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Microbial communities inhabiting the fairy ring of Floccularia luteovirens and isolation of potential mycorrhiza helper bacteria. Floccularia luteovirens, an important edible mushroom widely distributed in the Qinghai-Tibet plateau, is ecologically important as an ectomycorrhizal fungus and can form the fairy ring. To explore the influence of F. luteovirens fairy ring on soil microbial communities, we compared the soil microbial communities in three different fairy ring zones (inside the fairy ring (IN); beneath the fairy ring (ON); and outside the fairy ring (OUT)). A total of 1.77 million bacterial reads and 1.59 million fungal reads were obtained. Moreover, sequence clustering yielded 519,613 (57,735 per sample) bacterial OTUs, and 513,204 (57,023 per sample) fungal OTUs representing. Microbial diversity was lower in samples from the ON zone compared with the other two zones. Mycorrhiza helper bacteria (MHB) such as Bradyrhizobium and Paenibacillus were more common in the ON zone, and we isolated four potential MHB from rhizosphere soil. Canonical correspondence analysis showed that the soil nutritional condition and physical changes caused by F. luteovirens shaped the microbial communities in the ON zone. This is the first report on the study of soil microbial diversity influenced by fairy ring F. luteovirens, and further studies need to be conducted to study the ecological function influenced by this species.

New evidence of red blood cell rheological disorders in beta-thalassaemia minor. Haemorheological parameters, such as red blood cell deformability, membrane elastic modulus and membrane surface viscosity in twenty one thalassaemia heterozygous patients (14 beta0/beta and 7 beta+/beta) were compared with normal individuals (n = 15). Parameters were measured applying a laser diffractometric method (ektacytometry). Thalassaemia erythrocytes showed statistically significant lower deformability and higher elastic modulus. Surface viscosity showed no significant differences in thalassaemia. Creep and recovery curves were registered by diffractometry. The normal recovery curve was fitted by a first order exponential decay function, expressing the fitting degree by the chi2 coefficient. The shape of the recovery curve in beta-thalassaemia patients (beta0/beta or beta+/beta) was significantly different from the control group. The possible mechanism of red blood cells abnormal rheological behaviour in beta-thalassaemia minor could be explained by a surface charge reduction. Our results enable us to conclude that the shape of the recovery curve (chi2 coefficient) could be considered as a marker that might be useful in beta-thalassaemia diagnosis.

[Cleaniness and hygiene from infancy to adolescence in Karabuk, Safranbolu, Eflani and Eskipazar]. This paper on cleanliness and hygiene from infancy to adolescence is obtained from knowledge collected by means of an interview with women and men informed on the subject. This research is consisted of four main chapters: 1. Environmental and physical hygiene; 2. Baby and child care; 3. Beliefs regarding menstruation; it is commonly called regl - of French origin - in Turkish, which is called "colored" (renkli) days in this area, due to the similarity in the sound of the two words; 4. Beliefs and practices concerning circumcision. This essay deals in washing clothes with usual cleaning agents or using ash alone and ashed water without scrubbing. The practice of hair removal among women and girls is described. Swadding clothes, cradles, pots called havruz and subek for urination of babies in the district, are dealt with in detail. The customs and practices regarding menstruation are described and classified. Before the use of bikini underpants, pads and the menstruation cloth was one of the most important items of a girl's dowry. The techniques used in circumcision in this region were carefuly studied and the beliefs regarding circumcision were put down. This research was completed in fifty one weeks. Various objects obtained during the research have been handed over to the Medical History Museum of Cerrahpasa Medical School.

Control of neuronal gene expression. Some 30,000 genes are expressed exclusively in the rat brain, many of which contain a genetic element called an identifier sequence located in at least one of their introns. The identifier sequences are transcribed by RNA polymerase III exclusively in neurons to produce two RNA species, BC1 and BC2, of 160 and 100 to 110 nucleotides. This transcriptional event may define regions of chromatin that contain neuronal-specific genes and may poise these genes for transcription by polymerase II by rendering the gene promoters accessible to soluble trans-acting molecules.

Promising strategies for obesity pharmacotherapy: melanocortin-4 (MC-4) receptor agonists and melanin concentrating hormone (MCH) receptor-1 antagonists. Despite remarkable progress in the elucidation of energy balance and regulation, the development of new anti-obesity drugs is still at the stage of infancy. Herein we briefly reviewed several investigational anti-obesity agents currently under development, consisting of agents controlling appetite, modulating nutrient absorption and lipid metabolism, sensing and regulating nutrient status, stimulating energy expenditure, and reducing adiposity. In particular, two promising targets such as melanocortin-4 (MC-4) receptor and melanin concentrating hormone (MCH)-1 receptor will be highlighted in this review covering major medicinal chemistry efforts and biological aspects of the compounds synthesized. Considering the enthusiastic efforts to develop efficacious and safe anti-obesity drugs, a range of novel medications treating obesity more effectively than is currently managed by pharmacotherapy will be available in near future.

Citrate versus unfractionated heparin for anticoagulation in continuous renal replacement therapy. Unfractionated heparin is the most commonly used anticoagulant in continuous renal replacement therapy (CRRT), but it can increase the risk of bleeding. Citrate is a promising substitute. Our study was to assess the efficacy and safety of citrate versus unfractionated heparin in CRRT. We searched the MEDLINE, the EMBASE, the Cochrane Central Register of Controlled Trials, and the China National Knowledge Infrastructure Database until up to November 2011 for randomized controlled trials comparing citrate with unfractionated heparin in adult patients with acute kidney injury prescribed CRRT. The primary outcome was mortality and the secondary outcomes included circuit survival, control of uremia, risk of bleeding, transfusion rates, acid-base statuses, and disturbance of sodium and calcium homeostasis. Four trials met the inclusion criteria. Meta-analysis found no significant difference between two anticoagulants on mortality. Less bleeding and more hypocalcemic episodes were with citrate. Citrate was superior or comparable to unfractionated heparin in circuit life. Citrate anticoagulation in CRRT seems to be superior in reducing bleeding risk and with a longer or similar circuit life, although there is more metabolic derangement. Mortality superiority has not been approved.

Prevention of and treatment for hepatitis B virus infection after liver transplantation in the nucleoside analogues era. Post-transplant prophylaxis with hepatitis B immune globulin (HBIG) has significantly reduced hepatitis B virus (HBV) recurrence rates, but it is rather ineffective in patients with pretransplant viremia. Moreover, long-term HBIG administration is very expensive and may be associated with emergence of escape HBV mutants. Lamivudine has been widely used in the management of HBV transplant patients. Pretransplant lamivudine lowers HBV viremia, decreasing the risk of post-transplant HBV recurrence, but to try and minimize development of resistant HBV strains, it should start within the last 6 months of the anticipated transplantation timing. Preemptive post-transplant lamivudine monotherapy is associated with progressively increasing HBV recurrence rates, but combined therapy with lamivudine and HBIG at relatively low dosage is currently the most effective approach in this setting, even in HBV-DNA-positive patients, who also receive lamivudine in the pretransplant period. The most frequent therapy for post-transplant HBV recurrence is lamivudine, but the increasing resistance rates represent a rather challenging problem. Adefovir dipivoxil and entecavir are currently the most promising agents for lamivudine-resistant HBV strains. All these advances in anti-HBV therapy have made HBV liver disease an indication for liver transplantation irrespective of viral replication status, a complete turn around from 10 years ago.

Unravelling early events in the Taphrina deformans-Prunus persica interaction: an insight into the differential responses in resistant and susceptible genotypes. Leaf peach curl is a devastating disease affecting leaves, flowers and fruits, caused by the dimorphic fungus Taphrina deformans. To gain insight into the mechanisms of fungus pathogenesis and plant responses, leaves of a resistant and two susceptible Prunus persica genotypes were inoculated with blastospores (yeast), and the infection was monitored during 120 h post inoculation (h.p.i.). Fungal dimorphism to the filamentous form and induction of reactive oxygen species (ROS), callose synthesis, cell death and defence compound production were observed independently of the genotype. Fungal load significantly decreased after 120 h.p.i. in the resistant genotype, while the pathogen tended to grow in the susceptible genotypes. Metabolic profiling revealed a biphasic re-programming of plant tissue in susceptible genotypes, with an initial stage co-incident with the yeast form of the fungus and a second when the hypha is developed. Transcriptional analysis of PRs and plant hormone-related genes indicated that pathogenesis-related (PR) proteins are involved in P. persica defence responses against T. deformans and that salicylic acid is induced in the resistant genotype. Conducted experiments allowed the elucidation of common and differential responses in susceptible versus resistant genotypes and thus allow us to construct a picture of early events during T. deformans infection.

Is LARC for Everyone? A Qualitative Study of Sociocultural Perceptions of Family Planning and Contraception Among Refugees in Ethiopia. Objective Ethiopia is home to an increasingly large refugee population. Reproductive health care is a critical issue for these groups because refugee women are at high risk for unmet family planning needs. Efforts to expand contraceptive use, particularly long acting reversible contraceptive (LARC) methods are currently underway in several Ethiopian refugee camps. Despite availability of LARC methods, few refugee women opt to use them. The purpose of this study was to explore how culture influences contraceptive attitudes and behaviors, particularly towards LARC methods, among Ethiopia's refugee populations. Methods Focus group discussions and individual interviews were conducted with Eritrean and Somali refugees living in Ethiopia. The qualitative data was analyzed to identify important themes highlighting the relationship between cultural values and contraceptive attitudes and behaviors. Results Childbearing was highly valued among participants in both study groups. Eritreans reported desire to limit family size and attributed this to constraints related to refugee status. Somalis used cultural and religious faith to deal with economic scarcity and were less likely to feel the need to adapt contraceptive behaviors to reduce family size. Participants held overall positive views of the contraceptive implant. Attitudes toward the intrauterine device (IUD) were overwhelmingly negative due to its long-acting nature. Conclusions Culture, religion and refugee status form a complex interplay with family planning attitudes and behaviors among Eritrean and Somali refugees. For these populations, the three-year implant appears to be a more acceptable contraceptive method than the longer-acting IUD because it is in line with their reproductive plans.

[Expression of CD117, MITF and NAT10 and their prognostic values in sinonasal mucosal melanoma]. Objective: To investigate the correlation between the expression of CD117, MITF, NAT10 and clinical parameters in sinonasal mucosal melanoma (SNMM). Methods: Formalin-fixed paraffin-embedded tumor specimens of 80 cases of SNMM at the Eye, Ear, Nose and Throat Hospital, Fudan University, from December 1999 to November 2013 were analyzed for CD117, MITF and NAT10 expression by immunohistochemistry. Results: There were 40 men and 40 women. The median age was 61 years, age 26 to 85 years. There was no correlation of the expression of CD117, MITF and NAT10 with the patients' age, gender, tumor site, stage, therapy method and brain metastases (P>0.05). The expression of MITF and NAT10 was associated with lymph node metastasis and the tumors were more likely to metastasize when MITF and NAT10 were positive. However, expression of CD117 had no correlation with lymph node metastasis. Log-rank test revealed that the expression of CD117 was correlated with both three-year and five survival rate (P=0.012, P=0.023; respectively) and patients with tumor having low expression of CD117 had the worse outcome. COX test revealed that low CD117 expression, advanced age and lymph node metastasis were independent risk factors (P<0.05). No significant association was found between the expression of CD117, MITF and NAT10 with disease free survival (P>0.05). Conclusions: Patients with SNMM expressing low level of CD117 have decreased survival rate. Tumors with high level of MITF and NAT10 expression are more likely to metastasize. The expression level of CD117 can be used as an important indicator for the patient survival, and the expression of MITF and NAT10 can be used as a predictor of tumor metastasis.

Iron-catalysed transformation of molecular dinitrogen into silylamine under ambient conditions. Although stoichiometric transformations using transition metal-N(2) complexes have been well investigated towards the goal of nitrogen fixation under mild reaction conditions, only a few examples of the catalytic transformations of N(2) using transition metal-N(2) complexes as catalysts have been reported. In almost all the catalytic systems, the use of Mo is essential to realize the catalytic transformation of N(2), where Mo-N(2) complexes are considered to work as effective catalysts. Here we show the first successful example of the Fe-catalysed transformation of N(2) into N(SiMe(3))(3) under ambient conditions, in which iron complexes such as iron pentacarbonyl [Fe(CO)(5)] and ferrocenes have been found to work as effective catalysts. A plausible reaction pathway is proposed, where Fe(II)-N(2) complex bearing two Me(3)Si groups as ancillary ligands has an important role as a key reactive intermediate, with the aid of density-functional-theory calculations.

The hazard of the unrestrained occupant. A review of 208 cases involving injuries sustained by vehicle occupants was extracted from the computer storage at the Highway Safety Research Institute, University of Michigan, Ann Arbor. In addition, 157 new car crashes investigated by the authors were separately analyzed. Data analysis indicates injuries are sustained by direct occupant-to-occupant contact and by one occupant forcing another into or against one or more interior car structures. All body areas can be involved in this previously unreported injury mechanism, with the upper portion of the body more susceptibel to injury. Case histories from field accident investigations document a variety of these injury mechanisms.

