not associated in two of the four largest studies. Too few large prospective studies of apolipoprotein quantitation using validated assay methods, both in general unselected populations and in subgroups of persons with premature coronary artery disease or family histories of premature coronary artery disease, are available to make definitive recommendations concerning clinical utility. The data do not support use of apolipoprotein quantitation as a screening tool to predict coronary artery disease risk in the general population. However, the data suggest that quantitation of apo B and Lp(a) may be indicated in subgroups of persons with premature coronary artery disease or with family histories of premature coronary artery disease. In these persons, an increased apo B or Lp(a) level or both could be a clinical indication for more aggressive treatment of low-density lipoprotein cholesterol.

Evaluating the Need for Daily Image Guidance in Head and Neck Cancers Treated with Helical Tomotherapy: A Retrospective Analysis of a Large Number of Daily Imaging-based Corrections. Clinical implementation of image-guided intensity-modulated radiotherapy is rapidly evolving. Helical tomotherapy treatment delivery involves daily imaging before intensity-modulated radiotherapy delivery. This can be a time consuming resource-intensive process, which may not be essential in head and neck radiotherapy, where effective immobilisation is possible. This study aimed to evaluate whether an offline protocol implementing the shifts derived from the first few fractions can be an acceptable alternative to daily imaging for helical tomotherapy. We retrospectively analysed the set-up data of 2858 fractions of 100 head and neck cancer patients who were treated with daily online image guidance. Using summary data from all treatment fractions, we calculated the systematic error (∑) and random error (σ) in each of the three axes, i.e. mediolateral (x), craniocaudal (y), anteroposterior (z). We also calculated the translational vector of each fraction of individual patients. We then simulated two no-action-level offline protocols where set-up errors of the first three (protocol F3) or five fractions (protocol F5) were averaged and implemented for the remaining fractions. The residual errors in each axis for these fractions were determined together with the residual ∑ and σ. Planning target volume (PTV) margins using the van Herk formula were generated based on the uncorrected errors as well as for the F3 and F5 protocols. For each scenario, we tabulated the number of fractions where the residual errors were more than 5 mm (our default PTV margin). We also tried to evaluate whether errors tended to differ based on intent (radical or adjuvant), anatomical subsite or weight loss during treatment. Analysis from this large dataset revealed that in the tomotherapy platform, the highest set-up errors were in the anteroposterior (z) axis. The global mean was 5.4 mm posterior shift, which can be partly attributed to couch sag on this system. Uncorrected set-up errors resulted in systematic and random errors of ∑x,y,z of 1.8, 1.7 and 2 mm and σx,y,z of 1.7, 1.5 and 1.9 mm, with a required PTV margin in x, y, z axes of 5.7, 5.3 and 6.2 mm. Implementing average shifts from the first three or five fractions resulted in a substantial reduction in the residual systematic errors, whereas random errors remained constant. The PTV margins required for the residual errors after three and five fraction corrections were 3.8, 3.4 and 5.1 mm for F3 and 3.3, 2.9, 4.8 mm for F5. The proportions of fractions where there was >5 mm residual error were 1.6%, 1.1%, 2.9% in x, y and z axes in the F3 protocol and 1.5%, 0.8% and 2.6% with the F5 protocol. Although there was no difference in residual shifts > 5 mm, there was a statistically higher chance of residual errors > 3 mm larynx/hypopharynx subsites versus other sites. In patients who had more than 5% weight loss, there was no significant increase in residual errors with the F5 protocol and the required PTV margin was within our default PTV margins expansion. Correction of systematic errors by implementing average shifts from the first five fractions enables us to safely avoid daily imaging in this retrospective analysis. If this is validated in a prospective group it could lead to implementation of a resource sparing image-guided radiotherapy protocol both in terms of time and imaging dose. Patients with larynx/hypopharynx subsites may require more careful evaluation and daily online matching.

Modeling N-methyl-D-aspartate-induced bursting in dopamine neurons. Burst firing of dopaminergic neurons of the substantia nigra pars compacta can be induced in vitro by the glutamate agonist N-methyl-D-aspartate. It has been suggested that the interburst hyperpolarization is due to Na+ extrusion by a ouabain-sensitive pump [Johnson et al. (1992) Science 258, 665-667]. We formulate and explore a theoretical model, with a minimal number of currents, for this novel mechanism of burst generation. This minimal model is further developed into a more elaborate model based on observations of additional currents and hypotheses about their spatial distribution in dopaminergic neurons [Hounsgaard (1992) Neuroscience 50, 513-518; Llinás et al. (1984) Brain Res. 294, 127-132]. Using the minimal model, we confirm that interaction between the regenerative, inward N-methyl-D-aspartate-mediated current and the outward Na(+)-pump current is sufficient to generate the slow oscillation (approximately 0.5 Hz) underlying the burst. The negative-slope region of the N-methyl-D-aspartate channel's current-voltage relation is indispensable for this slow rhythm generation. The time-scale of Na(+)-handling determines the burst's slow frequency. Moreover, we show that, given the constraints of sodium handling, such bursting is best explained mechanistically by using at least two spatial, cable-like compartments: a soma where action potentials are produced and a dendritic compartment where the slow rhythm is generated. Our result is consistent with recent experimental evidence that burst generation originates in distal dendrites [Seutin et al. (1994) Neuroscience 58, 201-206]. Responses of the model to a number of electrophysiological and pharmacological stimuli are consistent with known responses observed under similar conditions. These include the persistence of the slow rhythm when the tetrodotoxin-sensitive Na+ channel is blocked and when the soma is voltage-clamped at -60 mV. Using our more elaborate model, we account for details of the observed frequency adaptation in N-methyl-D-aspartate-induced bursting, the origin of multiple spiking and bursting mechanisms, and the interaction between two different bursting mechanisms. Besides reproducing several well established firing patterns, this model also suggests that new firing modes, not yet recorded, might also occur in dopaminergic neurons. This model provides mechanistic insights and explanations into the origin of a variety of experimentally observed membrane potential firing patterns in dopaminergic neurons, including N-methyl-D-aspartate-induced bursting and its dendritic origin. Such a model, capable of reproducing a number of realistic behaviors of dopaminergic neurons, could be useful in further studies of the basal ganglia-thalamocortical motor circuit. It may also shed light on bursting that involves N-methyl-D-aspartate channel activity in other neuron types.

The effect of altering eligibility criteria for entry onto a kidney transplant waiting list. This paper concerns the allocation of kidneys from cadaveric donors to patients with end-stage renal disease (ESRD). Currently, the decision as to whether or not a particular patient should go onto the renal transplant waiting list is left to the discretion of the local dialysis centre, and is usually based almost entirely upon consideration of each case on its individual merits. Would this person like to have a renal transplant, is this possible, and would it seem reasonable to give them a chance? It could be argued that such an approach may not make best use of a scarce national resource. In this study we explore the effects of altering the eligibility criteria for transplantation to take explicit and quantitative account of the fact that some patients are more likely to die than others. We performed a survey of one unit's dialysis patients to ascertain the characteristics used in practice to determine who should go onto the transplant waiting list and who should not. We then created a computer model to simulate a cohort of ESRD patients, initially of the same size and characteristics as that in the unit surveyed, receiving renal replacement therapy over a period of 10 years. Using this model, we compared four strategies for defining eligibility for transplantation: (1) all patients eligible; (2) standard and medium risk patients eligible; (3) only standard risk patients eligible; and (4) no regrafts performed (standard and medium risk according to definitions in the Renal Association Standards Document). Strategies of allowing only standard or standard and medium risk patients onto the waiting list most closely reflected the current decisions made regarding eligibility. The different strategies considered in the models necessarily gave rise to very considerable variation in the size of the waiting list at the end of the 10 year period (range 98-368), which would have important practical implications. The predicted mean time of kidney function varied from 9.8 years for strategy 4 (no regrafts) to 10.8 years for strategy 3 (only standard risk patients eligible). However, the different strategies had very little effect on other parameters, such as numbers of deaths and the size of the dialysis population. Variation in decision making from centre to centre regarding access to renal transplantation could make up to a 10% (1 year) difference in the expected half-life of renal transplants performed. Information about recipient characteristics is therefore required when making comparisons between outcome in one transplant unit with that in another, or when comparing one immunosuppressive regime with another.

[Analysis of blood lead level and its influencing factors of workers in one lead acid storage cell enterprise]. To understand the blood lead level and its influencing factors of workers in one lead acid storage cell enterprise in Jiangsu Province. An occupational health field investigation was done to this storage cell enterprise at the end of June 2011 to measure the air lead fume (dust) concentration of workplaces. Health-care information of 1364 person-times from 2009 - 2011 was collected, including blood lead level, general state of health, life and health habit. One way ANOVA and ordinal multi-categorical logistic stepwise regression were used to analysis the influencing factors of blood lead level. The lead fume concentration range was 0.008-0.354 mg/m(3) among 12 measuring points, which 7 places were unqualified, while the concentration range of lead dust was 0.023 - 2.432 mg/m(3), 24 out of 27 measuring places were unqualified, both the qualified rate were low. The blood lead concentration of objects was (259.54 ± 106.62) µg/L, among which 96 people (7.04%) who ≥ 400 µg/L should be identified as suspected "observation object", blood lead concentration ≥ 600 µg/L was not found. The blood lead concentration of male (279.76 ± 114.93 µg/L) was significantly higher than female (242.44 ± 95.86) µg/L (t = 6.441, P < 0.01). The proportion of ≥ 400 µg/L in male (11.04%, 69/625) was significantly higher than female (3.65%, 27/739) (χ(2) = 28.237, P < 0.01). The blood lead concentration of workers who exposed to lead fume or dust (265.93 ± 103.70) µg/L was significantly higher than those of not exposed to lead (205.30 ± 115.62) µg/L (t = -6.037, P < 0.01), the blood lead concentration of workers who exposed to lead dust was (267.38 ± 98.02) µg/L significantly higher than those of exposed to lead fume (260.81 ± 121.80) µg/L (t = -2.408, P < 0.05). The proportion of ≥ 400 µg/L in workers who exposed to lead fume (dust) (7.60%, 93/1223) was significantly higher than those of not exposed to lead (2.13%, 3/141) (χ(2) = 4.538, P < 0.05). Ordinal multi-categorical logistic stepwise regression found that the lead fume concentration ≥ 0.03 mg/m(3), lead dust concentration ≥ 0.05 mg/m(3) (OR = 1.59, 95%CI: 1.06 - 2.39), length of service ≥ 3 years (OR = 1.82, 95%CI: 1.12 - 2.98), smoking (OR = 2.06, 95%CI: 1.27 - 3.37) can increase the level of blood lead concentration. Lead dust concentration of the enterprise exceeded the standard. Workers exposed to lead fume (dust) have more occupational health hazard of lead, of whom the blood lead concentration was high. Higher lead fume (dust) concentration in workplace, longer length of service, smoking were risk factors of high blood lead concentration.

One Hundred Pancreatectomies with Venous Resection for Pancreatic Adenocarcinoma. Introduction: Invasion of portal vein (PV)/ superior mesenteric vein (SMV) in pancreatic ductal adenocarcinoma (PDAC) is no longer a contraindication for resection when reconstruction is technically feasible. However, the literature data reached conflicting conclusions regarding the early and long-term outcomes of patients with venous resection and pancreatectomies for PDAC. The study aims to present the outcomes in a large series of patients with pancreatectomies and associated PV/ SMV resection for PDAC, in a single center experience. Patients Methods: The data of 100 patients with pancreatectomies and PV and/ or SMV resection performed between 2002 and 2016 (February, 1st) were retrospectively analyzed from a prospectively maintained electronic database, which included 474 pancreatectomies for PDAC. Only patients with a final pathological diagnosis of PDAC were included in the present study. Results: Overall, 21.1% of patients with pancreatectomies for PDAC required a venous resection (100 patients out of 474 patients). Segmental resection was performed in 77 patients (out of 100 patients with pancreatectomies and venous resection - 77%), while 23 patients (23%) have had tangential venous resection. In the group of patients with segmental venous resection, reconstruction was made by end-to-end anastomosis in 53 patients (out of 77 patients - 68.8%), while in 24 patients (out of 77 patients - 31.2%) a graft interposition was necessary. Negative resections margins were obtained in 63 patients (63%). Histological tumor invasion of the resected vein was confirmed in 64 patients (64%). Postoperative complications occurred in 47 patients (47%), with severe complications (i.e., Dindo-Clavien grade III-V) in 19 patients (19%). Postoperative pancreatic fistulae, delayed gastric emptying and post-pancreatectomy hemorrhage rates were 9%, 20% and 15%, respectively. PV/ SMV thrombosis occurred in 5 patients (5%). The 90-day mortality rate in the group of patients with venous only resection, without any associated procedures, was 8%. Adjuvant treatment was performed in 63 patients (63%), while only 2 patients (2%) underwent neoadjuvant chemotherapy. Median follow-up time was 105 months (range, 3 - 186 months), with a median overall survival time of 13 months (range, 3 - 186 months). In the group of patients with negative resection margins, the median overall survival time was 16 months (range, 3 - 186 months). Conclusions: PV/ SMV resection during pancreatectomies for PDAC is technically feasible, and grafts are rarely required for venous reconstruction. However, venous resection is associated with high postoperative complications rates, and the mortality rate is not neglectable. The main goal of such complex procedure is to obtain negative resection margins, a situation associated with encouraging survival rates.

Growth-dependent accumulation of monoalkylglycerol in Madin-Darby canine kidney cells. Evidence for a role in the regulation of protein kinase C. 1-O-Alkyl-sn-glycerol (alkylglycerol) forms the backbone of complex ether-linked glycerolipids, including biologically active lipids such as platelet-activating factor. Synthetic alkylglycerol itself possesses several potent pharmacological activities and has been shown to inhibit protein kinase C (PKC) in vitro. In spite of these properties, free alkylglycerol has been regarded only as a potential product of the inflammatory degradation of complex ether lipids rather than a natural cell constituent. To explore the possibility that endogenous alkylglycerol functions as a physiological regulator in normal cells, we measured its content, along with related monoglycerides and diglycerides, by high performance liquid chromatography and gas-liquid chromatography in Madin-Darby canine kidney (MDCK) cells. The content of free alkylglycerol increased up to 20-fold during the growth of MDCK cell cultures to a confluent density. The increase was greatest during the log phase of growth, in which the content of alkylglycerol rose from 6.0 +/- 1.3 nmol/10(8) cells in preconfluent cultures to 23.6 +/- 3.4 nmol/10(8) cells in confluent cultures. Analysis of the molecular species of alkylglycerol showed that the higher content in quiescent MDCK cells was due primarily to an increase in 1-O-octadecyl-sn-glycerol. In contrast, the levels of monoacylglycerol and the PKC activator diacylglycerol were lower in confluent, quiescent cultures than in preconfluent, proliferating cultures. A similar pattern of changes in the monoglyceride and diglyceride content was observed in interleukin-3-dependent CFTL-12 mast cells when cell proliferation was blocked by growth factor withdrawal. Growth of MDCK cells to a confluent density resulted in a decrease in particulate PKC enzyme activity to a level that was only 6% of that in proliferating cells. To explore whether the accumulation of cellular alkylglycerol contributes to growth-dependent changes in PKC activity, we examined the effects of adding alkylglycerol to the activity and subcellular distribution of the enzyme in MDCK cells. Treatment of cells with 1-O-dodecyl-sn-glycerol resulted in a decrease in the activity of membrane-associated PKC activity and inhibited 12-O-tetradecanoylphorbol-13-acetate-stimulated translocation of PKC from the cytosol to the membrane fraction. Alkylglycerol was also shown to inhibit the activity of purified PKC in vitro when present at levels similar to that of the diacylglycerol activator. We propose that the accumulation of alkylglycerol during the growth of MDCK cells to a confluent density contributes to the decrease in PKC activity. The control of cellular alkylglycerol levels may be a novel mechanism for the regulation of cellular physiology.

Mechanisms of autoimmunity in the context of T-cell tolerance: insights from natural and transgenic animal model systems. There are a number of mechanisms which cooperate to produce and maintain T-cell tolerance. First, and perhaps most important, is the clonal deletion in the thymus of T cells with high affinity for self antigens. However, to ensure that a wide repertoire of T cells is available in the periphery to combat foreign antigens, the threshold of clonal deletion may be set low enough so that T cells whose TCR's have sub-threshold affinity for self antigens mature and migrate to the periphery. T cells which recognize self antigen-derived peptides not expressed or presented in the thymus will also fail to be deleted. For those self-reactive T cells which are not deleted in the thymus, other mechanisms may produce tolerance, including an undefined alteration of signalling pathways which produces clonal anergy, and lowering the avidity of the TCR for its ligand by downregulating coreceptor and accessory molecules. Active suppression of T-cell responses in another well-described phenomenon whose mechanism is undefined. From our observations with the model systems discussed here, we have observed three distinct mechanisms by which T-cell tolerance can be circumvented, allowing autoimmune phenomena to occur. These mechanisms may have relevance for different types of autoimmune diseases seen in humans. In gld mice, the autoimmune disease seems to be related to a global defect in T-cell differentiation and function, which allows for the expansion of autoimmune B cells. While we showed that clonal deletion of V beta-bearing T cells is appropriate in certain cases, aberrant lymphokine secretion by the abnormal T cells or disruption of immune system regulation are most probably responsible for allowing autoantibody production. While human lupus erythematosis shares much of the pathology of lpr and gld mice, there is no expansion of T cells with a similar phenotype in human lupus. There are environmental factors which must play a role in the development of human lupus, since the incidence of the disease does not follow an absolute genetic pattern. The escape from clonal deletion and subsequent reactivation of autoimmune T cells which we observed in V beta 8.1 TCR-transgenic mice can be a model for human autoimmune diseases such as multiple sclerosis and type I diabetes, in which T cells are directed against a specific autoantigen. According to this model, susceptibility loci for autoimmune disease such as the MHC would function by producing different repertoires of T cells which in some cases could gain autoreactivity following activation.(ABSTRACT TRUNCATED AT 400 WORDS)

Sexual Quality of Life in Homosexual and Bisexual Men: The Relative Role of Minority Stress. Minority stress is an important risk factor for sexual problems in gay and bisexual men. It remains unclear whether and to what extent this stress is associated with the sexual quality of life in these groups. To investigate the significance of minority stress as a factor explaining the sexual quality of life in gay and bisexual men. The analysis is based on data collected in an Internet study on the sexuality of Polish gay, bisexual, and straight men. Multiple regression analysis was used to investigate the importance of minority stress in explaining the sexual quality of life in a group of 1,486 non-heterosexual men in the context of other predictors, including demographics, the level of current sexual function, sexual patterns and experiences, and mental and physical health. We used the Sexual Minority Stress Scale based on Ilan Meyer's Minority Stress Model, with its subscales relating to internalized homophobia, expectation of rejection, concealment, and sexual minority negative events. The level of sexual functioning was evaluated using 2 scales, the International Index of Erectile Functioning and the Premature Ejaculation Diagnostic Tool. Data on the remaining predictors were obtained using a survey that we developed. The men's sexual quality of life as rated on the Sexual Quality of Life Scale for Men was a dependent variable. Internalized homophobia (β = -0.28; P < .001) and sexual minority negative events (β = -0.09; P < .001) were statistically significant predictors of sexual quality of life in non-heterosexual men. Internalized homophobia (β = -0.28; P < .001) and erectile function (β = 0.29, P < .001) turned out to be the strongest predictors. Sexual orientation (gay vs bisexual) and its interactions with individual processes of minority stress were statistically nonsignificant. To evaluate and improve the sexual quality of life of non-heterosexual men, it is necessary to consider not only their sexual function, but also the minority stress they experience, particularly internalized homophobia. The major strengths of the study include a large sample size, a comprehensive assessment of minority stress, and the previously understudied Central European cultural context. The major limitations are the nonrepresentative sampling, retrospective data collection, and cross-sectional design. Internalized homophobia predicts poorer sexual quality of life in gay and bisexual men in Poland. Grabski B, Kasparek K, Müldner-Nieckowski Ł, et al. Sexual Quality of Life in Homosexual and Bisexual Men: The Relative Role of Minority Stress. J Sex Med 2019;16:860-871.

[Determination of in vitro susceptibilities of Brucella spp. strains against 11 different antibacterial gents isolated from blood cultures]. Brucellosis is a worldwide zoonotic disease and still continuous to be a major public health problem. In this study, it was aimed to identify the Brucella strains to the species level isolated from blood cultures, and to determine the rate of antimicrobial susceptibility against eleven antibacterial agents. A total of 106 Brucella spp. strains were included in the study, which were isolated from blood cultures in University of Health Sciences, Konya Training and Research Hospital, Medical Microbiology Laboratory between January 2011 and June 2013. Identification of the isolated strains were mainly based on conventional methods. In vitro antibacterial susceptibilities of azithromycin, ciprofloxacin, doxycycline, gentamicin, levofloxacin, moxifloxacin, rifampicin, streptomycin, tetracycline, tigecycline, and trimethoprim/sulfamethoxazole, were evaluated by using the gradient (E-test, bioMerieux, France) strip method. The bacterial suspensions adjusted to 0.5 McFarland turbidity was inoculated to Mueller Hinton agar plates, supplemented with 5% sheep blood, and E-test strips of selected antibacterial were applied. The plates were incubated in ambient air 48 hours at 37ºC and Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 29213 were used as quality control strains for antimicrobial susceptibility testing. Minimum inhibitors concentration (MIC) values were interpreted according to Clinical and Laboratory Standards Institute (CLSI) guidelines for slow-growing bacteria such as Haemophilus spp. Of the 106 Brucella spp. strains included in to the study, 90 were identified as Brucella melitensis, and 16 were Brucella abortus. MIC90 values of azithromycin, ciprofloxacin, doxycycline, gentamicin, levofloxacin, moxifloxacin, rifampicin, streptomycin, tetracycline, tigecycline, and trimethoprim/sulfamethoxazole were determined as 1 µg/ml, 0.25 µg/ml, 0.19 µg/ml, 0.25 µg/ml, 0.19 µg/ml, 0.75 µg/ml, 0.25 µg/ml, 0.75 µg/ml, 0.38 µg/ml, 0.64 µg/ml, and 0.19 µg/ml respectively. According to MIC90 values, gentamicin, moxifloxacin, and trimethoprim/sulfamethoxazole, were the most effective antibacterial agents. All the Brucella strains were sensitive to all the tested antibacterial agents except rifampicin. Only six isolates showed intermediate susceptibility to rifampicin. With regard to fluoroquinolones, the most active antibacterial agent was moxifloxacin, followed by ciprofloxacin and levofloxacin. In our study, no resistance was found for the classically recommended antibacterial agents used in the treatment of Brucella species in our hospital but antibiotic susceptibility patterns of Brucella spp. may vary geographically. As a result it was concluded that, the antimicrobial susceptibilities of Brucella species should be determined and controlled periodically to avoid the possible development of resistance problems in the future.

The relationship between activity clusters detected by an automatic activity monitor and endocrine changes during the periestrous period in lactating dairy cows. The aim of this study was to determine the relationship between observed estrous-related behavior, activity clusters (AC; detected by automatic activity monitor), endocrine profiles, and ovulation time. Twenty-one cows in estrus (after 2 cloprostenol treatments, 11 d apart) and 12 nonsynchronized cows, to establish Heatime (SCR Engineers Ltd., Netanya, Israel) herd baseline activity, were enrolled. Cows had Heatime monitors applied 3 wk before the trial to establish their own baseline activity level. Cows in standing estrus had ultrasonography and phlebotomy carried out every 4 h to determine dominant follicle size, endocrine profiles, and ovulation time. After ovulation, these procedures were repeated once on d 3 to 6. Heatime alerted estrus in 90% of cows, and incorrectly alerted 17% of AC. The mean±SEM duration for standing estrus was 9±1 and 13±1 h for estrous-related behavior. Estrous-related behavior began after the start of the proestrous estradiol-17β (E2) increase (59±6.5 h). Cows with longer durations of raised proestrous E2 had longer intervals from its onset to the start of standing estrus and AC. The AC duration increased with longer durations of estrous-related behavior. Higher peak E2 occurred with longer standing estrus and estrous-related behavior. As E2 concentration decreased after the peak, 90% of cows still had estrous-related behavior. Duration of estrous-related behavior increased with higher average E2 concentration during the last 8 h before the start of the LH surge. During this surge 90% of cows had all of their standing estrus. As yields increased, so did the magnitude of the preovulatory FSH surges. Higher surges occurred with shorter standing estrus and estrous-related behavior. Cows with shorter LH surges had longer standing estrus. Peak LH preceded the AC peak (6.6±0.8 h). Duration of overlap between the AC start and the LH surge end ranged between 0 and 14 h; 1 cow had none. No association was found between the AC characteristics with the E2, LH, or FSH profiles. In conclusion, the relationship between the timing of the E2 increase and estrous activity may be mediated by other factors (GnRH surge). Estrous-related behavior, but not endocrine profiles, was related to AC duration. Timing of standing estrus during the LH surge ensures that mating allows sperm maturation before ovulation. Based on the interval from the start of an AC to ovulation (27±1 h), the optimum time to artificial insemination is, on average, between 9 and 15 h after the AC start.

The relationship of laser-Doppler skin blood flow measurements to the cutaneous microvascular anatomy. The hairless plantar paw surface of the rat shows high skin blood flow with a substantial response to thermal stimulation. This contrasts with hair-covered areas such as the back, where there is much lower basal flow and thermal response. These properties are similar to the differences seen in humans between skin sites which have a high density of arterioles and venules (AV areas) and sites with predominantly nutritive (NUTR) capillary perfusion. However, there has been no previous study of the microvascular anatomy of rodent skin. We used NIH Image, a quantitative imaging program, to count the capillaries, arterioles, and venules in the skin of the plantar paw surface and the back of 14 Wistar-Kyoto rats. We also used laser-Doppler techniques to determine skin blood flow at these sites. We found significantly more vessels per unit area at the paw. There were twice as many capillaries in the paw (19.6 +/- 2.4 per mm2) compared to the back (9 +/- 1.5 per mm2) (P < 0.001). Similarly, there were three times as many venules (11.8 +/- 1.2 per mm2 vs 3. 48 +/- 0.45 per mm2; P < 0.001). The largest difference was in the number of arterioles (7.76 +/- 0.74 per mm2 vs 0.79 +/- 0.13 per mm2 at the back; P < 0.001). The greater microvascular density at the paw was reflected in a threefold higher basal blood flow (6.6 +/- 0. 44 ml/min/100 g) compared to that in the back (1.99 +/- 0.07 ml/min/100 g) (P < 0.001). Microvascular volume at the back was 0.14 +/- 0.01 x 10(6) RBC/ml in the basal state compared to 0.31 +/- 0.01 x 10(6) RBC/ml at the paw. Thus, the increased number of vessels at the paw resulted in a twofold increase in microvascular volume. The plantar paw surface has considerably more vessels than the back. As might be expected, there is a higher proportion of arterioles and venules compared to capillaries at the paw than at the back. Thus, the plantar paw surface is an AV site compared to the back, which is a NUTR site. Although our prior studies have largely assumed that we could use the paw and back as contrast sites comparable to AV and NUTR sites in humans, we have now for the first time conclusively established this fact. The increased microvascular density at the paw results in higher skin blood flow at this site.

Beta-endorphin, but not oxytocin, substance P or vasoactive-intestinal polypeptide, contributes to progesterone-induced prolactin secretion in monkeys. Progesterone (P) stimulates prolactin secretion through a neural mechanism in estrogen (E)-primed female monkeys. Several peptides, including beta-endorphin (BE), oxytocin (OT), substance P (SP) and vasoactive intestinal polypeptide (VIP) are potential prolactin stimulatory factors and could mediate the effect of P. We hypothesized that the antagonism of a pivotal peptidergic neural system would block P-induced prolactin secretion and that the function of a pivotal peptidergic system would be altered by changes in gonadal steroid concentrations. Therefore it was of interest (1) to examine the effect of infusion of antagonists to these peptides on P-induced prolactin secretion, and (2) to determine BE, OT, SP and VIP levels in the hypothalamus of monkeys of various reproductive states. For the antagonist studies, female monkeys (n = 8) were spayed, adapted to a vest and tether remote sampling system and catheterized prior to antagonist challenges. E-primed monkeys received P injections 48 h prior to antagonist administration. Prolactin increased within 36-48 h of P injection. All antagonist challenges were administered in varying doses during the P-induced prolactin elevation and blood samples were collected every 10 min for prolactin determinations. The opiate antagonist, naloxone (n = 5), reduced serum prolactin in a dose-related manner with a mean IC50 of 1.5 +/- 0.6 micrograms/kg/min. The OT (n = 4), SP (n = 4) or VIP (n = 4) antagonists did not reduce serum prolactin in a dose-related manner. We previously reported that the hypothalamic content of OT is increased by ovarian hormones. To determine whether the hypothalamic content of BE, SP or VIP was related to gonadal status, the peptide levels in 4 hypothalamic regions of monkeys in various physiological states were measured. BE (ng/mg protein) in the medial basal hypothalamus (MBH) was significantly greater in adult females (17.7 +/- 6.9; n = 6) as compared to spayed females (0.6 +/- 0.2; n = 3) and juvenile females (1.8 +/- 1.1; n = 3). Hypothalamic content of SP in the preoptic area and mammillary bodies, but not the MBH, was significantly greater in gonadal intact females than spayed females. VIP content (pg/mg protein) was not significantly different between adult, spayed and juvenile females nor between adult and juvenile males in any hypothalamic area. Taken together these results support a pivotal role for BE in the neural regulation of P-induced prolactin secretion. The involvement of OT, SP, and VIP in a specific manner at the pituitary level is not indicated.

