Selective, switchable fluorescent probe for heparin based on aggregation-induced emission.
A positively charged tetraphenylethene (TPE) derivative, TPE-4MN, was synthesized as a probe for heparin based on aggregation induced emission. On the addition of 5.0 μg/mL of heparin, TPE-4MN showed an enhanced emission of about 10-fold. The change in fluorescence at 475 nm was linear over a range of heparin concentrations of 0-1.0 μg/mL with an R = 0.99988 and the limit of detection (LOD) was calculated to be 0.75 μg/mL. The mechanism of the detection was proven to be through an ion pairing interaction. TPE-4MN showed good selectivity for heparin over other types of polysaccharides and could easily distinguish heparin from heparan sulfate, a glycosaminoglycan having a similar structure to that of heparin.


Dried blood spot analysis of (+) and (-) darunavir enantiomers on immobilized amylose tris-(3, 5-dimethylphenylcarbamate) LC and its application to pharmacokinetics.
Dried blood spot analysis is an innovative novel blood sampling technique gaining interest in drug discovery and development processes owing to its inherent advantages over the conventional whole blood, plasma or serum sample collection. The present manuscript describes the development and validation of a highly sensitive and precise method of evaluation of pharmacokinetics of (+) and (-) darunavir enantiomers on rat dried blood spots. The enantiomers on rat dried blood spots were extracted into methanol and separated by LC on a Chiralpak IA column using hexane and ethanol containing 0.1% DEA (75:25, v/v) as a mobile phase at 20°C; both the enantiomers were detected at 266 nm using a photodiode array detector. The method was validated in terms of selectivity, linearity, accuracy, precision and stability as per the US Food and Drug and Administration guidelines. The hematocrit effect on extraction recovery was evaluated and the mean recoveries of (-) and (+) enantiomers of darunavir from dried blood spots were found to be 85.76 and 88.91% respectively. The intra- and inter-day precision and accuracy were 3.1-8.4 and 0.8-4.8% respectively. The developed method was successfully applied to a pharmacokinetic study of (+) and (-) enantiomers of darunavir on rat dried blood spots.


A simple new method to calculate small intestine absorptive surface in the rat.
The rat is an established model for studying intestinal adaptations following abdominal surgery. In the study of functional and morphological adaptations of the small intestine, it is helpful to estimate the mucosal surface area. In order to simplify measurements and calculation we developed a new mathematical model for calculation of the mucosal surface area on histological sections. In contrast to other methods, it requires only cross-sections of small intestine and includes the measurement of only three histological parameters: length and width of villus and width of crypt. The new approach was compared with the most commonly used procedures, the Harris and the Fisher-Parsons methods, under experimental conditions. An animal study including single-pass perfusion, fixation, staining and subsequent histomorphometry of jejunum and ileum using these different methods was performed. The new method showed the least work and presented no significant differences compared with the precise Harris method. In conclusion, the method described is an adequate tool to estimate the mucosal surface area with less work and with comparable results to established methods. The less-complex method may be a valuable tool in experimental research of small intestine adaptations in rats.


[Tinea pedis and Onychomycosis in Children of the Mazahua Indian Community in Mexico].
Tinea pedis and onychomycosis in childhood are unusual, The previous reported prevalence range from 4.2 to 8.2%. In a mestizo population, in the South of Mexico a 3.4% has been found. To determine the frequency of dermatophytosis of feet and toenails in scholars in an Indian Mazahua community. A total of 456 children were studied. The age range from 5 to 15 years of age (average 11.4). Only 71 children with suggestive lesions of dermatophytosis were studied (15.57%). Mycological samples (66/71) and a KOH and Chlorazol black, and cultures on Mycocel agar were performed. 71 children (15.57%) presented suggestive lesions of dermatophytosis of the feet and toenails. A fungal infection was demonstrated in 13 cases (18%), 8 males and 5 females (mean age 12.3 years), but pathogenic fungi were isolated only in 7 (10%). All of them with tinea pedis and three also had toenail involvement (4.2%) and also Trichosporon sp was isolated in two cases and Candida albicans in one. We found a low frequency of tinea pedis and onychomycosis in children from this Mazahua community. The environmental factors such as humidity, and the frequently use of rubber and leather shoes instead of the traditional "huarache" (sandals), make them prone to maceration and can be cofactors in the development of mycotic infections and in the high incidence of pitted keratolysis (29.5%).


Lymphoma study group of JCOG.
The Lymphoma Study Group (LSG) of the Japan Clinical Oncology Group (JCOG) was initiated in 1978 by five institutions and now has 47 members. JCOG-LSG has focused on combined modalities, dose intensification and the incorporation of new agents for major disease entities of lymphoid malignancies. More than 30 trials including 10 randomized trials have been conducted for aggressive non-Hodgkin's lymphoma (NHL), adult T-cell leukemia-lymphoma (ATL), lymphoblastic lymphoma/acute lymphoblastic leukemia, Hodgkin's lymphoma (HL), multiple myeloma, NK/T-NHL and indolent B-NHL, and correlative epidemiological and pathological studies have been performed on human T-lymphotropic virus type-I and T/B cell phenotypes. The first trials for aggressive NHL revealed significant differences in the prognosis of ATL, non-ATL T-NHLs and B-NHLs, establishing a subclassification of ATL, and leading to the establishment of standard therapies for ATL and localized nasal natural killer/T-NHL. Recently, for B-NHLs including diffuse large B-cell lymphoma, mantle cell lymphoma, and indolent B-NHLs, regimens incorporating rituximab have been evaluated. The JCOG-LSG trials for HL led to the approval of dacarbazine for the National Health Insurance in Japan. The multicenter trials by the JCOG-LSG combining new modalities such as molecular-targeting agents will contribute to further improvements in the treatment of lymphoid malignancies.