Analysis of the origins of black carbon and carbon monoxide transported to Beijing, Tianjin, and Hebei in China. A novel back-trajectory approach was adopted to determine the origins of black carbon (BC) and carbon monoxide (CO) transported to Beijing, Tianjin and Hebei. Results showed that the transport efficiency was controlled mainly by mid-latitude westerlies in winter, the South Asian monsoon in summer and prevailing westerly and northwesterly winds in spring and autumn. Hebei was identified as the most important source region of both BC (respectively accounting for 55% and 49%) and CO (39% and 38%) transported to Beijing and Tianjin. Inner Mongolia contributed more to the effective emission intensity (EEI) in winter than in summer for both BC and CO transported to Beijing and Tianjin. Shandong was responsible for higher EEI in summer than in winter. The six provinces making the greatest contributions to BC transported to Hebei were Shandong (19%), Shanxi (19%), Inner Mongolia (17%), Beijing (11%), Henan (11%), and Tianjin (10%), whereas those making the greatest contributions to CO transported to Hebei were Shandong (20%), Inner Mongolia (10%), Tianjin (9%), Henan (9%), Shanxi (9%), and Beijing (8%). In summary, Hebei, Inner Mongolia, Shandong, Tianjin and Shanxi were determined as the dominant source regions of not only BC but also CO transported to Beijing. Hebei, Shandong, Beijing, Inner Mongolia, Henan, Liaoning and Shanxi were relatively important source regions for Tianjin. Shandong, Shanxi, Inner Mongolia, Beijing, Henan, Tianjin, Liaoning, Jiangsu and Anhui were the main source regions for Hebei. Residential and industrial sectors were the dominant sectors for BC and CO transported to the receptors, respectively. These results are consistent with the results of previous studies. Finally, comparing the observed ΔBC/ΔCO ratio with the enhancement ratio of the EEI of BC with that of CO (ΔEEIBC/ΔEEICO) at Miyun site, we further confirmed that the EEI can be used to represent the amounts of BC and CO reaching receptors.

Anesthesia and epidermolysis bullosa. Patients with epidermolysis bullosa (EB) may present for anesthesia with an unrelated surgical condition or, more commonly, for diagnostic or therapeutic procedures. Children in particular may require frequent anesthetics. Safe and effective management of anesthesia presents a significant challenge and although there is little rigorous evidence available to aid decision-making, in this article the elements of current good anesthesia care in EB are summarized.

[Comparative study of the state of health and nutrition of young children from rural and urban areas of the Uzbek SSR]. The study of the physical development including caliperometric investigations was conducted in 2620 infants. The food ingredients and caloric content were studied in the daily ration of 267 infants with premorbid signs. Parameters of the physical development (growth, body mass, chest circumference size, and standards of fat content in per cent) in infants can be recommended as reference ones in the region studied. The physical development of infants depended on proper organization of full value nutrition, both quantitative and qualitative.

Use of nutritional supplements among Mexican women and the estimated impact on dietary intakes below the EAR and above the UL. To describe supplement use practices among non-pregnant, non-lactating Mexican women (12-49 y) and estimate their impact on the proportion of women with intakes below the Estimated Average Requirement (EAR) and above the Upper Limit (UL) using data from a national probabilistic nutrition survey in Mexico (1999). Information was collected by questionnaire on the frequency and duration of supplement use in the previous 6 months (n = 17,794). Dietary intakes by 24-hour recall were determined in a representative sub-sample (n = 2,599). Frequency of use and available information on the nutrient content of supplements was used to estimate daily equivalent intakes. 17.6% of women reported to have used supplements. The majority of these took supplements once daily (71%) and for < or =2 months (75%). While nutrient intakes from diet alone did not differ between users and non-users, the proportion with intakes of Vitamins A, B(6), B(12), and C, folate, iron, and zinc < EAR were significantly greater among the supplement non-users when intakes from supplements were also considered. The proportion of women with intakes > UL was greater among supplement users than non-users for iron, folate and Vitamin B(6). Supplement use contributes to the adequacy of nutrient intakes but may also increase the possible risk of toxic intakes of some nutrients among Mexican women.

Potent and selective Kunitz domain inhibitors of plasma kallikrein designed by phage display. Phage displaying APPI Kunitz domain libraries have been used to design potent and selective active site inhibitors of human plasma kallikrein, a serine protease that plays an important role in both inflammation and coagulation. Selected clones from two Kunitz domain libraries randomized at or near the binding loop (positions 11-13, 15-19, and 34) were sequenced following five rounds of selection on immobilized plasma kallikrein. Invariant preferences for Arg at position 15 and His at position 18 were found, whereas His, Ala, Ala, and Pro were highly preferred residues at positions 13, 16, 17, and 19, respectively. At position 11 Pro, Asp, and Glu were favored, while hydrophobic residues were preferred at position 34. Selected variants, purified by trypsin affinity chromatography and reverse phase high performance liquid chromatography, potently inhibited plasma kallikrein, with apparent equilibrium dissociation constants (Ki*) ranging from approximately 75 to 300 pM. From sequence and activity data, consensus mutants were constructed by site directed mutagenesis. One such mutant, KALI-DY, which differed from APPI at 6 key residues (T11D, P13H, M17A, I18H, S19P, and F34Y), inhibited plasma kallikrein with a Ki* = 15 +/- 14 pM, representing an increase in binding affinity of more than 10,000-fold compared to APPI. Similar to APPI, the variants also inhibited Factor XIa with high affinity, with Ki* values ranging from approximately 0.3 to 15 nM; KALI-DY inhibited Factor XIa with a Ki* = 8.2 +/- 3.5 nM. KALI-DY did not inhibit plasmin, thrombin, Factor Xa, Factor XIIa, activated protein C, or tissue factor. Factor VIIa. Consistent with the protease specificity profile, KALI-DY did not prolong the clotting time in a prothrombin time assay, but did prolong the clotting time in an activated partial thromboplastin time assay > 3.5-fold at 1 microM.

Effects of digitalis on atrial vulnerability. The effects of digitalis on vulnerability to atrial fibrillation and flutter were assessed in man, using the model of repetitive atrial firing initiated by post-drive atrial extrastimulation. Nine patients without heart failure or significant mitral valve disease were tested before and 30 minutes after the administration of 0.01 mg/kg ouabain. When repetitive firing was manifested by flutter, neither the flutter cycle length nor the interval from the initiating beat to the first flutter beat was consistently altered by ouabain. Repetitive firing was found at the atrial site with the shortest functional refractory period. The vulnerable zone bordered this refractory period. The functional refractory period was lengthened after ouabain, from 231 +/- 13 to 246 +/- 15 msec (mean +/- standard error of the mean) (P less than 0.025). Partly because of prolonged refractoriness, the vulnerable zone was curtailed by ouabain, from 32.2 +/- 5.7 to 9.4 +/- 4.6 msec (P less than 0.001). This result suggests a protective effect of digitalis against atrial fibrillation and flutter independent of its hemodynamic actions.

Behavioural phenotype of a patient with a de novo 1.2 Mb chromosome 4q25 microdeletion. A female patient, 20 years of age, is reported with a history characterized by developmental and psychomotor delay, and during grammar-school period increasing learning problems, ritualistic behaviours and social withdrawal. Subsequently, challenging and autistic-like behaviours became prominent. The patient showed mild facial dysmorphisms, long thin fingers with bilateral mild short V metacarpals, and hyperlaxity of the joints. Neuropsychiatric examination disclosed obsessive, ritualistic behaviours and vague ideas of reference. Neuropsychological assessment demonstrated mild intellectual disability, mental inflexibility and incongruent affect. MRI-scanning of the brain showed no relevant abnormalities. Genome wide SNP array analysis revealed a 1.2 Mb de novo interstitial microdeletion in 4q25 comprising 11 genes, that was considered to be causative for the developmental delay, perseverative cognitive phenotype and dysmorphisms. To the authors knowledge, this is the first report of a de novo 4q25 microdeletion that presents with a specific behavioural phenotype.

Modelling of the temporal indoor radon variation in Bulgaria. In this study, temporal variations of indoor radon concentrations in Bulgaria were investigated. The radon concentrations were measured by nuclear track detectors as part of the Bulgarian National Survey, performed in the dwellings of 28 regional districts. The detectors were exposed through a year in two consecutive time periods of different lengths. For 2433 dwellings, measurements could be completed for both time periods, while for 345 dwellings they could only be completed for one of the periods. To estimate any missing radon concentrations, a temporal correction procedure was developed. This procedure, which included development of a linear correlation between the ln-transformed radon concentrations from the 9-month period [CRn(L)] and from the 3-month period [CRn(S)]. A normal distribution of the data, which is a condition for linear regression, was achieved when the ln-transformed radon concentrations were grouped by climate zone, then by regional districts, and finally by the presence/absence of a basement in the investigated building. The linear models obtained for each group showed reasonable coefficients of determination (R2 ≈ 0.50) and root mean square errors (RMSEs) of about 0.50. When these correlations were used to reconstruct radon concentrations in missing measurement periods, it turned out that the reconstructed data (for 345 dwellings) were within the 95% confidence interval of the measured data (for 2433 dwellings). The geometric means of CRn(L) and CRn(S) were 76 Bq/m3 and 100 Bq/m3, respectively, for 2433 dwellings, which are almost equal to those of 75 Bq/m3 and 98 Bq/m3, which represent the measured and reconstructed data together (for 2778 dwellings).

Supervising family therapy trainees in primary care medical settings: context matters. The purpose of this article is to identify and describe four essential skills for effective supervision of family therapy trainees in primary care medical settings. The supervision skills described include: (1) Understand medical culture; (2) Locate the trainee in the treatment system; (3) Investigate the biological/health issues; and (4) Be attentive to the self-of-the-therapist. Recommendations are also made to help supervisors become better prepared for the questions medical family therapy trainees bring to supervision.

[Absence of echoviral RNA sequences in medulla oblongata samples taken from patients who died of ALS]. The role of viral infection in the pathogenesis of ALS has been raised many times in the previous papers. The presence of an enterovirus genome has previously been confirmed using PCR RT and PCR in situ in spinal cord tissue samples taken from patients who died of ALS. Viral genome sequencing has also been used to show 91% and 88% homogeneity with ECHO 6 and 7 viruses, respectively. A year later the same method did not confirm the presence of the virus in spinal cord fragments taken from 30 patients who died of ALS nor in an 18 person control group. The present study was aimed to find persistent ECHO 6 and 7 viral infections in tissue samples taken from patients who died of ALS. RNA was isolated from frozen medulla oblongata samples taken from six patients who died of ALS (hospitalized in the Neurological Clinic CSK AM in the years 2000-2002). The presence of RNA was confirmed using RNA beta-actine. Oligo 2 and 3 as well as pEforward and pErevers primers were used for amplification. All samples returned negative results. In the samples studied no correlation was found between ECHO 6 and 7 viral infections and ALS.

Development and validation of a bioanalytical method using automated solid-phase extraction and LC-UV for the simultaneous determination of lumefantrine and its desbutyl metabolite in plasma. A bioanalytical method for the determination of lumefantrine (LF) and its metabolite desbutyl-lumefantrine (DLF) in plasma by solid-phase extraction (SPE) and liquid chromatography has been developed. Plasma proteins were precipitated with acetonitrile:acetic acid (99:1, v/v) containing a DLF analogue internal standard before being loaded onto a octylsilica (3 M Empore) SPE column. Two different DLF analogues were evaluated as internal standards. The compounds were analysed by liquid chromatography UV detection on a SB-CN (250 mm x 4.6 mm) column with a mobile phase containing acetonitrile-sodium phosphate buffer pH (2.0; 0.1 M) (55:45, v/v) and sodium perchlorate 0.05 M. Different SPE columns were evaluated during method development to optimise reproducibility and recovery for LF, DLF and the two different DLF analogues. The within-day precisions for LF were 6.6 and 2.1% at 0.042 and 8.02 microg/mL, respectively, and for DLF 4.5 and 1.5% at 0.039 and 0.777 microg/mL, respectively. The between-day precisions for LF were 12.0 and 2.9% at 0.042 and 8.02 microg/mL, respectively, while for DLF 0.7 and 1.2% at 0.039 and 0.777 microg/mL, respectively. The limit of quantification was 0.024 and 0.021 microg/mL for LF and DLF, respectively. Different amounts of lipids in plasma did not affect the absolute recovery of LF or DLF.

[Evaluation of patients with below knee amputation with respect to postoperative prosthesis fitting]. A follow-up of 78 patients who underwent amputations just below the knee at Herlev University Hospital in the county of Copenhagen during the period 1985-88 is reported. The examination was carried out at an average of 39 months later. There was a high early mortality postoperatively as well as in the subsequent years. Of the survivors, about 87% were found to be candidates for prosthetic fitting. Nearly all of these patients became functional ambulators. The long-term survival rate was primarily correlated to a reduced occurrence of concurrent medical diseases, especially of cardiovascular nature. All women with diabetes mellitus were deceased at the time of examination. This is a well-known phenomenon, relating diabetes with a six times higher mortality risk. The study indicates that the effort and expense of fitting and training patients with prostheses may be well worthwhile.