[Effects of meisoindigo on the expression of globin gene in vitro]. The pathophysiology of beta-thalassemia is the imbalance of the alpha and non-alpha globin chain which leads to a series of clinical symptoms of hemolytic anemia. Scientists continuously try to explore gene-activated drugs to increase the level of non-alpha globin chain or decrease the level of alpha globin chain in the treatment of beta-thalassemia. To probe into the effects on globin-gene expression of meisoindigo (Me) in cultured erythroid cells derived from peripheral blood, so as to provide the theoretical basis for applying Me in the treatment of beta-thalassemia. By using the two-step liquid culture of erythroid progenitor cells and reverse transcription polymerase chain reaction (RT-PCR), and by using alpha mRNA as an inner control, the level of gamma mRNA and beta mRNA in cultured erythroid cells derived from peripheral blood of 11 patients with severe beta-thalassemia and 6 normal volunteers were measured under the effect of different concentration (2.5 micro mol/L, 5 micro mol/L and 10 micro mol/L) of Me. (1) No statistic significance was found in the ratio of beta/alpha mRNA by Me in cultured cells from both normal individuals and beta-thalassemia. (2) Me can significantly increase the ratio of gamma/alpha mRNA and (beta + gamma)/alpha mRNA (that is non-alpha/alpha mRNA) in cultured cells from normal individuals and beta-thalassemia. The ratio of gamma/alpha mRNA was increased 0.31 - 0.45 times and the ratio of non-alpha mRNA/alpha mRNA increased 0.21 - 0.32 times in Me induced cells from normal individuals. No significant result was observed among the different concentrations of Me (2.5 micro mol/L, 5 micro mol/L and 10 micro mol/L) in normal individuals. With the increasing of Me concentrations, the ratios of gamma/alpha mRNA and alpha/alpha mRNA were increased in cultured cells from beta-thalassemia. The ratio of gamma/alpha mRNA was increased 0.33 - 1.17 times and the ratio of non-alpha/alpha mRNA increased 0.25 - 0.89 times in Me induced cells from beta-thalassemia. There was no significant difference between the concentrations of 2.5 micro mol/L and 5 micro mol/L concentration in beta-thalassemia. However, there was significant difference between the concentrations of 10 micro mol/L and the concentrations of 2.5 micro mol/L and 5 micro mol/L in beta-thalassemia. (3) The increase of the ratio of gamma/alpha mRNA and non-alpha/alpha mRNA in beta-thalassemia was higher than that in normal individual with induction by Me with a higher concentration (10 micro mol/L). Me can raise the ratio of gamma/alpha mRNA and non-alpha/alpha mRNA in cultured erythroid cells derived from peripheral blood of both normal individual and beta-thalassemia in the level of transcription, which can improve the imbalance of the alpha and non-alpha globin chain. So Me has a latent value in the therapy of beta-thalassemia.

A quantitative method of analyzing the interaction of slightly selective radioligands with multiple receptor subtypes. Subclasses of receptors exist for most neurotransmitters. Frequently, two subtypes of receptors coexist in the same tissue and, in some cases, they mediate the same physiological response. In tissues with two classes of binding sites for a given hormone, an estimate of the proportion of each class of binding sites is obtained by inhibiting the binding of a single concentration of a radioligand with a selective unlabeled ligand. Accurate estimates of the density of each class of receptors will only be obtained, however, if the radioligand is entirely nonselective. Selectivity of just 2- to 3-fold can markedly influence the results of subtype analysis. The conclusion that a radioligand is nonselective is usually based on the results of a saturation binding curve. If Scatchard analysis of such data results in a linear plot, then it is concluded that the radioligand is nonselective. However, Scatchard analysis cannot distinguish between a radioligand that is nonselective and one that is slightly selective. The use of a slightly selective radioligand can lead to errors of 50% or more, depending on the concentration of the radioligand relative to the Kd values of the two classes of sites. A new analytical method has been developed that can be used to quantitate 2- to 3-fold differences in the affinity of two distinct classes of binding sites for a radioligand. This new approach requires that a series of inhibition experiments with a selective unlabeled ligand be performed in the presence of increasing concentrations of the radioligand. Analysis of the resulting inhibition curves, utilizing the mathematical modeling program MLAB on the PROPHET system, yields accurate estimates of the density of each class of receptor as well as the affinity of each receptor for the labeled and unlabeled ligands. This approach was used to determine whether 125I-iodopindolol shows selectivity for beta 1- or beta 2-adrenergic receptors. A series of inhibition curves was generated with the unlabeled ligands ICI 89,406 (beta 1-selective) and ICI 118,551 (beta 2-selective), using membranes prepared from C6 glioma cells. These cells contain both beta 1- and beta 2-adrenergic receptors. 125I-Iodopindolol was determined to be 3-fold selective for beta 2-adrenergic receptors. Since the sensitivity of this approach is superior to that of Scatchard analysis, it is likely that other radioligands, previously thought to be nonselective, will be shown to be selective when analyzed by this method.

Hybrid formation between the intracellular faces of the bradykinin B2 and angiotensin II AT1 receptors and signal transduction. Most frequently, the physiologic functions of the angiotensin II (Ang II) type 1 receptor (AT1R) and bradykinin B2 receptor (BKB2R) are antagonistic, particularly with respect to the regulation of vascular tone. Despite major differences in their physiologic actions, the receptors share sequence similarities. Both link to Galpha(i) and Galpha(q) and transduce very similar signal paths, not only those relating to the traditional G-protein associated second messengers, but also those involved in transactivation mechanisms involving receptor tyrosine kinases. With respect to these paths, some differences in signaling may be accounted for by cell type specificity. However, alternative signal cascades for these two receptors are becoming increasingly evident. One such is the recruitment of signaling molecules upon receptor translocation and internalization. The AT1R translocates into clathrin-coated pits and internalizes upon recruitment of beta-arrestin 2 which then recruits ASK1 and JNK3. The BKB2R translocates and internalizes mainly via caveolae. Another signaling divergence may be due to the direct activation of small G-proteins by both receptors. AT1R activates the RhoA, Rac1, Cdc42 while BKB2R couples only with Rac1 and Cdc42. Both receptors may serve as docking stations for intracellular proteins. One such example is the YIPP motif within the C-terminus of the ATIR which associates with the JAK/STAT pathway. Another potential alternative is the activation of tyrosine/serine kinase phosphatases by BK. This mechanism may directly oppose some of the protein tyrosine/ serine kinase paths activated by AT1R. These alternative mechanisms in sum are potentially responsible for the diversion in signal transduction between these two receptors. Regardless of the route of action, our results suggest that in Rat-1 fibroblasts stably transfected with BKB2R, BK slightly decreases connective tissue growth factor (CTGF) mRNA level while in ATIR transfected cells Ang II increases CTGF mRNA markedly. To determine whether mutant hybrids can be formed between these two receptors which encompass some of the function of the donor receptor but bind the ligand of the recipient receptor, a series of hybrids were formed with BKB2R the recipient and AT1R the donor receptor. Some of these hybrids show resistance to exchanges with the AT1R and form receptors which either do not bind (IC1 exchanges) or demonstrate poor function but normal internalization (proximal C-terminus exchanges). However, other hybrids have proven very functional. For example, the IC2, IC3 and distal C-terminus of the BKB2R IC face can be replaced simultaneously with the AT1R resulting in an hybrid which binds BK, continues to signal, is internalized and resensitized. Formation of this and other less extensive hybrids is discussed. Some of these hybrids possess the capacity to function as the AT1R as exemplified by their ability to upregulate CTGF expression as wild-type (WT) AT1R.

Digital image archiving: challenges and choices. In the last five years, imaging exam volume has grown rapidly. In addition to increased image acquisition, there is more patient information per study. RIS-PACS integration and information-rich DICOM headers now provide us with more patient information relative to each study. The volume of archived digital images is increasing and will continue to rise at a steeper incline than film-based storage of the past. Many filmless facilities have been caught off guard by this increase, which has been stimulated by many factors. The most significant factor is investment in new digital and DICOM-compliant modalities. A huge volume driver is the increase in images per study from multi-slice technology. Storage requirements also are affected by disaster recovery initiatives and state retention mandates. This burgeoning rate of imaging data volume presents many challenges: cost of ownership, data accessibility, storage media obsolescence, database considerations, physical limitations, reliability and redundancy. There are two basic approaches to archiving--single tier and multi-tier. Each has benefits. With a single-tier approach, all the data is stored on a single media that can be accessed very quickly. A redundant copy of the data is then stored onto another less expensive media. This is usually a removable media. In this approach, the on-line storage is increased incrementally as volume grows. In a multi-tier approach, storage levels are set up based on access speed and cost. In other words, all images are stored at the deepest archiving level, which is also the least expensive. Images are stored on or moved back to the intermediate and on-line levels if they will need to be accessed more quickly. It can be difficult to decide what the best approach is for your organization. The options include RAIDs (redundant array of independent disks), direct attached RAID storage (DAS), network storage using RAIDs (NAS and SAN), removable media such as different types of tape, compact disks (CDs and DVDs) and magneto-optical disks (MODs). As you evaluate the various options for storage, it is important to consider both performance and cost. For most imaging enterprises, a single-tier archiving approach is the best solution. With the cost of hard drives declining, NAS is a very feasible solution today. It is highly reliable, offers immediate access to all exams, and easily scales as imaging volume grows. Best of all, media obsolescence challenges need not be of concern. For back-up storage, removable media can be implemented, with a smaller investment needed as it will only be used for a redundant copy of the data. There is no need to keep it online and available. If further system redundancy is desired, multiple servers should be considered. The multi-tier approach still has its merits for smaller enterprises, but with a detailed long-term cost of ownership analysis, NAS will probably still come out on top as the solution of choice for many imaging facilities.

Routine interval computed tomography to detect new soft-tissue disease might be unnecessary in patients with androgen-independent prostate cancer and metastasis only to bone. To identify patients with androgen-independent prostate cancer (AIPC) with bone metastasis and no soft-tissue metastases at the time of protocol enrollment, and analyse their disease progression by computed tomography (CT), bone scan, and prostate-specific antigen (PSA) level to determine the utility of routine interval CT in such patients. Bone is the most common metastatic site in patients with AIPC and the only site of metastatic disease for many; because some with initial bone metastasis eventually develop soft-tissue disease, many clinical trials use routine CT to monitor for the latter as a sign of disease progression, but the actual incidence of new soft-tissue metastases is unknown and the role of routine interval CT in monitoring for disease progression, especially for asymptomatic patients, is unclear. Thus we reviewed 175 cases of metastatic AIPC from three randomized phase II clinical trials (docetaxel/thalidomide, docetaxel/vaccine, and ketoconazole/alendronate) at the National Cancer Institute between 1995 and 2004. The patients' PSA levels were assessed every 4 weeks, and CT and bone scans were done every 2-3 months. We retrospectively identified patients with bone metastasis only and examined subsequent CT for the occurrence of soft-tissue disease. For patients with progressive disease, we also examined bone scan and PSA progression. Of 175 patients with metastatic prostate cancer, 105 (60%) had bone metastasis only, 12 (6.9%) had soft-tissue metastases only, and 58 (33.1%) had both bone and soft-tissue metastases. The median (range) follow-up was 8 (1-44) months for the 105 patients with bone metastasis only. During that time, two patients (1.9%) developed new soft-tissue disease; one developed right iliac fossa lymphadenopathy after 8 months and the other developed a perirectal mass after 12 months. The patient with new lymphadenopathy also had multiple new bone lesions identified by bone scan and PSA progression. The patient with the perirectal mass had PSA progression and a palpable abnormality. This review of patients with AIPC and bone metastasis only, followed for a median of 8 months on clinical trials, shows that the incidence of asymptomatic new soft-tissue disease as the only sign of disease progression is quite low. Therefore, routine CT to exclude new soft-tissue disease in this population appears to be unwarranted. We recommend that for these patients CT is done only at the time of disease progression, as shown by bone scan, PSA level, or clinical presentation. We do not exclude the possibility that patients who remain on trial for significantly longer periods might benefit from routine interval CT.

Cost and efficacy comparison of integrated pest management strategies with monthly spray insecticide applications for German cockroach (Dictyoptera: Blattellidae) control in public housing. The long-term costs and efficacy of two treatment methodologies for German cockroach, Blattella germanica (L.), control were compared in the public housing environment. The "traditional" treatment for German cockroaches consisted of monthly baseboard and crack and crevice treatment (TBCC) by using spray and dust formulation insecticides. The integrated pest management treatment (IPM) involved initial vacuuming of apartments followed by monthly or quarterly applications of baits and insect growth regulator (IGR) devices. Cockroach populations in the IPM treatment were also monitored with sticky traps. Technician time and the amount of product applied were used to measure cost in both treatments. Twenty-four hour sticky trap catch was used as an indicator of treatment efficacy. The cost of the IPM treatment was found to be significantly greater than the traditional treatment, particularly at the initiation of the test. In the first month (clean-out), the average cost per apartment unit was dollar 14.60, whereas the average cost of a TBCC unit was dollar 2.75. In the second month of treatment, the average cost of IPM was still significantly greater than the TBCC cost. However, after month 4 the cost of the two treatments was no longer significantly different because many of the IPM apartments were moved to a quarterly treatment schedule. To evaluate the long-term costs of the two treatments over the entire year, technician time and product quantities were averaged over all units treated within the 12-mo test period (total 600 U per treatment). The average per unit cost of the IPM treatment was (dollar 4.06). The average IPM cost was significantly greater than that of the TBCC treatment at dollar 1.50 per unit. Although the TBCC was significantly less expensive than the IPM treatment, it was also less effective. Trap catch data indicated that the TBCC treatment had little, if any, effect on the cockroach populations over the course of the year. Cockroach populations in the TBCC treatment remained steady for the first 5 mo of the test and then had a threefold increase during the summer. Cockroach populations in the IPM treatment were significantly reduced from an average of 24.7 cockroaches per unit before treatment to an average 3.9 cockroaches per unit in month 4. The suppressed cockroach populations (< 5 per unit) in the IPM treatment remained constant for the remaining 8 mo of the test.

Statistical methods for the analysis of two-arm non-inferiority trials with binary outcomes. The aim of this contribution is to give an overview of approaches to testing for non-inferiority of one out of two binomial distributions as compared to the other in settings involving independent samples (the paired samples case is not considered here but the major conclusions and recommendations can be shown to hold for both sampling schemes). In principle, there is an infinite number of different ways of defining (one-sided) equivalence in any multiparameter setting. In the binomial two-sample problem, the following three choices of a measure of dissimilarity between the underlying distributions are of major importance for real applications: the odds ratio (OR), the relative risk (RR), and the difference (DEL) of both binomial parameters. It is shown that for all three possibilities of formulating the hypotheses of a non-inferiority problem concerning two binomial proportions, reasonable testing procedures providing exact control over the type-I error risk are available. As a particularly useful and versatile way of handling mathematically nonnatural parametrizations like RR and DELTA, the approach through Bayesian posterior probabilities of hypotheses with respect to some non-informative reference prior has much to recommend it. In order to ensure that the corresponding testing procedure be valid in the classical, i.e. frequentist sense, it suffices to use straightforward computational techniques yielding suitably corrected nominal significance levels. In view of the availability of testing procedures with satisfactory properties for all parametrizations of main practical interest, the discussion of the pros and cons of these methods has to focus on the question of which of the underlying measures of dissimilarity should be preferred on grounds of logic and intuition. It is argued that the OR clearly merits to be given preference also with regard to this latter kind of criteria since the non-inferiority hypotheses defined in terms of the other parametric functions are bounded by lines which cross the boundaries of the parameter space. From this fact, we conclude that the exact Fisher type test for one-sided equivalence provides the most reasonable approach to the confirmatory analysis of non-inferiority trials involving two independent samples of binary data. The marked conservatism of the nonrandomized version of this test can largely be removed by using a suitably increased nominal significance level (depending, in addition to the target level, on the sample sizes and the equivalence margin), or by replacing it with a Bayesian test for non-inferiority with respect to the odds ratio.

Beyond the dichotomy: a tool for distinguishing between experimental, innovative and established treatment. The precise delineation of the research phase is a recurrent subject of debate: When is the evidence base firm enough to decide that a new technology or treatment no longer needs to be regarded as 'experimental'? We propose a framework that distinguishes between three instead of two types of treatment and describes a continuum from experimental over innovative to established treatment, offering a tool meant to facilitate decision-making about the introduction of new technologies in the clinic. Traditionally, guidelines from medical societies on the notion of 'experimental treatment' depart from a dichotomy between experimental and established treatment. However, in the field of reproductive medicine, there are several problems with a dichotomous framework. First, it does not offer an adequate account of the reality in the clinic. Secondly, this view may bring about several negative effects for the patient, such as techniques being considered established too early, holding risks unknown to patients. A further drawback of the dichotomy is that if a technique is no longer considered experimental, centres offering the technique may no longer consider it useful gathering and critically examining (follow-up) data. The framework and scoring tool were developed over several phases during which the authors operated as a consensus group of experts. The scoring tool reflects the continuous progression of a new procedure from experimental through innovative to established. For this evolution, four criteria were considered relevant. The first (efficacy) is a categorical criterion (pass/fail). The other three criteria (safety, procedural reliability and transparency and effectiveness) are ordinal in nature. Thresholds have been introduced for all four criteria to avoid that a technology scoring high on procedure and effectiveness but extremely low on safety could move to the next level because of a sufficiently high overall score. Only treatments that are rated above the thresholds for all four criteria could be considered at least innovative treatments. When they score 4 or higher on the last three criteria, they are considered established treatments. Knowledge about the procedures or techniques under discussion is essential in order to use the tool. The tool is designed to be used on a macro-level (e.g. by professional societies) although it could also be valuable in the local setting. Both the framework and the tool can bring more clarity on the notion of 'experimental treatment', especially with regard to how to decide when a specific technology or treatment falls in this category and when it can move into one of the other categories. none. none.

Guiding Principles for the use of Fluroquinolones in Out-patient Community Settings of India: Panel Consensus. Respiratory tract infections have been an important cause of morbidity and mortality worldwide that is looming large especially in context of antibiotic resistance that is confronted both by a pulmonologist as well as a general practitioner. A reflection to this trend has been the rising phenomenon of MICs as shown the respiratory pathogens towards conventional antibiotics including macrolides or β lactam/β lactamase inhibitor combinations. Respiratory fluoroquinolones offer broad yet potent cover of respiratory pathogens leading to their obvious choice for empirical therapy for clinical persisters or high risk cases with prior history of antibiotics not-withstanding the clinical concerns in tropical countries. To further assess the clinical role of respiratory quinolones in outpatient settings of India especially in line with the known endemicity of chronic infections or tuberculosis. Cross-sectional, national survey questionnaire survey to explore the clinical perceptions, attitude and insights on the clinical use of respiratory fluoroquinolones was rolled out amongst pulmonologists and consultant physicians practicing respiratory medicine in India. Descriptive statistics was utilized to describe the numerical and categorical data. Nationwide representative sample of fourteen pulmonologists provided response and clinical insight on the current management strategies for community acquired pneumonia (CAP) with 'respiratory' fluoroquinolones. Each of the doctor in the panel agreed that the ideal antibiotic for the treatment in CAP or lower respiratory tract infection (LRTI) should be highly effective with lesser side effects and broader spectrum covering atypical bacteria. Doctors agreed that most the fixed dose combination (FDC) has gone into disrepute probably because of pharmacokinetic incompatibility that could have further fuelled the epidemic of antibiotic resistance. 9 (64%) doctors suggested that there is omnipresence if not overwhelming presence of patient poor response to beta-lactam or fluoroquinolones in clinical practice. It was agreed that fluoroquinolones would be the rightful choice for patients with prior history of antibiotic use with or without comorbidities. Amongst the newer fluoroquinolones available, Garenoxacin offers broad and potent action against resistant strains for CAP. Despite the overwhelming concern of tropical infection in Indian context, Garenoxacin could be considered for mono- or add-on therapy in moderate to severe yet stable cases of CAP. Short course therapy of 5 to 10 days should offer no complimentary masking of anti-mycobacterial activity since the relevant minimum inhibitory concentration (MIC90) are high that are beyond the comprehension of suggested therapeutic dose of 400 mg tablets. The growing incidence of Macrolide resistance suggests the clinical role of new generation fluoroquinolones including Garenoxacin as a clinically useful therapeutic strategy for moderate to severe CAP as monotherapy or in combination.

Alterations in metabolic clearance of atrial natriuretic peptides in heart failure: how do they relate to the resistance to atrial natriuretic peptides? Deficiencies in activity of the atrial natriuretic peptide (ANP) system may be able to explain the disturbed electrolyte and fluid homeostasis occurring in chronic heart failure. Generally, in studies concerning the possible pathophysiologic role of ANP in heart failure, only the circulating levels of the hormone were measured. It has been shown, however, that plasma ANP levels exhibit marked variability attributable to the pulsatory pattern of secretion and to its very short plasma half-life. An evaluation of the main turnover parameters might represent a significant improvement in the assessment of the functioning of the overall ANP system. By using a tracer method, which does not alter the steady-state condition, a disturbed peripheral metabolism of ANP and a resistance to its biologic effects was demonstrated in patients with idiopathic dilated cardiomyopathy, even in those in the asymptomatic phase of the disease, showing ANP circulating levels, atrial pressure and volume, and cardiac index within the normal range. The altered degradation and distribution of ANP in patients with heart failure were demonstrated by a great increase in metabolic clearance (on average, 2.5-fold), production (on average, 6-fold), or both, and by a progressive reduction in the distribution spaces of the hormone when compared with normal subjects at the same sodium intake. The ratio between ANP disposal and the daily excretion of sodium (equal to the sodium intake in subjects at a strictly controlled sodium balance) may give a good index of the biologic activity (natriuresis) of the ANP system. Preliminary studies suggest that an index of biologic activity of the ANP system may be a useful tool for the comparison of the efficacy of different therapeutic strategies in heart failure. Indeed, after a 2-month treatment with an angiotensin-converting enzyme inhibitor, this index was returned to within the normal range, suggesting that the drug was able to "normalize" the peripheral distribution and degradation of the hormone in these patients. Although future studies in a large series of patients will be useful to assess this important issue, the setup of accurate methods able to evaluate the presence and degree of resistance to biologic activity of ANP may be a useful tool in the follow-up evaluation of patients with heart failure, and may pave the way for further progress in the knowledge of more general physiologic and pathophysiologic mechanisms of this important clinical condition.

The energetics of supported metal nanoparticles: relationships to sintering rates and catalytic activity. Transition metal nanoparticles on the surfaces of oxide and carbon support materials form the basis for most solid catalysts and electrocatalysts, and have important industrial applications such as fuel production, fuels, and pollution prevention. In this Account, I review my laboratory group's research toward the basic understanding of the effects of particle size and support material on catalytic properties. I focus on studies of well-defined model metal nanoparticle catalysts supported on single-crystalline oxide surfaces. My group structurally characterized such catalysts using a variety of ultrahigh vacuum surface science techniques. We then measured the energies of metal atoms in these supported nanoparticles, using adsorption calorimetry tools that we developed. These metal adsorption energies increase with increasing size of the nanoparticles, until their diameter exceeds about 6 nm. Below 6 nm, the nature of the oxide support surface reaches also greatly affects the metal adsorption energies. Using both adsorption calorimetry and temperature programmed desorption (TPD), we measured the energy of adsorbed catalytic intermediates on metal nanoparticles supported on single crystal oxide surfaces, as a function of particle size. The studies reveal correlations between a number of characteristics. These include the size- and support-dependent energies of metal surface atoms in supported metal nanoparticles, their rates of sintering, how strongly they bind small adsorbates, and their catalytic activity. The data are consistent with the following model: the more weakly the surface metal atom is attached to the nanomaterial, the more strongly it binds small adsorbates. Its strength of attachment to the nanomaterial is dominated by the number of metal-metal bonds which bind it there, but also by the strength of metal/oxide interfacial bonding. This same combination of bond strengths controls sintering rates as well: the less stable a surface metal atom is in the nanomaterial, the greater is the thermodynamic driving force for it to sinter, and the faster is its sintering rate. These correlations provide key insights into how and why specific structural properties of catalyst nanomaterials dictate their catalytic properties. For example, they explain why supported Au catalysts must contain Au nanoparticles smaller than about 6 nm to have high activity for combustion and selective oxidation reactions. Only below about 6 nm are the Au atoms so weakly attached to the catalyst that they bind oxygen sufficiently strongly to enable the activation of O₂. By characterizing this interplay between industrially important rates (of net catalytic reactions, of elementary steps in the catalytic mechanism, and of sintering) and their thermodynamic driving forces, we can achieve a deeper fundamental understanding of supported metal nanoparticle catalysts. This understanding may facilitate development of better catalytic nanomaterials for clean, sustainable energy technologies.

Assessments of antibacterial and physico-mechanical properties for dental materials with chemically anchored quaternary ammonium moieties: thiol-ene-methacrylate vs. conventional methacrylate system. Fabrication of low shrinkage stress and strain dental resins containing highly available immobilized bactericidal moieties has been reported. The goal of this study is producing dental restorative materials with long-last antibacterial activity and reduced secondary caries. It is anticipated that antibacterial properties of quaternary ammonium moieties chemically immobilized in the backbone of dental resins is directly depended on accessibility of these functions. In the present study the antibacterial effect of a series of antibacterial monomers polymerized in a ternary thiol-ene-methacrylate system were compared with corresponding classical methacrylate system against Streptococcus mutans (an oral bacteria Strain). Physical and mechanical properties of dental materials obtained from these two systems were also evaluated and compared. The viscosities of the resin matrixes were measured on a MCR 300 rheometer. Degree of conversion (DC%) of monomers was measured using FTIR spectroscopy. The shrinkage-strain of photocured resins was measured using the bonded-disk technique. A universal testing machine combined with a stress measurement device was utilized to measure the polymerization-induced shrinkage stress. Viscoelastic properties of the samples were also determined by dynamic mechanical thermal analysis (DMTA). Assessment of antibacterial properties was performed through agar diffusion test (AD) to confirm non-release behavior of chemically anchored moieties. Quantitative assay of antibacterial activity was evaluated through direct contact test (DCT) against S. mutans. Direct contact cytotoxicity assay with fibroblast cell line L-929 was also performed to find more insight regarding cytotoxicity of the antibacterial matrixes. The data were analyzed and compared by ANOVA and Tukey HSD tests (significance level=0.05). Neat methacrylate systems had significantly higher viscosity than thiol-ene-methacrylate analogous. The degree of conversion of methacrylate moieties in thiol-ene-methacrylate system was improved in comparison to conventional methacrylate system. Shrinkage stress and strain of thiol-ene-methacrylate system was lower than the neat methacrylate system. The thiol-ene-methacrylate systems show increased homogeneity and decreased glass transition temperature (Tg) and crosslink density (νc) in comparison to the neat methacrylate-based resins. The incorporated monofuctional quaternized monomer reduces degree of conversion, shrinkage stress and crosslink density of matrix. The results showed significant improvement in antibacterial activity and cytocompatibility of dental materials obtained from thiol-ene polymerization system. It was shown that with proper control of monomers molar ratio, significant improvement in antibacterial activity and cytocompatibility as well as acceptable mechanical properties can be attained for dental resins prepared through the application of thiol-ene polymerization methodology.