Family roots of empathy-related characteristics: the role of perceived maternal and paternal need support in adolescence.
Theories on empathy development have stressed the role of socialization in general and the role of parental support in particular. This 3-wave longitudinal study of middle adolescents (N = 678) aimed to contribute to the extant research on the socialization of empathy (a) by examining the relative contribution of perceived maternal and paternal need supportive parenting on over-time changes in adolescents' emotional and cognitive aspects of empathy (i.e., empathic concern and perspective taking, respectively) and (b) by considering the possibility of reciprocal relations between perceived parenting and adolescent empathy. Whereas paternal need support consistently predicted over-time changes in perspective taking in both sons and daughters, perceived maternal need support predicted changes in empathic concern among daughters only. In addition, although less consistently so, empathy dimensions also predicted over-time changes in perceived parenting. Results are discussed in terms of the nature of empathy and in the light of domain-specific effects of each parent.


Spread of poxviruses in livestock in Brazil associated with cases of double and triple infection.
The objective of this work is to describe the distribution of outbreaks of vaccinia virus (VACV), pseudocowpox virus (PCPV), and bovine papular stomatitis virus (BSPV) in Brazil. The Official Laboratory of the Brazilian Ministry of Agriculture received 89 samples from different locations in Brazil in 2015 and 2016 for diagnosis of vesicular and exanthematous disease. Poxvirus coinfections occurred in 11 out of 33 outbreaks, including the first reported triple infection by BPSV, PCPV, and VACV. This occurrence may be associated with the circulation of these viruses in Brazilian cattle.


Modified constraint-induced therapy in patients with chronic stroke exhibiting minimal movement ability in the affected arm.
The purpose of this study was to determine the efficacy of a reimbursable, outpatient modified constraint-induced therapy (mCIT) protocol administered to subjects with chronic stroke who initially exhibited minimal movement ability in their affected wrists and fingers. The subjects were 4 individuals who had experienced a stroke more than 1 year prior to study entry (mean age [+/-SD]=60.25+/-1.98 years, mean time since stroke=37.5+/-23.2 months). A multiple-baseline, preintervention-postintervention, single-blinded case series design was used. The intervention consisted of structured, 1/2-hour therapy sessions emphasizing affected arm use in valued activities, occurring 3 times per week for 10 weeks. Subjects' less affected arms also were restrained 5 days per week for 5 hours per day during the same 10-week period. The main outcome measures were the Action Research Arm Test (ARAT), the Motor Activity Log (MAL), and the Fugl-Meyer Assessment of Motor Recovery (FM). The subjects exhibited improvements in use of the more affected arm (+1.9, +1.8, +1.7, and +2.3 for subjects 1 through 4, respectively) and in quality of movement (+1.5, +2.1, +1.63, and +1.9 for subjects 1 through 4, respectively), as measured by the MAL. They also exhibited reduced impairment, as measured by the FM (+5.0, +6.5, +5.5, and +5.0 for subjects 1 through 4, respectively), and increased fine motor skill movement, as measured by the ARAT (+7.5, +7.0, +7.0, and +5.5 for subjects 1 through 4, respectively). The findings demonstrated that mCIT participation was efficacious because it led to increased use of the affected arm and of function and to increased ability to perform valued activities. The subjects reported some new ability to perform some valued activities. These outcomes are significant because few therapies are believed to effectively increase use of the affected arm and function in this population.


High reliability transformation of the basal fungus Mucor circinelloides by electroporation.
Molecular approaches to study the biology of the zygomycete Mucor circinelloides depend mainly on the existence of a polyethylene glycol-based transformation method, which is one of the most efficient in zygomycete fungi. However, the poor reliability and low transformation rates of this method are major obstacles in the molecular study of a number of biological processes. This paper describes an easy and reliable method to transform M. circinelloides protoplasts by electroporation. A high-voltage pulse of 25μF capacitance, 400Ω resistance, and 4kV/cm field strength were seen to be the optimal electrical conditions for delivering DNA into M. circinelloides protoplasts. Under these electrical conditions, successful transformations were carried out with several self-replicative plasmid and strain combinations, producing up to more than 500 transformants per μg DNA. Targeted DNA integration of a transgene (atfA gene of Acinetobacter baylyi) in a particular locus (carRP) was also achieved. This transformation method will considerably facilitate in-depth molecular genetic studies of the biology of this fungus.


Recurrence of multicystic ameloblastoma in soft tissue.
Ameloblastoma is characteristically considered to be a benign but locally aggressive and infiltrative odontogenic tumour with a high recurrence rate. Most recurrences of the solid or multicystic ameloblastoma occurred at the edges of the initial tumour or at the bony cavity left after the excision of a tumour. A case of an isolated soft tissue recurrence of ameloblastoma of the mandible in a 58-year-old man is presented. The report illustrates the need to take into consideration the adjacent soft tissue in cases of tumour with cortical bone perforation during surgical treatment. This is especially important in an environment where patients are not likely to attend follow-up review for a long period. It also demonstrates the ability of intraosseous ameloblastoma to grow in soft tissues.


Use of natural products as green reducing agents to fabricate highly effective nanodisinfectants.
Disinfection of water using nanoparticles (NPs) can be achieved through selection of either metals (M) or transition metal oxides (TMO). In this research, 64 formulations of silver-titania nanocomposites (Ag/TiO2) were prepared via a feasible wet-chemistry technique using different natural products as reducing agents. Four selected products successfully reduced Ag(+) ions to Ag, allowing Ag/TiO2 composite to efficiently inactivate microbes found in the activated sludge. The degree of antibacterial activity was measured using zone of inhibition, which indicated all formulations inactivated the bacteria with high potency (0.01 I/6 h). The results from this study and comparison of literature values collectively suggest that light roasted coffee acted as one of the best natural reducing agents due to its low antioxidant index (LAI). Our selection framework also suggested any M/TMO with an oxygen reduction potentials (ORP) range of -0.41 to +1.23 V and any natural product with a LAI (<0.5) would be suitable as a reducing agent. Collectively, the high ORP and low AI provide effective disinfection of water-borne microbes.