CDKN2A germline mutations in U.K. patients with familial melanoma and multiple primary melanomas. We report six of 16 U.K. melanoma families and two of 17 patients with multiple primary melanomas and a negative family history who have between them four different functionally damaging mutations of the CDKN2A (p16) gene: an Arg 24 Pro substitution in exon 1 in one family, a stop codon at codon 44 of exon 1 in one family, and a Met 53 Ile substitution in exon 2 in four families. One multiple primary melanoma patient also has the Met 53 Ile mutation and a second has a G-T substitution at the IVS2 + 1 splice donor site. Our data together with other recent publications from France and the U.S.A. indicate that screening melanoma kindreds with only two affected family members for CDKN2A mutations is justified.

Essential ECG clues in patients with congenital heart disease and arrhythmias. The prevalence of adults with congenital heart disease has dramatically increased during the last decades due to significant advances in the surgical correction of these conditions. As a result, patient's survival has been prolonged and arrhythmias have become one of the principal causes of morbidity and mortality for these patients. The surface 12-lead ECG may play a critical role in the identification of the underlying heart disease of the patient, the recognition of the arrhythmia mechanism and may also help in the planification of the ablation procedure in this setting. Finally, important prognostic information can be also obtained from the ECG in these patients. The present review will offer an overview of the principal utilities of the surface ECG in the diagnosis and management of patients with CHD and arrhythmias.

Further characterization of the interaction of histidine-rich glycoprotein with heparin: evidence for the binding of two molecules of histidine-rich glycoprotein by high molecular weight heparin and for the involvement of histidine residues in heparin binding. Rabbit histidine-rich glycoprotein (HRG, 94 kDa) binds heparin with high affinity (apparent Kd 60-110 nM). Eosin Y (1 equiv) bound to HRG was used as a reporter group to monitor associations of HRG with heparins of molecular mass 10, 17.5, and 30 kDa. The stoichiometries of the heparin-HRG complexes were determined by fluorescence and absorbance measurements as well as by analytical ultracentrifugation. Two types of complex form: complexes of 1 heparin:1 HRG and of 1 heparin:2 HRG. The 1:2 complex formation requires a minimum heparin chain length since 17.5-kDa but not 10-kDa heparin binds two HRG molecules. The formation of the 1:2 complexes of the larger heparin fractions is enhanced by divalent copper or zinc (1-10 equiv) bound to HRG. However, metal is not required for complex formation since all sizes of heparin examined interact tightly with HRG in the presence of ethylenediaminetetraacetic acid. Between 0.1 and 0.3 M ionic strength, both 1:1 and 1:2 complexes of heparin with HRG are progressively destabilized. No heparin-HRG complex is found at ionic strengths of 0.5 M. Between pH 8.5 and pH 6.5 both 1:2 and 1:1 complexes are found with 17.5-kDa heparin, but at pH 5.5 only 1:1 complexes are formed. The heparin-HRG interaction is progressively decreased by modification of the histidine residues of HRG, whereas modification of 22 of the 33 lysine residues of HRG has little effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Impact of bullying due to dentofacial features on oral health-related quality of life. The aim of this study was to investigate whether there is a relationship between self-reported bullying because of dentofacial features and oral health-related quality of life among a representative sample of Jordanian schoolchildren. This was a cross-sectional study in which a representative sample of sixth-grade students (age, 11-12 years) from randomly selected schools in Amman, Jordan, were asked to complete questionnaires distributed in the classroom in the presence of the researchers. The questionnaire used for this purpose was the short form of the Child Perceptions Questionnaire for 11- to 14-year-old children. The final sample size was 920 children (470 girls, 450 boys). There were significant differences between the sexes for the total Child Perceptions Questionnaire score and for the oral symptoms and the social well-being subscales, with boys reporting higher scores and thus more negative effects on their oral health-related quality of life. Comparison of the total scores and subscales scores for boys and girls subdivided into those who reported being bullied and not being bullied about their teeth showed that bullied boys had significantly greater effects on overall oral health-related quality of life and on all subscales than did not-bullied boys (P <0.001 for all comparisons). Bullied girls also had significantly greater effects on the overall oral health-related quality of life and all subscales than did not-bullied girls (P <0.001 for all comparisons). However, bullied boys and girls reported similar scores for the different subscales of the Child Perceptions Questionnaire; there were no significant differences. This study demonstrated a significant relationship between bullying because of dentofacial features and negative effects on oral health-related quality of life. The results highlight the importance of addressing the bullying problem among schoolchildren and provide important data for educational authorities to create antibullying programs to help students receive education in a safe and healthy environment.

SU-E-T-155: Dose Response Curve of EBT2 and EBT3 Radiochromic Films to a Synchrotron-Produced Monochromatic X-Ray Beam. This work investigates the dose-response curves of Gafchromic EBT2 and EBT3 radiochromic films using synchrotron-produced monochromatic x-ray beams. These dosimeters are being utilized for dose verification in photoactivated Auger electron therapy at the LSU Center for Advanced Microstructures and Devices (CAMD) synchrotron facility. Monochromatic beams of 25, 30 and 35 keV were generated on the tomography beamline at CAMD. Ion chamber depth-dose measurements were used to calculate the dose delivered to films irradiated simultaneously at depths from 0.7 - 8.5 cm in a 10×10×10-cms polymethylmethacrylate phantom. AAPM TG-61 protocol was applied to convert measured ionization into dose. Calibrations of films at 4 MV were obtained for comparison using a Clinac 21 EX radiotherapy accelerator at Mary Bird Perkins Cancer Center. Films were digitized using an Epson 1680 Professional flatbed scanner and analyzed using the optical density (OD) derived from the red channel. For EBT2 film the average sensitivity (OD/dose) at 50, 100, and 200 cGy relative to that for 4-MV x- rays was 1.07, 1.20, and 1.23 for 25, 30, and 35 keV, respectively. For EBT3 film the average sensitivity was within 3 % of unity for all three monochromatic beams. EBT2 film sensitivity shows strong energy dependence over an energy range of 25 keV - 4 MV. EBT3 film shows weak energy dependence, indicating that it would be the better dosimeter for Auger electron therapy. This research was supported by contract W81XWH-10-1-0005 awarded by The U.S. Army Research Acquisition Activity, 820 Chandler Street, Fort Detrick, MD 21702-5014. This report does not necessarily reflect the position or policy of the Government, and no official endorsement should be inferred.

Regulating the licensing of DNA replication origins in metazoa. Eukaryotic DNA replication is a highly conserved process; the proteins and sequence of events that replicate animal genomes are remarkably similar to those that replicate yeast genomes. Moreover, the assembly of prereplication complexes at DNA replication origins ('DNA licensing') is regulated in all eukaryotes so that no origin fires more than once in a single cell cycle. And yet there are significant differences between species both in the selection of replication origins and in the way in which these origins are licensed to operate. Moreover, these differences impart advantages to multicellular animals and plants that facilitate their development, such as better control over endoreduplication, flexibility in origin selection, and discrimination between quiescent and proliferative states.

Ethylene glycol or methanol intoxication: which antidote should be used, fomepizole or ethanol? Ethylene glycol (EG) and methanol poisoning can cause life-threatening complications. Toxicity of EG and methanol is related to the production of toxic metabolites by the enzyme alcohol dehydrogenase (ADH), which can lead to metabolic acidosis, renal failure (in EG poisoning), blindness (in methanol poisoning) and death. Therapy consists of general supportive care (e.g. intravenous fluids, correction of electrolytes and acidaemia), the use of antidotes and haemodialysis. Haemodialysis is considered a key element in the treatment of severe EG and methanol intoxication and is aimed at removing both the parent compound and its toxic metabolites, reducing the duration of antidotal treatment and shortening the hospital observation period. Currently, there are two antidotes used to block ADH-mediated metabolism of EG and methanol: ethanol and fomepizole. In this review, the advantages and disadvantages of both antidotes in terms of efficacy, safety and costs are discussed in order to help the physician to decide which antidote is appropriate in a specific clinical setting.

A cloud based architecture to support Electronic Health Record. We introduce a novel framework of electronic healthcare enabled by a Cloud platform able to host both Hospital Information Systems (HIS) and Electronic Medical Record (EMR) systems and implement an innovative model of Electronic Health Record (EHR) that is not only patient-oriented but also supports a better governance of the whole healthcare system. The proposed EHR model adopts the state of the art of the Cloud technologies, being able to join the different clinical data of the patient stored within the HISs and EMRs either placed into a local Data Center or hosted into a Cloud Platform enabling new directions of data analysis.

Cardiac sarcoidosis and coronary artery disease: a two-hit mechanism to left ventricular dysfunction (or is it)? This report describes a case of cardiac sarcoidosis in a 40-year-old man with minimal risk factors for coronary artery disease who was found to have a critical coronary lesion on angiography performed for declining left ventricular function. The case highlights the diagnostic and therapeutic issues surrounding cardiac sarcoidosis and raises the question of a possible link between sarcoidosis and premature coronary artery disease. It also stresses the importance of ruling out ischemia in any patient with declining left ventricular function.

Respiratory distress syndrome. Increasing knowledge of the pathophysiology of respiratory distress syndrome has led to improvements in clinical management. Future advances in prevention and therapy, including administration of agents to prevent prematurity or to accelerate lung maturation, provision of surfactant replacement, and new techniques of mechanical ventilation, will further decrease mortality and morbidity.

Interlimb coordination in cat locomotion investigated with perturbation. I. Behavioral and electromyographic study on symmetric limbs of decerebrate and awake walking cats. During locomotion of decerebrate and awake walking cats, perturbation (mechanical tap) was applied to the paw dorsum of the left forelimb (LF), and the responses of both forelimbs were recorded cinematographically and electromyographically (EMG). When the tap was applied during the LF stance phase, the duration of the ongoing LF stance was shortened by 10%; in the right forelimb (RF), the duration of the concomitant swing was shortened by 32%. A tap during the LF swing phase prolonged the duration of the ongoing LF swing phase and the concomitant RF stance phase by 55 and 15%, respectively. Analysis of RF joint angle excursions showed that the shortening of the RF swing phase was related mainly to acceleration of extension movement in the late swing phase; the prolongation of the RF stance phase was related to prolonged extension movement in the late stance phase. While EMG activities were relevant to these limb movements, a notable observation was that, by tapping the LF during the LF stance phase, EMG activity in the RF extensor started well before onset of the elbow extension movement to place down the limb; without the tap, the extensor activity started shortly after onset of the extension. Closely related to changes in phase durations of each forelimb, the period of bisupport phase where both forelimbs were in stance, was retained for more than 40% of that of unperturbed steps, even when the RF or LF made the first touchdown after the tap. The rostrocaudal level at RF touchdown after the tap was comparable to unperturbed steps. These findings on interlimb relation suggest that neural control ensures coordinated movements between symmetric limbs during locomotion.

Assessment of DNA strand breakage by the alkaline COMET assay in dialysis patients and the role of Vitamin E supplementation. Although the role of reactive oxygen species (ROS) in chronic renal failure (CRF) is not definitely demonstrated, a consistent number of observations has provided evidence for the presence of oxidative stress in uremic patients undergoing maintenance dialysis. In order to investigate this hypothesis further and to understand the role of antioxidant supplementation, peripheral blood lymphocytes were taken from 36 dialysis patients before and after Vitamin E supplementation in a dosage of 600 mg per day (2x300 mg) for 14 weeks and examined in the alkaline Comet assay for DNA strand breakage. The results were also compared with those of 36 controls with comparable age, sex, and smoking habits, and with no history of renal disease. The DNA breakage observed in the lymphocytes of patients before Vitamin E supplementation was significantly higher than in the controls (P<0.001) but a clear protective effect of Vitamin E supplementation were observed after 14 weeks of therapy.

Pulmonary stenosis and severe biventricular dysfunction: improvement following percutaneous valvuloplasty. A 15-year-old boy with severe pulmonary stenosis associated with severe right and left ventricular systolic dysfunction is reported. After successful percutaneous pulmonary valvuloplasty, there was an initial and early improvement in right ventricular (RV) function, followed by a delayed and more gradual improvement in left ventricular (LV) function. At long-term follow up, both RV and LV systolic functions were nearly normalized. Several mechanisms may be implicated, including ventricular interdependence, geometric factors, altered compliance and intrinsic alteration in the LV muscle. A delayed, but sustained, improvement in LV systolic function following relief of RV pressure overload suggests that the latter mechanism must have played an important role in the genesis of the LV dysfunction. Pulmonary stenosis associated with severe biventricular dysfunction may be treated primarily by percutaneous pulmonary balloon valvuloplasty with near-total recovery of the ventricular function.

[Fundamentals and results of cytostatic chemotherapy in some of the most common solid tumors]. In this review we discuss established cytostatic chemotherapies as well as developments and perspectives for the three most common tumour entities. Adjuvant and neoadjuvant therapy models for primary breast cancer are discussed, established and newer concepts in palliative care presented and open questions about high dose chemotherapy raised, which need to be settled before their routine use. Developments in the field of lung cancer therapy such as adjuvant and neoadjuvant approaches are pointed out and the importance of multimodal and interdisciplinary treatment modalities is underlined. Newer cytostatic drugs are compared with established agents. In the field of colorectal cancer several new thymidilatsynthase-inhibitors as well as drugs with different mode of action are available. With these new agents, [table: see text] cytostatic therapy of advanced stages and most probably also in the adjuvant setting could markedly be improved.