Bariatric Surgery in Women of Childbearing Age, Timing Between an Operation and Birth, and Associated Perinatal Complications. Metabolic changes after maternal bariatric surgery may affect subsequent fetal development. Many relevant perinatal outcomes have not been studied in this postoperative population, and the risks associated with short operation-to-birth (OTB) intervals have not been well examined. To examine the risk for perinatal complications in women with a history of bariatric surgery (postoperative mothers [POMs]) by comparing them with mothers without operations (nonoperative mothers [NOMs]) and examining the association of the OTB interval with perinatal outcomes. This investigation was a population-based retrospective cohort study (January 1, 1980, to May 30, 2013) at hospitals in Washington State. Data were collected from birth certificates and maternally linked hospital discharge data. Participants were all POMs and their infants (n = 1859) and a population-based random sample of NOMs and their infants frequency matched by delivery year (n = 8437). Bariatric operation before birth or categories of OTB intervals. The primary outcomes were prematurity, neonatal intensive care unit (NICU) admission, congenital malformation, small for gestational age (SGA), birth injury, low Apgar score (≤8), and neonatal mortality. Poisson regression was used to compute relative risks (RRs) and 95% CIs, with adjustments for maternal body mass index, delivery year, socioeconomic status, age, parity, and comorbid conditions. A total of 10 296 individuals were included in the analyses for this study. In the overall cohort, the median age was 29 years (interquartile range, 24-33 years). Compared with infants from NOMS, infants from POMs had a higher risk for prematurity (14.0% vs 8.6%; RR, 1.57; 95% CI, 1.33-1.85), NICU admission (15.2% vs 11.3%; RR, 1.25; 95% CI, 1.08-1.44), SGA status (13.0% vs 8.9%; RR, 1.93; 95% CI, 1.65-2.26), and low Apgar score (17.5% vs 14.8%; RR, 1.21; 95% CI, 1.06-1.37). Compared with infants from mothers with greater than a 4-year OTB interval, infants from mothers with less than a 2-year interval had higher risks for prematurity (11.8% vs 17.2%; RR, 1.48; 95% CI, 1.00-2.19), NICU admission (12.1% vs 17.7%; RR, 1.54; 95% CI, 1.05-2.25), and SGA status (9.2% vs 12.7%; RR, 1.51; 95% CI, 0.94-2.42). Infants of mothers with a previous bariatric operation had a greater likelihood of perinatal complications compared with infants of NOMs. Operation-to-birth intervals of less than 2 years were associated with higher risks for prematurity, NICU admission, and SGA status compared with longer intervals. These findings are relevant to women with a history of bariatric surgery and could inform decisions regarding the optimal timing between an operation and conception.

Flooding of lignite mines: isotope variations and processes in a system influenced by saline groundwater. The quality of both groundwaters and surface waters that arise during flooding of abandoned lignite open pits are influenced by regional and local factors. A typical regional factor is due to oxidised sedimentary sulfides. A more local factor is the interaction of shallow water with highly saline groundwater, which is important in Merseburg-Ost (Germany). Investigation of this system is aided by the use of many environmental isotope tracers but special problems can arise. In order to reveal processes in the mine environment (shallow groundwater, lake water) and to characterise mixtures with saline groundwater results are described using the tracers deltaD, delta18O, delta13C, delta34S, 87Sr/86Sr, 3H, 14C, 39Ar, and 222Rn. Deep highly saline groundwater had a radiocarbon concentration typically below 10 pMC. The values of delta13C(DIC) are around-5 per thousand. As delta13C of the aquifer rock samples (Permian, Zechstein carbonates) was in the range of-6...+5 per thousand, residence time corrections based on delta13C are questionable. Additional checks with 39Ar, as well as results from the variationof delta18O (or deltaD) with respect to the salinity, emphasise a Holocene age; as is also the case for most mineralised groundwaters and also for water having a low delta18O (and deltaD). For saline groundwater residing in the Zechstein aquifer the measured delta34S values of about 12 per thousand are close to those expected from the literature. In contrast, the 87Sr/86Sr ratio of dissolved strontium is far from the values anticipated for the aquifer rocks despite there being proportionality between the chloride concentration and the strontium concentration. Furthermore, the proportionality is not valid in lower mineralised water. The 87Sr/86Sr ratio can, therefore, hardly be used as a tracer for the distribution of ascending saline water. The amount of salt-water coming from below into the residual quarry basins is an essential contribution to the lake inventories. Therefore, 222Rn was used to assist in determining the renewal of salt-water layers that formed in deep lake locations. In the deep zones 222Rn concentrations up to 6 Bq/l were measured but were dominantly in equilibrium with 226Ra, which was found in all higher mineralised groundwater samples. Excess radon was limited to just a few decimetres above the lake sediment surface but does not appear to be caused by continuous groundwater discharge. Hydrochemical investigations of groundwater from the Quaternary aquifer were carried out over the last six years before flooding was complete. Apart from a slight downward shift of the average sulfate concentration, other changes showed virtually no trends. An increase of the sulfate concentration was mostly correlated with a decrease of delta34S for individual sites only, but not for the whole ensemble of sampling locations. Sulfate from pyrite oxidation plays an important role but cannot be attributed unequivocally to coal mining. There are hints that the conditions closer to the basin edges may differ from those remoter parts of the flood plain.

Development and validation of an automated monitoring system for oxygenated volatile organic compounds and nitrile compounds in ambient air. Few studies were conducted on oxygenated volatile organic compounds (OVOC) because of problems encountered during the sampling/analyzing steps induced by water in sampled air. Consequently, there is a lack of knowledge of their spatial and temporal trends and their origins in ambient air. In this study, an analyzer consisted of a thermal desorber (TD) interfaced with a gas chromatograph (GC) and a flame ionization detector (FID) was developed for online measurements of 18 OVOC in ambient air including 4 alcohols, 6 aldehydes, 3 ketones, 3 ethers, 2 esters and 4 nitriles. The main difficulty was to overcome the humidity effect without loss of compounds. Water amount in the sampled air was reduced by the trap composition (two hydrophobic graphitized carbons-Carbopack B:Carbopack X), the trap temperature (held at 12.5 degrees C), by diluting (50:50) the sample with dry air before the preconcentration step and a trap purge with helium. Humidity management allowed the use of a polar CP-Lowox column in order to separate the polar compounds from the hydrocarbon/aromatic matrix. The safe sampling volume for the dual-sorbent trap 75 mg Carbopack X:5mg Carbopack B was found to 405 mL for ethanol by analyzing a standard mixture at a relative humidity of 80%. Detection limits ranging from 10 ppt for ETBE to 90 ppt for ethanol were obtained for 18 compounds for a sampling volume of 405 mL. Good repeatabilities were obtained at two levels of concentration (relative standard deviation <5%). The calibration (ranging from 0.5 to 10 ppb) was set up at three different levels of relative humidity to test the humidity effect on the response coefficients. Results showed that the response coefficients of all compounds were less affected by humidity except for those of ethanol and acetonitrile (decrease respectively of 30% and 20%). The target compounds analysis shows good reproducibility with response coefficient variability of less then 10% of the mean initial value of calibration for all the compounds. Hourly ambient air measurements were conducted in an urban site in order to test this method. On the basis of these measurements, ethanol, acetone and acetaldehyde have shown the highest concentration levels with an average of 2.10, 1.75 and 1.37 ppb respectively. The daily evolution of some OVOC, namely ethanol and acetaldehyde, was attributed to emissions from motor vehicles while acetone has a different temporal evolution that can be probably associated with remote sources.

A monoscopic method for real-time tumour tracking using combined occasional x-ray imaging and continuous respiratory monitoring. Three major linear accelerator vendors offer gantry-mounted single (monoscopic) x-ray imagers. The use of monoscopic imaging to estimate three-dimensional (3D) target positions has not been fully explored. The purpose of this work is to develop and investigate a robust monoscopic method for real-time tumour tracking, combining occasional x-ray imaging and continuous external respiratory monitoring, and compare this with an established stereoscopic method. Monoscopic estimation of 3D target positions is a two-step procedure. Step (1) is similar to the stereoscopic approach using combined occasional x-ray imaging and real-time external respiratory monitoring, i.e. to establish the correlation between the target coordinates T(x, y, z) and the external respiratory signal (R) (sECM: stereoscopic external correlation model). However, in monoscopic estimation, the correlation between the two coordinates (xp, yp) projected on the imager plane and the external respiratory signal (mECM: monoscopic external correlation model) is established. With only a single projection, the component of the 3D target position, which is along the x-ray imaging direction, is unresolved. Therefore, step (2) is used to estimate the unresolved component (z( parallel)) by building a correlation model between the unresolved component and the two other components projected on the imager (ICM: internal correlation model) with a prior 3D target trajectory that may be obtained by 4DCT, MV/kV imaging or 4DCBCT. At the time of prediction, (xp, yp) are estimated from (R) using the correlation model in step (1), and then z( parallel) is estimated from the estimated (xp, yp) using the correlation model in step (2). The performance of the proposed method was evaluated under various model update intervals and compared with the stereoscopic estimation method using 160 tumour trajectory and external respiratory motion data recorded at 25 Hz from 46 thoracic and abdominal cancer patients who underwent hypofractionated stereotactic radiotherapy by a CyberKnife system. The precision of the input data used in this study to represent tumour motion was assessed using x-ray imaging to be 1.5 +/- 0.8 mm. Monoscopic imaging every 30/60 s with updating ICM every 120/180 s can estimate target positions with a 1 mm root-mean-square error (RMSE) for 63/53% or a 2 mm RMSE for 93/91%, respectively. In contrast, stereoscopic x-ray imaging every 30/60 s can estimate target motion within a 1 mm RMSE for 72/58% or a 2 mm RMSE for 95/92%, respectively. The overall 3D error of the monoscopic estimation is approximately 10% higher than comparable stereoscopic imaging methods when the period between imaging is 1 s or more, and 40% higher for continuous imaging. The promising result may be explained by the fact that superior/inferior motion-the major axis of tumour motion-is fully resolved even in the monoscopic view for coplanar treatments, and tumour motion in each dimension is relatively well correlated.

Physiotherapy and Occupational Therapy vs No Therapy in Mild to Moderate Parkinson Disease: A Randomized Clinical Trial. It is unclear whether physiotherapy and occupational therapy are clinically effective and cost-effective in Parkinson disease (PD). To perform a large pragmatic randomized clinical trial to evaluate the clinical effectiveness of individualized physiotherapy and occupational therapy in PD. The PD REHAB Trial was a multicenter, open-label, parallel group, controlled efficacy trial. A total of 762 patients with mild to moderate PD were recruited from 38 sites across the United Kingdom. Recruitment took place between October 2009 and June 2012, with 15 months of follow-up. Participants with limitations in activities of daily living (ADL) were randomized to physiotherapy and occupational therapy or no therapy. The primary outcome was the Nottingham Extended Activities of Daily Living (NEADL) Scale score at 3 months after randomization. Secondary outcomes were health-related quality of life (assessed by Parkinson Disease Questionnaire-39 and EuroQol-5D); adverse events; and caregiver quality of life. Outcomes were assessed before trial entry and then 3, 9, and 15 months after randomization. Of the 762 patients included in the study (mean [SD] age, 70 [9.1] years), 381 received physiotherapy and occupational therapy and 381 received no therapy. At 3 months, there was no difference between groups in NEADL total score (difference, 0.5 points; 95% CI, -0.7 to 1.7; P = .41) or Parkinson Disease Questionnaire-39 summary index (0.007 points; 95% CI, -1.5 to 1.5; P = .99). The EuroQol-5D quotient was of borderline significance in favor of therapy (-0.03; 95% CI, -0.07 to -0.002; P = .04). The median therapist contact time was 4 visits of 58 minutes over 8 weeks. Repeated-measures analysis showed no difference in NEADL total score, but Parkinson Disease Questionnaire-39 summary index (diverging 1.6 points per annum; 95% CI, 0.47 to 2.62; P = .005) and EuroQol-5D score (0.02; 95% CI, 0.00007 to 0.03; P = .04) showed small differences in favor of therapy. There was no difference in adverse events. Physiotherapy and occupational therapy were not associated with immediate or medium-term clinically meaningful improvements in ADL or quality of life in mild to moderate PD. This evidence does not support the use of low-dose, patient-centered, goal-directed physiotherapy and occupational therapy in patients in the early stages of PD. Future research should explore the development and testing of more structured and intensive physical and occupational therapy programs in patients with all stages of PD. isrctn.org Identifier: ISRCTN17452402.

Sources of energy and nutrients in the diets of infants and toddlers. To identify major sources of energy and 24 nutrients and dietary constituents in the diets of US infants and toddlers and to describe shifts in major nutrient sources as children age. Data from 24-hour recalls collected in the 2002 Feeding Infants and Toddlers Study were analyzed to determine the percentage contribution of foods and supplements to total intakes of energy, nutrients, and other dietary constituents. A total of 3,586 unique foods and dietary supplements were reported. Reported foods and supplements were classified into 71 groups based on similarities in nutrient content and use. Nine-hundred seventy-nine food mixtures were disaggregated into their ingredients and ingredients were classified into one of the 71 groups using the same decision rules that guided classification of foods analyzed at the whole food level. A national random sample of 3,022 US infants and toddlers 4 to 24 months of age. The population proportion formula was used to determine the percentage contribution of each of the 71 groups to total intakes. This was done by summing the weighted amount of a given nutrient provided by a given group for all individuals in the sample and dividing by the total weighted amount of that nutrient consumed by all individuals from all foods and supplements. Groups that provided at least 1% of the nutrient in question were rank-ordered. Separate tabulations were prepared for three age groups (4-5 months, 6-11 months, and 12-24 months). Infant formula, breast milk, and milk are major contributors of energy and most nutrients in the diets of infants and toddlers. Among toddlers, juices and fruit-flavored drinks are the second and third most important sources of energy. Fortified foods make substantial contributions to intakes of many essential nutrients, and these contributions increase as children age. For example, among toddlers, fortified grain-based foods make substantial contributions to intakes of vitamin A, iron, and folate, relative to foods that are naturally rich in these nutrients. Supplements also make substantial contributions to intakes of vitamins and selected minerals, particularly among toddlers. In assessing dietary intakes of infants and toddlers, dietetics professionals need to carefully consider contributions of fortified foods and supplements. Dietetics professionals should educate caregivers of infants and toddlers about the importance of foods (rather than just nutrients) in promoting health and about the importance of early feeding practices in the development of lifelong eating habits. Caregivers should be encouraged to avoid relying on fortified foods and supplements to meet nutrient needs and educated about the potential risk of excessive intakes. Caregivers of toddlers and infants over 4 to 6 months of age who are consuming solid foods should be encouraged to feed a wide variety of fruits, vegetables, and whole grains, as well as foods naturally rich in iron.

Prophylactic fluconazole is effective in preventing fungal colonization and fungal systemic infections in preterm neonates: a single-center, 6-year, retrospective cohort study. Despite the promising preliminary results observed in extremely low birth weight (ELBW) populations, the use of fluconazole to prevent fungal colonization and infection in preterm neonates in the NICU is still an open question and not yet recommended as a standard of care. We have reviewed our 6-year series to assess the effectiveness and safety of this form of prophylaxis. This retrospective study consisted of 465 neonates who weighed < 1500 g at birth and were admitted to our NICU in the period 1998-2003. Those who were born between 1998 and 2000 and did not receive fluconazole prophylaxis (group A, n = 240) were compared with those who were born between 2001 and 2003 and treated with fluconazole until the 30th day of life (45th for neonates < 1000 g at birth; group B, n = 225). Weekly surveillance cultures were obtained from all patients. Incidence of fungal colonization, incidence of systemic fungal infection (SFI), rate of progression from colonization to infection, and mortality rates attributable to fungi were calculated for both groups and separately for neonates who were < 1000 g (ELBW) and were 1001 to 1500 g (NE-VLBW) at birth. Overall fungal colonization was significantly lower in group B (24.0%) than in group A (43.8%; relative risk [RR]: 0.406; 95% confidence interval [CI]: 0.273-0.605). The same was true of neonates with colonization in multiple sites (2.6% vs 5.8%) and of those with colonization from high-risk sites (5.8% vs 19.2%). SFI incidence was significantly lower in group B (10 of 225 cases; 4.4%) than in group A (40 of 240 cases; 16.7%; RR: 0.233; 95% CI: 0.113-0.447). Reduction of both colonization and SFI in group B was greater in the ELBW neonates and also significant in the NE-VLBW neonates. Rate of progression from colonization to infection was significantly lower in group B (0.17 vs 0.38; RR: 0.369; 95% CI: 0.159-0.815). Crude mortality rate attributable to Candida species was 1.7% (4 of 240) in group A vs 0% (0 of 225) in group B. Overall mortality rate (any cause before hospital discharge) was similar in the two groups (11.2% vs 10.6%), but in colonized infants (n = 159), it was significantly lower in group B (3.7% vs 18.1%; RR: 0.174; 95% CI: 0.039-0.778). The incidence of natively fluconazole-resistant fungal species did not increase over the years, and patterns of sensitivity to fluconazole remained the same. No adverse reaction related to fluconazole occurred. Prophylactic fluconazole significantly reduces the incidence of colonization and systemic infection by Candida species in both ELBW and NE-VLBW neonates and decreases the rates of progression from initial colonization to massive colonization and to systemic infection. All VLBW neonates may benefit from fluconazole prophylaxis.

The burden of ankylosing spondylitis and the cost-effectiveness of treatment with infliximab (Remicade). In the past, treatment options for ankylosing spondylitis (AS) have been limited, and the introduction of new treatments such as infliximab will have a noticeable impact on health-care budgets. The objective of this study was therefore to assess the current burden of the disease and estimate the cost-effectiveness of infliximab treatments. A cross-sectional retrospective observational study of resource consumption and utility related to disease severity was performed in patients who had participated in a population survey between 1992 and 1994 at the University of Bath and patients regularly followed at the Royal National Hospital for Rheumatic Diseases in Bath for up to 9 years. Mean costs and utility were estimated using a regression model including age, gender, disease duration, disease activity and functional status, and disease development was expressed as annual progression of functional disability. Cost-effectiveness of infliximab was modelled using a 3-month placebo-controlled clinical trial with open 1-yr extension in 70 patients, over a total time frame of 2 yr. In the model, costs and utility controlled for disease severity and age from the observational study were assigned to individual patients. The effect of long-term treatment was evaluated in a hypothetical model over 30 yr. Fifty-seven per cent of patients answered the questionnaires. The mean age was 57 (s.d. 11.2) yr, 74% were male and mean disease duration was 30.2 (11.7) yr. Mean total costs were estimated at pound 6765 (s.d. pound 166). Indirect costs represented 57.9% and non-medical costs such as investments and informal care accounted for 16.5% of total costs. Mean utility was 0.67 (0.21). In the main model, mean costs for untreated patients are estimated at pound 25,128. For the infliximab group, mean costs (excluding treatment) are estimated at pound 17,240, a reduction of 31%. Thus, part of the treatment cost was offset by savings in other resources ( pound 7888), leaving an incremental cost of pound 6214. Treatment increased the number of quality-adjusted live years (QALYs) by 0.175 QALYs, leading to a cost per QALY gained of pound 35,400 for the first year of treatment. When treatment is assumed to continue for the full 2 yr, the cost per QALY is pound 32,800. When infliximab infusions are given every 8 weeks instead of every 6 weeks, the cost per QALY is reduced to pound 17,300. In the long-term model, the cost per QALY is estimated at pound 9600. Non-medical costs and production losses dominate costs in AS, and economic evaluation must therefore adopt a societal perspective. The cost of treatment with infliximab is partly offset by reductions in the cost of the disease and patients' quality of life is increased, leading to a cost per QALY gained in the vicinity of pound 30,000 to pound 40,000 in the short term, but potentially below pound 10,000 in the long term.

Leukodepletion for patients undergoing heart valve surgery. There is some evidence for the benefits of leukodepletion in patients undergoing coronary artery surgery. Its effectiveness in higher risk patients, such as those undergoing heart valve surgery, particularly in terms of overall clinical outcomes, is currently unclear. To assess the beneficial and harmful effects of leukodepletion on clinical, patient-reported and economic outcomes in patients undergoing heart valve surgery. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 3 of 12) in The Cochrane Library, the NHS Economic Evaluations Database (1960 to April 2013), MEDLINE Ovid (1946 to April week 2 2013), EMBASE Ovid (1947 to Week 15 2013), CINAHL (1982 to April 2013) and Web of Science (1970 to 17 April 2013) on 19 April 2013. We also searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), the US National Institutes of Health (NIH) clinical trials database and the International Standard Randomised Controlled Trial Number Register (ISRCTN) in April 2013 for ongoing studies. No language or time period restrictions were applied. We examined the reference lists of all included randomised controlled trials and contacted authors of identified trials. We searched the 'grey' literature at OpenGrey and handsearched relevant conference proceedings. Randomised controlled trials comparing a leukocyte-depleting arterial line filter with a standard arterial line filter, on the arterial outflow of the heart-lung bypass circuit, in elective patients undergoing heart valve surgery. Data were collected on the study characteristics, three primary outcomes (1. post-operative in-hospital all-cause mortality within three months, 2. post-operative all-cause mortality excluding inpatient mortality < 30 days, 3. length of stay in hospital, 4. adverse events and serious adverse events) and seven secondary outcomes (1. tubular or glomerular kidney injury, 2. validated health-related quality of life scales, 3. validated renal injury scales, 4. use of continuous veno-venous haemo-filtration, 5. length of stay in intensive care, 6. costs of care). Data were extracted by one author and verified by a second author. Insufficient data were available to perform a meta-analysis or sensitivity analysis. Eight studies were eligible for inclusion in the review but data on prespecified review outcomes were available from only one, modestly powered (24 participants) study (Hurst 1997). There were no differences between a leuko-depleting versus standard filter in length of stay in the intensive care unit (ICU) (mean difference (MD) 0.80 days; 95% confidence interval (CI) -0.24 to 1.84) or length of hospital stay (MD 0.20 days; 95% CI -1.78 to 2.18). There are currently insufficient good quality trials with valve surgery patients to inform recommendations for changes in clinical practice. A future National Institute for Health Research (NIHR)-funded feasibility study (recruiting mid-year 2013) comparing leukodepletion with a standard arterial line filter in patients undergoing elective heart valve surgery (the ROLO trial) will be the largest study to date and will make a significant contribution to future updates of this review.

Growth Inhibition Effect and Validation of Stable Expressed Reference Genes for Near-Infrared Photothermal Therapy Mediated by Gold Nanoflower Particles on Human Tongue Carcinoma Tca-8113 Cells. Compared with surgery, radiotherapy, chemotherapy and other conventional cancer treatments, near-infrared (NIR) photothermal therapy mediated by gold nanoparticles had advantages of non-invasive, safe, non-drug resistance and small side effects. Especially for tongue cancer and other head and neck tumors, NIR gold nanoparticle-mediated photothermal therapy is more conducive to preserve the anatomic and functional integrity of stomatognathic system, improving the life quality of patients. However, the toxic organic phase substances are commonly used in conventional gold nanoparticles preparation process in order to increase the stability of the material which limited its application in the biomedical field. In this study, a new type of gold nanoflower (GNF) particles were synthesized by seeding approach in aqueous phase, with better biocompatibility and free of organic substances. Then, the photo-thermal conversion curve under the irradiation of NIR laser ray were investigated. The absorption peak of prepared GNF particles was 719 nm and they had high efficient photothermal conversion in near-infrared region. Furthermore, we investigated the inhibition effect of NIR photothermal therapy with different laser power mediated by the GNF particles on human tongue carcinoma cells by detecting the relative growth rate, cell cycle, and apoptosis and necrosis. The results showed that NIR photothermal therapy mediated by prepared GNF particles could inhibit proliferation of tongue carcinoma Tca-8113 cells obviously, and the relative growth rate of Tca-8113 cells decreased along with the increasing of GNF concentration and laser power. At last, we validated the expression stabilities of 12 commonly used reference genes (18S, ACTB, ALAS1, GAPDH, TBP, HPRT1, RPL29, HMBS, PPIA, PUM1, GUSB, and B2M) after the above treatment through real-time quantitative polymerase chain reaction (RT-qPCR). Three commonly used software, geNorm, NormFinder, and BestKeeper are used to compare stability between reference genes. The final ranking of the candidate reference genes expression stability was TBP > PPIA > RPL29 > B2M > 18S rRNA > GAPDH > GUSB > ACTB > HPRT1 > ALAS1 > HMBS > PUM1. The combination of TBP + PPIA is best for normalizing the relative quantitation. The results suggested that GNF particles had high photothermal conversion in NIR region and was ideal mediated material for tumor NIR photothermal therapy. NIR photothermal therapy mediated by GNFs could inhibit the growth rate of tongue carcinoma Tca-8113 cells obviously. The recommend reference genes can be used for improving the accuracy of gene expression studies in the molecular mechanism of near-infrared (NIR) photothermal therapy mediated by the gold nanoflower (GNF) particles.

Thiamine and magnesium deficiencies: keys to disease. Thiamine deficiency (TD) is accepted as the cause of beriberi because of its action in the metabolism of simple carbohydrates, mainly as the rate limiting cofactor for the dehydrogenases of pyruvate and alpha-ketoglutarate, both being critical to the action of the citric acid cycle. Transketolase, dependent on thiamine and magnesium, occurs twice in the oxidative pentose pathway, important in production of reducing equivalents. Thiamine is also a cofactor in the dehydrogenase complex in the degradation of the branched chain amino acids, leucine, isoleucine and valine. In spite of these well accepted facts, the overall clinical effects of TD are still poorly understood. Because of the discovery of 2-hydroxyacyl-CoA lyase (HACL1) as the first peroxisomal enzyme in mammals found to be dependent on thiamine pyrophosphate (TPP) and the ability of thiamine to bind with prion protein, these factors should improve our clinical approach to TD. HACL1 has two important roles in alpha oxidation, the degradation of phytanic acid and shortening of 2-hydroxy long-chain fatty acids so that they can be degraded further by beta oxidation. The downstream effects of a lack of efficiency in this enzyme would be expected to be critical in normal brain metabolism. Although TD has been shown experimentally to produce reversible damage to mitochondria and there are many other causes of mitochondrial dysfunction, finding TD as the potential biochemical lesion would help in differential diagnosis. Stresses imposed by infection, head injury or inoculation can initiate intermittent cerebellar ataxia in thiamine deficiency/dependency. Medication or vaccine reactions appear to be more easily initiated in the more intelligent individuals when asymptomatic marginal malnutrition exists. Erythrocyte transketolase testing has shown that thiamine deficiency is widespread. It is hypothesized that the massive consumption of empty calories, particularly those derived from carbohydrate and fat, results in a high calorie/thiamine ratio as a major cause of disease. Because mild to moderate TD results in pseudo hypoxia in the limbic system and brainstem, emotional and stress reflexes of the autonomic nervous system are stimulated and exaggerated, producing symptoms often diagnosed as psychosomatic disease. If the biochemical lesion is recognized at this stage, the symptoms are easily reversible. If not, and the malnutrition continues, neurodegeneration follows and results in a variety of chronic brain diseases. Results from acceptance of the hypothesis could be tested by performing erythrocyte transketolase tests to pick out those with TD and supplementing the affected individuals with the appropriate dietary supplements.

Comparison of different regimens of proton pump inhibitors for acute peptic ulcer bleeding. Treatment with proton pump inhibitors (PPIs) improves clinical outcomes in patients with peptic ulcer bleeding. However, the optimal dose and route of administration of PPIs remains controversial. To evaluate the efficacy of different regimens of PPIs in the management of acute peptic ulcer bleeding using evidence from direct comparison randomized controlled trials (RCTs).We specifically intended to assess the differential effect of the dose and route of administration of PPI on mortality, rebleeding, surgical intervention, further endoscopic haemostatic treatment (EHT), length of hospital stay, transfusion requirements and adverse events. We searched CENTRAL (in The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE (from inception to September 2010) and proceedings of major gastroenterology meetings (January 2000 to September 2010), without language restrictions. Original investigators were contacted to request missing data. RCTs that compared at least two different regimens of the same or a different PPI in patients with acute peptic ulcer bleeding, diagnosed endoscopically. Two reviewers independently selected studies, extracted data and assessed risk of bias. We synthesized data using the Mantel-Haenszel random-effects method and performed multivariate meta-regression with random permutations based on Monte Carlo simulation. We measured heterogeneity with the I² statistic and Cochrane Q test and assessed publication bias with funnel plots and Egger's test. We graded the overall quality of evidence using the GRADE approach. Twenty two RCTs were included; risk of bias was high in 17 and unclear in 5. The main analysis included 13 studies (1716 patients) comparing "high" dose regimens (72-hour cumulative dose > 600 mg of intravenous PPI) to other doses; there was no significant heterogeneity for any clinical outcome. We found low quality evidence that did not exclude a potential reduction or increase in mortality, rebleeding, surgical interventions or endoscopic haemostatic treatment (EHT) with "high" dose regimens. For mortality, pooled risk ratio (RR) was 0.85 (95% confidence interval (CI) 0.47 to 1.54); pooled risk difference (RD) was 0 more deaths per 100 patients treated with "high" dose (95% CI from 1 fewer to 2 more deaths per 100 treated). For rebleeding, pooled RR was 1.27 (95% CI 0.96 to 1.67); pooled RD was 2 more rebleeding events per 100 patients treated with "high" dose (95% CI from 0 fewer to 5 more rebleeding events per 100 treated). For surgical interventions, pooled RR was 1.33 (95% CI 0.63 to 2.77); pooled RD was 1 more surgical intervention per 100 patients treated with "high" dose (95% CI from 1 fewer to 2 more surgical interventions per 100 treated). For further EHT, pooled RR was 1.39 (95% CI 0.88 to 2.18), pooled RD was 2 more events per 100 patients treated with "high" dose PPI (95% CI from 1 fewer to 5 more events per 100 treated). We found moderate quality evidence suggesting no important difference between the two regimens with regards to length of hospital stay (mean difference (MD) 0.26 days; 95% CI -0.08 to 0.6 days) or blood transfusion requirements (MD 0.05 units; 95% CI -0.21 to 0.3 units). There was visual and statistical evidence of "inverse" publication bias for mortality (missing small studies with favourable outcomes for "high" dose), but not for any other outcome. The results were similar for all subgroup analyses (according to risk of bias, geographical location, route of administration for non-"high" dose regimens, continuous infusion vs. bolus administration for intravenous non-"high" regimens group), sensitivity analyses (restriction to patients who had EHT for high risk stigmata, use of different dose thresholds for comparative regimens) and post hoc analyses (inclusion of all studies (N = 22) that compared at least two PPI regimens with different cumulative 72 hour doses; restriction of the previous analysis to patients who had EHT for high risk stigmata). Meta-regression analysis did not show any statistically significant associations between treatment effect (for the outcomes of mortality, rebleeding and surgical intervention) and the three study-level factors that were assessed (geographical location (Asia versus not Asia), route of PPI administration (intravenous versus oral), within-study ratio among the 72-hour cumulative doses of the two PPI regimens). There is insufficient evidence for concluding superiority, inferiority or equivalence of high dose PPI treatment over lower doses in peptic ulcer bleeding.