Peptide-modified optical filters for detecting protease activity.
The organic derivatization of silicon-based nanoporous photonic crystals is presented as a method to immobilize peptides for the detection of protease enzymes in solution. A narrow-line-width rugate filter, a one-dimensional photonic crystal, is fabricated that exhibits a high-reflectivity optical resonance that is sensitive to small changes in the refractive index at the pore walls. To immobilize peptide in the pore of the photonic crystal, the hydrogen-terminated silicon surface was first modified with the alkene 10-succinimidyl undecenoate via hydrosilylation. The monolayer with the succinimide ester moiety at the distal end served the dual function of protecting the underlying silicon from oxidation as well as providing a surface suitable for subsequent derivatization with amines. The surface was further modified with 1-aminohexa(ethylene glycol) (EG(6)) to resist nonspecific adsorption of proteins common in complex biological samples. The distal hydroxyl of the EG(6) is activated using the solid-phase coupling reagent disuccinimidyl carbonate for selective immobilization of peptides as protease recognition elements. X-ray photoelectron spectroscopy analysis reveals high activation and coupling efficiency at each stage of the functionalization. Exposure of the peptide-modified crystals to the protease subtilisin in solution causes a change in the refractive index, resulting in a shift of the resonance to shorter wavelengths, indicating cleavage of organic material within the pores. The lowest detected concentration of enzyme was 37 nM (7.4 pmol in 200 microL).


Triamcinolone suppresses human tenocyte cellular activity and collagen synthesis.
Glucocorticoid injection is widely used in tendon disorders. Despite previous studies on the histologic and biomechanical changes in tendons after glucocorticoid injections, the role of glucocorticoid in tendon rupture still is controversial. It was hypothesized that glucocorticoid has a direct deleterious effect on human tenocytes, suppressing its cellular activity and collagen production. Primary cultures of human tenocytes were obtained from explants of healthy patellar tendon harvested during anterior cruciate ligament reconstructions. The effects on cell viability and cell proliferation were measured by [3-(4,5-demethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and 5-bromo-deoxyuridine incorporations. The effect on collagen synthesis was measured by H-proline incorporation assay. Triamcinolone acetonide at 10 to 10 mol/L decreased human tenocyte viability to 45% to 88% of control in a dose-dependent manner. Cell proliferation was suppressed to 87% +/- 8% at all doses. Treatment with 1 micromol/L triamcinolone acetonide reduced the amount of collagen synthesis as measured by H-proline incorporation from 40 +/- 2 cpm/1000 cells to 27 +/- 4 cpm/1000 cells. The suppressed human tenocyte cellular activity and reduced collagen production may lead to disturbed tendon structure and predispose the tendon to subsequent spontaneous rupture.


Enhanced apoptosis of glioma cell lines is achieved by co-delivering FasL-GFP and TRAIL with a complex Ad5 vector.
Brain tumors (BTs) are among the most malignant forms of human cancer. Unfortunately, current treatments are often ineffective and produce severe side effects. Cytotoxic gene therapy is an alternative treatment strategy, with the potential advantages of reduced toxicity to normal brain tissue. Apoptosis-inducing "death ligands" Fas ligand and TNF-related apoptosis-inducing ligand (TRAIL) are genes with substantial cytotoxic activity in susceptible tumor cells. Here, we compared the effectiveness of Ad vector-mediated delivery of Fas ligand-green fluorescent protein (FasL-GFP) fusion protein, human TRAIL, and both genes simultaneously. We examined a panel of 13 cell lines (eight derived from primary isolates) for susceptibility to Ad5-based vector infection and for sensitivity to FasL- and TRAIL-mediated apoptosis. All cell lines were efficiently transduced, but, as expected, varied in their sensitivity to ligand-induced apoptosis. Generally, sensitivity to FasL-GFP correlated with cell surface FasR levels, but no such correlation was seen for TRAIL and its functional receptors, DR4 and DR5. The vector expressing both FasL-GFP and TRAIL was more effective than either of the single-gene vectors at comparable transduction levels, and it was effective against a broader range of cell lines. In five cell lines, coexpression resulted in apoptosis levels greater than those predicted for strictly additive activity of the two death ligands. We believe that Ad vector-mediated delivery of multiple death ligands may be developed as a potential BT therapy, either alone or in conjunction with surgical resection of the primary tumor.


Genotoxicity, carcinogenicity and acid-suppressing medications.
With the availability of increasingly potent acid-suppressing medications, questions continue to rise concerning the safety of these compounds in regards to carcinogenetic potential. In this review, we examine current concepts and procedures relating to genotoxicity, the potential for a chemical agent to interact with and alter the genomic information of the cell, and carcinogenesis. A description and discussion of commonly utilized techniques for the determination of (a) in vitro mutagenicity, (b) in vitro and in vivo DNA damage and repair, (c) in vitro and in vivo chromosomal damage and (d) chronically dosed animal tumorigenesis development is presented. Observations from these procedures as they have been applied to a review of the safety of acid-suppressing medications will be discussed. An evaluation of reports relating to potential genotoxic and carcinogenic hazards of therapeutically relevant acid-suppressing medications (cimetidine, ranitidine, omeprazole) is presented. Information related to the effect of prolonged administration of acid-suppressing medications, alterations of serum gastrin levels, and the potential for tumor promotion is discussed.


[A simulating excorporeal experimental system for automatic drug injection based on predictive control in vascular interventional therapy].
This paper discusses an in vitro simulating experiment for drug injection based on predictive control in vascular interventional therapy. The relationship between the model of drug injection and the pulsatile blood flow was studied. The experimental model for predictive control of drug injection was tested and verified so as to support the future animal experimental modeling with the data acquired from the in vitro simulating experiment.


[New strategy on medical research after completion of genome sequencing].
Real advances in biotechnology made it possible to complete human whole genome sequencing within a short duration. Although the genome includes a huge amount of information about biological functions and the interest is now directed to the study using genomic information, the genomic strategy is not clearly understood. The following 4 studies were therefore presented and discussed about the strategy after the completion of the genomic sequence in the 74th Annual Meeting of Japanese Pharmacological Society: 1) Asthma and atopic dermatitis: models for genetic and genomic investigations of complex genetic diseases, by W.C.O. Cookson (University of Oxford, Asthma Genetics Group, Wellcome Trust Centre for Human Genetics); 2) Molecular classification by global gene expression profiling: application on oncogenomic research, by H. Aburatani (Genome Science Division, Research Center for Advanced Science and Technology, University of Tokyo); 3) Functional genomic search of disease-related genes using microarrays with normalized rat cDNA library, by G. Tsujimoto, et al. (Department of Molecular, Cell Pharmacology, National Children's Medical Research Center: and 4) Acute ischemic change of mRNA expression in the hippocampus by GeneChip array analysis: a starting point for post-genome strategy, by S. Asai, et al.