Second meal effect: modified sham feeding does not provoke the release of stored triacylglycerol from a previous high-fat meal. The present study was carried out to determine whether cephalic stimulation, associated with eating a meal, was sufficient stimulus to provoke the release of stored triacylglycerol (TAG) from a previous high-fat meal. Ten subjects were studied on three separate occasions. Following a 12 h overnight fast, subjects were given a standard mixed test meal which contained 56 g fat. Blood samples were taken before the meal and for 5 h after the meal when the subjects were randomly allocated to receive either water (control) or were modified sham fed a low-fat (6 g fat) or moderate-fat (38 g fat) meal. Blood samples were collected for a further 3 h. Compared with the control, modified sham feeding a low- or moderate-fat meal did not provoke an early entry of TAG, analysed in either plasma or TAG-rich lipoprotein (TRL) fraction (density <1.006 kg/l). The TRL-retinyl ester data showed similar findings. A cephalic phase secretion of pancreatic polypeptide, without a significant increase in cholecystokinin levels, was observed on modified sham feeding. Although these data indicate that modified sham feeding was carried out successfully, analysis of the fat content of the expectorant showed that our subjects may have accidentally ingested a small amount of fat (0.7 g for the low-fat meal and 2.4 g for the moderate-fat meal). Nevertheless, an early TAG peak following modified sham feeding was not demonstrated in the present study, suggesting that significant ingestion of food, and not just oro-sensory stimulation, is necessary to provoke the release of any TAG stored from a previous meal.

Delayed visual maturation in otherwise normal infants. Children may present in early infancy for evaluation of decreased visual responsiveness. Most such infants have systemic or ocular abnormalities that explain their poor fixation and tracking. Some infants, however, have no other medical or ocular problems. This study evaluated prognostic factors in this latter group of otherwise normal infants with decreased visual responsiveness. This was a retrospective cohort study in which medical records of infants evaluated for decreased visual responsiveness were reviewed to identify children who had no history of premature birth or systemic problems associated with developmental delay. Examination findings that were predicted to indicate a good prognosis included: the presence of some reaction to light, normal pupil responses, no nystagmus, and no structural ocular abnormalities. Follow-up information was obtained from office visits and telephone interviews. Main outcome measures were visual acuity and developmental status. Thirty-two children met the criteria noted above. Six were excluded due to lack of follow-up. Four were normal by the time of their initial examination. Follow-up for the remaining patients ranged from 3 months to 11 years (mean 2.94 years). One patient developed strabismus and required surgery. The remaining patients all had normal vision and development. Otherwise normal infants who present for evaluation of decreased visual responsiveness have a good prognosis if they have some reaction to light, normal pupil responses, absence of nystagmus, and no structural ocular abnormalities. The developmental prognosis for these infants appears to be good. Additional testing at the time of initial evaluation is not indicated.

Revisiting Incentive-Based Contracts. Incentive-based pay is rational, intuitive, and popular. Agency theory tells us that a principal seeking to align its incentives with an agent's should be able to simply pay the agent to achieve the principal's desired results. Indeed, this strategy has long been used across diverse industries-from executive compensation to education, professional sports to public service-but with mixed results. Now a new convert to incentive compensation has appeared on the scene: the United States' behemoth health-care industry. In many ways, the incentive mismatch story is the same. Insurance companies and employers are concerned about constraining the cost of care, and patients are concerned about quality of care. Physicians lack an adequate financial incentive to pay attention to either. Health care's recent move away from the traditional fee-for-service compensation model to incentive pay is perhaps unsurprising. But there is a problem: mixed preliminary evidence and potential mal-effects on vulnerable third-party patients. This Article employs a new lens-the legal and behavioral literature on optimal contract specificity-to suggest why incentive pay is problematic and why the health-care experience will be no different than other industries. The use of incentive pay is a change in contractdrafting strategy, a decision to write a more detailed, control-based contract rather than one that relies on discretion. The contracts literature suggests that this strategy will only work well where simple compliance is the goal rather than creativity or innovation. The health industry will not succeed in implementing incentive pay better than other industries have. What it needs is to recognize the limits of incentive pay and implement it sparingly. The new Trump Administration may be particularly primed to heed this call.

Effect of haloperidol and risperidone on amyloid precursor protein levels in vivo. The neurotoxic beta-amyloid peptide of Alzheimer's disease is formed from the amyloid precursor protein (APP), which is a member of an evolutionarily highly conserved gene family with significant functional importance. Because behavioral and psychiatric symptoms treated with antipsychotics may influence the course of the disease, we have investigated traditional and atypical antipsychotic drugs, administered through the intraperitoneal route, for their effects on rat cortical APP. Western-immunoblotting was utilized for semi-quantitative evaluation of APP levels. Treatment with haloperidol resulted in an acute elevation of cortical APP both in therapeutic and toxic doses, however, it had no significant chronic impact on APP. Atypical antipsychotic risperidone did not change cortical APP concentration. These results indicate that both haloperidol and risperidone are considered to be relatively safe with respect to APP metabolism. Possible mechanisms, including involvement of calcium and APP itself as a receptor, are discussed.

Head-shaking nystagmus (HSN): the theoretical explanation and the experimental proof. Head-shaking nystagmus (HSN) is induced by oscillating the head at high frequency in the horizontal plane. This test is used in the clinic to detect the presence of a unilateral loss of vestibular function. HSN has been described as monophasic with fast-phase direction towards either side, or biphasic with the direction of fast phases reversing after a few seconds. Loss of vestibular function amplifies existing non-linearities in the vestibular system, so that imposed sinusoids can induce biases which are the source of HSN. Fifty-one patients suffering from loss of peripheral vestibular function (43 partial, 11 total unilateral tests) were exposed to whole-body sinusoidal stimulation, with increasing head velocities (90-220 degrees/s) at 1/6Hz, to explore the consistency of per-rotatory induced biases. A bias was induced in all cases, but it wandered on either side, healthy or pathologic, unless test head velocities were larger than approximately 180 degrees/s. Given this condition, the slow-phase bias was located towards the pathologic side for all patients with significant bias ( > 5 degrees/s). These observations demonstrate that the sign and amplitude of the bias is variable and is not correlated with the lesioned side, unless high head velocities are imposed. This explains why the direction of the initial phase of HSN in the clinic seems so labile. Subsequent monophasic or biphasic characteristics of HSN are simply the reflection of interactions between two main time constants associated with "velocity storage" and "gaze holding" in the vestibular central processes.

A cognitive-behavioral treatment for depression in rural American Indian middle school students. Rural American Indian (AI) middle school students with depressive symptoms who participated in a culturally modified version of the Adolescent Coping with Depression (CWD-A) course (n = 8) reported significant improvement in depressive symptoms at post-intervention and at 3-month follow-up. There was also a nonsignificant but clinically relevant decrease in participants' anxiety symptoms. Students reported satisfaction with the intervention, and it was potentially more cost-effective and less stigmatizing than the individualized treatment-as-usual interventions to which it was compared. These results suggest the CWD-A is a promising approach for reducing depressive and anxiety symptoms in rural AI students and should be further evaluated with a larger sample of students.

Delineation of a cellular hierarchy in lung cancer reveals an oncofetal antigen expressed on tumor-initiating cells. Poorly differentiated tumors in non-small cell lung cancer (NSCLC) have been associated with shorter patient survival and shorter time to recurrence following treatment. Here, we integrate multiple experimental models with clinicopathologic analysis of patient tumors to delineate a cellular hierarchy in NSCLC. We show that the oncofetal protein 5T4 is expressed on tumor-initiating cells and associated with worse clinical outcome in NSCLC. Coexpression of 5T4 and factors involved in the epithelial-to-mesenchymal transition were observed in undifferentiated but not in differentiated tumor cells. Despite heterogeneous expression of 5T4 in NSCLC patient-derived xenografts, treatment with an anti-5T4 antibody-drug conjugate resulted in complete and sustained tumor regression. Thus, the aggressive growth of heterogeneous solid tumors can be blocked by therapeutic agents that target a subpopulation of cells near the top of the cellular hierarchy.

Metastatic pulmonary adenocarcinoma 13 years after curative resection for pancreatic cancer: report of a case and review of Japanese literature. For the majority of patients, ductal adenocarcinoma of the pancreas remains a lethal disease. Currently, surgical extirpation for localized disease offers the only chance for long-term survival. We report a patient who underwent successful resection of isolated lung metastasis occurring 13 years after pancreatic cancer resection. A 59-year-old woman underwent distal pancreatectomy for pancreatic cancer 13 years previously, followed by adjuvant chemotherapy, and was followed-up at the outpatient clinic of a local hospital. From around June 2010, she noticed bloody sputum, so she visited a local hospital. Since her chest X-ray and CT revealed a 1.5 cm mass shadow in the segment 10 of her right lung and she was referred to the Respiratory Disease Center of our hospital. As a result of through examinations, she was strongly suspected of having lung metastasis of pancreatic cancer, and underwent partial pneumonectomy. Postoperative histopathological examination of the resected specimen was consistent with lung metastasis of pancreatic cancer. She is still alive and currently receives third line of chemotherapy. Patients who have achieved long-term survival after pancreatic cancer resection and can tolerate surgery may benefit from resection of a lung metastasis of pancreatic cancer in terms of survival, if it controls the metastasis.

Accessibility of a critical prion protein region involved in strain recognition and its implications for the early detection of prions. Human prion diseases are characterized by the accumulation in the brain of proteinase K (PK)-resistant prion protein designated PrP27 - 30 detectable by the 3F4 antibody against human PrP109 - 112. We recently identified a new PK-resistant PrP species, designated PrP*20, in uninfected human and animal brains. It was preferentially detected with the 1E4 antibody against human PrP 97 - 108 but not with the anti-PrP 3F4 antibody, although the 3F4 epitope is adjacent to the 1E4 epitope in the PrP*20 molecule. The present study reveals that removal of the N-terminal amino acids up to residue 91 significantly increases accessibility of the 1E4 antibody to PrP of brains and cultured cells. In contrast to cells expressing wild-type PrP, cells expressing pathogenic mutant PrP accumulate not only PrP*20 but also a small amount of 3F4-detected PK-resistant PrP27 - 30. Remarkably, during the course of human prion disease, a transition from an increase in 1E4-detected PrP*20 to the occurrence of the 3F4-detected PrP27 - 30 was observed. Our study suggests that an increase in the level of PrP*20 characterizes the early stages of prion diseases.

Toward Enediyne Mimics: Methanolysis of Azoesters and a Bisazoester. Enediyne anticancer antibiotics have attracted tremendous interest in the past decade. The inherent difficulty in synthesizing these structurally complex natural products with the strained enediyne moiety has motivated a search for simpler molecules that mimic enediyne chemistry. The ultimate objective is to identify molecules that produce 1,4-benzenoid diradicals, which are known to induce DNA cleavage in the natural products. Toward this goal, several aromatic azoesters have been synthesized, and EPR reveals the presence of radical intermediates in their methanolysis. A 1,4-bisazoester has also been synthesized, and its methanolysis products have been studied by reversed-phase HPLC. The formation of 1,2-dicyanobenzene from the 1,4-bisazoester is consistent with the existence of a 1,4-diradical intermediate.

Predictive factors of outcome in patients transplanted for hepatitis B. This study aimed to (1) identify the variables that affect graft and patient survival in recipients transplanted for hepatitis B virus (HBV) disease; and (2) assess factors associated with an increased risk of graft cirrhosis at 5 years after liver transplantation (LT). A total of 104 chronically infected HBV patients were considered for this study and all received tacrolimus- or cyclosporine A (CSA)-based immunosuppressive regimens. The overall 5-year patient and graft survival rates were 80% and 73%, respectively. Univariate Cox proportional hazards regression analysis indicated that older recipient age and higher body mass index (BMI) at LT, LT more than or equal to 1998, arterial hypertension, hyperlipidemia, and CSA-based immunosuppression correlated with decreased patient survival. In the multivariate model, advanced recipient age, higher BMI, CSA-based immunosuppressive therapy, and increasing cold ischemia time were associated with worse patient survival. Recipient age and BMI at time of LT and posttransplant hypertriglyceridemia also affected graft survival. Log-rank analysis showed that a viral load of more than 10 copies/mL and antiviral therapy at LT, post-LT biliary complications, HBV recurrence, nucleos(t)ide analogue monoprophylaxis (without hepatitis B immunoglobulin), and short-term (< or = 1 year) mycophenolate mofetil therapy were significant risk factors for graft cirrhosis within 5 years of LT. Various recipient factors at the time of LT and post-LT virological status, antiviral prophylaxis, cholestasis, cardiovascular risk profile, and immunosuppressive regimen affect the outcome of HBV patients after LT. Prospective studies are warranted to define optimal immunosuppression for recipients transplanted for hepatitis B.