Intravitreal bevacizumab combined with/without triamcinolone acetonide in single injection for treatment of diabetic macular edema. Diabetic macular edema (DME) is a common manifestation of diabetic retinopathy (DR) that forms the main cause of central visual impairment. This study aimed to compare the efficacy and safety of a single intravitreal injection of bevacizumab alone versus bevacizumab combined with triamcinolone acetonide in eyes with diabetic macular edema (DME). A total of 40 eyes in 40 Chinese patients (22 male and 18 female) diagnosed with diabetic macular edema were enrolled in this prospective, randomized, consecutive study. Among them, 21 patients in group 1 were treated with intravitreal injection of bevacizumab (1.25 mg/0.05 ml), and the other 19 patients in group 2 accepted intravitreal bavacizumab (1.25 mg/0.05 ml) combined with triamcinolone acetonide (2 mg/0.05 ml). All patients were examined at baseline and followed up at 4, 6 and 12 weeks after the injection. Changes in mean best correct visual acuity (BCVA) using ETDRS chart, central retina thickness (CRT) measured by optical coherence tomography (OCT), and intraocular pressure (IOP) were focused on. In group 1, mean BCVA improved from (41.76 ± 15.59) letters (baseline) to (56.24 ± 18.56) letters, (52.57 ± 12.31) letters and (48.41 ± 17.90) letters at 4, 6 and 12 weeks post-injection, respectively (P = 0.004, P = 0.011 and P = 0.026, respectively). Mean CRT decreased from (525.76 ± 184.10) µm (baseline) to (270.33 ± 202.67)µm, (303.12 ± 168.43) µm and (402.26 ± 196.21) µm, respectively (P = 0.009, P = 0.016 and P = 0.030, respectively). In group 2, mean BCVA improved from (39.89 ± 12.27) letters (baseline) to (55.31 ± 19.27) letters, (51.25 ± 13.48) letters and (46.97 ± 16.23) letters at 4, 6 and 12 weeks after injection, respectively (P = 0.003, P = 0.010 and P = 0.027, respectively). Mean CRT decreased from (554.50 ± 169.05) µm (baseline) to (292.76 ± 196.05) µm, (323.46 ± 164.05) µm and (426.38 ± 169.05) µm, respectively (P = 0.009, P = 0.014 and P = 0.028, respectively). However, there was no significant difference between these two groups with regard to mean BCVA (F = 1.602, P = 0.216) and CRT (F = 0.412, P = 0.526). At 12 weeks after the injection, 11 of the patients in group 1 and nine patients in group 2 appeared recurrent macular edema and needed repeat injections. There was one patient in group 2 appeared transient intraocular pressure increases. Intravitreal injection of bevacizumab combined with/without triamcinolone acetonide had a beneficial effect on DME. However, the significant effect was not permanent. Our results showed that no significant differences were detected between intravitreal bevacizumab combined with/without triamcinolone acetonide for the eyes with diabetic macular edema in Chinese patients.

[The physician-patient relationship in post-modernism]. The doctor-patient relationship represents a particular link that goes beyond formality and it is projected in time, space and emotionalism. It takes place in the midst of a cultural, social, physiological, scientific and technical context which at the same time is conditioned by local, regional, national and foreign influences as a consequence of globalization. Different ethnical groups, social stratification, economic structures, philosophical concepts, religious beliefs and moral values play a pivotal role. The technological advances have shown an exponential increase during the last forty years. This phenomenon was accompanied by deep changes that varied from philosophical to strictly technical aspects which were significatively intensified during the post Second World War period. The consequences have been unfortunate for physicians and particularly for patients. Those consequences came out by philosophical reviews, the economical liberalism and neoliberalism development, a new concept for science, the priorization of technique development together with changes in both ethical value scales and economic & politic power hegemonies. The great reports of philosophy have tried to justify these social changes. The end of modern meta discourses such as Iluminism, Idealism, and Marxism, incited the liberal and neoliberal discourse. Knowledge has been affected not only in the research field but in the teaching field as well. Today, the discourse in vogue is the performance. The "organic conjugation" of technique and profit precedes its union with science. The State disengagement in managing the great social problems in many countries, the globalization and the concentration of the capital has redefined the power. Neither the patient nor the medicine escapes from this reality. The final results are generations of physicians quite right informed but unable to solve or even face the minimum problems of a patient, and what is worst, they run the risk of feeling frustrated and resentful. Everything is thought and done through technique, and there is a fact that appears to justify this action "The malpractice judgement industry". The economical monopoly of private or sindical Healthcare Providers and self-managed Hospitals projects are rapidly and notoriously modifying the medical labour market. There seems to exist only one element that the doctor and the patient have in common in this new culture: loneliness. There is also a human communication failure that separates them: the patient is in more need of human comprehension than ever before and the doctor has a cultural inability to offer it. To sum up, the relationship between the doctor and the patient is still a theme of deep preoccupation, even more nowadays when everything seems to indicate that this relationship has suffered a significant impairment.

Kainic acid-induced excitotoxicity is associated with a complex c-Fos and c-Jun response which does not preclude either cell death or survival. c-fos and c-jun mRNA induction and c-Fos and c-Jun protein expression were examined in the brains of adult rats subjected to systemic kainic acid (KA) injection at convulsant doses. Induction of c-fos and c-jun mRNA, as seen with in situ hybridization, occurred in the piriform and entorhinal cortices, neocortex, amygdala, hippocampus, dentate gyrus, and discrete thalamic nuclei. This was followed by c-Fos protein expression, as revealed with immunohistochemistry, in the same regions. However, the distribution of c-Jun protein expression differed depending on the antibody used. The distribution of cells immunostained with the antibody c-Jun (AB-1) was similar to that of c-jun mRNA, but the distribution of cells immunostained with the antibody c-Jun/AP1 (N) was restricted to a few neurons in the pyramidal cell layer of CA1 and CA3, layer II of the piriform and entorhinal cortices, basal amygdala, and discrete thalamic nuclei. Although the regional distribution of c-Fos- and c-Jun-immunoreactive cells in the hippocampus, layer II of the entorhinal and piriform cortices, basal amygdala, and discrete thalamic nuclei matched the distribution of cells committed to dying, c-Fos- and c-Jun-immunoreactive cells in the neocortex and dentate gyrus survived. Therefore, the present data show that c-fos and c-jun are not predictors of either cell death or survival, but rather, markers of cells sensitive to KA excitotoxicity. Western blots to c-Fos showed a double band at p62 in samples containing the hippocampus and entorhinal and piriform cortices (hip samples) and in samples containing the neocortex (cortex samples). The upper band was abolished following preincubation of the samples with alkaline phosphatase, thus suggesting c-Fos phosphorylation. Western blots to c-Jun (AB-1) showed a single band at about p39 in hip and cortex. However, Western blots to c-Jun/AP1 (N) identified two bands. One band at about p39 was seen in control rats and the cortex of KA-treated rats. Another band at p26 was observed only in hip samples of KA-treated rats. In addition, decreased c-Jun N-terminal kinase 1 (JNK-1) expression, as revealed on Western blots, was coincidental with the appearance of the p26 c-Jun-immunoreactive band in KA-treated rats. These results show that c-Fos and different Jun-related antigens are expressed following KA excitotoxicity, and that posttranslational modifications involving phosphorylation of c-Fos and Jun(s) may occur following KA injection. These results also stress the necessity of examining the composition of Fos and Jun-related antigens and the metabolic state of Fos and Jun(s) in different experimental models of nervous system injury.

Active site inhibited factor VIIa (DEGR VIIa) attenuates the coagulant and interleukin-6 and -8, but not tumor necrosis factor, responses of the baboon to LD100 Escherichia coli. Antitissue factor antibody attenuated the coagulopathic and lethal responses to LD100 Escherichia coli, whereas active site inhibited factor Xa inhibited only the coagulopathic response. In this study, we wished to determine: (1) whether active site inhibited factor VIIa blocks the coagulopathic and/or attenuates the lethal effects of LD100 E coli and (2) whether these effects are accompanied by attenuation of the inflammatory cytokine response to LD100 E coli. Eight baboons infused for 2 hours with LD100 E coli also were given five bolus infusions of DEGR VIIa of 280 microg/kg at T = -10 minutes, +2, 4, 6, and 8 hours and observed for changes in vital signs, and the concentrations of hemostatic components (fibrinogen, platelets, fibrin degradation products) and inflammatory mediators (tumor necrosis factor [TNF], interleukin-6 [IL-6], IL-8) at T = 0, 1, 2, 4, 6, and 8 hours. Eight control baboons were also infused with LD100 E coli alone and followed as described above. Four of the eight baboons treated with DEGR VIIa were permanent 7-day survivors versus none in the control group. The mean survival times for the treated and control groups were 116 +/- 22 and 26 +/- 8 hours, respectively. These values differed significantly from each other, (P = .0008). The decrease in platelet and fibrinogen concentrations and the increase in fibrin degradation products observed in the control group were significantly attenuated in the treated group, as was thrombosis of renal glomerular capillaries. Treatment with DEGR VIIa showed no effect on the peak TNF response to LD100 E coli at T = 2 hours (170 +/- 32 v 120 +/- 35 ng/mL). DEGR VIIa, however, did attenuate the IL-6 and IL-8 responses at T = 8 hours (ie, the IL-6 concentrations were 81 +/- 10 for treated and 1,256 +/- 236 for the control groups and the IL-8 concentrations were 28 +/- 3.9 for the treated and 60 +/- 8.2 for the control group). These values for IL-6 and IL-8 differed significantly from each other between the treated and control groups (P = .0001 and .0074, respectively). It should be noted that the initial responses of IL-6 and IL-8 up to T = 4 hours were not attenuated. We concluded that DEGR VIIa treatment attenuates inflammatory, as well as hemostatic system responses to LD100 E coli. We hypothesize that this occurs through interference with the assembly and/or interactions of tissue factor/VIIa complexes.

Field turbidity method for the determination of lead in acid extracts of dried paint. Lead, which can be found in old paint, soil, and dust, has been clearly shown to have adverse health effects on the neurological systems of both children and adults. As part of an ongoing effort to reduce childhood lead poisoning, the US Environmental Protection Agency promulgated the Lead Renovation, Repair, and Painting Program (RRP) rule requiring that paint in target housing built prior to 1978 be tested for lead before any renovation, repair, or painting activities are initiated. This rule has led to a need for a rapid, relatively easy, and an inexpensive method for measuring lead in paint. This paper presents a new method for measuring lead extracted from paint that is based on turbidimetry. This method is applicable to paint that has been collected from a surface and extracted into 25% (v/v) of nitric acid. An aliquot of the filtered extract is mixed with an aliquot of solid potassium molybdate in 1 M ammonium acetate to form a turbid suspension of lead molybdate. The lead concentration is determined using a portable turbidity meter. This turbidimetric method has a response of approximately 0.9 NTU per microg lead per mL extract, with a range of 1-1000 Nephelometric Turbidity Units (NTUs). Precision at a concentration corresponding to the EPA-mandated decision point of 1 mg of lead per cm(2) is <2%. This method is insensitive to the presence of other metals common to paint, including Ba(2+), Ca(2+), Mg(2+), Fe(3+), Co(2+), Cu(2+), and Cd(2+), at concentrations of 10 mg mL(-1) or to Zn(2+) at 50 mg mL(-1). Analysis of 14 samples from six reference materials with lead concentrations near 1 mg cm(-2) yielded a correlation to inductively coupled plasma-atomic emission spectroscopy (ICP-AES) analysis of 0.97, with an average bias of 2.8%. Twenty-four sets of either 6 or 10 paint samples each were collected from different locations in old houses, a hospital, tobacco factory, and power station. Half of each set was analyzed using rotor/stator-25% (v/v) nitric acid extraction with measurement using the new turbidimetric method, and the other half was analyzed using microwave extraction and measurement by ICP-AES. The average relative percent difference between the turbidimetric method and the ICP-AES method for the 24 sets measured as milligrams of lead per cm(2) is -0.63 +/- 32.5%; the mean difference is -2.1 +/- 7.0 mg lead per cm(2). Non-parametric and parametric statistical tests on these data showed no difference in the results for the two procedures. At the federal regulated level of 1 mg of lead per cm(2) paint, this turbidimetric method meets the performance requirements for EPA's National Lead Laboratory Accreditation Program (NLLAP) of accuracy within +/-20% and has the potential to meet the performance specifications of EPA's RRP rule.

Does preoperative antimüllerian hormone level influence postoperative pregnancy rate in women undergoing surgery for severe endometriosis? To compare postoperative pregnancy rates as they relate to presurgery antimüllerian hormone (AMH) level in patients with stage 3 and 4 endometriosis. Retrospective comparative study using data prospectively recorded in the North-West Inter-Regional Female Cohort for Patients with Endometriosis (CIRENDO) database. University tertiary referral center. One hundred eighty patients with stage 3 and 4 endometriosis and pregnancy intention, managed from June 2010 to March 2015, were divided into two groups according to their preoperative AMH levels: group A (AMH ≥2 ng/mL) and group B (AMH <2 ng/mL). Surgical procedure involved ovarian endometrioma ablation by plasma energy along with resection of various localizations of the disease. Postoperative conception was either spontaneous or used assisted reproductive technology, depending on patient characteristics. Patient characteristics, preoperative symptoms, infertility history, intraoperative findings, and probability of pregnancy were recorded and compared between the two groups. Among 180 women enrolled in the study, 134 (74.4%) were assigned to group A and 46 (25.6%) to group B. The women's ages were, respectively, 30 ± 3.8 and 32 ± 4.6 years. Pregnancy was achieved by 134 (74.4%) patients, and conception was spontaneous in 74 of them (55.2%). Pregnancy rates in groups A and B were, respectively, 74.6% (100 women) and 73.9% (34 women), while spontaneous conception represented 54% (54 women) and 58.8% (20 women). The probability of pregnancy at 12, 24, and 36 months after surgery in groups A and B was comparable, respectively, 65% (95% confidence interval [CI], 55%-75%), 77% (95% CI, 86%-68%), and 83% (95% CI, 90%-75%) versus 50% (95% CI, 69%-34%), 77% (95% CI, 90%-61%), and 83% (95% CI, 94%-68%). Supplementary analysis in women with normal (≥2 ng/mL), low (1-1.99 ng/mL), and very low (<1 ng/mL) AMH level showed an inverse relationship between AMH level, age, and antecedents of miscarriage; however, postoperative pregnancy rates were comparable among the three groups at 12 and 24 months, respectively, 59.5% (95% CI, 49.3%-70%) and 77.4% (95% CI, 68%-85.4%); 57.1% (95% CI, 34%-83%) and 78.6% (95% CI, 55.2%-94.8%); and 46.7% (95% CI, 25.6%-73.7%) and 73.3% (95% CI, 50.4%-91.7%). The probability of postoperative pregnancy was comparable between women with low and normal AMH level who were managed for stage 3 and 4 endometriosis and who were a mean age of 30 years. However, the small sample size might have been unable to detect differences in pregnancy and live-birth rates between the two groups. As the majority of pregnancies were spontaneous, our results suggest that surgical management may be offered to young patients with severe endometriosis and reduced ovarian reserve with good fertility outcomes.

Cortical encroachment after cephalomedullary nailing of the proximal femur: evaluation of a more anatomic radius of curvature. : A unique complication of using full-length intramedullary nails for pertrochanteric and subtrochanteric femur fractures is nail penetration of the anterior cortex at the distal end of the femur because of a mismatch of the anatomic femoral bow with that of currently available cephalomedullary nails (CMNs). This study was performed to determine the rate of distal femoral cortical penetration after stabilization of the proximal femur in a consecutive series of patients using a long CMN with a curvature of 180 cm and to examine the final location of the nails within the femoral canal. : Retrospective chart review. : Level 1 trauma center with tertiary care. : Between June 2005 and September 2008, 271 consecutive proximal femoral fractures or impending fractures were stabilized using a specially designed CMN [pertrochanteric nail (PTN) system; Biomet, Warsaw, IN]. Fifty-seven fractures were excluded because of inadequate lateral radiographs, leaving 214 nails in 212 patients available for analysis. : The proximal femur fractures or impending fractures were stabilized with a full-length CMN with a shaft diameter of 11 mm and a radius of curvature of 180 cm. : Nail position was determined from the lateral radiograph, which included the minimal distance from the nail to the anterior cortex of the distal femur and the relative position of the nail within the medullary canal, at a level within 2 cm proximal to the superior pole of the patella. Based on the nail position within the distal femoral canal, the following were calculated: (1) the overall rate of distal femoral anterior cortical penetration, (2) the distribution of nail distances to the anterior cortex, and (3) the proportion of nails lying in each quarter of the space available for the nail. : Four surgeries (1.9%) were performed for pathologic fracture and 22 (10.3%) for impending pathologic fracture. The remaining 188 CMNs were used to stabilize OTA Type 31A1 fractures (52 nails, 24.3%), Type 31A2 fractures (62 nails, 29%), Type 31A3 fractures (15 nails, 6.5%), and Type 32 fractures (59 nails, 27.6%). Of the 214 cases available for radiographic analysis, there was 1 case (0.47%) of distal femoral anterior cortical penetration. Of the remaining 213 CMNs, 40% of nails ended up far anterior, 48% anterior, 10% posterior, and 2% far posterior. Sixteen percent (1/6) were within 3 mm of the anterior cortex and half were within 7 mm. The average distance from nail to the anterior cortex was 8.5 mm. : Use of a CMN with a radius of curvature of 180 cm to stabilize the proximal femur resulted in a very low rate of distal femoral anterior cortical penetration. However, most of the intramedullary nails ended up in the anterior half of the space available for the nail with 16% within 3 mm of the anterior cortex. These results highlight the importance of being aware of the complication of anterior cortical impingement and perforation during CMN insertion. : Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Tolerable hearing aid delays. III. Effects on speech production and perception of across-frequency variation in delay. Signal processing strategies that attempt to mimic the frequency resolution of the healthy cochlea require finer frequency resolution at low frequencies than at high. The filtering required will cause more delay to the low-frequency end of the spectrum than to the high-frequency end, which may have disturbing effects. In a real-time application, making the delay constant across frequency would require the higher frequency components to be subjected to a compensating delay, leading to a larger overall delay, which may also give rise to disturbing effects (Stone & Moore, 1999, 2002). This experiment assessed the effects of frequency-dependent delay on subjective and objective measures of speech production and perception. Digital filtering was used to introduce across-frequency delays of 0, 4, 9, 15, or 24 msec. The low frequencies were always more delayed than the high frequencies, with a smooth variation in delay between the low and the high frequencies. In addition, there was a 2.5 msec delay that did not vary with frequency arising from the processes of analog-digital-analog conversion and equalization. Ten subjects with symmetric, bilateral, moderate hearing impairment of cochlear origin were fitted binaurally with Phonak PicoNet2 BTE linear hearing aids. The aids were programmed to provide insertion gains closely approximating the NAL (RP) (Byrne & Dillon, 1986) prescription for each subject and ear. The output of an omnidirectional microphone, attached on top of each aid, fed a digital filtering unit that introduced the across-frequency delay. Audio shoes reintroduced the signal back into the BTE aids. Subjects were tested in a counterbalanced order for their identification of vowel-consonant-vowel (VCV) syllables. In a second session, the same subjects spoke from a script: their utterances were recorded on tape, speech production rates were measured and subjective ratings of the disturbance of the delay were obtained. Subjects required some training to recognize the effects of the delay and rate them consistently. Subjective disturbance increased progressively with increasing across-frequency delay. A 9-msec delay was significantly more disturbing than a 0-msec delay. A delay of about 20 msec led to a mean rating of "disturbing." VCV identification decreased significantly once the across-frequency delay was 15 msec or greater. However, word production rates were not significantly affected by across-frequency delay over the range tested. Relatively small across-frequency delays (9 to 15 msec) give rise to significant changes in speech identification and subjective disturbance. A delay of 9 to 15 msec, constant across frequency, would have a smaller effect (Stone & Moore, 1999). It appears desirable to compensate, at least in part, for across-frequency delays introduced by any processing.

[Immunopathology of American tegumentary leishmaniasis]. The complex cell mediated immune response in parasitic diseases can be evaluated in different body compartments. In the present work we describe the results of studies of peripheral blood lymphocytes and the cutaneous lesions in the three clinical forms of tegumentary leishmaniasis. These clinical forms, that constitute a clinical, histological and immunological spectrum, are: localized cutaneous leishmaniasis (LCL), diffuse cutaneous (DCL9, and the intermediate forms that include mucous and verrocous leishmaniasis (MCL). The overall results suggest that the cytokine pattern of lymphocytes in the blood and lesions of LCL, the self-limiting form of the disease, is T-helper type 1. This leads to the cure of the lesions in these patients, either spontaneously or after appropriate therapy. The disseminated disease in DCL patients is resistant to chemotherapy, and is characterized by a Th2 cytokine pattern, with a an absence of IL-2 AND ifn-gamma production when the lymphocytes are specifically stimulated by leishmanial antigen. This is probably why these patients are unable to control the infection, and allows the cutaneous dissemination of the parasite. The intermediate MCL form is characterized by destructive lesions of the oral and nasopahryngeal mucosas, with a tendency to the chronicity of the infection. The cytokine pattern of MCL patients is a mixture of Type 1 and Type 2 responses. This may be responsible for the progression of the disease in these patients, as it is possible that when both types of cytokines are produced, the Type 2 responses can predominate over the Type 1 and the disease is maintained in a chronic, although activated, state. The examination of the cutaneous lesions demonstrated that the epidermis in the DCL lesions is deficient in ICAM-1 accessory signals and MHC-II expression by keratinocytes, and presents a variable number of Langerhans cells. In MCL lesions, the expression of ICAM-1 and MHC-II is elevated, and Langerhans cells are absent in the damaged epithelium. The epidermis of LCL lesions show ICAM-1 in patches and MHC uniformly expressed by keratinocytes. DCL lesions are characterized by low CD4/CD8 and memory/naive T cell ratios, low numbers of T gamma delta cells, and an apparent defect in the expression of LFA-1 directional receptors. The cytokine patterns are Th1 and Th2, with the latter predominating. MCL granulomas manifest high CD4/CD8 and memory/naive Tcel ratios, low numbers of T gamma delta, a high coefficients of cellular adhesion, with a mixed Th1/Th2 cytokine pattern. LCL granulomas are characterized by a normal CD4/CD8 ratio, a high memory/naive cell ratio, numerous groups of T gamma delta, a high expression of directional receptors, and Th1/Th0 cytokine patterns. We discuss the results in the context of the immunological effects, both in immunotherapy and immunoprophylasis, of the combined vaccine of BCG plus promastigotes of Leishmania. In immunotherapy we demonstrate that the combined vaccine simulates a Th1 response in LCL patients. As an immunoprophylactic vaccine in healthy individuals from an endemic area of leishmaniasis, it stimulates a Th1 response (positivity in the Montenegro cutaneous reactions, proliferative responses in vitro and production of IFN-gamma), with a low specific antibody response. This demonstrates that the combined vaccine is potentially useful both in the treatment of LCL patients, as well as being potentially protective applied as immunoprophylaxis in the control of leishmaniasis.

Effect of rodent diets on the sexual development of the rat. Five rodent diets have been evaluated for their possible effect on the sexual development of the rat. Groups of 12 pregnant Alpk rats were fed one of the following combinations of diets during pregnancy and postnatally: RM3/RM1, AIN-76A/AIN-76A, RM3/AIN-76A, Teklad Global 2016 (Global)/Global and Purina 5001/Purina 5001. AIN-76A is phytoestrogen-free while the other diets contained varying amounts of phytoestrogens. The phytoestrogens genistein and daidzein were determined in the diets studied, and the concentrations found agreed with earlier estimates. RM3/RM1 was selected as the control group, as this has been used routinely in this laboratory for the past decade. Determinations were made in offspring of the times of vaginal opening and first estrus among the females, and of prepuce separation and testes descent among the males. At postnatal day (PND) 26 the females from 6 of the 12 litters were terminated and tissue weights measured. Males from 6 of the 12 litters were similarly studied at PND 68. Animals from the remaining litters were transferred to RM1 diet at PND 70. Termination of the study was at PND 128 (males) and PND 140 (females) when body weights and tissue weights were determined. Marked differences in body weight, sexual development, and reproductive tissue weights were observed for rats maintained on AIN-76A or Purina 5001, with only minimal effects among rats maintained on the Global diet. These comparisons were against RM3/RM1 as the reference diet. However, using Purina 5001 as the reference diet reversed the direction of the differences seen when using RM3/RM1 as the reference diet. The differences observed when using RM3/RM1 as reference diet occurred mainly postnatally. In addition, the fact that similar differences were seen for the phytoestrogen-free diet, AIN-76A, and the phytoestrogen-rich diet, Purina 5001, indicate that these effects are more likely to be caused by nutritional differences between the diets that then have centrally mediated effects on rodent sexual development, rather than individual dietary components affecting peripheral estrogen receptors (ER). This proposal is supported by abolition of the uterotrophic activity of AIN-76A and Purina 5001 (relative to RM3/RM1) in the immature rat by coadministration of the gonadotrophin-releasing hormone (GnRH) antagonist ANTARELIX: The present data indicate that choice of diet may influence the timing of sexual development in the rat, and consequently, that when evaluating the potential endocrine toxicity of chemicals, the components of rodent diets used should be known, and as far as is possible, controlled.

Effect of aerosolized antipseudomonals on Pseudomonas positivity and bronchiolitis obliterans syndrome after lung transplantation. To describe the effects of aerosolized antipseudomonals (AAPs) on Pseudomonas (PS) culture positivity, bronchiolitis obliterans syndrome (BOS), and acute cellular rejection (ACR) in lung transplant recipients (LTRs). Single-center, retrospective cohort study was performed of adult LTRs treated with either AAP for ≥28 days vs no AAP therapy or AAP therapy <28 days, indexed to a matched median date post lung transplantation (LT). Primary outcome was freedom from PS positivity by positive bronchoalveolar lavage or bronchial wash at 1 year. Secondary outcomes were freedom from BOS or BOS progression and ACR burden (defined by the novel composite rejection standardized score. Normality was assessed, and univariate and multivariate parametric and non-parametric statistical tests were used to assess baseline characteristics and outcomes, where appropriate. Freedom from events was compared using the Kaplan-Meier method with log-rank conversion and risk was assigned using multivariable Cox proportional hazards (PH) modeling. In total, 293 LTRs (105 with AAP, 188 with no AAP) were included. Median ages in AAP and control cohorts were 51 (30-63) and 62 (54-67) years (P<.01). Median AAP duration was 198 (interquartile range 94-395) days. Time to median positive PS culture was similar between AAP (median 1.02 [95% confidence interval {CI} 0.74-1.22] years) and control (median 0.96 [95% CI 0.72-1.21] years). Log-rank test for time-to-PS positivity was similar for both groups (log-rank P=.26). Incidence of PS culture positivity at 1 year was similar in APP vs controls (59.0% vs 54.8%, P=.48). In the non-cystic fibrosis (CF) subgroup, AAP use was protective against PS recurrence on univariate Cox PH model (hazard ratio [HR] 0.55, 95% CI 0.38-0.83) and on multivariate Cox PH adjusting for age and induction (HR 0.56, 95% CI 0.38-0.83). Incidence of new-onset BOS or BOS progression in APP vs control at 1 (17.1% vs 14.9%, P=.61) and 3 (38.1% vs 37.8%, P=.96) years was similar. CRSS was similar in APP vs control group at 1 year (0.42 vs 0.33, P=.41). AAP use was not associated with less PS positivity, BOS, or ACR in all LTRs. In the non-CF subgroup analysis, treatment with AAPS was associated with protection against recurrent PS. Limitations include retrospective design, heterogeneous AAP therapy among LTRs, and potential convenience sampling of LTRs receiving AAPs for >28 days at our center. Larger assessments and better controlled analyses are required to further define efficacy of AAPs after LT.