Effects of surface roughness on self- and transport diffusion in porous media in the Knudsen regime.
The effect of surface roughness on Knudsen diffusion in nanoporous media is investigated by means of dynamic Monte Carlo simulations in three-dimensional rough fractal pores. These simulations yield new insight and explain a number of apparent inconsistencies by revealing a striking difference between the roughness dependence of transport diffusion and gradientless (self- or tracer) diffusion. Both analytical and simulation results show a significant roughness dependence of self-diffusion in the Knudsen regime. Transport diffusion, on the other hand, is roughness independent, as the fluxes do not depend on the detailed residence time and molecular trajectories.


Effects of Moringa oleifera leaf extract on growth performance, physiological and immune response, and related immune gene expression of Macrobrachium rosenbergii with Vibrio anguillarum and ammonia stress.
In order to study the effects of Moringa oleifera leaf extract on Macrobrachium rosenbergii under high ammonia exposure, freshwater prawns were randomly divided into five groups: a control group was fed with basal diet, and four treatment groups fed with basal diet supplemented with 0.25%, 0.5% and 1.0% M. oleifera leaf extract and 0.025% Enrofloxacin for 60 days, respectively. Then, freshwater prawns were exposed to high ammonia stress for 72 h and Vibro anguillarum infection. The growth, antioxidant capabilities, related immune genes as well as resistance to infection by V. anguillarum were determined. The results showed that compared with the control group, the weight gain, specific growth rate and protein efficiency rate, haemolymph catalase (CAT), superoxide dismutase (SOD) and inducible nitric oxide synthase (iNOS) increased while feed conversion ratio, haemolymph aspartate aminotransferase, alanine aminotransferase, nitrogen oxide (NO), hepatopancreas heat shock proteins (HSP70), immune deficiency (IMD) expression levels decreased in the group of 0.5% M. oleifera leaf extract before the stress. After ammonia stress, the group of 0.5% M. oleifera leaf extract also could improve the haemolymph SOD, glutathione peroxidase, NO, iNOS, hepatopancreas HSP70 expression levels and reduce haemolymph CAT, hepatopancreas peroxiredoxin 5 and NF kappa B inhibitor alpha expression level compared with the control group. The rate of mortality of the prawns challenged with V. anguillarum was lower in the supplemented groups in comparison with the control group with the lowest being in the group of 0.5% M. oleifera leaf extract. Antioxidant activities as well as biochemical parameters in the enrofloxacin group (0.025%E) were not significantly enhanced both pre and post challenge in comparison with the M. oleifera leaf extract groups, showing the superiority of the natural herb over the synthetic antibiotic. In summary, this study suggested that at an inclusion rate of 0.5%, M. oleifera leaf extract could increase the growth performance, even has positive effects on physiological and immune function and prevents high ammonia stress in the Freshwater prawn, M.rosenbergii.


Folate-related genes and the risk of tobacco-related cancers in Central Europe.
Folate has been hypothesized to protect against aero-digestive cancers although the evidence is not yet conclusive due to possible confounding by other dietary factors. Sequence variants in folate pathway were suggested to be associated with plasma folate levels and are unlikely to be confounded by other lifestyle factors. We therefore investigated the effects of key folate genetic variants on the risk of aero-digestive cancers and their potential effect modification by folate intake in a multicenter study in Central Europe. A total of 2250 lung cases, 811 upper aero-digestive tract cases and 2899 controls were recruited with blood samples. The methylenetetrahydrofolate reductase (MTHFR) C677T variant was associated with an increased risk of lung cancer with an odds ratio (OR) for homozygote variant of 1.37 [95% confidence interval (CI) = 1.10-1.71]. The two MTHFR variants were in strong linkage disequilibrium, and 677T-1298A appeared to be the primary haplotype associated with cancer risk. The risk estimates for MTHFR 677T/677T genotype was more prominent among lung cancer patients with young onset (OR = 1.92, 95% CI = 1.12-3.29). When stratified by dietary intake of folate, the effect of the MTHFR 677T variant was more prominent among subjects with low intake of folate: the ORs for 677T/677T genotype among subjects with the lowest decile were 2.60 (95% CI = 1.39-4.88) and 4.14 (95% CI = 1.47-11.7) for lung and upper aero-digestive tract cancer, respectively. In conclusion, we identified a moderate effect of MTHFR C677T on lung cancer risk and a possible effect modification by folate intake that is consistent with the functional data. These results support an important role of folate in protecting against tobacco-related cancers.


Alcohol, marijuana, and perceptions of influence on social and sexual behavior among African American adolescent female detainees.
Juvenile detainees comprise a population that engages in high-risk behavior. This study examined sexual risk and substance use behavior and the perceptions of African American female adolescent detainees (N = 765) regarding the influence of alcohol and marijuana use on their social and sexual behaviors. Overall, 58% and 64% reported alcohol and marijuana use, respectively. Alcohol's perceived influence on sexual behavior (p < .001) was significantly different between those who drank and those who did not; marijuana's influence on social (p < .01) and sexual (p < .001) behavior was significantly different between those who used marijuana and those who did not. There is a need for further study of the influence of substance use on social and sexual behavior among African American female adolescent detainees.