Raman crystal lasers in the visible and near-infrared. Raman lasers based on potassium gadolinium tungstate and lead tungstate crystals pumped by a to approximately 120 ps Nd: YAG laser at 1.064 microm were developed. High reflection mirrors for the Stokes wavelength have been used to generate near-infrared and eye safe spectral region of 1.15 - 1.32 microm. Second harmonic generation of the generated Raman lasers was observed. Eifficient multiple Stokes and anti-Stokes picosecond generation in 64 crystals have been shown to exhibit stimulated Raman scattering on about 700 lines covering the whole visible and near-infrared spectrum. All stimulated Raman scattering (SRS) wavelengths in the visible and near-infrared spectrum are identified and attributed to the SRS-active vibration modes of these crystals.

[An analysis by scanning electron microscopy and surface roughness meter of the impact of the CO2 laser on the dentin]. The aim of the study was to compare the morphology of craters produced on the dentinal surface by CO2 laser beams (LASERSAT CO2) before and after the removal of the carbonized layer, besides with different settings of the power and duration of the laser beam. Thirty-three recently extracted non carious young third molar teeth were sectioned from vestibular and lingual surfaces, exposing a planed dentinal surface. Twenty impacts were made on each of dentinal surface producing 20 individual craters. The duration and the power of each laser beam were different on each tooth. The duration varied from 0.1 to 0.4 second (0.1-0.2-0.3-0.4 s). The power varied from 1 to 5 watts (1, 2, 3, 4, 5 w). Specimens obtained for a power of 3 and 4 watts and a duration of 0.1 and 0.2 second were examined with a JEOL 35CF (25 KV, magnification: x 30, x 110, x 200), before and after the removal of the carbonized layer. The carbonized layer of the craters was removed with an air polisher (HEATCO). Craters obtained for all duration values as well as for all power values were analyzed with a profilometer. The chosen profilometer was: TALISURF 10; horizontal amplification Vh = 20; vertical amplification Vv = 200. Samples were observed by a SEM and the craters depth and diameter were measured with a profilometer. Then, the carbonized layer of the craters was removed with an air polisher and the cleaned dentinal surface was observed again with the SEM and the profilometer.(ABSTRACT TRUNCATED AT 250 WORDS)

Maturational differences in hepatic microhemodynamics in rats. Age-related changes in the hepatic microcirculation may contribute to the increased susceptibility of the immature liver to microvascular injury. We quantified sinusoidal and acinar diameters, sinusoidal red cell velocities (VRBC), and sinusoidal volume flows to characterize microhemodynamics of weanling and adult rat livers with and without hepatic artery (HA) ligation using intravital fluorescence videomicroscopy. Despite a 20% faster heart rate and a nearly 20% lower mean arterial and portal vein pressure in weanling rats relative to those in the adults, weanling periportal and pericentral sinusoidal velocities were approximately 30 and 25% faster, respectively, than those in adults. Furthermore, the HA was found to contribute more to maintenance of sinusoidal VRBC in the immature liver as demonstrated by a significant decrease in both periportal and pericentral VRBC following HA ligation. HA ligation had no effect on VRBC of either zone in adults. Zonal volume flow (HA intact), however, was maintained independent of age. These results suggest a lower extrasinusoidal resistance in the weanling. The 25% shorter acinar diameter that we found in weanling livers likely contributes to a lower extrasinusoidal resistance by allowing a higher ratio of inflow vessels to volume of tissue. Shorter sinusoidal pathways in weanling livers also decreases sinusoidal resistance 1.3-fold relative to that in the adult, countering the approximately 1.5 times increase in resistance due to the smaller caliber of sinusoidal vessels so that overall sinusoidal resistance is not age-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Detection and distribution patterns of telomerase activity in insects. Telomeres of most insects consist of pentanucleotide (TTAGG)n repeats, although the repeats are absent in Diptera and some other insect species, where the telomere regions are perhaps maintained without telomerase. To understand various and unusual telomere formation in insects, we have studied the characteristic features of a putative insect telomerase that has not been previously described. Using a modified telomeric repeat amplification protocol (TRAP), we first detected the telomerase activity in crickets, cockroaches and two Lepidopteran insects. The telomerase from crickets and cockroaches required dATP, dGTP and dTTP but not dCTP as a substrate and sequence analyses of the products of TRAP revealed that the (TTAGG)n repeats are synthesized by telomerase. The cockroach telomerase was detected both in somatic (fat body, muscle and neural tissues) and germ line (testis) cells, suggesting that expression of this enzyme is not regulated in a tissue-specific manner at an adult stage. While we detected high levels of telomerase activity in crickets and cockroaches, we could not detect activity in all tissues and cell cultures of the silkworm, Bombyx mori and in two Drosophila and one Sarcophaga cell lines. This supports the theory that Dipteran insects maintain their telomeres without telomerase.

Development of a species-specific isotope dilution GC-ICP-MS method for the determination of thiophene derivates in petroleum products. A species-specific isotope dilution technique for accurate determination of sulfur species in low- and high-boiling petroleum products was developed by coupling capillary gas chromatography with quadrupole ICP-MS (GC-ICP-IDMS). For the isotope dilution step 34S-labeled thiophene, dibenzothiophene, and mixed dibenzothiophene/4-methyldibenzothiophene spike compounds were synthesized on the milligram scale from elemental 34S-enriched sulfur. Thiophene was determined in gasoline, 'sulfur-free' gasoline, and naphtha. By analyzing reference material NIST SRM 2296, the accuracy of species-specific GC-ICP-IDMS was demonstrated by an excellent agreement with the certified value. The detection limit is always limited by the background noise of the isotope chromatograms and was determined for thiophene to be 7 pg absolute, which corresponds to 7 ng sulfur/g sample under the experimental conditions used. Dibenzothiophene and 4-methyldibenzothiophene were determined in different high-boiling petroleum products like gas oil, diesel fuel, and heating oil. In this case a large concentration range from about < 0.04 to more than 2,000 microg g(-1) was covered for both sulfur species. By parallel GC-ICP-MS and GC-EI-MS experiments (EI-MS electron impact ionization mass spectrometry) the substantial influence of co-eluting hydrocarbons on the ICP-MS sulfur signal was demonstrated, which can significantly affect results obtained by external calibration but not those by the isotope dilution technique.

Contrasting parental perspectives with those of teenagers and young adults with cancer: comparing the findings from two qualitative studies. To compare and contrast the issues raised in narrative data gathered from parents of teenagers and young adults with cancer with interview data gathered from young adults being treated for cancer. A narrative correspondence method elicited contributions from the parents of 28 young adults with cancer. In-depth qualitative interviews were undertaken with 28 young adults in treatment for cancer or soon after their treatment. The secondary analysis of the two data sets illuminates contrasting familial perspectives. While some of the topics raised by parents are also addressed by young people, their perspectives differ thus offering a 'mirror image' of the same issue. The contrast in priorities can contribute to stress within the family and can increase the danger of conflict over key decisions that may impact upon the health of the young adult with cancer. If the potential conflicts are anticipated and understood and as a consequence handled with skill by professionals in the setting of care, this can benefit family relationships which can be thrown into crisis by the illness. It is thus important that a model of care that incorporates such an understanding is widely implemented in order to mitigate the negative impact on family dynamics when cancer is diagnosed in young adulthood.

Hyaluronic acid and Arg-Gly-Asp peptide modified Graphene oxide with dual receptor-targeting function for cancer therapy. Graphene oxide (GO) modified with hyaluronic acid (HA) and Arg-gly-asp peptide (RGD) was designed as a dual-receptor targeting drug delivery system to enhance the specificity and efficiency of anticancer drug delivery. Firstly, GO-HA-RGD conjugate was characterized to reveal its structure and morphology. Whereafter, doxorubicin (Dox) as a model drug was loaded on GO-HA-RGD carrier, which displayed a high loading rate (72.9%, GO:Dox (w/w) = 1:1), pH-response and sustained drug release behavior. Cytotoxicity experiments showed that GO-HA-RGD possessed excellent biocompatibility towards SKOV-3 and HOSEpiC cells. Additionally, the GO-HA-RGD/Dox had a stronger cytotoxicity for SKOV-3 cells than either GO-HA/Dox (single receptor) or GO/Dox (no receptor). Moreover, celluar uptake studies illustrated that GO-HA-RGD conjugate could be effectively taken up by SKOV-3 cells via a synergic effect of CD44-HA and integrin-RGD mediated endocytosis. Hence, GO-HA-RGD nanocarrier is able to be a promising platform for targeted cancer therapeutic.

Signal transduction inhibitors, hibarimicins A, B, C, D and G produced by Microbispora. II. Structural studies. The structure of hibarimicins A, B, C, D and G which are inhibitors for tyrosine specific protein kinase are determined using spectroscopic techniques. Hibarimicins described in this report consist of a common aglycon and six deoxyhexoses. The aglycon contains a highly oxidized naphtylnaphthoquinone as a chromophore. Among them, hibarimicin B was identical with angelmicin B.

Stimulating PACalpha increases miniature excitatory junction potential frequency at the Drosophila neuromuscular junction. Photoactivated adenylate cyclase alpha (PACalpha) is a light-activated adenylate cyclase that was originally cloned from the eye spot of the protozoan Euglena gracilis. PACalpha has been shown to rapidly increase intracellular cyclic adenosine monophosphate (cAMP) in vivo in Xenopus oocytes and HEK293 cells, increase the spike width in Aplysia sensory neurons, and modify behavior in Drosophila. Using the GAL4 UAS system, we heterologously expressed PACalpha in motorneurons and quantified the effects of its activation at the neuromuscular junction of the Drosophila third instar wandering larva, a well-characterized model synapse. By recording from body-wall muscle 6, we show that the presynaptic activation of PACalpha with blue light significantly increased miniature excitatory junction potential (mEJP) frequency in the presence of calcium with a delay of about 1 minute. Similar effects have been observed in previous studies that utilized adenylate cyclase agonists (Forskolin) or membrane-permeable cAMP analogs [dibutyryl cAMP and 4-chlorophenylthio-(CPT)-cAMP] to increase presynaptic cAMP concentrations. PACalpha's efficacy in combination with its specificity make it an invaluable tool for the rapid regulation of cAMP in vivo and for investigating the mechanisms by which cAMP can modulate synaptic transmission and neuronal plasticity in Drosophila.

[Insulin-heparin complex, its physiological properties]. An insulin-heparin complex was obtained in vitro. The hypoglycemic effect of insulin, included into this complex as compared with free insulin, was increased more than 2-fold when it was tested in animals with stable alloxane diabetes. Contrary to insulin, administration of the insulin-heparin complex increased the anticoagulation properties of blood and exhibited the non-enzymatic fibrinolytic activity towards the unstabilized fibrin both in presence or in absence of inhibitors of fibrinolysis, caused by plasmin.

Effect of postharvest storage on the expression of the apple allergen Mal d 1. Consumption of fresh apples can cause allergy in susceptible individuals. A competitive enzyme-linked immunosorbent assay (ELISA) has been developed to determine Mal d 1 levels in apple pulp using a monoclonal antibody (BIP-1). The ELISA was able to rank ten cultivars according to their Mal d 1 content (between 3.8 and 72.5 mug/g pulp). For the first time, it has been demonstrated that growing conditions and postharvest storage, using three different treatments over a 5 month period in 2 consecutive years, increase Mal d 1 expression at a translational and transcriptional level (3.5- and 8.5-fold under controlled atmosphere storage). Expression of three major Mal d 1 isoforms was observed by real-time polymerase chain reaction over the 5 month storage period, and Mal d 1.02 was the most highly expressed isoform. In conclusion, Mal d 1 gene expression was significantly increased during modified atmosphere storage. Individuals suffering from birch pollen-apple allergy syndrome might experience fewer problems consuming freshly picked apples.

[Study of the relationship between the trace element content and the physiological properties of Salmonella typhi during submerged cultivation]. The content of trace elements in the cells served as one of the characteristics of physiological condition of the population. The character of the changes in the trace elements content depending on the rate of the microbial multiplication pointed to the importance of the mineral sources of nutrition for the development of the cells analyzed.

Maturation-related changes in catecholamine-dependent cyclic AMP and protein kinase in the rabbit myocardium. It has been shown that the sensitivity to isoproterenol of myocardial inotropic response increases with growth in rabbits. In the present study we attempted to delineate the biochemical mechanisms involved in this maturation-related change. We investigated cyclic AMP generation and protein kinase activation by isoproterenol in the ventricular myocardium of rabbits aged 1 day, 1 week, and 1 month. In contrast to an increase in inotropic response, both the sensitivity to isoproterenol of cyclic AMP generation and the sensitivity to exogenous cyclic AMP of protein kinase activation decreased with maturation from 1 day to 1 month of age. ED50 of isoproterenol (mean +/- SE) on cyclic AMP generation in myocardial slices was 1.83 +/- 0.42 x 10(-7) M for 1-day-old, 3.70 +/- 0.61 x 10(-7) M for 1-week-old, and 8.32 +/- 1.20 x 10(-7) M for 1-month-old rabbits. Likewise, the ED50 of isoproterenol on adenylate cyclase activation was 0.65 +/- 0.11 x 10(-7) M, 2.04 +/- 0.32 x 10(-7), and 15.2 +/- 2.5 x 10(-7) M in 1-day, 1-week- and 1-month-old rabbits, respectively. The ED50 of cyclic AMP on protein kinase activation was 1.50 +/- 0.64 x 10(-8) M for 1-day-old and 7.08 +/- 1.52 x 10(-8) M for 1-month-old rabbits. This apparent discrepancy between inotropic response and biochemical response in the sensitivity to isoproterenol indicates that the biochemical mechanism of the maturation-related change in inotropic response was at a step or steps distal to protein kinase activation.