Selective inhibition of tumor necrosis factor-alpha prevents nucleus pulposus-induced histologic changes in the dorsal root ganglion. The possibility to prevent nucleus pulposus-induced structural changes of the dorsal root ganglion (DRG) by selective tumor necrosis factor-alpha (TNF-alpha) inhibition was assessed in an experimental model in the rat spine. To evaluate the role of TNF-alpha in the mediation of nucleus pulposus-induced structural changes by using selective inhibition and to confirm the effect of TNF-alpha inhibitor at the point of histologic findings. TNF-alpha is known to be released from the nucleus pulposus, and has been suggested to play a key role in chemical damage of the adjacent nerve tissue. The TNF-alpha inhibitor prevents the reduction of nerve conduction velocity and may limit the nerve fiber injury, intracapillary thrombus formation, and intraneural edema formation caused by nucleus pulposus. However, there is no report on the effect of the inhibitor regarding histologic findings and the appearance of the TNF-alpha in the DRG exposed to nucleus pulposus. 1) Rats were treated with an intraperitoneal injection of infliximab. Nucleus pulposus from the disc was obtained 1, 3, 7, 14, and 21 days after the injection. The TNF-alpha-positive cells were observed using immunohistochemistry. 2) Disc herniation of the nucleus pulposus was made on the L4-L5 disc in rats. Two groups were treated with selective TNF-alpha inhibitor 1 day before or 3 hours after surgery. The other group received no TNF-alpha inhibitor. The L4 DRG was resected 1, 3, 7, 14, and 21 days after surgery. The specimens were processed for hematoxylin and eosin staining and immunohistochemistry using rabbit antisera to TNF-alpha. The histologic findings and TNF-alpha-positive cells were observed by light microscopy. 1) While positively stained immunoreactive TNF-alpha appeared between 7 and 21 days, no immunoreactive TNF-alpha was observed 1 and 3 days after injection in the nucleus pulposus. 2) The histologic changes of the DRG caused by nucleus pulposus were smaller in the infliximab treatment group than those in the nontreatment group. The number of immunoreactive TNF-alpha cells was high 1 and 3 days after surgery in the DRGs of disc herniation rats that were treated without an injection of the inhibitor, low on day 7 and 14, and very low on day 21 after surgery. No immunoreactive TNF-alpha was observed in the DRGs of the TNF-alpha inhibitor treatment groups on day 1, 3, and 21 after surgery. Weakly stained cells were sometimes observed in rats at day 7 and 14 after surgery. Infliximab may prevent the histologic damage induced by nucleus pulposus. When rats were given a single intraperitoneal injection of infliximab at the beginning of disc herniation, the histologic damage seemed to be reduced in comparison with the nontreated rats.

Raman and infrared spectroscopic investigations on aqueous alkali metal phosphate solutions and density functional theory calculations of phosphate-water clusters. Phosphate (PO(4)(3-)) solutions in water and heavy water have been studied by Raman and infrared spectroscopy over a broad concentration range (0.0091-5.280 mol/L) including a hydrate melt at 23 degrees C. In the low wavenumber range, spectra in R-format have been constructed and the R normalization procedure has been briefly discussed. The vibrational modes of the tetrahedral PO(4)(3-)(aq) (T(d) symmetry) have been assigned and compared to the calculated values derived from the density functional theory (DFT) method for the unhydrated PO(4)(3-)(T(d)) and phosphate-water clusters: PO(4)(3-).H(2)O (C(2v)), PO(4)(3-).2H(2)O (D(2d)), PO(4)(3-).4H(2)O (D(2d)), PO(4)(3-).6H(2)O (T(d)), and PO(4)(3-).12H(2)O (T), a cluster with a complete first hydration sphere of water molecules. A cluster with a second hydration sphere of 12 water molecules and 6 in the first sphere, PO(4)(3-).18H(2)O (T), has also been calculated. Agreement between measured and calculated vibrational modes is best in the case of the PO(4)(3-).12H(2)O cluster and the PO(4)(3-).18H(2)O cluster but far less so in the case of the unhydrated PO(4)(3-) or phosphate-water cluster with a lower number of water molecules than 12. The asymmetric, broad band shape of v(1)(a(1)) PO(4)(3-) in aqueous solutions has been measured as a function of concentration and the asymmetric and broad band shape was explained. However, the same mode in heavy water has only half the full width at half-height compared to the mode in normal water. The PO(4)(3-) is strongly hydrated in aqueous solutions. This has been verified by Raman spectroscopy comparing v(2)(H(2)O), the deformation mode of water, and the stretching modes, the v(1)OH and v(3)OH of water, in K(3)PO(4) solutions as a function of concentration and comparison with the same modes in pure water. A mode at approximately 240 cm(-1) (isotropic R spectrum) has been detected and assigned to the restricted translational mode of the strong hydrogen bonds formed between phosphate and water, P-O...HOH. In very concentrated K(3)PO(4) solutions (C(0) > or = 3.70 mol/L) and in the hydrate melt, formation of contact ion pairs (CIPs) could be detected. The phosphate in the CIPs shows a symmetry lowering of the T(d) symmetry to C(3v). In the less concentrated solutions, PO(4)(3-)(aq) solvent separated ion pairs and doubly solvent separated ion pairs exist, while in very dilute solutions fully hydrated ions are present (C(0) < or = 0.005 mol/L). Quantitative Raman measurements have been carried out to follow the hydrolysis of PO(4)(3-)(aq) over a very broad concentration range. From the hydrolysis data, the pK(3) value for H(3)PO(4) has been determined to be 12.45 at 23 degrees C.

A limited and customized follow-up seems justified after endovascular abdominal aneurysm repair in octogenarians. The objective of this study was to determine whether long-term follow-up after endovascular aneurysm repair (EVAR) is justified in octogenarians. Between September 1996 and October 2011, all patients, including octogenarians, treated for an abdominal aortic aneurysm (AAA) by EVAR were included in a prospective database. Patients older than 80 years and with a nonruptured infrarenal aneurysm treated electively or urgently were included in the study (study group [SG]). Patients with ruptured aneurysms and patients who died during surgery or within the first postoperative month were excluded from further analysis. The control group (CG) consisted of patients younger than 80 years, matched for gender and AAA diameter. All patients were evaluated 4 to 8 weeks after EVAR and then annually thereafter. Follow-up data were complemented by review of the computerized hospital registry and charts and by contact of the patient's general practitioner or referring hospital. Primary outcomes were stent- or aneurysm-related complications and interventions. Secondary outcomes were additional surgical complications and patient survival. A total number of 193 patients (SG, n = 97; CG, n = 96) were included for analysis. Median age was 80 years, and 88.6% were male. Median follow-up time was 33.6 months (interquartile range [IQR], 12.9-68.3). Stent- and procedure-related postoperative complications were comparable between groups (SG, 41.2%; CG, 39.6%; P = .82). Median time to complication was 2.3 months (IQR, 0.2-19.4) in the SG compared with 18.1 months (IQR, 6.8-50.5) in the CG. The 2-year complication-free survival rates were 58% (SG) and 60% (CG). Interventions were performed significantly less frequently in octogenarians (SG, 8.2%; CG, 19.8%; P < .05). Median time to intervention was 11.1 months (IQR, 2.0-31.0) in the SG compared with 54.3 months (IQR, 15.0-93.2) in the CG. The 2-year intervention-free survival rates were 90% (SG) and 92% (CG). During follow-up, 98 patients died (SG, n = 54; CG, n = 44); median time to death was 31.8 months (IQR, 13.3-66.0) in the SG compared with 44.4 months (IQR, 15.0-77.7) in the CG. One aneurysm-related death occurred in the CG. The 2- and 5-year survival rates were 71% and 32% for the SG compared with 77% and 66% for the CG (P < .05). Because of the low incidence of secondary procedures and AAA-related deaths in octogenarians, long-term and frequent follow-up after EVAR seems questionable. An adapted and shortened follow-up seems warranted in this patient group.

[Parental education to reduce blood lead levels in children with mild and moderate lead poisoning: a randomized controlled study]. To evaluate the effectiveness of parental education on reducing lead exposure of children by examining the changes in blood lead levels of children whose parents receiving or not receiving educational intervention. Two hundred children with confirmed blood lead levels beyond 100 microg/L were selected. They were randomized into two groups, 107 children in study group and 93 in control. At the beginning of the study, parents of both study and control groups were called for interview to complete KABP questionnaire and lead study questionnaire. The study group was provided with interventional measures while control group was not contacted until the end of study. Intervention of parental education was undertaken by means of a TV program, a set of slides and a brochure, and focused on the questions regarding harmful effects of lead poisoning, the sources of environmental lead and prevention of this preventable disease. Tests for blood lead level were repeated for both study and control groups 3 months after the determination of the initial blood lead level. All the relevant knowledge of health effect, lead sources and prevention of childhood lead poisoning of participating parents of study group were improved significantly (chi(2) = 14.06, 13.07, 10.08, 28.26, P < 0.01) after educational intervention while parents control group also were significantly improved in the sub-catalogs of concept and prevention (chi(2) = 7.69, 8.64, P < 0.01), but not the health effect and sources of childhood lead poisoning. Children and parents' behavior in study group was improved accordingly and significantly. Less children ate popcorn (chi(2) = 4.08, P < 0.05), less children drank tap-water in the morning (chi(2) = 23.04, P < 0.01), more kids washed their hands before eating (chi(2) = 5.82, P < 0.05), less kids played on road side (chi(2) = 9.60, P < 0.01), and more parents changed their coat or took shower or washed hands before going home after work (chi(2) = 4.00, P < 0.05). But in the control group only the number of kids playing on road side was decreased significantly (chi(2) = 9.60, P < 0.01). A general decline in blood lead levels was detected in both groups with statistical significance at P < 0.01. However, the decrease in blood lead levels was more remarkable in the study group. There was average reduction of 55 microg/L (35%) in blood lead levels for study group (t = 4.979, P < 0.01) and an almost 33 microg/L (20%) for control (t = 3.398, P < 0.01). The reduction in blood lead level was 22 microg/L greater in study group (t = 3.531, P < 0.01). The study also showed that the effectiveness of the educational interventions depended upon various aspects. Fourteen variables were included in the stepwise multiple regression equation of blood lead level changes. Such as parents' occupational exposure to lead, the improvement of knowledge about prevention of childhood lead poisoning, the chang of habit of snacks intake, parents' education levels, the change of attitude of parents for the childhood lead poisoning, etc. Educating parents is proved to be an effective approach for children with mild and moderate lead poisoning.

[Establishing self-management for chronic spinal cord injury patients: a qualitative investigation]. Self-management is essential for individuals with chronic cervical spinal cord injury, but some cases of self-neglect have been reported. The objective of this study was to examine the establishment of self-management in order to help inform community care practice. This was a qualitative study applying a grounded theory approach with semi-structured home interviews. We interviewed 29 individuals with cervical spinal cord injuries (aged 26-77 years) who were members of each of the three branches of the nationwide self-help group, or the clients of a home-visit nursing care station. Qualitative analysis was implemented from a time transition perspective consisting of the faint awareness period, the seeking period, and the adaptation period. The analysis included the perceptions and methods of self-management. The process of establishing self-management was abstracted into a core category of "continuous adaptation to minimize the extent to which the individual's life was disrupted and to allow them to continue to live within the community". This in turn consisted of seven categories. In the faint awareness period, subjects perceived that they "hardly recognized health maintenance needs", that they had difficulties in acknowledging the necessity of controlling physical conditions, and that they were dependent on caregivers. In the seeking period, they were "driven by handling uncontrollable changes" and they coped with those changes in their own way and sometimes did not consider it necessary to see a doctor. In this period, a process of "searching for the methods of being healthy somehow" begun and they started to understand the degree to which they could cope without medication, together with their own responsibilities, and searched for the best coping methods and acted on advice. In the adaptation period, individuals were "struggling to continue the established health methods"; "managing stress"; "prioritizing their own beliefs over medical regimens"; and "confidently modifying the established self-management methods". They employed self-monitoring, preventative measures for secondary difficulties, and stress management techniques. However, they also avoided medication through self-determination and they prioritized their established lifestyle over medically ideal behavior. Subjects learned sustainable self-management methods through trial and error, although in each period of adaptation, they sometimes failed to acknowledge the necessity of health maintenance and medical care, and they coped with their health care needs in their own way. Future research is essential to develop self-management programs that include the patient's own perspectives, to teach health maintenance methods that enable patients to balance social participation and self-management, and to establish cooperative networks among professionals who support the patient's home care.

Mechanical modulation of vertebral growth in the fusionless treatment of progressive scoliosis in an experimental model. Wedging of apical spinal segments was measured during creation and correction of an experimental scoliosis in a goat model. To create and correct apical vertebral wedge deformities in a progressive experimental scoliosis model by purely mechanical means. The creation and correction of vertebral wedge deformities has been previously described in a rat tail model using external fixation. Experimental scoliosis was created in 14 goats using a posterior asymmetric tether with convex rib resection and concave rib tethering. After a period of up to 13 weeks, all tethers were removed and goats were randomized into treated (n = 8) and untreated (n = 6) groups. Treated goats underwent anterior thoracic stapling with four shape memory alloy staples along the convexity of the maximal curvature. Goats were followed for an additional 7 to 13 weeks during treatment. Serial radiographs were used to document progression or correction of the maximal scoliotic deformity as well as to measure the wedging of the apical spinal segment (two adjacent vertebrae and the intervening disc). During the tethering period, all goats achieved a progressive, structural, lordoscoliotic curve of significant magnitude (mean: 61 degrees, range: 49 to 73 degrees). Wedging of the apical spinal segment measured 11.1 degrees at the beginning and 22.4 degrees at the end of the tethering period. The increase in apical spinal segment wedging of +11.3 degrees (10.7 degrees vertebral/0.6-degree disc) was significant (P = 0.001). During the treatment period, the scoliosis in the stapled goats measured 56.8 degrees at the beginning and 43.4 degrees at the end for an average correction of -13.4 degrees (range: 0 to-22 degrees) (P = 0.001), whereas the untreated goats measured 67.0 degrees at the beginning and 59.8 degrees at the end for an average correction of -7.2 degrees (range: +7 to -21 degrees) (P = 0.19). Additionally, wedging of the apical spinal segment in the stapled goats measured 22.5 degrees at the beginning and 20.3 degrees at the end for an average correction of -2.2 degrees (-0.6 degrees vertebral/-1.6-degree disc); wedging of the apical vertebral segment in the untreated goats measured 22.3 degrees at the beginning and 25.8 degrees at the end of the treatment period for an average progression of +3.5 degrees (3.5 degrees vertebral/0.0-degree disc). The difference in apical spinal segment correction versus progression in the stapled (-2.2 degrees) versus control (+3.5 degrees) goats was significant (P < 0.05). This study demonstrates the ability to create wedge deformities at the apex of an experimental scoliosis in a large animal model and to control the progression of these deformities using anterior thoracic staples.

Vehicle interior air quality conditions when travelling by taxi. Vehicle interior air quality (VIAQ) was investigated inside 14 diesel/non-diesel taxi pairs operating simultaneously and under normal working conditions over six weekday hours (10.00-16.00) in the city of Barcelona, Spain. Parameters measured included PM10 mass and inorganic chemistry, ultrafine particle number (N) and size, lung surface deposited area (LDSA), black carbon (BC), CO2, CO, and a range of volatile organic compounds (VOCs). Most taxi drivers elected to drive with windows open, thus keeping levels of CO2 and internally-generated VOCs low but exposing them to high levels of traffic-related air pollutants entering from outside and confirming that air exchange rates are the dominant influence on VIAQ. Median values of N and LDSA (both sensitive markers of VIAQ fluctuations and likely health effects) were reduced to around 104 #/cm3 and < 20 µm2/cm3 respectively under closed conditions, but more than doubled with windows open and sometimes approached 105 #/cm3 and 240 µm2/cm3. In exceptional traffic conditions, transient pollution peaks caused by outside infiltration exceeded N = 106 #/cm3 and LDSA= 1000 µm2/cm3. Indications of self-pollution were implicated by higher BC and CO levels, and larger UFP sizes, measured inside diesel taxis as compared to their non-diesel pair, and the highest concentrations of CO (>2 ppm) were commonly associated with older, high-km diesel taxis. Median PM10 concentrations (67 µg/m3) were treble those of urban background, mainly due to increased levels of organic and elemental carbon, with source apportionment calculations identifying the main pollutants as vehicle exhaust and non-exhaust particles. Enhancements in PM10 concentrations of Cr, Cu, Sn, Sb, and a "High Field Strength Element" zircon-related group characterised by Zr, Hf, Nb, Y and U, are attributed mainly to the presence of brake-derived PM. Volatile organic compounds display a mixture which reflects the complexity of traffic-related organic carbon emissions infiltrating the taxi interior, with 2-methylbutane and n-pentane being the most abundant VOCs, followed by toluene, m-xylene, o-xylene, 1,2,4-trimethylbenzene, ethylbenzene, p-xylene, benzene, and 1,3,5-trimethylbenzene. Internally sourced VOCs included high monoterpene concentrations from an air freshener, and interior off-gassing may explain why the youngest taxi registered the highest content of alkanes and aromatic compounds. Carbon dioxide concentrations quickly climbed to undesirable levels (>2500 ppm) under closed ventilation conditions and could stay high for much of the working day. Taxi drivers face daily occupational exposure to traffic-related air pollutants and would benefit from a greater awareness of VIAQ issues, notably the use of ventilation, to encourage them to minimise possible health effects caused by their working environment.

[Prisons following reform. Current status and prospects]. The Author has examined the period successive to July 1975, namely, from the approval of the new prison System to the present day, highlighting the manifold negative aspects due to the incomplete application of the reform and not neglecting to review also the positive aspects of the regulations applied. The Author laid special stress on the distorted interpretations given to some different regulations of the System and on the ensuing wrong procedure that has been established, whose correction represents the only way not only towards a proper application of the reforming law, but also for preventing the most serious risk the reform is liable to run; that of being made the object of revisions and abrogations that might ultimately change their nature and jeopardise their objectives. The Author reviews the practical consequences of both the erroneous interpretations of the law and of its misapplications, dwelling on Article 30 in the first place, which has prompted some to define the law the "reform of leaves". Also examined was the problem of the special prisons, the usefulness of which is confirmed by the Author, who upholds the view that they must function in full observance of the regulations, for reasons of equity and opportuneness. From the rehabilitation treatment angle, the prison work, the participation of the extramural community, the "leasure time", the assistance after release. Still in the framework of his critical approach as to the prison reality, the Author illustrates the situation of the health service, and reviews the positive points that have been achieved in the implementation of some reform institutions, with special regard to the new disciplinary approach and its satisfactory results that have already been statistically observed. More adequate talks and correspondence by letter or through the telephone, a better compensation for the prison work, the convict representation in some sectors of intramural life, the measures as an alternative to enprisonment, all these actions represent the practical results of the reform achieved so far in a rather satisfactory way. After dealing with the figure of the surveillance judge, of the director and of the military personnel of prisons, setting forth observations and proposals to enhance their work, the Author declares, by way of conclusion, that he is fully convinced that the reform will ultimately attain its important targets, laying stress on the fact that the good will and the contribution of all those who are called upon to participate in its realization, may prove instrumental in shortening the period of time required for making the reform fully operative.

Salt-sensitive hypertension in ANP knockout mice: potential role of abnormal plasma renin activity. Atrial natriuretic peptide (ANP), a peptide hormone produced by the heart, exerts a chronic hypotensive effect. Knockout mice with a homozygous disruption of the pro-ANP gene (-/-) are incapable of producing ANP and are hypertensive relative to their wild-type (+/+) siblings. Previous studies showed that arterial blood pressure (ABP) was further increased in conscious -/- mice kept for 2 wk on 2% salt, but not in anesthetized -/- mice after 1 wk on 8% salt. To determine whether inconsistencies in observed effects of salt on ABP of -/- mice are due to duration of increased salt intake and/or the state of consciousness of the animals, we measured ABP from an exteriorized carotid catheter during and after recovery from anesthesia with ketamine-xylazine in adult +/+ and -/- mice kept on low (LS; 0.008% NaCl)- or high (HS; 8% NaCl)-salt diets for 3-4 wk. Conscious ABP +/- SE (mmHg) of +/+ mice did not differ significantly on either diet (HS, 113 +/- 3; LS, 110 +/- 5). However, on HS diet -/- mice had significantly higher ABP (135 +/- 3; P < 0.001) than both -/- (115 +/- 2) and +/+ (110 +/- 5) mice on LS diet. Anesthesia decreased ABP in all groups, but the the genotype- and diet-related differences were preserved. Plasma renin activity (PRA, ng ANG I.ml-1.h-1) in blood collected at termination of experiment was appropriately different on the 2 diets in +/+ mice (HS, 4.9 +/- 1.9; LS, 21 +/- 2.8). However, PRA failed to decrease in -/- mice on HS diet (HS, 18 +/- 2.9; LS, 19 +/- 3.7). Independent of genotype, concentration of endothelin-1 (ET-1, pg/mg protein) and endothelial constitutive NOS (ecNOS, density/100 micrograms protein) was significantly elevated in kidneys of mice fed on HS diet (ET-1 -/-, 31 +/- 4.7 and +/+, 32 +/- 4.1; ecNOS -/-, 160 +/- 19 and +/+, 156 +/- 19) compared with mice fed on LS diet (ET-1 -/-, 19 +/- 1.9 and +/+, 21 +/- 1.8; ecNOS -/-, 109 +/- 13 and +/+, 112 +/- 18). We conclude that, regardless of the state of alertness, -/- mice develop salt-sensitive hypertension after prolonged feeding on HS, in part due to their inability to reduce PRA, whereas the specific renal upregulation of ecNOS and ET-1 in response to HS intake may be an ANP-independent adaptive adjustment aimed at improving kidney function and counteracting the pressor effect of salt.

Muscularity and fatness of infants and young children born small- or large-for-gestational-age. There is growing interest in the extent to which body composition, both short- and long-term, differs in infants and children born at the extremes of birth weight. This is because a growing number of studies have linked low birth weight and fetal growth restriction to the chronic diseases in adulthood that often are obesity-related, and there is also evidence to suggest that heavy infants may be at increased risk for obesity in later life, again with the attendant obesity-related chronic diseases. Our objective was to compare anthropometric indices of body composition of infants and young children born small-for-gestational-age (SGA, <10th percentile) or large-for-gestational age (LGA, >/=90th percentile) with those of normal birth weight status (appropriate-for-gestational-age, AGA) in a US sample. National sample of US-born non-Hispanic white, non-Hispanic black, and Mexican-American infants and young children, 2 to 47 months of age, examined in the third National Health and Nutrition Examination Survey (NHANES III, 1988-1994), for whom birth certificates were obtained. The primary outcomes were normalized anthropometric indices (z scores or standard deviation units [SDU]) of nutritional status and body composition (mid-upper arm circumference, triceps and subscapular skinfolds, mid-upper arm muscle and mid-upper arm fat areas (UFA), and the arm fat index). The outcomes thus were scaled to permit comparison across chronologic ages. The prevalence of SGA was 8.6%, appropriate-for-gestational-age 80.9%, and LGA 10.5%. From ages 2 to 47 months, for infants and young children born SGA, there was a persistent overall deficit in muscularity (mid-upper arm circumference and mid-upper arm muscle area) of approximately -0.50 SDU, but less of a deficit in fatness, particularly at the youngest ages. For infants and young children born LGA, there was a surfeit in muscularity of approximately 0.45 SDU, with less of a surfeit in fatness, particularly at the youngest ages. Across all ages, the mean UFA showed a statistically significant deficit for SGA children (-0.27 +/- 0.10 SDU) and surfeit for LGA children (0.24 +/- 0.08 SDU). At individual ages for UFA and at individual and all ages combined for skinfold thicknesses, there were no significant differences in level of subcutaneous fatness in the three birth-weight-for-gestational-age groups. There was a tendency in the first year for the arm fat index (% arm fat) to be significantly higher for SGA infants, but the effect did not persist after the first year. SGA infants remain smaller and LGA infants larger in size through early childhood, but the discrepancies in weight are primarily attributable to differences in lean body mass (muscularity). Fatness is less affected. Thus, based on the fatness indicators used, at any given weight for infants and children 2 to 47 months of age, percent body fat appears to be relatively higher for children who were SGA at birth and lower in those who were LGA at birth. These differences in body composition for SGA infants support the evidence documenting a link between disturbances in intrauterine growth and chronic disease associated with subsequent adiposity in adulthood.

Finite Element Simulation Study of a Frontal Driver Airbag Deployment for Out-of-Position Situations. As more and more active restraint devices are added by vehicle manufacturers for occupant protection, the history of driver frontal airbags illustrates that the design performance of such devices for in-position (IP) occupants often have to be limited in order to reduce their aggressiveness for out-of-position (OOP) situations. As of today, a limited number of publications dealing with FE simulation of airbag deployment for OOP are available. The objective of our study was to evaluate the feasibility of airbag deployment simulations based on an extensive set of well-defined physical test matrix. A driver frontal airbag was chosen (European mid-size car sample) for this study. It was deployed against a force plate (14 tests in a total of 6 configurations), and used with Hybrid III 50(th) percentile dummy (HIII) in OOP tests (6 tests, 4 configurations). Special attention was paid to control the boundary conditions used in experiments in order to improve the modeling process. The initial positioning of the dummy (chin against the top of the steering wheel rim, and back of the torso parallel to the plane of the rim) for both physical and numerical dummies was maintained from 23 targets digitized using a 3D Faro arm. Specific test position/conditions that were deemed important were repeated to understand the sensitivity and variation. The software used for the FEM simulations was Radioss, using uniform pressure method. The bag was meshed and folded using Excel and Matlab routines. The inflator characteristics were adapted from data provided by the inflator manufacturer. The body-block test conducted at 7 mm was used to tune the different model parameters and the remaining body-block, 50(th)%le HIII OOP and plate tests were used for validation. The results show comparison of simulation and tests records. The simulations show a satisfactory matching of the test results within the first 60 ms and capture the key events of the bag deployment in a promising manner. The major study limitation remains the confirmation/validation aspect of the study as opposed to prediction. Indeed, the model was developed based on the physical tests. The airbag deployment pattern to was found to be very sensitive to physical and numerical input parameters in the test and models respectively. It is not yet possible to transfer the methodology in order to design an airbag a priori. However, such a model is very useful for the understanding of the loading patterns, injury mechanisms and sensitivity studies.

Comparative morphological remarks on the origin of the posterior femoral cutaneous nerve. The origin and course of the posterior femoral cutaneous nerve were observed macroscopically in 38 Japanese adult cadavers which were dissected in the University of Hokkaido, Faculty of Medicine during the years 1971/72 and the results obtained were compared with those from some other mammals (rat, rabbit, dog and cat) and a number of bibliographical findings on the other animals. On the basis of the archetype of the pudendal plexus, the site of origin of the posterior femoral cutaneous nerve was divided into seven portions as follows: the sciatic nerve or inferior gluteal nerve (I) and its originating roots (RI), the bigeminal nerve (B) and its originating roots (RB), the part of junction of I and B (CIB), the pudendal nerve (P) and its originating roots (RP). According to the arising mode, the posterior femoral cutaneous nerve was calssified into seven types: Type A (the sciatic nerve type); the nerve arises from I and RI (horse, rat, bird, frog and salamander). Type B (the sciatic transitional type); the nerve arises from I, RI, CIB, RB and B (MAN AND MONKEY). Type C (the bigeminal nerve type); the nerve arises from CIB, RB and B (gorilla, chimpanzee, orangutan, cat and sphenodon). Type D (the pudendal transitional type); the nerve arises from CIB, RB, B, RP and P (dog). Type E (the pudendal nerve type); the nerve arises from RP and P (pig, cattle and rabbit). Type F (the mixed type); a mixture of A to E types. These various patterns in the posterior femoral cutaneous nerve may be explained by the comparative anatomical explanation on the limb medial rotation given in Braus' text-book of Anatomy (Bd. I, S. 273). From these descriptions it is reasonable to presume that the main trunk of the posterior femoral cutaneous nerve of the tetrapod below the Aves arises from the sciatic nerve and is analogous to the gluteal branches of mammals, with its main stem still retained in the pudendal nerve. If the cutaneous area supplied by the posterior femoral cutaneous nerve expands to the lateral border of the buttock in company with the lower limb medial rotation, the part between this area and that supplied by the pudendal nerve is enlarged. At first, these expanded areas are probably supplied by the branches of the pudendal nerve, which gradually become independent to become the main stem of the posterior femoral cutaneous nerve in mammals. This nerve seems, therefore, to be primarily a division of the pedendal nerve, and so in man has various types of arising patterns, A to E, in accordance with the scheme in the phylogeny. Those hypothetical changes are observed in the human sacral plexus, from which the cutaneous nerve arises with a fan-shaped overlapping.