[Sunitinib and hypothyroidism].
Sunitinib inhibits numerous tyrosine kinase receptors involved in tumor growth, angiogenesis, and metastatic invasion. It is indicated in case of metastatic renal carcinomas and gastrointestinal stromal tumors (GIST) resistant to imatinib. Prospective and retrospective studies have shown association between use of sunitinib and hypothyroidism affecting more than 50% of patients in some series. More amazing, was the non-visualisation of thyroid tissue evaluated with thyroid ultrasonography in two cases. Mechanisms of this side effect are not elucidated. Some studies have suggested destructive thyroiditis but no evidence of autoimmunity has been demonstrated. Anti angiogenic effect could be another hypothesis. Recently antithyroperoxidase activity of sunitinib has been demonstrated. Because hypothyroidism is easily accessible to treatment, screening of thyroid abnormalities is mandatory every three months to improve quality of life of these patients. This unique thyroid side effect of sunitinib with the non-visualisation of thyroid suggests a possible and promising antitumor activity in thyroid cancer.


No influence of patellar fixation technique on clinical outcomes of double-bundle medial patellofemoral ligament reconstruction: a systematic review.
To compare clinical outcomes of double-bundle medial patellofemoral ligament (MPFL) reconstruction with different patellar fixation techniques including Kujala score, functional failure and complications. Pubmed, Embase, and Cochrane Library databases were searched for studies with clinical results of double-bundle MPFL reconstruction. The hamstring tendon autografts were used, and femoral fixation was performed with bone tunnel and an interference screw, and knee fixation angle was less than or equal to 45°. Patellar fixation methods were broadly categorized into 3 treatment groups: suture anchor (SA), bone tunnel (BT) and suture techniques (SU). Pooled means for Kujala score and pooled estimates for functional failure rate and complication rate were compared. 21 studies (23 groups) consisting of 691 knees met the inclusion criteria. 12 groups with 344 knees were in SA group, 5 groups of 161 knees were in BT group and 6 groups with 186 knees were in SU group. Statistically significant differences in Kujala score were found among three groups, 90.2 (95% CI 88.7-91.7) in SA group, 88.7 (95% CI 85.3-92.2) in BT group and 89.4 (95% CI 84.2-94.6) in SU group (all P < 0.001), but these differences were not clinically significant. No statistically significant differences were found in the positive apprehension sign rate, recurrent subluxation or dislocation rate, and major or minor complication rate among three groups. Patellar fixation with bone tunnel, suture anchor or suture techniques were all effective in the double-bundle MPFL reconstruction. The present systematic review failed to show that one technique was better than the others. More high-quality trials and randomized controlled trials are needed.


Outcome of kidney transplantation in Canadian Aboriginal children in the province of British Columbia.
Renal transplantation remains the therapy of choice for children and adolescents with ESRD. Differences in graft survival are observed in kidney transplant recipients of different race and ethnicities. Data in pediatric populations are limited and confounded by disparities in access to health care. We performed a retrospective single Canadian centre database review to determine the short- and long-term outcomes of kidney transplantation in Aboriginal children compared to non-Aboriginals. A total of 159 primary renal transplant recipients at BCCH between 1985 and 2005 were examined (15% Aboriginal). Aboriginal children had different etiologies of ESRD, and a higher percentage of females, but were similar in age at transplantation, cold ischemia time and living donation rate. Early graft outcomes such as delayed graft function, episodes of acute rejection in the first year post-transplant and estimated glomerular function rate at one yr were similar in both groups. Long-term graft survival, however, was significantly worse in the Aboriginal group, with a significantly increased rate of late rejections: 50% compared with 26.7% among non-Aboriginals (p = 0.03). In a province with uniform access to health care, significant differences in long-term graft outcome exist among Aboriginal children compared with non-Aboriginals.


Immune responses evoked by infection with Vibrio anguillarum in zebrafish bath-vaccinated with a live attenuated strain.
Live attenuated vaccines are a promising application to control bacterial fish diseases. A live attenuated Vibrio anguillarum vaccine candidate was established in our laboratory to protect fish against vibriosis. To elucidate the mechanism of immunoprotection, it is necessary to compare the different immune responses to infection between vaccinated and non-vaccinated fish. In this study, the expression levels of pathogen-specific antibodies and immune-related genes upon challenge at 28 days post-vaccination were compared between vaccinated and non-vaccinated zebrafish. In the results, the specific antibody levels against virulent V. anguillarum in the vaccinated group did not rise significantly following infection, which suggested that high-affinity antibodies were induced by the vaccine. In the non-vaccinated group, the specific IgM response was triggered at 3 days post-infection and showed a delayed antibody response. Meanwhile, the transcription levels of the genes encoding the pro-inflammatory cytokine IL-1β and the chemokine IL-8 were more highly up-regulated in non-vaccinated fish than in vaccinated fish. This suggests that the overwhelming inflammatory response trigged by infection in non-vaccinated zebrafish was controlled in vaccinated zebrafish. Interestingly, the expression levels of adaptive immune-related genes were increased in vaccinated fish after challenge, compared to the non-vaccinated fish. These results suggest that inoculation with the live attenuated vaccine triggered protection by curbing inflammation and strengthening the adaptive immune response.


Diabetes in Indigenous Australians: possible ways forward.
Reducing the burden of diabetes will require action well beyond the health service sphere.


The therapeutic potential of renin angiotensin aldosterone system (RAAS) in chronic pain: from preclinical studies to clinical trials.
The prevalence rate of chronic pain is 15% to 25% in adults while the therapeutic arsenal is still insufficient, especially in relieving neuropathic pain. Peripheral pain transmission is conducted by the small Aδ and C sensory nerve fibres. They express elements from the renin-angiotensin-aldosterone system (RAAS), a well-known blood pressure regulator. Recently, studies have demonstrated the role of angiotensin II, its derivatives and aldosterone in the modulation of pain perception, by interacting with receptors expressed by sensory nerve fibres or through the central nervous system. Here, we assess the effects of RAAS modulators in the conduction of pain with molecular, preclinical and clinical approaches, in normal or pathological conditions. Currently, some clinical studies have been carried out on the pain-relieving effect of RAAS modulators and suggest their potential in the management of chronic, inflammatory or neuropathic pain.