The psychopharmacology of aggressive behavior: a translational approach: part 1: neurobiology. Patients with mental disorders are at an elevated risk for developing aggressive behavior. In the last 19 years, the psychopharmacological treatment of aggression has changed dramatically because of the introduction of atypical antipsychotics into the market and the increased use of anticonvulsants and lithium in the treatment of aggressive patients.Using a translational medicine approach, this review (part 1 of 2) examines the neurobiology of aggression, discussing the major neurotransmitter systems implicated in its pathogenesis, namely, serotonin, glutamate, norepinephrine, dopamine, and γ-aminobutyric acid, and also their respective receptors. The preclinical and clinical pharmacological studies concerning the role of these neurotransmitters have been reviewed, as well as research using transgenic animal models. The complex interaction among these neurotransmitters occurs at the level of brain areas and neural circuits such as the orbitoprefrontal cortex, anterior cortex, amygdala, hippocampus, periaqueductal gray, and septal nuclei, where the receptors of these neurotransmitters are expressed. The neurobiological mechanism of aggression is important to understand the rationale for using atypical antipsychotics, anticonvulsants, and lithium in treating aggressive behavior. Further research is necessary to establish how these neurotransmitter systems interact with brain circuits to control aggressive behavior at the intracellular level.

Transferrin, C3 complement, haptoglobin, plasminogen and alpha 2-microglobulin in patients with urogenital tumors. The serum levels of transferrin, haptoglobin, C3 proactivator, plasminogen and alpha 2-macroglobulin have been measured in patients suffering from urogenital cancer. In this randomized study, we found a frequent decrease of transferrin coinciding with the elevation of C3-proactivator and haptoglobin. The serum concentration of plasminogen and alpha 2-macroglobulin were rarely observed in the pathological range excluding cancer-associated changes. Tumor metabolites and/or the circulating immune complex may account for the alteration of transferrin, haptoglobin and C3-proactivator, more than primary cancer-related synthesis of these proteins.

[Chemotherapy of elderly patients with colorectal cancer]. Elderly patients will be the largest group of oncology patients in the future. Because of minimal participation of older patients in randomized clinical trials there is a lack of evidence-based data to make correct decisions with regard to chemotherapy and/or targeted therapy in this age group. Elderly patients have similar benefits from systemic therapies as younger counterparts, but many elders have substantial co-morbidities, which may limit the life expectancy and the effectiveness of systemic therapy. Close collaboration between oncologists and geriatrists will help make decisions on the management of elderly patients suffering from cancer.

Perceptions of hyperbaric oxygen therapy among podiatrists practicing in high-risk foot clinics. Foot ulceration is a devastating and costly consequence of diabetes. Hyperbaric oxygen therapy is recognised as an adjunctive therapy to treat diabetes-related foot ulceration, yet uptake is low. Semi-structured interviews were conducted with 16 podiatrists who manage patients with foot ulcers related to diabetes to explore their perceptions of, and the barriers/facilitators to, referral for hyperbaric oxygen. Podiatrists cited logistical issues such as location of facilities as well as poor communication pathways, lack of delegation and lack of follow up when patients presented for hyperbaric treatment. In general, podiatrists had an understanding of the premise of hyperbaric oxygen therapy and evidence to support its use but could only provide very limited citations of key papers and guidelines to support their position. Podiatrists stated that they felt a patient was lost from their care when referred for hyperbaric oxygen and that aftercare might not be adequate. Improved referral and delegation pathways for patients presenting for hyperbaric oxygen, as well as the provision of easily accessible evidence to support this therapy, could help to increase podiatrists' confidence in deciding whether or not to recommend their patients for hyperbaric oxygen therapy.

Entomological investigation of a sylvatic yellow fever area in São Paulo State, Brazil. Following reports of two autochthonous cases of sylvatic yellow fever in the State of São Paulo, Brazil, in 2000, entomological surveys were conducted with the objective of verifying the occurrence of vector species in forest environments close to or associated with riparian areas located in the western and northwestern regions of the State. Culicidae were captured in 39 sites distributed in four regions. Haemagogus leucocelaenus and Aedes albopictus were the most abundant species and were captured in all the regions studied. H. leucocelaenus was the most abundant species in the municipalities of Santa Albertina and Ouroeste, where the two cases of sylvatic yellow fever had been reported. Mosquitoes from the janthinomys/capricornii group were only found at eight sites in the São José do Rio Preto region, while Sabethes chloropterus was found at one site in Ribeirão Preto. H. leucocelaenus showed its capacity to adapt to a secondary and degraded environment. Our results indicate a wide receptive area for yellow fever transmission in the State of São Paulo, with particular emphasis on the possibility of H. leucocelaenus being involved in the maintenance of this sylvatic focus of the disease.

Regression of cardiac hypertrophy. Experimental animal model. Regression of cardiac hypertrophy has been proven to occur in experimental animals following some types of antihypertensive therapy. However, no direct and necessary correlation can be found between hypertension and cardiac hypertrophy. The effect of different antihypertensive drugs on regression of cardiac hypertrophy varies despite the same degree of reduction in arterial pressure in hypertensive control subjects. Therapy with alpha-methyldopa resulted in reversal of hypertrophy with effective blood pressure control, whereas treatment with vasodilators, namely hydralazine and minoxidil, either did not alter (hydralazine) degree of myocardial hypertrophy or increase it (minoxidil) despite normalization of blood pressure. The biochemical profile of the myocardium after regression of hypertrophy following antihypertensive therapy is not homogeneous; for example, reversal with alpha-methyldopa is associated with increased collagen content, whereas reversal with Captopril did not alter collagen content of the heart. Adrenergic factors seem to play an important role in the modulation of myocardial structure to variations in arterial pressure. Furthermore, in each type of hypertrophy in hypertension, a combination of different factors might be responsible, and it may not be correct to assume that the same factors must be involved in the regression of all types of myocardial hypertrophy.

Detection, Visualization, and Quantification of Neutrophil Extracellular Traps (NETs) and NET Markers. Neutrophil extracellular traps (NETs) have been identified as a key player in the pathogenesis of infection and inflammation in human and animals. On the one hand, NETs have been characterized as fundamental to the innate immune defense against different pathogens since they are able to entrap and immobilize invading pathogens. On the other hand, NETs have been shown to contribute to several diseases, based on their detrimental consequences. This chapter describes methods to detect NETs and NET markers in blood-derived isolated neutrophils of human, pigs, and horses in vitro, as well as NETs and NET marker detection in body fluids from in vivo studies. To avoid nonspecific background in NET-formation, a well-established isolation method for the neutrophils from fresh blood is needed. After stimulation of neutrophils to release NETs, NETs are stained with different antibodies to confirm the presence of extracellular DNA extrusion consisting of histone-DNA complexes, as well as granule components (e.g., myeloperoxidase or elastase). Furthermore, specific methods to quantify NETs and NET markers in the cerebrospinal fluid (CSF) and bronchoalveolar lavage fluid (BALF) are described in detail. In addition to immunofluorescence microscopy, quantification of NET markers from in vivo experiments in various body fluids is described (e.g., nuclease activity, free extracellular DNA, or cationic host defense peptides, such as the porcine PR-39 in BALF and CSF).

Methodological aspects of classifying low--and medium intensity of hyperostosis spongiosa orbitae. Low- and medium expressions of hyperostosis spongiosa orbitae are occurring rather frequently compared to strong or very strong ones, yet their notation and differentiation is sometimes rather difficult. By means of original photographs of low and medium intensity degrees of this pathological trait methodological facilitation of notation is intended. This could serve as a stimulus for a more frequent incorporation of this bone condition in skeletal studies let alone minimal interobserver differences.

Effect of partial release of the posterior cruciate ligament in total knee arthroplasty. Appropriate tension of the posterior cruciate ligament, which often is tight in deep flexion, is difficult to achieve after posterior cruciate ligament retaining total knee arthroplasty. Kinematics and maximum flexion after partial release of the posterior cruciate ligament were evaluated in this study. A partial release improved the maximum flexion angle and maintained anteroposterior stability without causing undesirable changes in kinematics, whereas full resection of the posterior cruciate ligament caused unfavorable anteroposterior instability. Partial posterior cruciate ligament release eliminated excessive rollback movement caused by a tight posterior cruciate ligament and also shifted the point of articular surface contact anteriorly. These results indicate that partial release of the posterior cruciate ligament may improve knee function in patients with a tight posterior cruciate ligament after total knee arthroplasty.

Conformationally constrained analogues of diacylglycerol. 20. The search for an elusive binding site on protein kinase C through relocation of the carbonyl pharmacophore along the sn-1 side chain of 1,2-diacylglycerol lactones. Previous studies with 1,2-diacylglycerol (DAG) lactones, which behave as high-affinity ligands for protein kinase C (PK-C), have established the importance of maintaining intact the pharmacophore triad of two carbonyl moieties (sn-1 and sn-2) and the primary alcohol. In addition, docking studies of DAG-lactones into an empty C1b receptor of PK-Cdelta (as it appears in complex with phorbol 13-O-acetate) have revealed that in either of the two possible binding alternatives (sn-1 or sn-2) only one carbonyl group of the DAG-lactone is involved in binding. Therefore, the unknown receptor for the orphaned carbonyl appears to lie outside the boundaries of this binary complex, possibly residing at the membrane or near the membrane-protein interface. A strategy to locate the optimal location of the unengaged carbonyl was conceived by utilizing a small group of DAG-lactones (1-4) with a highly branched chain adjacent to the sn-2 carbonyl such that sn-2 binding is favored. With these compounds, various locations of the sn-1 carbonyl along the side chain were tested for their binding affinity for PK-C. The results indicate that the location of the side chain sn-1 carbonyl in a DAG-lactone must have perfect mimicry to the sn-1 carbonyl of the parent DAG for it to display high binding affinity. A proposed model from this work is that the missing pharmacophore in the ternary complex, which includes the membrane, is close to the membrane-protein interface.

Electrodermal responses in patients with unilateral brain damage. Skin conductance responses (SCR) to emotional and to nonemotional stimuli were measured in 16 right and 16 left unilateral brain-damaged patients. Replicating findings by Morrow, Vrtunski, Kim and Boller (1981), those patients with a lesion in the left hemisphere showed higher SCR's to emotional than to nonemotional stimuli while those with a right lesion showed no difference between them. This pattern of results remained when variance in performance on a Facial Expression Recognition task was partialled out, suggesting that the absence of differentiated arousal in right-brain-damaged patients is unrelated to their impairment in perceptual analysis.

Exercise capacity after lobectomy in patients with chronic obstructive pulmonary disease. The aim of this study is to clarify whether patients with chronic obstructive pulmonary disease (COPD) lose less exercise capacity after lobectomy than do those without COPD, to the same extent as ventilatory capacity and lobectomy for selected patients with severe emphysema improve exercise capacity like ventilatory capacity. Seventy non-COPD patients (N group), 16 mild COPD patients (M group), and 14 moderate-to-severe COPD patients (S group) participated. Pulmonary function and exercise capacity tests were performed on the same day preoperatively and six months to one year after lobectomy. The S group lost significantly less FEV(1) (forced expiratory volume in 1 s) after lobectomy than did the N or M group (P<0.0001 and P<0.005). However, their loss of exercise capacity was equivalent to that for the N and M groups. For the S group, there was a significant, negative correlation between preoperative FEV(1) % of predicted and percentage change in FEV(1) and maximum oxygen consumption (VO2 max) after lobectomy (r=-0.93, P<0.0001 and r=-0.64, P=0.01). In moderate-to-severe COPD patients, patients with a lower preoperative FEV(1) % of predicted experienced a smaller decrease in FEV(1) and VO2 max after lobectomy.

[Cutaneous squamous cell carcinoma]. Squamous cell carcinoma (SCC) of the skin accounts for 20 % of non-melanoma skin cancer and is one of the most frequent types of cancer in Caucasian populations. Diagnosis is based on the clinical features and should be histopathologically confirmed to adequately address the prognosis and treatment. Complete surgical excision with histopathological control of excision margins is the gold standard in the treatment of primary SCC. Sentinel lymph node biopsies (SLNB) can be considered in SCC with a tumor thickness of >6 mm but there is currently no evidence concerning prognostic and therapeutic effects. Radiotherapy can be discussed as an alternative to surgery for inoperable tumors or as adjuvant therapy for a high risk of recurrence. In SCC with distant metastases various chemotherapeutic agents are used; however, there is no standard regimen. The epidermal growth factor receptor (EGFR) inhibitors and immune checkpoint blockers can be discussed as treatment options, preferentially in clinical trials. There is no standard follow-up schedule for patients with SCC. A risk-adapted follow-up is recommended based on the risk of metastatic spread or development of new lesions primarily by dermatological control and supplemented by ultrasound investigations in high risk patients.