Educational and training systems in Sweden for prehospital response to acts of terrorism. Sweden has a long tradition in planning for disaster situations in which the National Board of Health and Welfare has a key responsibilty within the health sector. One important part of this disaster preparedness is education and training. Since 11 September 2001, much focus has been placed on the acts of terrorism with special reference to the effects of the use of chemical, biological, or nuclear/radiological (CBNR) agents. In the health sector, the preparedness for such situations is much the same as for other castastrophic events. The National Board of Health and Welfare of Sweden is a national authority under the government, and one of its responsibilities is planning and the provision of supplies for health and medical services, environmental health, and social services in case of war or crises. "Joint Central Disaster Committees" in each County Council/Region in the country are responsible for overseeing major incident planning for their respective counties/regions. The "Disaster Committee" is responsible for ensuring that: (1) plans are established and revised; (2) all personnel involved in planning receive adequate information and training; (3) equipment and supplies are available; and (4) maintenance arrangements are in place. Sweden adopts a "Total Defense" strategy, which means that it places a high value in preparing for peacetime and wartime major incidents. The Swedish Emergency Management Agency coordinates the civilian Total Defense strategy, and provides funding to the relevant responsible authority to this end. The National Board of Health and Welfare takes responsibility in this process. In this area, the main activities of the National Board of Health and Welfare are: (1) the establishment of national guidelines and supervision of standards in emergency and disaster medicine, social welfare, public health, and prevention of infectious diseases; (2) the introduction of new principles, standards, and equipment; (3) the conducting education and training programmes; and (4) the provision of financial support. The budget for National Board of Health and Welfare in this area is approximately 160 million SEK (US dollar 18 million). The National Board of Health and Welfare also provides funding to the County Councils/Regions for the training of healthcare professionals in disaster medicine and crises management by arranging (and financing) courses primarily for teachers and by providing financial support to the County Councils/Regions for providing their own educational and training programmes. The National Board of Health and Welfare provides funding of approximately 20 million SEK (US dollar 2.4 million) to the County Councils/Regions for this training of healthcare professionals in disaster medicine and crises.

Efficacy of neuroendoscopic procedures in minimally invasive preferential management of pineal region tumors: a prospective study. This prospective study is based on a consecutive series of 20 patients with pineal region tumors who underwent minimally invasive preferential management. The purpose of this report is to discuss the role of neuroendoscopic procedures in the management of pineal region tumors. If the tumor markers alpha-fetoprotein and human chorionic gonadotropin were not detected in serum and there was significant ventricular dilation visualized on neuroimages, neuroendoscopic surgery was first applied for tumor debulking with tissue diagnosis and gross morphological analysis of the tumor and the intraventricular structures, followed by third ventriculostomy. Subsequent procedures were determined on the basis of verified individual tumors. For treatment of germinomas and pineoblastomas, if no tumor dissemination was confirmed by pre-, intra-, or postoperative findings, stereotactic radiotherapy or radiosurgery was performed after one course of chemotherapy with the ICE regimen (isofomid, cisplatin, and etoposide) and followed by two additional courses of chemotherapy. For treatment of malignant germ cell tumors, after extensive surgery, adjuvant chemotherapy with the ICE regimen was performed in three courses in all cases. Then radiotherapy was started using various methods, depending on the evidence of tumor dissemination. For treatment of teratomatous and neuroectodermal tumors other than pineoblastomas, extensive surgical removal was performed. As for adjuvant therapy, if the tumor was a low-grade glioma or if the patient was younger than 5 years of age, postoperative treatment did not include radiotherapy. If the tumor was a malignant teratoma or high-grade glioma, conventional focal radiotherapy was performed, followed by chemotherapy with ICE for 1 year. All but two treated patients had ventriculomegaly. Neuroendoscopic procedures were performed in six of 15 treated patients. Neuroendoscopic biopsy with tumor debulking offered enough material for tissue diagnosis, including immunohistochemical analysis and, in one case, revealed evidence of tumor dissemination undetectable on neuroimaging. With one exception, no shunt was required in any patient undergoing endoscopic third ventriculostomy. Stereotactic radiotherapy was performed in indicated cases. Favorable therapeutic outcomes were obtained in all cases of germinoma and pineoblastoma, with follow-up periods ranging from 24 months to 6.5 years. Our minimally invasive preferential regimen clarified the precise indication for neuroendoscopic procedures, and the majority of our patients with dilated ventricles and no evidence of tumor markers were treated satisfactorily with effective neuroendoscopic procedures as the initial procedure, avoiding unnecessary craniotomy and radiotherapy and promising excellent therapeutic outcomes. The treatment for malignant pineal region tumors remains a subject for further study.

Social norms information for alcohol misuse in university and college students. Drinking is influenced by youth perceptions of how their peers drink. These perceptions are often incorrect, overestimating peer drinking norms. If inaccurate perceptions can be corrected, young people may drink less. To determine whether social norms interventions reduce alcohol-related negative consequences, alcohol misuse or alcohol consumption when compared with a control (ranging from assessment only/no intervention to other educational or psychosocial interventions) among university and college students. The following electronic databases were searched up to July 2015: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, PsycINFO. The Cumulative Index to Nursing and Allied Health Literature (CINAHL) only to March 2008. Reference lists of included studies and review articles were manually searched. No restriction based on language or date was applied. Randomised controlled trials or cluster-randomised controlled trials that compared a social normative intervention versus no intervention, alcohol education leaflet or other 'non-normative feedback' alcohol intervention and reported on alcohol consumption or alcohol-related problems in university or college students. We used standard methodological procedures as expected by Cochrane. Each outcome was analysed by mode of delivery: mailed normative feedback (MF); web/computer normative feedback (WF); individual face-to-face normative feedback (IFF); group face-to-face normative feedback (GFF); and normative marketing campaign (MC). A total of 70 studies (44,958 participants) were included in the review, and 63 studies (42,784 participants) in the meta-analyses. Overall, the risk of bias assessment showed that these studies provided moderate or low quality evidence.Outcomes at four or more months post-intervention were of particular interest to assess when effects were sustained beyond the immediate short term. We have reported pooled effects across delivery modes only for those analyses for which heterogeneity across delivery modes is not substantial (I(2) < 50%).Alcohol-related problems at four or more months: IFF standardised mean difference (SMD) -0.14, 95% confidence interval (CI) -0.24 to -0.04 (participants = 2327; studies = 11; moderate quality evidence), equivalent to a decrease of 1.28 points in the 69-point alcohol problems scale score. No effects were found for WF or MF.Binge drinking at four or more months: results pooled across delivery modes: SMD -0.06, 95% CI -0.11 to -0.02 (participants = 11,292; studies = 16; moderate quality evidence), equivalent to 2.7% fewer binge drinkers if 30-day prevalence is 43.9%.Drinking quantity at four or more months: results pooled across delivery modes: SMD -0.08, 95% CI -0.12 to -0.04 (participants = 21,169; studies = 32; moderate quality evidence), equivalent to a reduction of 0.9 drinks consumed each week, from a baseline of 13.7 drinks per week.Drinking frequency at four or more months: WF SMD -0.11, 95% CI -0.17 to -0.04 (participants = 9929; studies = 10; moderate quality evidence), equivalent to a decrease of 0.17 drinking days/wk, from a baseline of 2.74 days/wk; IFF SMD -0.21, 95% CI -0.31 to -0.10 (participants = 1464; studies = 8; moderate quality evidence), equivalent to a decrease of 0.32 drinking days/wk, from a baseline of 2.74 days/wk. No effects were found for GFF or MC.Estimated blood alcohol concentration (BAC) at four or more months: peak BAC results pooled across delivery modes: SMD -0.08, 95% CI -0.17 to 0.00 (participants = 7198; studies = 11; low quality evidence), equivalent to a reduction in peak BAC from an average of 0.144% to 0.135%. No effects were found for typical BAC with IFF. The results of this review indicate that no substantive meaningful benefits are associated with social norms interventions for prevention of alcohol misuse among college/university students. Although some significant effects were found, we interpret the effect sizes as too small, given the measurement scales used in the studies included in this review, to be of relevance for policy or practice. Moreover, the significant effects are not consistent for all misuse measures, heterogeneity was a problem in some analyses and bias cannot be discounted as a potential cause of these findings.

[Substance use, affective problems and personality traits: test of two association models]. The International Consortium of Psychiatric Epidemiology has confirmed the high comorbidity in community-drawn samples between substance use disorders and anxiety or depression. In the same way, associations between substance use and specific personality traits (such as novelty seeking, harm avoidance or antisocial personality) have also been extensively documented. Self-medication and social deviance are among the most commonly evoked explanatory models for these forms of comorbidity, and are based on findings that affective disorders and specific personality traits often precede the onset of substance use disorders. The self-medication model postulates that an individual chooses a specific substance according to its psychopharmacologic action on the given psychological state of the person. By contrast, the social deviance model posits that this form of comorbidity is due to the fact that persons consuming certain substances may have affective or personality characteristics that are more severe or more deviant than non-consumers (or than consumers of socially well-accepted substances). In this way, the individual does not use a particular substance to assuage pre-existing disorders but, due to a more deviant personality, is less influenced by social norms and may more easily turn to using illicit substances or to polyconsumption. However, a major limitation of the current scientific literature concerning tests of these models is that previous investigations have been based in overwhelming majority on clinical populations. The examination only of clinical samples renders difficult the identification of causal (or primary) risk factors for the emergence of substance use disorders from the potential consequences of substance use itself. The goal of the current study was therefore to simultaneously compare both models of association using a non clinical population of substance users. In addition to selecting subjects based on use (rather than abuse or dependence), multiple comparisons were corrected with a Bonferroni adjustment. A two-phase sampling plan was used with post-stratification on substances use. In the first stage, an initial sample of 685 students was pre-selected based on responses to a battery of self-questionnaires, including information concerning recent consumption of substances (alcohol, cannabis, cocaine, heroin, acid, solvents, and so on), anxiety levels measured by the State and Trait Anxiety Inventory (STAI, Spielberger, 1983) and depression levels evaluated by the Center of Epidemiologic Studies Depression Scale (CES-D, Radloff, 1977). Based on responses to these questionnaires, 98 subjects were selected in the second phase to compose four groups of substance users: non consumers (those who did not use any substance during the last month); consumers of alcohol only, consumers of cannabis (with or without alcohol) and consumers of other illicit substances (with or without cannabis or alcohol). These subjects were then invited to participate in a brief laboratory-based meeting where they completed the Temperament and Character Inventory (TCI, Cloninger, 1992), which assessed different personality characteristics such as novelty seeking (NS), harm avoidance (HA) or antisocial personality disorder (APD). The hypotheses concerning self-medication were tested by multiple logistic regression by comparing each group of substance consumption to the non-consumer group relative to levels of anxiety, depression and scores of novelty seeking and harm avoidance. The social deviance model was tested by ANOVAs using contrasts which allowed for a test of a linear tendency across the four groups of consumption relative to each of the personality traits (novelty seeking, harm avoidance and antisocial personality). Results of multiple logistic regressions showed no difference between non-consumers and any group of consumers with regard to anxiety, depression and harm avoidance. However, consumers of other illicit substances significantly differed from non-consumers for novelty seeking trait (qOR=8.4; p<0.05). Results of the ANOVA also showed no differences between the four groups with regard to scores of harm avoidance and level of antisocial personality but again a comparison of novelty seeking scores was significant, F(94)=6.46, p<0.05. Moreover, the contrast method demonstrated that novelty seeking scores increased linearly and significantly (p<0.001) from the group of non-consumers to the group of the consumers of the most deviant substances. The results obtained in this non-clinical sample are in favor of social deviance model which posits that the personality trait of novelty seeking is associated to the consumption of the most illicit and deviant substances (such as heroin or cocaine). On the other hand, no support was found for the hypothesis of self-medication which assumes that specific substances should be particularly associated with specific psychological characteristics or vulnerabilities.

ONTRAK TESTCUP: a novel, on-site, multi-analyte screen for the detection of abused drugs. We developed a rapid, sensitive, and simple-to-use multi-analyte diagnostic device for the detection of drugs of abuse in urine: the ONTRAK TESTCUP. No sample or reagent handling is necessary with this device, and the device also serves as the sample collection cup. The TESTCUP contains immunochromatographic reagents that qualitatively and simultaneously detect the presence of benzoylecgonine, morphine, and cannabinoids (delta9-tetrahydrocannabinol [THC] in urine. It is based on the principle of competition between the drug in the sample and membrane- immobilized drug conjugate for antidrug antibodies coated on blue-dyed microparticles. Each drug assay has its own strip, which contains an antibody specific to benzoylecgonine, morphine, or THC. A sample is collected in the TESTCUP, a lid is placed on it, and a chamber at the top of the cup is filled with urine by inverting the cup for 5 s. Urine proceeds down immunochromatographic strips, and the assays are developed. In approximately 3-5 min, the Test Valid bars appear, a decal is removed from the detection window, and the results are interpreted. The appearance of a colored bar at the detection window for each drug indicates a negative result. The absence of color in any specific drug detection window indicates a positive result for that drug. If a positive result is obtained, the same device (cup) can be used for gas chromatographic-mass spectrometric (GC-MS) confirmation. When the precision of the TESTCUP was evaluated, the results obtained were as follows: for urine controls containing drug at 50% of its cutoff concentration, the results were greater than or equal to 96, 98, and 96% negative for benzoylecgonine, morphine, and THC, respectively; for urine controls containing drug at 120% of its cutoff concentration, the results were greater than or equal to 97, 100, and 98% positive for benzoylecgonine, morphine, and THC, respectively. The correlations of clinical sample results using the TESTCUP versus results by GC-MS and the ONTRAK and OnLine assays were assessed. There was 100% agreement between samples prescreened positive by GC-MS and positive by TESTCUP for all three assays. There was 100% agreement between TESTCUP and ONTRAK results and between TESTCUP and OnLine results when testing clinical samples positive and negative for cocaine (benzoylecgonine) or THC. Greater than 99% agreement was observed between TESTCUP and ONTRAK results and between TESTCUP and OnLine results when testing clinical samples positive and negative for morphine. The cross-reactivity of the TESTCUP assay to related drugs and drug metabolites was also determined, and the results were similar to those of the ONTRAK and OnLine assays.

Tonotopic and functional organization in the auditory cortex of the big brown bat, Eptesicus fuscus. 1. In Eptesicus the auditory cortex, as defined by electrical activity recorded from microelectrodes in response to tone bursts, FM sweeps, and combinations of FM sweeps, encompasses an average cortical surface area of 5.7 mm2. This area is large with respect to the total cortical surface area and reflects the importance of auditory processing to this species of bat. 2. The predominant pattern of organization in response to tone bursts observed in each cortex is tonotopic, with three discernible divisions revealed by our data. However, although cortical best-frequency (BF) maps from most of the individual bats are similar, no two maps are identical. The largest division contains an average of 84% of the auditory cortical surface area, with BF tonotopically mapped from high to low along the anteroposterior axis and is part of the primary auditory cortex. The medium division encompasses an average of 13% of the auditory cortical surface area, with highly variable BF organization across bats. The third region is the smallest, with an average of only 3% of auditory cortical surface area and is located at the anterolateral edge of the cortex. This region is marked by a reversal of the tonotopic axis and a restriction in the range of BFs as compared with the larger, tonotopically organized division. 3. A population of cortical neurons was found (n = 39) in which each neuron exhibited two BF threshold minima (BF1 and BF2) in response to tone bursts. These neurons thus have multipeaked frequency threshold tuning curves. In Eptesicus the majority of multipeaked frequency-tuned neurons (n = 27) have threshold minima at frequencies that correspond to a harmonic ratio of three-to-one. In contrast, the majority of multipeaked neurons in cats have threshold minima at frequencies in a ratio of three-to-two. A three-to-one harmonic ratio corresponds to the "spectral notches" produced by interference between overlapping echoes from multiple reflective surfaces in complex sonar targets. Behavioral experiments have demonstrated the ability of Eptesicus to use spectral interference notches for perceiving target shape, and this subpopulation of multipeaked frequency-tuned neurons may be involved in coding of spectral notches. 4. The auditory cortex contains delay-tuned neurons that encode target range (n = 99). Most delay-tuned neurons respond poorly to tones or individual FM sweeps and require combinations of FM sweeps. They are combination sensitive and delay tuned.(ABSTRACT TRUNCATED AT 400 WORDS)

Cadaver kidney allocation in the north Italy transplant program on the eve of the new millennium. The identification of parameters impacting on cadaver kidney graft outcome is of paramount importance to ensure proper organ allocation, a process that must take into account ethical, biological, social and administrative factors. This is particularly critical in countries where organ procurement is largely insufficient. In the present chapter we report the results of studies carried out to determine the impact of 17 factors on graft survival and function at 4 years posttransplant in 2,917 recipients transplanted from January 1990-September 1997 in the North Italy Transplant program (NITp). Patient and graft survival rates at 4 years (+/- SEM) were 93.5 +/- 0.5% and 81.4 +/- 0.8%, respectively. Excellent graft function at 4 years was shown by 69.8% of recipients. Younger donor age, absence of pretransplant transfusions, patient dialysis center in the NITp area and level of HLA match showed a statistically significant positive association with graft survival. Younger donor age and male donor gender showed a statistically significant association with excellent graft function at 4 years. These global outcomes were confirmed when the analysis was limited to the subset of the 2,617 adult recipients and to the subset of 1,211 cases for whom both donor and recipient HLA-DRB1 types were available before transplant. The results were used to develop a computer-assisted, refined version of the NITp adult kidney allocation algorithm that was named NITK3. A preliminary evaluation of 472 transplants allocated in 12 months with NITK3 compared with 459 transplants allocated in the preceding 12 months according to the previous algorithm (NITK2) showed a significantly higher proportion of recipients who had been on the waiting list for more than 3 years (33.1% vs 21.1%). The use of NITK3 was also associated with a significantly increased ability to transplant alloimmunized patients (17.7% vs 9.5% with NITK2) and recipients with 0-1 HLA mismatches (21.2% vs 13.5% with NITK2). Differences in 6-month graft survival rates and in the percentage of patients with excellent function at 6 months were not statistically significant in recipients transplanted with NITK3 versus NITK2. Survival rates were 96.9% and 92.4%, respectively. Percentages of patients with excellent renal function were 68.3% and 70.5%, respectively. These preliminary data suggest that NITK3 improves HLA match and reduces the number of patients on the waiting list for 3 or more years without determining significant modifications of 6-month graft survival and function. Moreover, it facilitates the achievement of a fair local balance between organs retrieved and transplanted, the compliance of operators with objective allocation rules and the documentation of the whole allocation process.

The use of the analyst as an autistic shape. In this paper I describe through detailed clinical material the challenges posed by patients who employ entangled autistic defenses. I discuss the complicated nature of treating a patient who employed entangled autistic defenses and utilized my voice in an effort to preserve an undifferentiated state of dual unity. My patient's pursuit of dual unity took a very concrete form in her attempt to mitigate the terror of separateness. This concreteness was expressed via the patient's urgent request that I read letters she wrote to me between sessions. This type of autistic defense placed great strain on my ability to think analytically and I also became increasingly concrete in my response to the patient. Crucial to the analyst's regaining a space in which to think and a sense of separateness is the ability to contact the ground floor of her separate bodily experience. This is just the beginning step in the analyst separating herself from the powerful press to join the patient in a state of dual unity. Interpretation in action (Ogden, 1994) was an effective way to convey the importance of creating and tolerating internal space in myself and begin to create internal space in the patient. Previously such space had been closed down in order to manage primitive fears of annihilation. When a patient is absorbed in an entangling autistic retreat words do not reach the patient on a symbolic level but rather are experienced primarily as an assault on the need for dual unity with the analyst. The patient's need to be wrapped in a sensation based world of dual unity is preferable to a world of spoken words that carry the danger of delineating psychic separateness. In essence there is no self to speak words, only a whirl of an amorphous sensation self lacking definition. I believe with certain kinds of patients it may be necessary to first lose and then work to regain one's analytic mind, as I have powerfully described in the case of Linda. Linda's profound loss of connection to the ground floor of her experience could only begin to be addressed when I worked to extricate myself from 'our magic carpet ride' of dual unity, contacting the reality of my bodily experience, and begin to tolerate the terror I felt regarding my separateness from Linda. I also describe the confusing vacillation between entangled and encapsulated defenses in patients like Linda as previously identified by Cohen and Jay (1996). Ultimately, this kind of slow difficult analytic work began to help Linda develop a capacity to think and provided an alternative to the deadened world of her autistic protections.

A new method to assess the fluidodynamic behaviour of an angiographic contrast agent. To propose a new method for the assessment of the fluidodynamic behaviour of angiographic contrast agents. The method enables measurement of the spatial distribution and time dependence of the contrast agent along a pseudo-vessel on images obtained with an X-ray image intensifier. A particular phantom was devised consisting of a plexiglas box with an insert into which a latex tube with a 0.4 cm in diameter was placed in order to simulate the tortuous flow of a blood vessel. The box, which is filled with water to simulate the thickness of a normal patient, is connected to an injection and pumping system which serve to keep the contrast agent flowing in the pseudo-vessel tube. The pseudo-vessel tube was filled with plain water in one case and with saline solution in another case to assess their different dilution capabilities. The phantom and the flow of contrast agent were imaged with a conventional X-ray image intensifier system and the images were stored in digital format during 35 second acquisitions at a speed of 4 frames per second; for any frame it is possible to measure the mathematical contrast in any position in the image. Further, a diagram showing the time dependence of the spatial distribution of the mathematical contrast is proposed. The X axis shows the spatial distribution of the mathematical contrast, whereas the Y axis shows its temporal variation with a gray level proportional to the mathematical contrast value. By building an horizontal profile of this diagram one can obtain the spatial distribution at a fixed time, while by building a vertical profile one can obtain the temporal variation at a fixed point. Several different contrast agents were so tested. The proposed method allows different fluido-dynamic behaviour patterns of contrast agents and flowing media to be shown. Owing to the different chemical characteristics of water and saline solution these media have different dilution capabilities (higher for water) and this is well demonstrated by the diagram profiles obtained for each. The system has also allowed the detection of a particular behaviour of some contrast agents, whose spatial distribution was non uniform even in the last frames, thus showing a tendency to maintain their bolus-nature over time. An interesting feature which can be noticed in all the temporal profiles is the presence of a "pre-bolus", i.e. the contrast is higher at the very beginning of the flow, then decreases and after some time starts to increase again. Though the initial contrast value obviously depends on the iodine concentration employed, the method shows the contrast variation as a function of time is different for different contrast agents. The method and the equipment proposed provide a good description of the fluidodynamic behaviour of different contrast agents, but do not constitute a reference method for testing haemodynamic behaviour which, "in vivo", is obviously affected by several other chemical and metabolic factors. However, the method allows evaluation of the contrast agents from a physical and fluidodynamic point of view, showing that the iodine content is not the only feature affecting their behaviour. The method can be used in quality control to test the constancy of the physical behaviour of different contrast agents.

[Influence of impaired renal function and magnesium oxide administration on serum magnesium levels in elderly inpatients]. This study aimed to clarify whether serum magnesium (Mg) levels increased in elderly inpatients with impaired renal function receiving magnesium oxide (MgO) administration. We recruited a total of 1,282 inpatients (505 men, 777 women, mean age 79.6 years) in this study. Fasting blood samples were obtained early in the morning. Serum Mg was measured using xylidyl blue method. Estimated glomerular filtration rate (eGFR) levels were calculated according to the formula for ethnic Japanese, inserting sex, age and serum creatinine (cr) levels into the formula. Inpatients were divided into 5 groups according to eGFR levels (ml/min/1.73 m(2)): <30 eGFR (group 1), ≥ 30 but <60 (group 2), ≥ 60 but <90 (group 3), ≥ 90 but <130 (group 4), and ≥ 130 (group 5). Division into a further 4 groups was also carried out, into the same groups (1-3) as described above and ≥ 90 (group 4). In these subgroups we investigated how serum Mg levels changed according to different eGFR levels, or after being given MgO. In 552 inpatients not given MgO and 372 given MgO, the percentages of subjects with ≥ 2.7 mg/dl of serum Mg were 38.5% in those not given MgO and 78.5% in those given MgO in group 1, 28.1% and 49%, respectively, in group 2, 0% and 23.1% to 29.6% in groups 3 to 5; the percentage of patients with < 2.4 mg/dl of serum Mg was higher in groups 1 to 5 in those not given MgO than in those given MgO. These findings suggest an increase in serum Mg levels after initiation of MgO administration. At an average of 6.9 months in 22 men and 6.4 months in 39 women, both groups not receiving MgO serum Mg increased significantly, while eGFR reduced considerably. At an average of 6.4 months in 18 men and 10 months in 30 women who received MgO, serum Mg increased considerably, although eGFR did not show any significant change. In 4 cases spanning 4 to 14 months, seesawing alterrations between eGFR and serum Mg were often noted. We measured subjects from the 4 subgroups (divided according to eGFR), comprising 88 inpatients not given MgO, 116 who were given daily doses of 0.5 g to 1.5 g MgO, and 118 who were given daily doses of 2 g to 3 g MgO. In those without MgO serum Mg was markedly higher in group 1 than in groups 3 and 4. In all 4 groups, serum Mg was markedly higher in those given MgO than in those not given MgO. In group 1 only, serum Mg was markedly higher in those given daily doses of 2 g to 3 g than in those given 0.5 g to 1.5 g MgO. In 23 subjects with serum Mg levels of over 3.8 mg/dl (normal range: 1.7 mg/dl to 2.6 mg/dl), 7 not given MgO had markedly lower eGFR levels than 16 given MgO, and the mean levels of serum Mg were similar among these. The highest levels of serum Mg were 5.2 mg/dl in those not given MgO and 5.9 mg/dl in those given MgO. The important factors associated with elevated serum Mg levels noted in this study were: a reduction in eGFR to below 30 ml/min/1.73 m(2), and MgO administration for treatment of chronic constipation and the simultaneous occurrence of the above two factors.

Meta-analysis and systematic review of laparoscopic versus open mesh repair for elective incisional hernia. The utility of laparoscopic repair in the treatment of incisional hernia repair is still contentious. The aim was to conduct a meta-analysis of RCTs investigating the surgical and postsurgical outcomes of elective incisional hernia by open versus laparoscopic method. A search of PubMed, Medline, Embase, Science Citation Index, Current Contents, and the Cochrane Central Register of Controlled Trials published between January 1993 and September 2013 was performed using medical subject headings (MESH) "hernia," "incisional," "abdominal," "randomized/randomised controlled trial," "abdominal wall hernia," "laparoscopic repair," "open repair", "human" and "English". Prospective RCTs comparing surgical treatment of only incisional hernia (and not primary ventral hernias) using open and laparoscopic methods were selected. Data extraction and critical appraisal were carried out independently by two authors (AA and MAM) using predefined data fields. The outcome variables analyzed included (a) hernia diameter; (b) operative time; (c) length of hospital stay; (d) overall complication rate; (e) bowel complications; (f) reoperation; (g) wound infection; (h) wound hematoma or seroma; (i) time to oral intake; (j) back to work; (k) recurrence rate; and (l) postoperative neuralgia. These outcomes were unanimously decided to be important since they influence the practical and surgical approach towards hernia management within hospitals and institutions. The quality of RCTs was assessed using Jadad's scoring system. Random effects model was used to calculate the effect size of both binary and continuous data. Heterogeneity amongst the outcome variables of these trials was determined by the Cochran Q statistic and I (2) index. The meta-analysis was prepared in accordance with PRISMA guidelines. Sufficient data were available for the analysis of twelve clinically relevant outcomes. Statistically significant reduction in bowel complications was noted with open surgery compared to the laparoscopic repair in five studies (OR 2.56, 95 % CI 1.15, 5.72, p = 0.02). Comparable effects were noted for other variables which include hernia diameter (SMD -0.27, 95 % CI -0.77, 0.23, p = 0.29), operative time (SMD -0.08, 95 % CI -4.46, 4.30, p = 0.97), overall complications (OR -1.07, 95 % CI -0.33, 3.42, p = 0.91), wound infection (OR 0.49, 95 % CI 0.09, 2.67, p = 0.41), wound hematoma or seroma (OR 1.54, 95 % CI 0.58, 4.09, p = 0.38), reoperation rate (OR -0.32, 95 % CI 0.07, 1.43, p = 0.14), time to oral intake (SMD -0.16, 95 % CI -1.97, 2.28, p = 0.89), length of hospital stay (SMD -0.83, 95 % CI -2.22, 0.56, p = 0.24), back to work (SMD -3.14, 95 % CI -8.92, 2.64, p = 0.29), recurrence rate (OR 1.41, 95 % CI 0.81, 2.46, p = 0.23), and postoperative neuralgia (OR 0.48, 95 % CI 0.16, 1.46, p = 0.20). On the basis of our meta-analysis, we conclude that laparoscopic and open repair of incisional hernia is comparable. A larger randomized controlled multicenter trial with strict inclusion and exclusion criteria and standardized techniques for both repairs is required to demonstrate the superiority of one technique over the other.