Skin lysyl oxidase activity is not rate limiting for collagen crosslinking in the glucocorticoid-treated rat.
Lysyl oxidase activity in the skin of rats receiving triamcinolone diacetate (12 mg/kg) for three consecutive days was decreased by sixty-four percent as compared to control values. A decrease of lysyl oxidase activity was observed twelve hours after the initial glucocorticoid injection. The decreased lysyl oxidase activity was accompanied by a forty-nine percent decrease of acetic acid extractable collagen. There was also a forty-two percent decrease in the alpha/beta ratio of the acetic acid soluble skin collagen of glucocorticoid-treated animals. These data indicate that although skin lysyl oxidase activity is decreased by glucocorticoid treatment, the crosslinking of acid extracted collagen as measured by the alpha/beta ratio and collagen solubility is increased. Accordingly lysyl oxidase activity is not rate limiting for collagen crosslink formation in the skins of rats treated with glucocorticoids.


Trans-obturator-tape procedure--"inside out or outside in": current concepts and evidence base.
Surgical treatment of female stress urinary incontinence has become very popular as a consequence of the good results given by the minimally invasive tension-free vaginal tape. This has attracted great attention from industry, resulting in a proliferation of new slings and different implantation techniques. This review focuses on published literature on the two trans-obturator procedures, outside in or inside out, recently described. Tension-free vaginal tape was originally reported as a very safe procedure. However, analyses performed in Scandinavia and Austria and several clinical case reports have emphasized the risk of serious complications, related to the penetration of the retropubic space. Two new surgical approaches have been introduced maintaining the position under the mid-urethra of the tension-free vaginal tape but reducing or even eliminating complications related to the penetration of the retropubic space by placing the tape between the two obturator foramens, from outside to inside or from inside to outside. Efficacy reported results are very close to those reported in most of the observational series of tension-free vaginal tape. Both trans-obturator procedures have been reported with very few complications. Anatomical dissections have shown that these two procedures can be very safe, but that the tip of the tunneller could injure the bladder, the urethra or the obturator pedicle. Surgeons have to respect the key points of the procedures. No evidence-based conclusion can yet be drawn on these two procedures. Long-term follow-up trials and tracker studies including very large cohorts of patients are needed.


Comparison of total intravenous anesthesia vs. inhalational anesthesia on brain relaxation, intracranial pressure, and hemodynamics in patients with acute subdural hematoma undergoing emergency craniotomy: a randomized control trial.
The major goals of anesthesia in patients with severe traumatic brain injury (TBI) are-maintenance of hemodynamic stability, optimal cerebral perfusion pressure, lowering of ICP, and providing a relaxed brain. Although both inhalational and intravenous anesthetics are commonly employed, there is no clear consensus on which technique is better for the anesthetic management of severe TBI. Ninety patients, 18-60 years of age, of either gender, with GCS < 8, posted for emergency evacuation of acute subdural hematoma were enrolled in this prospective trial, and they were randomized into two groups of 45 each. Patients in group P received propofol infusion at 100-150 mg/kg/min for maintenance of anesthesia and those in group I received ≤ 1 MAC of isoflurane. Hemodynamic parameters were monitored in all patients. ICP was measured at the dural opening and brain relaxation was assessed by the operating surgeon on a four-point scale (1-perfectly relaxed, 2-satisfactorily relaxed, 3-firm brain, and 4-bulging brain) at the dural opening. It was reassessed at dural closure. Brain relaxation, both at dural opening and closure, was significantly better in patients who received propofol compared to those who received isoflurane. ICP was significantly lower (25.47 ± 3.72 mmHg vs. 23.41 ± 3.97 mmHg) in the TIVA group. Hemodynamic parameters were well maintained in both groups. In patients with severe TBI, total intravenous (Propofol)-based anesthesia provided better brain relaxation, maintained a lower ICP along with better hemodynamics when compared to inhalational anesthesia. Clinical trials registry (NCT03146104).


Genotypic heterogeneity and phenotypic mimicry among unrelated patients referred for catecholaminergic polymorphic ventricular tachycardia genetic testing.
Mutations in the RyR2-encoded cardiac ryanodine receptor/calcium release channel and in CASQ2-encoded calsequestrin cause catecholaminergic polymorphic ventricular tachycardia (CPVT1 and CPVT2, respectively). The purpose of this study was to evaluate the extent of genotypic and phenotypic heterogeneity among referrals for CPVT genetic testing. Using denaturing high-performance liquid chromatography and DNA sequencing, mutational analysis of 23 RyR2 exons previously implicated in CPVT1, comprehensive analysis of all translated exons in CASQ2 (CPVT2), KCNQ1 (LQT1), KCNH2 (LQT2), SCN5A (LQT3), KCNE1 (LQT5), KCNE2 (LQT6), and KCNJ2 (Andersen-Tawil syndrome [ATS1], also annotated LQT7), and analysis of 10 ANK2 exons implicated in LQT4 were performed on genomic DNA from 11 unrelated patients (8 females) referred to Mayo Clinic's Sudden Death Genomics Laboratory explicitly for CPVT genetic testing. Overall, putative disease causing mutations were identified in 8 patients (72%). Only 4 patients (3 males) hosted CPVT1-associated RyR2 mutations: P164S, V186M, S3938R, and T4196A. Interestingly, 4 females instead possessed either ATS1- or LQT5-associated mutations. Mutations were absent in >400 reference alleles. Putative CPVT1-causing mutations in RyR2 were seen in <40% of unrelated patients referred with a diagnosis of CPVT and preferentially in males. Phenotypic mimicry is evident with the identification of ATS1- and LQT5-associated mutations in females displaying a normal QT interval and exercise-induced bidirectional VT, suggesting that observed exercise-induced polymorphic VT in patients may reflect disorders other than CPVT. Clinical consideration for either Andersen-Tawil syndrome or long QT syndrome and appropriate genetic testing may be warranted for individuals with RyR2 mutation-negative CPVT, particularly females.