Exposure to bisphenol A from bis-glycidyl dimethacrylate-based dental sealants. Bisphenol A (BPA) is a common component of composites and dental sealants. The potential exists for human exposure after sealant placement. The authors prospectively enrolled 15 men in an exposure assessment study; 14 completed the study. After placement of clinically appropriate amounts of one of two sealants, the authors measured BPA in saliva and urine samples collected at prescribed intervals after the sealants were placed. They used selective and sensitive isotope-dilution mass-spectrometry-based methods for BPA measurements, thus providing the most reliable results. Helioseal F (Ivoclar Vivadent, Amherst, N.Y.) leached negligible amounts of BPA. Urinary and salivary BPA levels in subjects who received these sealants were similar to baseline levels. Delton Light Cure (LC) Opaque pit-and-fissure sealant (Dentsply/Ash, York, Pa.) leached more BPA, resulting in low-level BPA exposures similar to those used in laboratory animal testing. BPA exposure after Delton LC sealant placement was significantly higher than exposure after placement of Helioseal F. Patients treated with Delton LC had significantly higher doses of BPA (110 microg) than did those treated with Helioseal F (5.5 microg) (P < .0001). Placement of clinically relevant amounts of Delton LC sealant resulted in low-level BPA exposure; however, exposure was negligible after placement of Helioseal F. Saliva collection after sealant placement likely reduced systemic absorption of BPA from dental sealants. Sealants should remain a useful part of routine preventive dental practice, especially those that leach negligible amounts of BPA. Dental sealants may be a point source for low-level BPA exposure at levels that show health effects in rodents. Further research is required to determine whether human exposure to BPA at these levels causes adverse effects.

Association of antiphospholipid antibodies with systemic lupus erythematosus in a child presenting with chorea: a case report. A 16-year-old girl, diagnosed 1 year previously as having Sydenham chorea, was found to have systemic lupus erythematosus according to the American Rheumatism Association criteria. She now presented with pulmonary emboli and renal involvement and responded to immunosuppressive and anticoagulant therapy. The high levels of anticardiolipin antibodies returned to normal along with the clinical symptoms. We suggest that anticardiolipin antibodies are relevant to the development of chorea and thrombo-embolic complications and that these auto-antibodies should be sought for in similar cases.

Neighbourhood income gradients in hospitalisations due to motor vehicle traffic incidents among Canadian children. To investigate income gradients in motor vehicle traffic injury hospitalisation for vehicle occupants and pedestrians/cyclists among children in urban and rural Canada. Four years (2001/02-2004/05) of acute-care hospitalisation discharge records for children aged 0-19 years were analysed. International Classification of Disease codes were used to determine hospitalisations due to motor vehicle traffic incidents for occupants and pedestrians/cyclists. Rates of injury (per 10 000 person years) were calculated by neighbourhood income quintiles for urban and rural areas. Among children (0-19 years), rates of vehicle occupant hospitalisation were higher in rural (5.07, 95% CI 4.90 to 5.25) than urban areas (2.08, 95% CI 2.03 to 2.14). In rural areas, children from lower income neighbourhoods had higher vehicle occupant hospitalisation rates than those from the richest neighbourhoods (5.52, 95% CI 5.13 to 5.93 vs 4.30, 95% CI 3.97 to 4.66). In urban areas vehicle occupant hospitalisation rates were similar among children from the poorest and richest neighbourhoods--but higher among children from middle income neighbourhoods. In urban areas, but not rural areas, the hospitalisation rate for pedestrians/cyclists systematically increased with decreasing neighbourhood income. In urban areas the pedestrian/cyclist hospitalisation rate was four times higher for children from the poorest (1.40, 95% CI 1.25 to 1.57) than from the richest (0.34, 95% CI 0.28 to 0.43) neighbourhoods. While vehicle occupant and pedestrian/cyclist motor vehicle traffic injuries are more frequent among children from lower income neighbourhoods, gradients are most pronounced for pedestrians/cyclists in urban areas.

[Toxicological-hygienic assessment of the low-alcohol tonic (energizing) carbonated drinks]. The impact of the low-alcohol tonic (energizing) carbonated drinks on biochemical and hematological indices, on the functional state of the central nervous system and cardiovascular system was studied within the experiment over the outbred white male rats. The gained results were compared to indices of animals receiving the same concentrated solution of ethanol used for drinks preparation as well as to figures of intact group animals. The results gained from all compared animals groups had no significant differences.

Genes associated to lactose metabolism illustrate the high diversity of Carnobacterium maltaromaticum. The dairy population of Carnobacterium maltaromaticum is characterized by a high diversity suggesting a high diversity of the genetic traits linked to the dairy process. As lactose is the main carbon source in milk, the genetics of lactose metabolism was investigated in this LAB. Comparative genomic analysis revealed that the species C. maltaromaticum exhibits genes related to the Leloir and the tagatose-6-phosphate (Tagatose-6P) pathways. More precisely, strains can bear genes related to one or both pathways and several strains apparently do not contain homologs related to these pathways. Analysis at the population scale revealed that the Tagatose-6P and the Leloir encoding genes are disseminated in multiple phylogenetic lineages of C. maltaromaticum: genes of the Tagatose-6P pathway are present in the lineages I, II and III, and genes of the Leloir pathway are present in the lineages I, III and IV. These data suggest that these genes evolved thanks to horizontal transfer, genetic duplication and translocation. We hypothesize that the lac and gal genes evolved in C. maltaromaticum according to a complex scenario that mirrors the high population diversity.

Short cardiac iodine-123-metaiodobenzylguanidine imaging protocol in heart failure. For assessment of cardiac sympathetic nervous activity, the conventional protocol for iodine-123-metaiodobenzylguanidine ((123)I-MIBG) imaging requires several hours. To establish whether it is possible to shorten the conventional (123)I-MIBG imaging protocol, anterior planar imaging was performed in 42 heart failure (HF) patients at 5, 15 and 180 min. The washout rate of (123)I-MIBG from 5 to 15 min (WR5-15 min) was calculated as a novel index. WR5-15 min closely correlated with the conventional washout rate and inversely correlated with the heart to mediastinum ratio. Univariate Cox analysis revealed that rapid WR5-15 min, augmented plasma B-type natriuretic peptide level, and decreased left ventricular ejection fraction (LVEF) were predictors for cardiac events. Multivariate analysis showed WR5-15 min and LVEF were independent predictors. The cardiac event rate was markedly higher (73%) in patients when both WR5-15 min and LVEF were abnormal. WR5-15 min obtained from anterior planar imaging is useful for evaluating the severity of HF and clinical outcome, and may shorten the cardiac (123)I-MIBG scintigraphy protocol.

Metal assisted catalyzed etched (MACE) black Si: optics and device physics. Metal-assisted catalyzed etching (MACE) of silicon (Si) is a controllable, room-temperature wet-chemical technique that uses a thin layer of metal to etch the surface of Si, leaving behind various nano- and micro-scale surface features, including nanowires (NWs), that can be tuned to achieve various useful engineering goals, in particular with respect to Si solar cells. In this review, we introduce the science and technology of MACE from the literature, and provide an in-depth analysis of MACE to enhance Si solar cells, including the outlook for commercial applications of this technology.

[Quantitative analysis in nuclear nephrourology: clearance, uptake and transit time]. Radionuclide renal study is only a method that can provide anatomical as well as functional information on the kidney. There have been many reports on quantification of the renal function using radionuclides. They are summarized to two groups: blood and/or urine sampling method and external counting method. The former is accurate and reproducible in quantification of the renal function, but is rarely applicable in a routine practice due to technical complexity. On the contrary, the external counting method by means of a gamma camera and dedicated computer system is simple and practical in a routine use, but is less in reliability of quantitated renal function than sampling method. In this paper, technical and diagnostic characteristics of the quantitative methods on renal function using the radionuclide are reviewed.

Modulation of swimming behavior in the medicinal leech. I. Effects of serotonin on the electrical properties of swim-gating cell 204. The effects of serotonin on the electrical properties of swim-gating neurons (cell 204) were examined in leech (Hirudo medicinalis) nerve cords. Exposure to serotonin decreased the threshold current required to elicit swim episodes by prolonged depolarization of an individual cell 204 in isolated nerve cords. This effect was correlated with a more rapid depolarization and an increased impulse frequency of cell 204 in the first second of stimulation. In normal leech saline, brief depolarizing current pulses (1 s) injected into cell 204 failed to elicit swim episodes. Following exposure to serotonin, however, identical pulses consistently evoked swim episodes. Thus, serotonin appears to transform cell 204 from a gating to a trigger cell. Serotonin had little effect on the steady-state current-voltage relation of cell 204. However, serotonin altered the membrane potential trajectories in response to injected current pulses and increased the amplitude of rebound responses occurring at the offset of current pulses. These changes suggest that serotonin modulates one or more voltage dependent conductances in cell 204, resulting in a more rapid depolarization and greater firing rate in response to injected currents. Thus, modulation of intrinsic ionic conductances in cell 204 may account in part for the increased probability of swimming behavior induced by serotonin in intact leeches.

Identification of a 3-gene model as a powerful diagnostic tool for the recognition of ALK-negative anaplastic large-cell lymphoma. Anaplastic large-cell lymphomas (ALCLs) are a group of clinically and biologically heterogeneous diseases including the ALK(+) and ALK(-) systemic forms. Whereas ALK(+) ALCLs are molecularly characterized and can be readily diagnosed, specific immunophenotypic or genetic features to define ALK(-) ALCL are missing, and their distinction from other T-cell non-Hodgkin lymphomas (T-NHLs) remains controversial. In the present study, we undertook a transcriptional profiling meta-analysis of 309 cases, including ALCL and other primary T-NHL samples. Pathway discovery and prediction analyses defined a minimum set of genes capable of recognizing ALK(-) ALCL. Application of quantitative RT-PCR in independent datasets from cryopreserved and formalin-fixed paraffin-embedded samples validated a 3-gene model (TNFRSF8, BATF3, and TMOD1) able to successfully separate ALK(-) ALCL from peripheral T-cell lymphoma not otherwise specified, with overall accuracy near 97%. In conclusion, our data justify the possibility of translating quantitative RT-PCR protocols to routine clinical settings as a new approach to objectively dissect T-NHL and to select more appropriate therapeutic protocols.

A Review of Regulations Applied to Spices, Herbs, and Flavorings-What Has Changed? A review of the world-wide regulations pertaining to spices, extracts, and flavorings. The areas covered include (1) guidance documents from trade organizations as well as international and regional regulatory bodies, (2) decontamination of spices and herbs, (3) extraction solvents used to make spice and herb oleoresins, and (4) general flavoring regulations. Specific links and references to guidance documents and regulations have been provided where they have been published on government, organization, and trade association websites.

Fat cell invasion in long-term denervated skeletal muscle. There are several differences between red and white muscles submitted to different experimental conditions, especially following denervation: a) denervation atrophy is more pronounced in red than white muscles; b) the size of the fibers in the red muscles does not vary between different parts of the muscle before and after denervation, when compared to white muscles; c) the regional difference in the white muscles initially more pronounced after denervation than red muscle; d) red muscle fibers and fibers of the deep white muscle present degenerative changes such as disordered myofibrils and sarcolemmal folds after long-term denervation; e) myotube-like fibers with central nuclei occur in the red muscle more rapidly than white after denervation. Denervation of skeletal muscles causes, in addition to fibers atrophy, loss of fibers with subsequent regeneration, but the extent of fat cell percentage invasion is currently unknown. The present article describes a quantitative study on fat cell invasion percentage in red m. soleus and white m. extensor digitorum longus (EDL) rat muscles at 7 weeks for up to 32 weeks postdenervation. The results indicate that the percentage of fat cells increase after denervation and it is steeper than the age-related fat invasion in normal muscles. The fat percentage invasion is more pronounced in red compared with white muscle. All experimental groups present a statistically significant difference as regard fat cell percentage invasion.

Biorhythms and possible central regulation of magnesium status, phototherapy, darkness therapy and chronopathological forms of magnesium depletion. Biological clock and magnesium status are linked. Central magnesium regulation may be hypothetized. Balanced magnesium status is requested to obtain efficiency of suprachiasmatic nuclei and of pineal gland. Conventional bright light therapy appears as a speedy and efficient antidepressant medication useful for the treatment of various types of depression, and of non migrainous headaches also. Although decrease in melatonin production seems accessory, increases of serotonergy and perhaps of Reactive Oxygen Species constitute the main mechanisms of action. Chromatotherapy emphazizes the effects of short exposure to specific colors. Although the increased production of melatonin constitutes the best marker of darkness, it is only an accessory mechanism of its action. The psycholeptic sedative effects of darkness, like those of magnesium, rely on direct membraneous and oxidant actions, neural mediated effects (i.e. stimulation of inhibitory neuromodulators such as GABA and taurine), and on antagonism of neuroactive gases (CO and NO). Darkness therapyper se, partial substitutive therapy with melatonin and with their mimicking agents (Mg, L-Tryptophan,Taurine) apply to all the chronopathological forms of magnesium depletion with decreased production of melatonin: sleep disorders, migraine, chronic fatigue syndrome, fibromyalgia, some forms of asthma and of sudden infant death syndrome. Further research should assess the importance of the chronopathological forms of magnesium depletion in the physiopathology of these disorders.