Meta-analysis of endovascular vs open repair for traumatic descending thoracic aortic rupture. Traumatic thoracic aortic injuries are associated with high mortality and morbidity. These patients often have multiple injuries, and delayed aortic repair is frequently used. Endoluminal grafts offer an alternative to open surgical repair. We performed a meta-analysis of comparative studies evaluating endovascular vs open repair of these injuries. A systematic search of studies reporting treatment of traumatic aortic injury was performed using the following databases: Medline/PubMed, CINAHL, Proquest, Up to Date, Database of Abstracts of Reviews of Effects (DARE), ClinicalTrials.gov, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews. Search terms were thoracic aortic trauma, traumatic thoracic aortic injury, traumatic aortic rupture, stent graft repair, and endovascular repair. Outcomes analyzed were procedure-related mortality, overall 30-day mortality, and paraplegia/paraparesis rate using odds ratios (OR) and 95% confidence intervals (CI). Publication bias was investigated using funnel plots. Assessment of homogeneity was performed using the Q test; statistical heterogeneity was considered present at P < .05. Weighted averages of age, interval to repair, and injury severity score were compared with the Welch t test; P < .05 was considered statistically significant. Seventeen retrospective cohort studies from 2003 to 2007 were included. All were nonrandomized; no prospective randomized trials were found. These studies reported on 589 patients; 369 were treated with open repair, and 220 underwent thoracic stent graft placement. There was no significant difference in age (mean 38.8 years for both) or interval to repair (mean 1.5 days for endoluminal repair; 1 day for open repair). Injury severity score was higher for patients undergoing endoluminal repair (mean, 42.4 vs 37.4 for open repair, P < .001). Procedure-related mortality was significantly lower with endoluminal repair (OR, 0.31; 95% CI, 0.15-0.66; P = .002). Overall 30-day mortality was also lower after endoluminal repair (OR, 0.44; 95% CI, 0.25-0.78; P = .005). Sixteen studies reported data for postoperative paraplegia; 215 patients were treated with endograft placement and 333 with open repair. The risk of postoperative paraplegia was significantly less with endoluminal repair (OR, 0.32; 95% CI, 0.1-0.93; P = .037). The Q test did not indicate significant heterogeneity for the outcomes of interest; publication bias was limited. Meta-analysis of retrospective cohort studies indicates that endovascular treatment of descending thoracic aortic trauma is an alternative to open repair and is associated with lower postoperative mortality and ischemic spinal cord complication rates.

Reduction of resuscitation fluid volumes in severely burned patients using ascorbic acid administration: a randomized, prospective study. High-dose ascorbic acid (vitamin C) therapy (66 mg/kg per hour) attenuates postburn lipid peroxidation, resuscitation fluid volume requirements, and edema generation in severely burned patients. A prospective, randomized study at a university trauma and critical care center in Japan. Thirty-seven patients with burns over more than 30% of their total body surface area (TBSA) hospitalized within 2 hours after injury were randomly divided into ascorbic acid and control groups. Fluid resuscitation was performed using Ringer lactate solution to maintain stable hemodynamic measurements and adequate urine output (0.5-1.0 ml/kg per hour). In the ascorbic acid group (n = 19; mean burn size, 63% +/- 26% TBSA; mean burn index, 57 +/- 26; inhalation injury, 15/ 19), ascorbic acid was infused during the initial 24-hour study period. In the control group (n = 18; mean burn size, 53% +/- 17% TBSA; mean burn index, 47 +/- 13; inhalation injury, 12/18), no ascorbic acid was infused. We compared hemodynamic and respiratory measurements, lipid peroxidation, and fluid balance for 96 hours after injury. Two-way analysis of variance and Tukey test were used to analyze the data. Heart rate, mean arterial pressure, central venous pressure, arterial pH, base deficit, and urine outputs were equivalent in both groups. The 24-hour total fluid infusion volumes in the control and ascorbic acid groups were 5.5 +/- 3.1 and 3.0 +/- 1.7 mL/kg per percentage of burn area, respectively (P<.01). In the first 24 hours, the ascorbic acid group gained 9.2% +/- 8.2% of pretreatment weight; controls, 17.8% +/- 6.9%. Burned tissue water content was 6.1 +/- 1.8 vs 2.6 +/- 1.7 mL/g of dry weight in the control and ascorbic acid groups, respectively (P<.01). Fluid retention in the second 24 hours was also significantly reduced in the ascorbic acid group. In the control group, the ratio of PaO2 to fraction of inspired oxygen at 18, 24, 36, 48, and 72 hours after injury was less than that of the ascorbic acid group (P<.01). The length of mechanical ventilation in the control and ascorbic acid groups was 21.3 +/- 15.6 and 12.1 +/- 8.8 days, respectively (P<.05). Serum malondialdehyde levels were lower in the ascorbic acid group at 18, 24, and 36 hours after injury (P<.05). Adjuvant administration of high-dose ascorbic acid during the first 24 hours after thermal injury significantly reduces resuscitation fluid volume requirements, body weight gain, and wound edema. A reduction in the severity of respiratory dysfunction was also apparent in these patients.

Reducing Preventable Hospitalizations With Two Models of Transitional Care. Transitional care is an emerging model of health care designed to decrease preventable adverse events and associated utilization of health care through temporary follow-up after hospital discharge. This study describes the approaches and outcomes of two distinct transitional care programs serving different populations: one is provided by master's-prepared clinical nurse specialists (CNS) with a chronic disease self-management focus, another by physicians specializing in palliative care (PPCs). Existing research has shown that transitional care programs with intensive follow-up reduce hospitalizations, emergency department (ED) visits, and costs. Few studies, however, have included side-by-side descriptions of the efficacy of transitional care programs varying by healthcare providers or program focus. This is a retrospective cohort study comparing the number of ED visits and hospitalizations in the 120 days before and after the intervention for patients enrolled in each transitional care program. Each program included post-hospitalization home visits, but included differences in program focus (chronic disease vs. palliative), assessment and interventions, and population (rural vs. urban). Data from participants in the CNS program (September 2014 to December 2014) were analyzed (n = 98). The average age of participants was 69 years and 65% were female. Data were collected from patients from the PPC program from September 2014 to April 2015 (n = 71). Thirty participants died within 120 days after the intervention and were excluded; the remaining 41 were included in the analysis. Participants had an average age of 81 years and 63% were female. For the CNS program, a secondary analysis of existing data was performed. For the PPC program, a review of patient charts was done to collect data on encounters. A Wilcoxon matched-pairs signed-rank test was performed to test for significance. Patients in the CNS intervention had significantly fewer ED visits (p < .005) and hospitalizations (p < .005) in the 4 months after the intervention than in the 4 months before the intervention. Patients in the PPC program had a nonsignificant reduction in ED visits (p = .327) and a significant reduction in hospitalizations postintervention (p = .03). Both transitional programs have value in decreasing rehospitalizations. The CNS intervention also significantly reduced ED visits for their target population. Further study with randomized controlled trials is needed to allow for a better understanding of the healthcare workforce best fitted to enhance transitional care outcomes. Future study to examine the cost savings of each of the interventions is also needed. Transitional care programs have the potential to prevent unnecessary utilization of health care at the critical periods of transition that leave patients vulnerable to adverse events and poor outcomes.

Thromboxane A2 mediates increased pulmonary microvascular permeability following limb ischemia. Lower torso ischemia and reperfusion lead to respiratory dysfunction characterized by pulmonary hypertension and increased lung microvascular permeability. This is associated with lung leukosequestration and thromboxane (TX) generation. This study tests the role of elevated TX levels following muscle ischemia in mediating remote lung injury. Anesthetized sheep prepared with chronic lung lymph fistulae underwent 2 hours of bilateral hind limb tourniquet ischemia. In untreated controls (n = 7), 1 minute after reperfusion there was a transient increase in plasma immunoreactive (i)-TXB2 levels from 211 to 735 pg/ml (p less than 0.05), and at 30 minutes, lung lymph i-TXB2 levels rose from 400 to 1,005 pg/ml (p less than 0.05). At 1 minute, the mean pulmonary arterial pressure (MPAP) increased from 13 to 38 mm Hg (p less than 0.05) and pulmonary microvascular pressure (Pmv) from 7 to 18 mm Hg (p less than 0.05). Lung lymph flow (QL) rose from 4.3 to 8.3 ml/30 min (p less than 0.05), the lymph/plasma (L/P) protein ratio was unchanged from 0.6, and the lymph protein clearance increased from 2.6 to 4.6 ml/30 min (p less than 0.05). Two hours after reperfusion, neutrophils were observed sequestered in lung capillaries and proteinaceous exudates were found in alveoli in contrast to sham-operated animals (n = 3). To maximize lung vascular surface area and achieve a pressure independent L/P protein ratio a left atrial balloon was inflated during one group of ischemia-reperfusion experiments (n = 5). This resulted in a baseline rise in MPAP to 20 mm Hg (p less than 0.05); a 4.3-fold increase in QL (p less than 0.05), a decrease in the L/P ratio from 0.70 to 0.28 (p less than 0.05) and a protein reflection coefficient (sigma d) of 0.72. During reperfusion the L/P ratio rose to 0.49 (p less than 0.05) and the sigma d decreased to 0.51 (p less than 0.05), documenting an increase in lung microvascular permeability. In contrast to untreated ischemic controls, inhibition of TX synthetase with OKY 046 (n = 6) reduced plasma i-TXB2 levels to 85 pg/ml (p less than 0.05) but also increased i-6-keto-PGF1 alpha levels to 78 pg/ml relative to 15 pg/ml in untreated controls (p less than 0.05). OKY 046 prevented the increase in MPAP, Pmv, QL, and lymph protein clearance (p less than 0.05). Lung histology was normal in distinction to the leukosequestration in untreated ischemic controls.(ABSTRACT TRUNCATED AT 400 WORDS)

[The clinical significance of GastroPanel in diagnostics of Helicobacter pylori eradication efficiency in patients with dyspepsia with correlation of family history of gastric cancer]. Gastric cancer remains a significant medical and social problem. Familial, hereditary, social, and demographic factors increase the susceptibility of subjects to cancer development, especially those infected with Helicobacter pylori (H. pylori). Apart from genetic studies, there are ongoing biochemical studies of possible practical value in assessment of the risk of gastric cancer development. The GastroPanelBiohit test, that include determination of the levels of gastrin (G-17), pepsinogen I (PGI), pepsinogen II (PGII) and antibodies IgG/IgA against H. pylori in serum, allowed us to determine whether there are any abnormal changes in the gastric mucosa. The aim of the study was to determine whether GastroPanel parameters, identified in patients with dyspeptic symptoms (with or without history of gastric cancer in first degree relatives) before and after successful eradication of H. pylori, have any clinical value, especially in gastric cancer development. The study comprised 61 patients aged 18-56 years with symptoms of dyspepsia. In all patients, the preliminary urea breath test (UBT) for the presence of H. pylori was performed and the positive result qualified for further study. For final analysis, 42 patients were approved, who were divided into two groups: group I (a control group) - 22 patients with negative family history of gastric cancer among the relatives of first degree, group II - 20 patients with positive history of gastric cancer among the relatives of first degree. All the patients had the gastroscopy with the biopsy of gastric mucosa for the histopathological evaluation. Additionally, the GastroPanel test was performed. In the blood serum of the patients with H. pylori infection, the concentrations of gastrin (G-17), pepsinogen I (PGI) and pepsinogen II (PGII) did not depend on family history of gastric cancer (p > 0.05). Successful eradication of H. pylori decreases the levels of G-17, PGI and PGII (statistical significance p < 0.05), and this correlates with the histopathological changes of gastric mucosa. The patients with positive family history of gastric cancer had more intense H. pylori colonization of gastric mucosa (IV degree of insensitivity of infection in UBT; group I - 22% vs group II - 69%) as compared to the control group. After effective eradication of H. pylori, statistically significant decreases of IgG H. pylori antibodies and of the level of gastrin (p < 0.05) in blood serum were seen (in a 3 months follow up) only in the control group. Independently of the history of familial gastric cancer, the GastroPanelBiohit test provides important clinical data useful for diagnosis, for assessment of effectiveness of H. pylori eradication therapy and in evaluation of the degree of the inflammatory changes in gastric mucosa.

[Relationship between wrist bone mineral density and synovitis, erosion by ultrasonography in female rheumatoid arthritis patients]. To find the correlation of wrist bone mineral density (BMD) to wrist synovitis and erosion, by comparing wrist BMD and ultrasonography. A number of 80 female RA patients were examined by BMD measurement of the femoral neck, spine and non-dominant wrist using dual-energy X-ray absorptiometry (DXA). Synovitis of the wrist was examined by ultrasonography. The wrist joint (radiocarpal joint, dorsal midline, and carpoulnar joint) was assessed in the same side of DXA, with transverse and longitudinal scans for USGS synovial hypertrophy and proliferation, tenosynovitis,tendinitis and bone erosion. Colour and power doppler ultrasonography (PDUS) were used to sum the synovitis score. We found: (1) In the study, 80 female RA patients were enrolled, the mean age was 54.6±13.3 (27.0-80.0) years, the disease duration was 48 (12-116) months, and the body Mass Index was 23.0±4.0 (14.8-31.2) kg/m2. The Wrist BMD (g/cm2) in RA significantly reduced, compared with normal controls(0.297±0.121 vs. 0.420±0.180,P<0.01). (2) The Wrist BMD (g/cm2) exceeded in early RA compared with the established RA (0.326±0.103 vs. 0.285±0.132,P<0.01); the positive rate of severe osteoporosis in wrist was lower in early RA compared with the established RA (47.8% vs. 64.9%, P<0.05); the positive rate of bone erosion in wrist by ultrasound was lower in early RA compared with the established RA (39.1% vs. 56.1%, P<0.01). (3) The wrist BMD (g/cm2) in RA with high disease activity reduced compared with moderate and low disease activity (0.267±0.140 vs. 0.280±0.126) and (0.267±0.140 vs. 0.320±0.103) respectively, P<0.05). The percentages of positive ACPA in the high and moderate disease activity groups were significantly higher than those in the remission group (85% vs. 81.8% and 92.6% vs. 81.8%, respectively). DAS28ESR was correlated with wrist BMD (r=-0.288, P<0.01). (4) A significant positive correlation was found between wrist and spine/femur BMD (r=0.634, P<0.01, r=0.795, P<0.01), and a negative correlation between wrist and disease duration and DAS28ESR (r=-0.286, r=-0.301, P<0.01). There was a highly significant positive correlation between wrist BMD and femur BMD (r=0.95, P<0.05). (5) RA patients in wrist osteoporosis group had higher RF positive rate and ACPA rate than wrist osteopenia group (75.5% vs. 55.6%, P<0.05,100% vs. 83.3%, P<0.05). The patients of BMD osteoporosis group had higher DAS28ESR compared with osteopenia group (5.3±1.8 vs. 3.7±1.5, P<0.01). The percentages of synovitis (61.5% vs. 51.7%, P<0.05), tendenitis (14.3% vs. 10.0%, P<0.05) and bone erosion (54.2% vs. 46.2%, P<0.05) in wrist by ultrasonography in osteoporosis group were higher than those of osteopenia group. (6) The wrist BMD in negative bone erosion group by ultrasonography was lower than that in positive bone erosion group [(0.333±0.107) g/cm2 vs. (0.264±0.125) g/cm2, P<0.01], also the PDUS score was higher than positive bone erosion group (4.53±1.40 vs. 2.55±2.66, P<0.01). Compared with negative bone erosion group, the patients in positive bone erosion group had longer disease duration (96.0±104.7) months vs. (66.2±78.0) months, P<0.05), higher percentage of RF (81.0% vs. 53.8%, P<0.01), ACPA (92.7% vs. 79.5%, P<0.05). and higher DAS28ESR (5.4±1.8 vs. 4.2±2.0, P<0.05). The percentage of wrist synovitis in positive bone erosion group was higher (75.6% vs. 30.8%, P<0.01) than that of negative bone erosion group, and moreover, the percentage of severe osteoporosis in the wrist was significantly higher (75.0% vs. 46.4%, P<0.01). (7) A stepwise multivariate linear regression model was constructed to explore the relationship between the different clinical factors studied and a low wrist BMD. Statistically significant variables were age (P=0.001), disease duration (P=0.017), DAS28ESR (P=0.021), and ACPA (P=0.05). This study shows a highly significant correlation between hand BMD with disease duration and disease activity, and female RA patients with high titer of ACPA have lower wrist BMD.

A comparison of the efficacy and safety of iopamidol-370 and iodixanol-320 in patients undergoing multidetector-row computed tomography. To prospectively compare the effects on heart rate (HR) and contrast enhancement efficacy of iopamidol-370 and iodixanol-320 in contrast-enhanced, multidetector-row computed tomography (CE-MDCT). IMPACT is a multicenter, double-blind study involving 166 patients undergoing CE-MDCT of the liver (n = 121) or peripheral arteries (n = 45) randomized to receive equi-iodine doses (40 gI) of iopamidol-370 or iodixanol-320 intravenous at 4 mL/s. CE-MDCT was performed using 16-MDCT scanners according to predefined imaging protocols. HR was measured with the patient in the supine position before and continuously for 5 minutes after contrast medium administration. Mean and peak increases in HR and the proportion of subjects with predefined HR increases (>5 to <10, 10 to <15, 15 to <20, >20 bpm) were compared in the 2 populations. Liver images were assessed by 2 independent, blinded readers for contrast enhancement [Hounsfield unit (HU)], using predefined regions-of-interest during the arterial and portal-venous phase of enhancement. Effects on HR: Eighty-four subjects received iopamidol-370 whereas 82 received iodixanol-320. Mean age, gender distribution, weight, total iodine dose, dose/body weight, concomitant medications and use of beta-blockers were comparable in the 2 groups. Mean baseline HR was similar in the 2 groups (iopamidol-370: 72.3 +/- 12.5 bpm; iodixanol-320: 74.5 +/- 11.9 bpm). Mean changes from baseline to peak postdose were similar in the 2 groups (8.0 +/- 9.3 bpm after iopamidol-370 and 8.4 +/- 14.7 after iodixanol-320, P = 0.72). The proportion of subjects in each group having increases of <5, >5 to <10, 10 to <15, 15 to <20, or >20 bpm was comparable (P = 0.87). Two subjects experienced postcontrast tachycardia (HR increase >70 bpm, peak HR of 146 and 164 bpm), both in the iodixanol-320 group (2.4%). Contrast Enhancement: Of the 121 patients undergoing liver CT, 60 received iopamidol-370 whereas 61 received iodixanol-320. Mean age, gender distribution, weight, total iodine dose, and dose/body weight were comparable in the 2 groups. Iopamidol-370 provided significantly higher HU values in abdominal aorta during the arterial phase of enhancement for both readers [R1: 301.3 +/- 80.2 vs. 273.6 +/- 65.9 HU, 95% confidence interval (6.1-56.8), P = 0.02; R2: 302.0 +/- 73.6 vs. 275.1 +/- 62.9 HU, 95% confidence interval (2.3-51.3), P = 0.03]. No significant difference was observed between the 2 contrast medium during the portal venous phase of enhancement. When the same injection rate and iodine dose is used, the effects on HR of bolus intravenous injections of iopamidol-370 and iodixanol-320 were similar. Iopamidol-370 provides significantly greater enhancement during the arterial phase and similar enhancement during the portal venous phase compared with iodixanol-320.

SSEA-1 isolates human endometrial basal glandular epithelial cells: phenotypic and functional characterization and implications in the pathogenesis of endometriosis. Can the basal epithelial compartment of the human endometrium be defined by specific markers? Human endometrial epithelial cells from the basalis express nuclear SOX9 and the cell-surface marker SSEA-1, with some cells expressing nuclear β-catenin. In vitro, primary endometrial epithelial cells enriched for SSEA-1+ show some features expected of the basalis epithelium. The endometrial glands of the functionalis regenerate from the basalis gland stumps following menstruation. Endometriosis is thought to originate from abnormal dislocation of the basalis endometrium. In the highly regenerative intestinal epithelium, SOX9 and nuclear β-catenin are more highly expressed in the intestinal crypt, the stem/progenitor cell region. A large prospective observational study analysing full-thickness human endometrial hysterectomy samples from 115 premenopausal women, 15 post-menopausal women and ectopic endometriotic lesions from 20 women with endometriosis. Full-thickness endometrium from hysterectomy tissues was analysed by immunohistochemistry for SSEA-1, SOX9 and β-catenin. Primary human endometrial epithelial cells from short-term cultures were sorted into SSEA1+/- fractions with a cell sorter or magnetic beads and analysed for markers of differentiation and pluripotency and telomere lengths (TLs) using qPCR, telomerase activity [telomere repeat amplification protocol (TRAP)] and growth in 3D culture. Similar to the intestinal crypt epithelium, human endometrial basal glandular epithelial cells expressed nuclear SOX9 and contained a rare subpopulation of cells with nuclear β-catenin suggestive of an activated Wnt pathway. The embryonic stem cell-surface marker, SSEA-1, also marked the human endometrial basal glandular epithelial cells, and isolated SSEA-1(+) epithelial cells grown in monolayer showed significantly higher expression of telomerase activity, longer mean TLs, lower expression of genes for steroid receptors and produced a significantly higher number of endometrial gland-like spheroids in 3D culture compared with SSEA-1(-) epithelial cells (P = 0.009). Cells in ectopic endometriosis lesions also expressed SSEA-1 and nuclear SOX9, suggesting that the basalis contributes to ectopic lesion formation in endometriosis following retrograde menstruation. This is a descriptive study with only short-term culture of the primary human epithelial cells in vitro. The surface marker SSEA1 enriches for an endometrial epithelial cell subpopulation from the basalis. Since the functional endometrium originates from these cells, it is now possible to study basalis epithelium for stem/progenitor cell activity to extend our current understanding of endometrial biology in health and diseases. The work included in this manuscript was funded by Wellbeing of Women project grant RG1073 (D.K.H. and C.G.). We also acknowledge the support by National Health and Medical Research Council, RD Wright Career Development Award 465121 and Senior Research Fellowship 1042298, and the Victorian Government's Operation Infrastructure Support Program to C.G. and MRC G0601333 to T.V.Z. All authors have no conflict of interest to declare. N/A.

Polymorphism of glutathione S-transferase M1 and lung cancer risk among African-Americans and Caucasians in Los Angeles County, California. Glutathione S-transferase M1 (GSTM1) is active in the detoxication of a number of carcinogens, including polyaromatic hydrocarbons, such as those present in cigarette smoke. In about 30%-55% of individuals, depending on the ethnic group, there is a virtual absence of GSTM1 enzyme activity due to deletion of both copies of the GSTM1 gene (GSTM1 null genotype). This genetic polymorphism of the GSTM1 gene locus has been proposed as a risk factor for lung cancer. However, results across studies are inconsistent. We conducted a case-control study of patients with incident lung cancer and population control subjects to examine the association between homozygous deletion of the GSTM1 gene and lung cancer risk among African-Americans and Caucasians. At 35 hospitals in Los Angeles County, California, we identified patients with a first diagnosis of lung cancer between September 1, 1990, and January 6, 1994. Of the 859 potentially eligible case patients, 207 had died by the time their physicians had received our request for permission to contact them. We enrolled 356 eligible case patients (167 African-Americans and 189 Caucasians) and 731 eligible control subjects (258 African-Americans and 473 Caucasians, all residents of Los Angeles County). Samples of white blood cell DNA sufficient for determination of the GSTM1 genotype by a polymerase chain reaction-based assay were obtained from 342 case patients and 716 control subjects. The odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with homozygous deletion of the GSTM1 gene, in total and after stratification by a number of relevant characteristics, were estimated by logistic regression analysis. For patients with all lung cancers combined, the GSTM1 null genotype was associated with an OR of 1.29 (95% CI = 0.94-1.77). The OR was similar among African-Americans (OR = 1.20; 95% CI = 0.72-2.00) and Caucasians (OR = 1.37; 95% CI = 0.91-2.06). The association was strongest for squamous cell carcinoma (OR = 1.57; 95% CI = 0.93-2.63). We observed an OR of 1.77 (95% CI = 1.11-2.82) for the GSTM1 null genotype in relation to lung cancer risk among smokers of less than 40 pack-years, but no association among heavier smokers (OR = 0.90; 95% CI = 0.56-1.44). Our data do not support a substantial association between homozygous deletion of the GSTM1 gene and the risk of lung cancer overall in this population. However, our data do suggest an elevated risk for lighter smokers with this genotype. Because the power of our analyses within strata of lifetime smoking history was limited, larger studies will be needed to confirm these findings.

Allelopathic effects of microcystin-LR on the germination, growth and metabolism of five charophyte species and a submerged angiosperm. Microcystins (MCs) are produced by cyanobacteria in aquatic environments and adversely affect macrophytes at very high concentrations. However, the effects of MC on macrophytes at concentrations of environmental relevance are largely unknown. The main objective of this study was to analyze the allelopathic effects of MC-LR at natural concentrations (1, 8 and 16 μg MC-LR/L) on five charophyte species (Chara aspera, C. baltica, C. hispida, C. vulgaris and Nitella hyalina) and the angiosperm Myriophyllum spicatum. Macrophyte specimens were obtained from a restored area located in Albufera de València Natural Park, a protected coastal Mediterranean wetland. Two different experiments were conducted involving (i) the addition of MC-LR to natural sediment to evaluate its effects on seed germination and (ii) the addition of MC-LR to water cultures of macrophytes to evaluate its effects on growth and metabolic functions. In water, the MC-LR concentration decreased by 84% in two weeks; the loss was not significant in sediment. The first seedlings (all C. hispida) emerged from the wetland sediment following a delay of a few days in the presence of MC-LR. The germination rates in 8 and 16 μg MC-LR/L treatments were 44% and 11% of that occurring in the absence of MC, but these differences disappeared over time. The final density was 6-7 germlings/dm(3). Final germling length was unaffected by MC-LR. Rotifers (Lecane spp.) emerging from the natural sediment during the experiment were favored by MC-LR; the opposite pattern was observed in the cladoceran Daphnia magna. The growth rates of C. vulgaris, C. baltica and N. hyalina were unaffected by MC exposure, whereas those of C. hispida and C. aspera were reduced in the MC treatments relative to the control treatment. The concentration of chlorophyll-a and the in vivo net photosynthetic rate were lower in the presence of MC-LR, even at the lowest concentration, for all of the characeans tested. M. spicatum was sensitive to the presence of MC-LR in the culture medium; the growth and chlorophyll-a concentrations were reduced. Therefore, environmentally relevant concentrations of MC might induce important changes in macrophyte meadows and the structure of the associated plankton community. Synchrony or delay in the processes evaluated here in response to environmentally relevant concentrations of cyanobacteria MC exudates can enhance understanding of the turning point to alternative states and the point of no return in eutrophicated shallow lakes.