[Central pain processing in chronic low back pain. Evidence for reduced pain inhibition].
A study of patients with low back pain (LBP) had revealed altered central pain processing. At an equal pain level LBP patients had considerably more neuronal activation in the somatosensory cortices than controls. In a new analysis of this dataset, we further investigated the differences in central pain processing between LBP patients and controls, looking for possible pathogenic mechanisms. Central pain processing was studied by functional magnetic resonance imaging (fMRI), using equally painful pressure stimuli in a block paradigm. In this study, we reanalyzed the fMRI data to statistically compare pain-elicited neuronal activation of both groups. Equally painful pressure stimulation resulted in a significantly lower increase of regional cerebral blood flow (rCBF) in the periaqueductal gray (PAG) of the LBP patients. The analysis further revealed a significantly higher increase of rCBF in LBP than in HC in the primary and secondary somatosensory cortex and the lateral orbitofrontal cortex (LOFK), elicited by these same stimuli. These findings support a dysfunction of the inhibitory systems controlled by the PAG as a possible pathogenic mechanism in chronic low back pain.


Electrocardiogram of the humpback whale (Megaptera novaeangliae), with specific reference to atrioventricular transmission and ventricular excitation.
The objective of the study was to record the electrocardiogram (ECG) of a large whale to obtain crucial data for comparative electrophysiologic analysis. The data were needed to establish the mismatch between heart size and PR interval and QRS duration in mammals. In the waters off the coast of Newfoundland, in two humpback whales (Megaptera novaeangliae) with an estimated weight of 30,000 kg a 1-lead ECG was recorded, enabling reliable assessment of P waves and QRS complexes. It was found that both the PR interval (atrioventricular [AV] transmission time) and QRS duration (ventricular excitation) are extremely short for animals of this size. These findings are difficult, if not impossible, to explain on the basis of currently accepted electrophysiologic theories. However, the narrow QRS complex may be due to a very dense His-Purkinje network in the ventricular wall of whales. Alternative mechanisms that can explain the function of the mammalian AV node need to be considered and explored. The results of the study may be of value for the understanding of the ECG in humans.


Pharmacokinetics, safety and efficacy of darunavir/ritonavir in treatment-experienced children and adolescents.
To assess pharmacokinetics, safety and efficacy of darunavir/ritonavir (DRV/r) and optimized background regimen in treatment-experienced patients (6-17 years). Forty-eight-week, open-label, two-part, phase II study. In part I, 44 patients were randomized (1: 1 ratio) to receive a body weight-adjusted, adult-equivalent dose (group A) or a 20-33% higher DRV/r twice daily (b.i.d.) dose (group B). Pharmacokinetics, safety and efficacy were assessed following 2-week dosing (part I), which determined dosing for part II (evaluated 48-week safety and efficacy). In part I, both groups met the protocol-specified criteria for pharmacokinetics and showed favorable tolerability and efficacy. The following body-weight doses were selected: DRV/r 375/50 mg b.i.d. (20-<30 kg), 450/60 mg b.i.d. (30-<40 kg) and 600/100 mg b.i.d. (> or =40 kg); these gave an AUC24h, C0h and Cmax of 102, 114 and 112%, respectively, versus the corresponding mean adult pharmacokinetic parameter. In part II, 80 patients received DRV/r (median age: 14 years, mean baseline HIV-1 RNA: 4.64 log(10)copies/ml). One patient (1%) discontinued (treatment-unrelated grade 3 anxiety). An abnormal mean baseline triglyceride level was normalized at 48 weeks (P < 0.01). At week 48, 65% had at least 1.0 log(10)HIV-1 RNA reduction; 59 and 48% achieved HIV-1 RNA less than 400 and less than 50 copies/ml, respectively (time-to-loss-of-virologic response). Mean age-adjusted weight z-score increased by 0.2 (P = 0.003). In treatment-experienced children and adolescents, DRV/r showed comparable exposure to adults with appropriate dose selection, favorable safety and tolerability, improved body weight and significant virologic response. DRV/r is a valuable therapeutic option for this population.


Therapeutic use of cephazolin to prevent complications of spine surgery.
Discitis, caused by pyogenic organisms, is a potential complication of any procedure which involves entering the intervertebral disc during open or percutaneous procedures. While there are wide variations in the severity of symptoms, the characteristic feature of discitis is the development of increasingly severe back pain, which is not relieved by rest, or narcotic analgesics. While there is a tendency to spontaneous resolution over time, a self-limiting course does not always eventuate. Serious complications resulting from spread of the infective process can lead to vertebral osteomyelitis or to the formation of an epidural abscess with further risk of neural compression. Clinical and experimental evidence now supports the prophylactic use of a suitable antibiotic, but some uncertainties exist about the benefits of antibiotic therapy in treating established discitis. While cephazolin is a widely favoured choice of antibiotic, the timing of its administration to prevent or treat discitis has been complicated by the lack of suitable methods for detecting and measuring the concentration of cephazolin in the plasma and disc in experimental and clinical conditions. This paper describes a high-performance liquid chromatography technique for detecting the antibiotic cephazolin. The results conclude cephazolin can be detected in the plasma and disc after administering an intravenous bolus dose. However, concentration of cephazolin in the outer disc was 12 times greater than that of the inner disc.


Extracellular proteins as a potential marker of active Staphylococcus aureus infection in bone.
The potential of extracellular protein antigens of Staphylococcus aureus as markers of infection of bone was investigated by immunoblotting. Serum from patients with S. aureus bone infection showed levels of IgG antibodies to a preparation of soluble extracellular proteins of 17-81 kDa which were significantly higher than those found in serum from normal controls. By contrast, immunoblots of various whole cell or cell wall-derived antigens gave complex patterns of response which were unsuitable for positive diagnosis of S. aureus bone infection.


A case of variant angina exacerbated by administration of rifampicin.
Rifampicin, an antituberculosis agent, is known to be a potent inducer of microsomal drug-metabolizing enzymes in the liver. Elimination or clearance of many drugs has been reported to be enhanced, and their effectiveness reduced; however, no report in the literature has dealt with the interaction between rifampicin and dihydropiridine calcium entry-blocking drugs such as nifedipine. We present here evidence for the possible interaction between rifampicin and nifedipine in a patient with angina pectoris, which was exacerbated during coadministration or rechallenge with rifampicin. The peak plasma level and area under the curve were reduced and the apparent oral clearance of nifedipine was increased by rifampicin, suggesting that rifampicin enhanced the elimination of nifedipine via induction of a hepatic microsomal drug-metabolizing enzyme, as has been reported on other drugs widely metabolized in the liver.