Sleeping money: investigating the huge surpluses of social health insurance in China. The spreading of social health insurance (SHI) worldwide poses challenges for fledging public administrators. Inefficiency, misuse and even corruption threaten the stewardship of those newly established health funds. This article examines a tricky situation faced by China's largest SHI program: the basic health insurance (BHI) scheme for urban employees. BHI accumulated a 406 billion yuan surplus by 2009, although the reimbursement level was still low. Using a provincial level panel database, we find that the huge BHI surpluses are related to the (temporarily) decreasing dependency ratio, the steady growth of average wages, the extension of BHI coverage, and progress in social insurance agency building. The financial situations of local governments and risk pooling level also matter. Besides, medical savings accounts result in about one third of BHI surpluses. Although these findings are not causal, lessons drawn from this study can help to improve the governance and performance of SHI programs in developing countries.

Status of antioxidant systems in human carcinoma of uterine cervix. Lipid peroxides, glutathione content and the activities of antioxidant enzymes were estimated in patients who had carcinoma of the uterine cervix, and the values were compared with those of normal. The results showed a remarkable reduction in glutathione content and in the activities of catalase and superoxide dismutase in neoplastic tissue in stages II, III and IV (P < 0.001) whereas the activities of glutathione peroxidase and glutathione reductase were significantly lower in stage III and IV patients than that of normal controls. The tissue level of lipid peroxides and the activity of glutathione-S-transferase were found to be significantly higher than that of normals from stage II onwards. These observations suggested the impaired antioxidant status in carcinoma of the uterine cervix.

Oxidative stress in stable cystic fibrosis patients: do we need higher antioxidant plasma levels? Oxidative stress plays an important role in cystic fibrosis (CF). However, there is a lack of validated biomarkers of oxidative damage that correlate with the antioxidant needs of patients with CF. To investigate oxidative stress in stable pediatric CF patients and evaluate if vitamin supplementation may be tailored to individual needs and oxidative status. Lipid-adducts 4-hydroxynonenal (HNE-L) and malonaldehyde (MDA-L) (chromolipids) were elevated in the majority of patients despite normal plasma vitamin E, A and C. HNE-L and MDA-L increased with age, while plasma vitamins decreased. The most relevant correlation was identified between vitamin C and chromolipids. Patients with pancreatic insufficiency (PI) showed significantly higher plasma chromolipids despite no differences in plasma vitamins. The majority of patients showed elevated plasma chromolipids that increased with age. Antioxidant vitamin reference ranges provide incomplete information on the redox status. CF patients with PI showed excessive oxidative stress damage.

The role of neopterin as a monitor of cellular immune activation in transplantation, inflammatory, infectious, and malignant diseases. The accumulated knowledge about the organization and function of the human immune system contributes to a better understanding of the pathogenesis of most diverse disorders and is opening new avenues for therapeutic regimens. To gain further insight into the complex interactions within the components of the immune system, it has become increasingly necessary to develop rapid and simple methods to monitor the status of the immune system in patients. The determination of neopterin concentrations in human body fluids allows to investigate sensitively the cell-mediated immune status to be investigated with considerable sensitivity. In recent years it was shown that production and release of neopterin is inducible in human monocytes/macrophages by interferon gamma. Increased neopterin levels indicate endogenous formation of gamma interferon, and monitoring of neopterin levels therefore permits the activation status of the cell-mediated immune system to be examined. Neopterin concentrations in serum and in urine increase in parallel to the clinical course of infections with viruses, intracellular bacteria, and parasites. In patients with human immunodeficiency virus infection neopterin concentration in serum and urine is a significant predictor of disease progression, the statistical power being similar to CD4+ T-cell numbers. In patients with autoimmune disorders, neopterin levels correlate with the extent and the activity of the disease. Neopterin concentrations are also sensitive indicators of immunological complications in allograft recipients. In certain malignant diseases neopterin concentrations correlate with the stage of the disease and bear prognostic information. Results of neopterin measurements agree with the important role that the cellular immune system plays in these disorders.

Socio-Economic Disparity is Not Linked to Outcome Following Heart Transplantation in New Zealand. Socio-economic deprivation (SED) is emerging as a risk factor for acute graft rejection (AR) and reduced survival of heart transplant (HT) recipients. The study aim was to evaluate any association between SED status of HT recipients and the development of early AR and long-term survival in New Zealand. This was a retrospective cohort study. Over a 30-year period, 329 HT recipients were identified from the Australian and New Zealand Heart Transplant Registry. All patients were divided into two groups according to the 2013 New Zealand Deprivation Index (NZDep2013) Score. Heart transplant recipients with NZDep2013 scores of 1,030 and above that corresponded to the eighth, ninth and tenth NZDep2013 deciles were allocated to the higher SED group and those with NZDep2013 scores below 1,030 to the lower SED group. The incidence of early AR in the higher SED group was 1.158/person-years and in the lower SED group 1.156/person-years. The crude incidence rate ratio was 1.0 (95% CI: 0.71-1.44; p = 0.9997). The prevalence of early AR in the higher SED group was 1.13/person-years and 1.15/person-years in the lower SED group. The crude prevalence rate ratio was 0.98/person-year (95% CI: 0.68-1.41/person-years; p = 0.468). In the higher SED group, mortality was 5.6/100 person-years (95% CI: 4.3-7.4/100 person-years) and 5.2/100 person-years (95% CI: 4.3-6.3/100 person-years) in the lower SED group. The adjusted mortality rate ratio estimate was 1.2 (95% CI: 0.8-1.7; p = 0.426). The higher and lower SED groups had similar survival (p = 0.196). Socio-economic disparity in New Zealand HT recipients has no negative impact on the development of AR or survival.

A randomized controlled trial of the NEAT expandable tip continence device. Urethral devices are one conservative management option for stress and mixed urinary incontinence, but there is little published data about their use. The aims of this study were to assess the safety and efficacy of a new urethral device (NEAT) and compare it with the Reliance Insert. The ease of use of both devices was then evaluated. Twenty-four women with mixed or stress urinary incontinence, patients at our tertiary care urogynecology unit and who met the inclusion and exclusion criteria, were enrolled in the study. Study subjects were blinded and randomly assigned to a device group. Device efficacy was assessed by pad weighing at 0 and 4 months. Success was defined as a 50% or greater reduction in urine loss using the formula 100[(pad weight without device -pad weight with device)/pad weight with device]. Safety was evaluated using urinalysis and urine cultures. Ease of use assessment scales were also completed. Eleven patients were randomized to the Reliance Insert and 13 to the NEAT device. There were no significant differences between the two groups in age, height, weight, duration of incontinence, pad weight, leakage score, parity or quality of life score. Based on the pad weight success formula, there was no significant difference in device success between the two groups at 4 months. Women who were postmenopausal had a trend towards a higher level of success in reduction of their pad weight. Previous treatment, diagnosis and hormone replacement therapy all had no relationship to device success. Leakage score data showed that subjects had a significant decrease in urine leakage when using either device. There was no statistically significant difference in ease of use between the two devices. Adverse symptoms most commonly noted were awareness of the device (62.5%), urgency (29.2%), and urethral discomfort or pain (20.8%). One urinary tract infection (UTI) was observed. The most common finding on urinalysis was trace hematuria (15.8%). Our conclusions are that the NEAT device appears to be at least as effective and safe as the Reliance Insert. Both devices are effective at decreasing urine leakage in patients with stress or mixed urinary incontinence. The risk of UTI is low, but these devices may cause trace hematuria.

Short-chain fatty acid enemas fail to decrease colonic hypersensitivity and inflammation in TNBS-induced colonic inflammation in rats. Short-chain fatty acid (SCFA) (especially butyrate) enemas are widely used to reduce symptoms associated with human inflammatory bowel disease. The purpose of this study was to evaluate their real effect on colonic sensitivity in rats. The effects of saline and SCFA enemas (acetate, propionate and particularly butyrate) were studied on visceral pain thresholds following colonic distension in control rats and in rats with colitis (instilled with trinitrobenzene sulfonic acid (TNBS)). Butyrate enemas (40 mM twice daily for 14 days) decreased colonic pain thresholds in control rats; they did not reduce the TNBS-induced hypersensitivity, but on the contrary increased its duration (without modifying the inflammation score). This pronociceptive effect was confirmed in control rats receiving twice daily enemas of 80 mM for 3 days and two enemas of 240 mM of a butyrate solution. The other SCFA enemas did not modify the hypersensitivity of rats with colitis and induced proinflammatory effects. The beneficial effect of SCFA (especially butyrate) enemas on hypersensitivity and inflammation in inflammatory bowel disease is questionable and needs to be thoroughly investigated in humans.

Stripping voltammetry in environmental and food analysis. The review covers over 230 papers published mostly in the last 5 years. The goal of the review is to attract the attention of researchers and users to stripping voltammetry in particular, its application in environmental monitoring and analysis of foodstuffs. The sensors employed are impregnated graphite, carbon paste, thick film carbon/graphite and thin film metallic electrodes modified in-situ or beforehand. Hanging mercury drop electrodes and mercury coated glassy carbon electrodes are also mentioned. Strip and long-lived sensors for portable instruments and flow through systems are discussed as devices for future development and application of stripping voltammetry.

Sacroiliac dysfunction in construction workers. In the literature of manual medicine the sacroiliac joint is widely accepted as a potential source of low back pain. On the other hand, some investigations have detected sacroiliac joint dysfunction without concomitant low back pain. The prevalence of sacroiliac dysfunction in the population has been noted in the medical literature to be between 19.3% and 47.9%. However, the prevalence of sacroiliac dysfunction in the general population and for construction workers is unknown. This article presents results from the Hamburg Construction Workers Study in respect to sacroiliac diagnostics. The prevalence of and connection between sacroiliac dysfunction and low back pain are particularly interesting. The sacroiliac joint diagnostics were studied in a cross-section investigation of a cohort of 480 male construction workers. Manual examination is the standard in the diagnostics of sacroiliac joint conditions at present. The assessment of sacroiliac joint function by standing flexion test, the spine test, the iliac compression test, and the iliac springing test was operationalized as two categories: sacroiliac dysfunction I and II. A prevalence of 29.0% was found for dysfunction I and 6.3% for dysfunction II, whereas a prevalence of 7.9% was found for the coprevalence of low back pain and sacroiliac dysfunction on the day of examination. This study demonstrated no statistical associations between low back pain and sacroiliac joint dysfunction. The reason why symptomatic and asymptomatic sacroiliac dysfunctions exist has not yet been sufficiently explained. The identification of pain-provoking factors should be the aim of subsequent investigations. A further study with a prospective design will be necessary to answer the questions that remain.

v-Src transformation is mediated through farnesylated proteins. Src is an oncoprotein which has been implicated in a number of human malignancies in which it has been shown to be overexpressed and highly activated. The precise mechanism of Src transformation, however, is still poorly understood. We hypothesized that Ras and other farnesylated proteins may mediate Src transformation. To test this hypothesis, v-Src-transfected rat fibroblasts (3Y1) were treated every 72 h with a 15 microM concentration of a farnesyl-transferase inhibitor (FTI). At 2 weeks, a focus formation assay was performed to assess transformation potential. Untreated and FTI-treated v-Src-transfected 3Y1 cells formed a mean of 39 (+/-2.6) and 29.8 (+/-2.9) foci per well, respectively. This 24% decrease was judged to be statistically significant (P = 0.02). Moreover, foci (>90%) in the FTI-treated wells were also consistently smaller than foci in the untreated wells. Western blots with antibody directed toward H-Ras confirmed complete inhibition of Ras farnesylation in the treated cell lines. The specificity of this inhibition was verified by Western blot using antibody specific for Rap1A. The transforming potential of v-Src is inhibited, but not eliminated by FTI treatment. This suggests that v-Src transformation is mediated in part by farnesylated proteins, one of which may be Ras.

Evolutionary implications of the frequent horizontal transfer of mismatch repair genes. Mutation and subsequent recombination events create genetic diversity, which is subjected to natural selection. Bacterial mismatch repair (MMR) deficient mutants, exhibiting high mutation and homologous recombination rates, are frequently found in natural populations. Therefore, we have explored the possibility that MMR deficiency emerging in nature has left some "imprint" in the sequence of bacterial genomes. Comparative molecular phylogeny of MMR genes from natural Escherichia coli isolates shows that, compared to housekeeping genes, individual functional MMR genes exhibit high sequence mosaicism derived from diverse phylogenetic lineages. This apparent horizontal gene transfer correlates with hyperrecombination phenotype of MMR-deficient mutators. The sequence mosaicism of MMR genes may be a hallmark of a mechanism of adaptive evolution that involves modulation of mutation and recombination rates by recurrent losses and reacquisitions of MMR gene functions.

[Distribution of admission costs]. This article is based on a system of information at hospital and departmental level (clinical-economical method of analysis). The method and its employment in planning adjustments to the increasing requirements have been reviewed in previous articles. The analysis may also be employed for description of the expenses involved in admission of various patients groups, one of the objects being review of the employment of resources in departments and hospitals and their relationships to the composition of the patients populations involved. Some of the results of description of the expenses from Ringkøbing Hospital in 1988 are demonstrated.