Prophylactic laser treatment appears to promote choroidal neovascularisation in high-risk ARM: results of an interim analysis. The Drusen Laser Study (DLS) of high-risk age-related maculopathy (ARM) is a randomised, controlled clinical trial designed to answer two questions: (1). Do drusen resolve after macular laser photocoagulation (2). Does macular laser photocoagulation prevent choroidal neovascularisation (CNV) in high-risk eyes? In this report, we present the results of the interim, pooled analysis of CNV prophylaxis for patients in the Unilateral Group of the DLS. The DLS is a randomised controlled clinical trial of prophylactic macular photocoagulation for high-risk ARM. Patients in the Unilateral Group had a neovascular complication in the first eye; their fellow eye (Study Eye) had visual acuity of 6/12 or better and drusen. Following informed consent, patients were randomised to the Treatment Group or the No Treatment Group. Patients randomised to treatment received 12 light spots of argon laser photocoagulation to their Study Eye: four burns were placed 750 microm from the centre of the fovea at 12, 3, 6, and 9 o'clock, and the eight remaining burns were placed 1500 microm from the centre of the fovea at 12, 1:30, 3, 4:30, 6, 7:30, 9, and 10:30 o'clock. Drusen were treated directly only if they were present at the protocol treatment locations. All patients were followed in an identical fashion at regular intervals. Best-corrected visual acuity was measured and recorded by a masked observer. Fluorescein angiography was performed at baseline and yearly review, as well as nonprotocol visits if symptoms suggested CNV. Five clinical centres utilised and conformed to a common DLS protocol. Patient care and data collection methodologies were deemed sufficiently similar to permit a pooled data analysis. There were 156 patients included in the interim analysis, and timed information was available on 153. CNV occurred in 21 of 81 (26%) patients in the Treatment Group and in 13 of 75 (17%) patients in the No Treatment Group (P=0.19). Kaplan-Meier survival analysis showed earlier onset of CNV in the Treatment Group compared to patients in the No Treatment Group (statistical significance not calculated). Visual acuity loss at 2 years occurred in nine of 54 (17%) patients in the Treatment Group compared to the two of 48 (4%) patients in the No Treatment Group (P=0.056). We are only the second group to identify possible laser-induced CNV despite other similar studies in progress. Equipoise of the DLS investigators was lost, and recruitment was halted. We feel ethically bound to notify the ophthalmic community of this finding.

[Influence on the movement of a complete denture caused by differences in artificial tooth materials]. An experiment using modal analysis was used to ascertain the activity of complete dentures and artificial teeth. Three types of artificial teeth were used: a porcelain tooth, a resin tooth and a hard resin tooth. Animation and displacement values were used as criteria in determining the influence that differences in tooth materials had on the activity of the complete denture. The experiment was conducted to act as an aid in denture design and the following results were obtained: 1. The resonance frequency for the different test materials ranged from mode 4 to mode 7. 2. Regarding displacement value, a value of 1 micron or more was obtained in the 1 octave bandwidth for the 250 Hz band, 500 Hz band and the 1 kHz band. Among these, maximum displacement for the upper complete denture was as follows: When a porcelain tooth was used and a vibration of 1 for mode 1 (197 Hz) was applied, the value for the 3 cusp tip was 39.48 microns and that for the labial denture border side was 43.35 microns. As for the lower complete denture, when a porcelain tooth was used and 5 oscillation was applied for mode 1 (309 Hz), the value for the 3 cusp tip was 68.38 microns and that for the rear part of the denture border was 139.2 microns. 3. Regarding the activity of the complete denture in the 250 Hz and 1 kHz bands, when a porcelain tooth was used, a curve mode was observed for the upper complete denture in the labiolingual direction with the cervical line as the border. When the resin tooth and hard resin tooth were used, it was difficult to recognize any change with the cervical line as the border. It was also difficult to recognize a change at the cervical section for the lower complete denture. 4. As for the 500 Hz band, when a porcelain tooth and a resin tooth were used, there were frequencies (300 Hz-400 Hz) at which twisting in a labiolingual direction at the cervical section was recognized for the upper complete denture as well as frequencies (400 Hz-600 Hz) where this was not recognized. A rigid body mode was recognized when the hard resin tooth was used. In addition, differences in the location for applying for vibration had an influence on the activity of the lower complete denture.

Modeling the relationship between scanned rump and 12th-rib fat in young temperate and tropical bovines: model development and evaluation. A decision support tool for predicting subcutaneous fat depths called BeefSpecs, based on the Davis growth model (DGM), has been developed by the Cooperative Research Centre for Beef Genetic Technologies. Currently, the DGM predicts 12th-rib fat thickness (RFT, mm). To allow predictions of fat thickness at the P8 rump (P8FT, mm) site, the standard carcass fat measurement in the Australian beef industry, a relationship was developed between ultrasound RFT and P8FT in steers and heifers from temperate (Angus, Hereford, Shorthorn, and Murray Grey) and tropical (Brahman, Belmont Red, and Santa Gertrudis) breed types. Model development involved fitting various combinations of sex, breed type (BrT), BW, age, and RFT to produce 6 models. The models were challenged with data from 3 independent data sets: 1) Angus steers from 2.4 generations of divergent selection for and against residual feed intake; 2) 2 tropically adapted genotypes [Brahman and tropically adapted composites (combinations of Belmont Red, Charbray, Santa Gertrudis, Senepol, and Brahman breeds)]; and 3) a study using sires from Charolais, Limousin, Belgian Blue, and Black and Red Wagyu breeds and 3 genetic lines of Angus to create divergence in progeny in terms of genetic potential for intramuscular fat percent and retail beef yield. When challenged with data from Angus cattle, the mean biases (MB, mm) for models A to F were -1.23, -0.56, -0.56, -0.02, 0.14, and 0.04, and the root mean square errors of predictions (mm) were 1.53, 0.97, 0.97, 0.92, 0.93, and 0.91, respectively. When challenged with data from Brahman cattle, MB were 0.04, -0.22, -0.14, 0.05, -0.11, and 0.02 and root mean square errors of predictions were 1.30, 1.29, 1.27, 1.23, 1.37, and 1.29, respectively. Generally, model accuracy indicated by MB tended to be less for model E, which contained age rather than BW as a covariate. Models B and C were generally robust when challenged with data from Angus, Brahman, and Tropical Composite cattle as well as crossbred cattle with temperate sires. Model D, which did not contain age, performed the most consistently and was selected for inclusion in the DGM: P8FT, mm = -3.6 (+/-0.14) + 1.3 (+/-0.13) x sex + 0.11 (+/-0.13) x BrT + 0.014 (+/-4.8E(-4)) x BW + 0.96 (+/-0.01) x RFT - 0.73 (+/-0.08) x sex x BrT - 3.8E(-3) (+/-4.2E(-4)) x sex x BW - 0.09 (+/-0.01) x sex x RFT + 1.3E(-3) (+/-3.7E(-4)) x BrT x BW + 0.24 (+/-0.01) x BrT x RFT (adjusted R(2) = 0.86; SE = 0.013). Model D has been implemented in BeefSpecs to predict P8FT.

Bilateral temporal lobe volume reduction parallels cognitive impairment in progressive aphasia. Patients with isolated aphasia in the absence of other cognitive abnormalities have been the focus of several studies during the past decade. It has been called primary progressive aphasia (PPA), and the typical features of this syndrome are marked atrophy of the left temporal lobe according to the radiological examination and a language disorder as the initial symptom. In previous studies of PPA, the selection of the patients was based mainly on linguistic symptoms. Now, when computed tomography or magnetic resonance imaging scans are part of the routine investigation of cognitive impairment and suspected dementia, the patients with lobar atrophy will be found at an earlier stage. In the present study, we used a new approach and defined the study group by selecting patients with obvious left temporal lobe atrophy, assessed by MRI, and we referred to them as patients with temporal lobe atrophy (TLA). To identify the features that distinguish TLA from other primary neurodegenerative disorders. Six patients with TLA were compared with patients with Alzheimer disease (AD), patients with frontal lobe dementia (FLD), and healthy control subjects. The investigations included magnetic resonance imaging volumetry, single photon emission computed tomography, and neuropsychologic and linguistic evaluations. In the TLA group, the mean volume of the left temporal lobe was 35% smaller than the right, while in the AD and FLD groups, the atrophy was symmetrical and bilateral. In the TLA group, the absolute volumes of the temporal lobes were significantly smaller on the left side compared with the AD and FLD groups, whereas there was no difference on the right side. The cerebral blood flow pattern in TLA was asymmetric and differed from that in the other study groups. All patients with TLA had a history of progressive Wernicke-type aphasia, ranging from 2 to 6 years. They showed primary verbal memory impairment but had preserved visuospatial functions. The clinical condition of all patients with TLA deteriorated during the study period; severe aphasia developed, and the patients exhibited signs of frontal lobe dysfunction. Serial volumetric measurements in 4 of 6 patients showed an annual 8% to 9% decrease of both left and right temporal lobes. The initial marked asymmetry in cognitive function found in patients with TLA contrasts with the general decline found in patients with AD. The bilateral degenerative process evident in patients with TLA paralleled the clinical deterioration, indicating TLA to be a non-AD lobar atrophy that develops into generalized cognitive dysfunction and dementia.

Inhibition of vasospasm with lymphocyte function-associated antigen-1 monoclonal antibody in a femoral artery model in rats. The authors have previously shown that a monoclonal antibody (mAb) that recognizes intercellular adhesion molecule-1 (ICAM-1), also known as CD54, when administered systemically inhibits experimental vasospasm in a rat femoral artery model, suggesting that ICAM-1 and leukocyte-endothelial adhesion play a crucial role in the molecular chain of events leading to posthemorrhagic vasospasm. In this report the authors confirm this hypothesis with mAbs directed against lymphocyte function-associated antigen-1 ([LFA-1] CD11a/CD18), the molecule on the surface of leukocytes that interacts with ICAM-1. Femoral arteries in 38 Sprague-Dawley rats were isolated and exposed to autologous blood. Twenty-nine animals were then randomized into three groups and received intraperitoneal injections of anti-LFA-1 mAb (10 rats), anti-ICAM-1 mAb (10 rats), or an isotype-matched control mAb (nine rats). Injections were administered at 3 hours and 3, 6, and 9 days after surgery. Before their deaths, six animals underwent spleen harvest, and splenocytes were used in fluorescence-activated cell sorter (FACS) analysis to verify saturation of appropriate binding sites. Animals were killed at 12 days and vessels were harvested for histological study and measurement of the luminal cross-sectional area. Nine animals were randomized as earlier, killed 24 hours after a single injection of mAb, and evaluated for periadventitial infiltration of granulocytes and macrophages. Results of FACS analysis demonstrated saturation of both LFA-1 and ICAM-1 binding sites in animals treated with the respective mAb. The mean ratios of blood-exposed to saline-exposed luminal cross-sectional areas (expressed as the percentage of lumen patency) were 90.1 +/- 5.8% (mean +/- standard error of the mean) for animals treated with the anti-LFA-1 mAb (p = 0.0218), 94.2 +/- 3.3% for animals treated with the anti-ICAM-1 mAb (p = 0.0067), and 62 +/- 7.4% for animals treated with the isotype-matched control mAb. Macrophage and granulocyte counts in the periadventitial region were 39.5 +/- 3.2/hpf for animals treated with anti-LFA-1 mAb (p = 0.001), 42 +/- 3.7/hpf for animals treated with anti-ICAM-1 mAb (p = 0.003), and 72.2 +/- 6.2/hpf for control animals. The systemic administration of anti-LFA-1 or anti-ICAM-1 mAb initiated 3 hours after exposure to autologous blood inhibits the development of delayed chronic vasospasm at 12 days in a rat femoral artery model and leads to a significant reduction in periadventitial inflammatory cells at 24 hours. The authors conclude that blocking the migration of inflammatory cells across the endothelial surface of an artery after adventitial exposure to blood prevents the initiation of biological cascades necessary for the subsequent development of chronic vasospasm.

The prevention of early-onset neonatal group B streptococcal disease. To review the evidence in the literature and to provide recommendations on the management of pregnant women in labour for the prevention of early-onset neonatal group B streptococcal disease. The key revisions in this updated guideline include changed recommendations for regimens for antibiotic prophylaxis, susceptibility testing, and management of women with pre-labour rupture of membranes. Maternal outcomes evaluated included exposure to antibiotics in pregnancy and labour and complications related to antibiotic use. Neonatal outcomes of rates of early-onset group B streptococcal infections are evaluated. Published literature was retrieved through searches of MEDLINE, CINAHL, and The Cochrane Library from January 1980 to July 2012 using appropriate controlled vocabulary and key words (group B streptococcus, antibiotic therapy, infection, prevention). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to May 2013. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). The recommendations in this guideline are designed to help clinicians identify and manage pregnancies at risk for neonatal group B streptococcal disease to optimize maternal and perinatal outcomes. No cost-benefit analysis is provided. There is good evidence based on randomized control trial data that in women with pre-labour rupture of membranes at term who are colonized with group B streptococcus, rates of neonatal infection are reduced with induction of labour. (I) There is no evidence to support safe neonatal outcomes with expectant management in this clinical situation. 1. Offer all women screening for colonization with group B streptococcus at 35 to 37 weeks' gestation with culture taken from one swab first to the vagina and then to the rectum (through the anal sphincter). (II-1A) This includes women with planned Caesarean delivery because of their risk of labour or ruptured membranes earlier than the scheduled Caesarean delivery. (II-2B) 2. Because of the association of heavy colonization with early onset neonatal disease, provide intravenous antibiotic prophylaxis for group B streptococcus at the onset of labour or rupture of the membranes to: • any woman positive for group B streptococcus by vaginal/rectal swab culture screening done at 35 to 37 weeks' gestation (II-2B); • any woman with an infant previously infected with group B streptococcus (II-3B); • any woman with documented group B streptococcus bacteriuria (regardless of level of colony-forming units) in the current pregnancy. (II-2A) 3. Manage all women who are < 37 weeks' gestation and in labour or with rupture of membranes with intravenous group B streptococcus antibiotic prophylaxis for a minimum of 48 hours, unless there has been a negative vaginal/rectal swab culture or rapid nucleic acid-based test within the previous 5 weeks. (II-3A) 4. Treat all women with intrapartum fever and signs of chorioamnionitis with broad spectrum intravenous antibiotics targeting chorioamnionitis and including coverage for group B streptococcus, regardless of group B streptococcus status and gestational age. (II-2A) 5. Request antibiotic susceptibility testing on group B streptococcus-positive urine and vaginal/rectal swab cultures in women who are thought to have a significant risk of anaphylaxis from penicillin. (II-1A) 6. If a woman with pre-labour rupture of membranes at ≥ 37 weeks' gestation is positive for group B streptococcus by vaginal/rectal swab culture screening, has had group B streptococcus bacteriuria in the current pregnancy, or has had an infant previously affected by group B streptococcus disease, administer intravenous group B streptococcus antibiotic prophylaxis. Immediate obstetrical delivery (such as induction of labour) is indicated, as described in the Induction of Labour guideline published by the Society of Obstetricians and Gynaecologist in September 2013. (II-2B) 7. At ≥ 37 weeks' gestation, if group B streptococcus colonization status is unknown and the 35- to 37-week culture was not performed or the result is unavailable and the membranes have been ruptured for greater than 18 hours, administer intravenous group B streptococcus antibiotic prophylaxis. (II-2B) 8. If a woman with pre-labour rupture of membranes at < 37 weeks' gestation has an unknown or positive group B streptococcus culture status, administer intravenous group B streptococcus prophylaxis for 48 hours, as well as other antibiotics if indicated, while awaiting spontaneous or obstetrically indicated labour. (II-3B).

Improved Outcome of Cardiac Extracorporeal Membrane Oxygenation in Infants and Children Using Magnetic Levitation Centrifugal Pumps. Extracorporeal membrane oxygenation (ECMO) has traditionally been and, for the most part, still is being performed using roller pumps. Use of first-generation centrifugal pumps has yielded controversial outcomes, perhaps due to mechanical properties of the same and the ensuing risk of hemolysis and renal morbidity. Latest-generation centrifugal pumps, using magnetic levitation (ML), exhibit mechanical properties which may have overcome limitations of first-generation devices. This retrospective study aimed to assess the safety and efficacy of veno-arterial (V-A) ECMO for cardiac indications in neonates, infants, and children, using standard (SP) and latest-generation ML centrifugal pumps. Between 2002 and 2014, 33 consecutive neonates, infants, and young children were supported using V-A ECMO for cardiac indications. There were 21 males and 12 females, with median age of 29 days (4 days-5 years) and a median body weight of 3.2 kg (1.9-18 kg). Indication for V-A ECMO were acute circulatory collapse in ICU or ward after cardiac repair in 16 (49%) patients, failure to wean after repair of complex congenital heart disease in 9 (27%), fulminant myocarditis in 4 (12%), preoperative sepsis in 2 (6%), and refractory tachy-arrhythmias in 2 (6%). Central cannulation was used in 27 (81%) patients and peripheral in 6. Seven (21%) patients were supported with SP and 26 (79%) with ML centrifugal pumps. Median duration of support was 82 h (range 24-672 h), with 26 (79%) patients weaned from support. Three patients required a second ECMO run but died on support. Seventeen (51%) patients required peritoneal dialysis for acute renal failure. Overall survival to discharge was 39% (13/33 patients). All patients with fulminant myocarditis and with refractory arrhythmias were weaned, and five (83%) survived, whereas no patient supported for sepsis survived. Risk factors for hospital mortality included lower (<2.5 kg) body weight (P = 0.02) and rescue ECMO after cardiac repair (P = 0.03). During a median follow-up of 34 months (range 4-62 months), there were three (23%) late deaths and two late survivors with neurological sequelae. Weaning rate (5/7 vs. 21/26, P = NS) and prevalence of renal failure requiring dialysis (4/7 vs. 13/26, P = NS) were comparable between SP and ML ECMO groups. Patients supported with ML had a trend toward higher hospital survival (1/7 vs. 12/26, P = 0.07) and significantly higher late survival (0/7 vs. 10/26, P = 0.05). The present experience shows that V-A ECMO for cardiac indications using centrifugal pumps in infants and children yields outcomes absolutely comparable to international registry (ELSO) data using mostly roller pumps. Although changes in practice may have contributed to these results, use of ML centrifugal pumps appears to further improve end-organ recovery and hospital and late survival.

Labia majora labioplasty in HIV-related vaginal lipodystrophy: technique description and literature review. We present a rare case involving severe hypertrophy of the labia majora. This 39-year-old married woman developed a clinically noticeable bilateral lipodystrophy of her labia majora following the administration of chronic antiretroviral therapy. Different combination drug regimens that included drugs like Crixivan(®), Epivir(®), and Zerit(®) were administered to the patient from 1998 to 2005. The patient is currently on a single drug regimen of Atripla(®) with the disease under control and no other comorbidities. The severity of the pubic protuberance created an appearance resembling male genitalia, even when covered by underwear. This anatomical abnormality obviously impaired her social life and forced her to avoid wearing tight pants, swimming garments, and tight clothes in general. She also avoided any sexual activity. Her pubic hair was shaved. Crural creases and vulvar mucosa were marked in order not to be violated. The estimated amount of skin and fat to be removed was marked. Intraoperative tailor-tacking suturing was used to mark the extent of the resection of the labia majora. Sutures were left in place to verify the accurate tension of the remaining skin. The procedure was performed with the patient under general anesthesia. Labial skin resection was performed by sharp dissection. Electrocautery was then used to excise the lobulated fat accumulation. Two layers of 3/0 Vicryl(®) sutures were used in the lax subcutaneous tissue. 4/0 Vicryl(®) rapide was used on the skin to approximate wound edges. Suction drains were left in place for 48 h to reduce the dead space and to manage postoperative bleeding. The patient was instructed to keep ice and compression pads on the area for the first 24 h and to keep the area clean. This was followed by the application of antibiotic ointment two times a day on the wounds to avoid blood crust formation and to keep the skin soft. Stitches were removed on POD 14 after an overall uneventful postoperative course. The sensitivity of the labia majora's interior aspect was preserved, even initially. With the legs slightly open, the labia majora just covered the entrance to the vagina. The clitoris and labia minora became visible again, restoring a normal anatomical appearance. Moderate edema was observed for 4 weeks after surgery. The surgical technique used provided an excellent result according to the patient, who regained her self-confidence and started having a normal sexual life again. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The incidence of metastases after multimodal therapy for cancer of the head and neck. Combined therapeutic regimens integrating chemotherapy, radiation therapy, and surgery are reported to be effective in treating advanced squamous cell carcinomas of the head and neck. The current study evaluates 58 consecutive patients with advanced (T4, N3) head and neck cancers. Forty patients (multimodal group) were treated with 2 courses of chemotherapy (cisplatin 2 mg/kg; methotrexate 280-560 mg/m2 with leucovorin rescue; bleomycin 30 mu X 3) followed by radiation therapy and surgery. Eighteen patients (combined group) were treated with preoperative radiation therapy followed by surgery. In the multimodal group there were 27 (67.5%) partial responses and nine (22.5%) complete responses, for an overall response rate of 90%. Response rates by site of primary lesion were: oral cavity, 11 of 11; oropharynx, 13 of 17; hypopharynx, 5 of 5; and larynx 7 of 7. Distant metastases (skin, lung, bone, central nervous system [CNS]) appeared in 16 patients (40%) (P less than 0.05 versus combined) at a median time of 8.5 months after diagnosis, 15 in patients having a partial (11) or complete (4) response. Thirteen patients (33%) developed distant metastases within 1 year of diagnosis (P less than 0.05 versus combined). In 11 of these patients, the primary lesion and neck disease were resectable. Two thoracotomies were performed for solitary pulmonary metastases; one was resected for cure. Fifteen patients (38%) underwent curative resection; 11 (73%) were alive at 1 year, and ten (67%) were free of disease. Overall survival was 20 of 40 (50%) at 1 year. In the combined group, there were 14 partial responses (78%) and no complete responses. Early distant metastases appeared in two patients (12.5%), at 2 and 6 months after diagnosis. Seven patients (38%) underwent curative resection; six of seven (86%) were alive at 1 year, four of seven (57%) were disease-free. Six of 16 patients at risk (37.5%) survived 1 year. After combined therapy, six of ten patients (60%) with responses to therapy survived 1 year versus 12 of 20 responders (57%) without distant metastases in the multimodal group. It is concluded that multimodal therapy for advanced head and neck cancer results in a higher response rate than with conventional combined therapy. The incidence of early and postoperative distant metastases was increased after the multimodal regimen. At 1 year there were no differences in survival between the combined and multimodal groups for responders without early metastases. Further observation is needed to determine the net long-term effects of this regimen. A prospective randomized comparison of combined and multimodal therapy for advanced lesions is indicated.

[ISOLATION AND IDENTIFICATION OF RAT INTERVERTEBRAL DISC NUCLEUS PULPOSUS CELLS AT DIFFERENT SEGMENTS AND COMPARATIVE STUDY ON BIOLOGICAL CHARACTERISTICS]. Corresponding author: WANG Yuntao, E-mail: [email protected] To isolate nucleus pulposus cells (NPCs) from the caudal and lumbar intervertebral disc of rat, and to identify the morphology and to compare the characteristics. The whole spine was separated from 8-week-old Sprague Dawley rats under the sterile conditions. NPCs of different segments (lumbar group: L1, 2-L6, S1; caudal group: C1, 2-C17, 18) were cultured by adherent cultivation approach. Cellular morphologic change was noted by HE staining and continuous observation under inverted phase contrast microscope. Besides, the aggrecan and collagen type II expression were examined by toluidine blue and immunocytochemistry staining respectively. The total protein contents, senescence level, and the cell viability of passage 1-5 (P1-5) were detected. The growth curves of the P1 cells in lumbar and caudal groups were determined by cell counting kit 8. The NPCs were isolated and identified successfully. The adherence time of the primary cells (the cell fusion reached 90%) in lumbar group was significantly longer than that in caudal group in primary generation (P < 0.05). HE staining showed that cytoplasm was pink with the blue nucleus. Lumbar disc NPCs were spindle. The larger caudal disc NPCs were polygonal or irregular. Toluidine blue staining showed that the proteoglycan was stained as blue. In the cytoplasm of cells, collagen type II was stained as brown surround the blue-black nucleus. The cell viability had no significant difference between lumbar and caudal groups and between different passages in the same group (P > 0.05). The caudal disc NPCs reached their logarithmic growth phase after 3 days of culture, while the cells in lumbar segments did after 4-5 days of culture. The cell proliferation in caudal segments was more than that in lumbar segments at 3-9 days (P < 0.05). The difference in the total protein contents was not significant between cells at P1-5 in 2 groups (P > 0.05), and the caudal disc NPCs had higher protein contents than lumbar disc NPCs (P < 0.05). There was no significant difference in cell senescence rate between cells at P1, P2, and P3 in 2 groups (P > 0.05), but significant difference was shown in senescence rate between 2 groups in cells at P4 and P5 (P < 0.05). Caudal disc NPCs have a better status, which is more suitable for experiment as a seed cell than the lumbar disc NPCs in the same generation.

Use of Speckle Tracking Echocardiography to Assess Left Ventricular Systolic Function in Patients with Surgically Repaired Tetralogy of Fallot: Global and Segmental Assessment. Patients with repaired Tetralogy of Fallot (rToF) can have significant right and left ventricular dysfunction which can impact clinical outcome. Conventional echocardiographic evaluation using ejection fraction can be limited in detecting early stages of deteriorating left ventricular (LV) systolic function. Speckle-tracking echocardiography (STE) provides a promising emerging tool for early detection of LV systolic dysfunction. The aim of this cross-sectional study is to evaluate the left ventricular global and regional function using STE in rToF patients with preserved left ventricular ejection fraction to detect early signs of LV dysfunction. The study is a retrospective review of the medical records and transthoracic echocardiograms of rTOF patients who were seen in the pediatric cardiology clinic at our institution from August 2016 till May 2018. The rTOF group was compared with a matched healthy control group. Offline strain analysis of TTE studies was completed in each subject according to mode set by the American Society of Echocardiography. Twenty-two patients with rTOF and 22 age-matched controls (rTOF 18.7 ± 6 years and control 14.6 ± 9.6 years, P value 0.19) were included during the study period. The rTOF group consisted of 12 males and 10 females, whereas the control group consisted of 15 males and 7 females. There was no significant difference in terms of LV ejection fraction using both 2-chamber as well as 4-chamber views. Global LV longitudinal strain was significantly lower in the rTOF group compared with the control group (rTOF - 15.92 ± 3.16 vs control - 22.79 ± 2.45, P value 0.00). All 17 segments showed significantly lower longitudinal strains in rTOF group compared with the control group. Global circumferential left ventricle strain was significantly lower in the rTOF patients compared with the control group (- 17.24 ± 5.86 vs - 22.74 ± 3.99, P value 0.001). 13 out of 16 segments had lower circumferential strains in the rTOF patients compared with controls. Asymptomatic surgically repaired TOF patients exhibited abnormal segmental and global left ventricle longitudinal and circumferential strains despite having normal left ventricle ejection fraction. Our findings suggest subclinical damage to the left ventricle systolic function post-surgical repair of TOF. 2-D speckle-tracking echocardiography may be used as a valuable method in the early recognition of left myocardial systolic function impairment in patients after TOF repair. The application of this method to guide clinical decision and management of rTOF patients such as earlier pulmonary valve replacement or risk stratification for sudden cardiac death needs further investigation.

Factors influencing the quality of life after burst fractures of the thoracolumbar transition. Dorsal stabilisation has represented the standard procedure for the treatment of burst fractures of the thoracolumbar spine for a long time, but in the last few years the combined dorsoventral stabilisation has gained in significance due to its higher mechanical stability. However, there are no data yet available indicating whether the patients benefit from the combined operation with regard to their postoperative quality of life and what the advantages are in comparison with the dorsal procedures. Therefore, the question was researched in the framework of a matched-pairs analysis of patients suffering from an unstable fracture of the thoracolumbar transition. From a consecutive series of patients treated in our clinic between 1995 and 2000, 10 patients with combined and 10 patients with a purely dorsal stabilisation were selected and included in the study. Their quality of life was summed up in retrospect with the SF-36 questionnaire. The X-rays were analysed, and the Cobb angle as well as the sagittal index were calculated. Only patients with burst fractures of the thoracolumbar transition without accompanying co-morbidity and neurological deficits were included in the study. Both of the treated groups were matched with regard to sex, age and radiological patterns of injury. Patients who had undergone only a dorsal stabilisation showed a significant loss of correction according to the sagittal index at the time of the examination (0.88+/-0.02 postoperative vs 0.77+/-0.03 at 4 years postoperatively, p=0.01). In the group of patients treated with the combined therapy, there was no statistically relevant loss of correction with regard to the sagittal vertebral profile. The SF-36 questionnaire showed a reduced quality of life in both groups compared with an age-referenced norm population, especially concerning the parameters of bodily health. No statistically relevant difference was observed between the two groups. Further, there was no statistically relevant association between the parameters of the SF-36 and the clinical and radiological data. After performing several regression analyses it could be shown that the patient's mental health is a strong predictor of the postoperative vitality (r=0.803, p<0.01). However, none of the remaining parameters was able to predict the postoperative quality of life. The patients in this study showed a reduced quality of life, independent of the method of surgical treatment. Although better radiological results could be seen for the combined procedure, regarding the postoperative quality of life no advantage could be proved compared with the dorsally stabilized patients. Furthermore, there was no relation between the radiological results and the quality of life parameters. Therefore, it can be assumed that the injury itself seems to be the main cause of the decreased quality of life after a burst fracture of the thoracolumbar transition.