Immunoglobulin and circulating immune complex kinetics during immunoadsorption onto protein A sepharose.
Immunoadsorption onto protein A sepharose can be applied to eliminate immunoglobulins, autoantibodies and circulating immune complexes from the circulation. In vivo kinetic studies showed that all IgG subclasses are removed from the patient's plasma although IgG3 elimination is variable and dependent on the presence of other immunoglobulins. IgG elimination half time was 4.8 days during intermittent and 2.9 days for daily therapy in the absence of immunosuppression. Autoantibodies and immune complexes can be cleared effectively but administration of intravenous immunoglobulins should be avoided because of competition for protein A binding sites. Redistribution/ denovo synthesis (half time 2.1-8.8 d for IgG 1-4) occurred in the absence of immunosuppression.


The effect of South Asian ethnicity on satisfaction with primary cleft lip and or palate repair.
To evaluate the effect of South Asian ethnicity on satisfaction with cleft lip and or palate repair, post-primary repair. All data were gathered from patients attending the adult cleft service in the West Midlands. Subjects had unilateral or bilateral cleft lip with, or without, palatal involvement. Patients were aged between 16 and 65. Clefts were non-syndromic. 15 South Asian and 95 Caucasian subjects were compared. Satisfaction with cleft repair was assessed using the Satisfaction with Appearance scale (SWA), which is a scale of 0-100. Data gathered were analysed using multiple linear regression with ethnicity, age, gender, cleft type and deprivation score as independent variables. South Asians were found to be less satisfied with many aspects of their cleft surgery. Satisfaction with nose and speech were found to be significantly less in the South Asian group compared with the Caucasian group (mean difference >20, p<0.01). Multiple linear regression showed that ethnicity was still significant when adjusted for age, gender, cleft type and deprivation score. This study found significant differences in levels of satisfaction between South Asian and Caucasian groups, despite a small sample size. These findings highlight the need for further clinically orientated research in this field.


Exploring the limits of semiconductor-laser-based optical frequency combs.
We report a study on the performance limits of stabilized optical frequency combs from semiconductor mode-locked diode lasers. Operating characteristics such as the number of comb lines, comb tooth linewidth, the physical parameters that affect the independent control of pulse repetition rate and offset frequency, and the potential for self-stabilization, are explored.


Gastrointestinal neuropeptides suppress human colonic lamina propria lymphocyte DNA synthesis.
Gastrointestinal neuropeptides have been shown to modulate the circulatory immune system, but their effect on the mucosal immune system is not well defined. We studied the effect of VIP, SOM, S-P and Bomb on thymidine incorporation into human colonic lamina propria lymphocyte (LPL) DNA. Physiologic concentrations of VIP, SOM, S-P and Bomb significantly suppressed thymidine incorporation into Con A-stimulated human LPL. These neuropeptides did not affect DNA synthesis when LPL were induced with phorbol ester (PDB) and calcium ionophore (ionomycin). Our data suggest that a) VIP, SOM, S-P, and Bomb may have a regulatory role in the human mucosal immune system, and b) Bomb should be added to the list of neuropeptides which affect the gut immune system.


Defining and mitigating the challenges of an older and obese population in minimally invasive gynecologic cancer surgery.
The incidence of endometrial cancer (EC) is steadily increasing due in large part to an aging world population and rise in rates of obesity. Patients with obesity and advancing age can be seen as vulnerable populations, as they are both often subject to physician bias regarding surgical choices and assumptions regarding long-term outcomes. As we operate on an older and/or obese patient population, it is increasingly important that we adopt peri-operative management strategies and surgical techniques to best serve this complex patient population. Careful orchestration pre-, intra- and postoperatively is key to successful outcomes in robotic and laparoscopic surgery. Here, we review existing literature regarding EC in women with older age and/or obesity, outline recommendations for peri-operative management and common intra-operative issues-specifically common anesthetic issues surrounding cardiovascular, respiratory and neuromuscular systems-that are of heightened importance in women with older age and/or obesity. The goal of this review is to help define and mitigate common complications for these vulnerable patients with an EC diagnosis who, in accordance with carefully assessed health risks, can and should be offered standard of care surgery and treatment.


[Diabetes mellitus and chronic renal insufficiency].
In the nineties of the 20th century diabetic nephropathy has become the leading cause of regular dialysis treatment (RDT) in developed countries. In particular type 2 diabetics are involved. A similar trend can be observed also in the Czech Republic which holds in this respect the first place among countries of the former eastern block (33% patients with RDT) suffer from diabetes. The cause of the increase of patients with diabetic nephropathy and renal failure caused by diabetes is not only the rising prevalence and incidence of type 2 diabetes in the population but in particular the better care provided to patients with type 2 diabetes which enables them to survive macro- and microvascular complications incl. diabetic nephropathy. It is estimated that diabetic nephropathy affects 4-8% patients attending diabetic clinics. With regard to the increasing number of diabetics in RDT, moreover associated with their high polymorbidity, this is a serious medical and economic problem. The main factors which influence in the diabetic patients the risk of development of diabetic nephropathy are long-term control of glycaemia, genetic (ethnic) factors, age and sex. The decisive factor influencing in patients with diabetic nephropathy the progression of chronic renal insufficiency is control of the blood pressure. Including diabetics in RDT is not associated only with medical problems but also with socio-economic issues. The quality of life of diabetics is much lower and the survival of diabetics treated within the framework of RDT is still almost half as compared with the survival of non-diabetic patients. Decision on the selection of the dialysis method is not easy. Medical differences are well defined but should not be considered absolute. It is important to consider also which method is preferred by the patient. Optimally the decision is taken during the period of dispensarization. Both dialyzation methods have comparable results and survival although for diabetics under 50 years of age a more favourable prognosis of peritoneal dialysis is reported. However, the risk of "failure of the method" is in general higher in peritoneal dialysis.


Is transperineal prostate biopsy more accurate than transrectal biopsy in determining final Gleason score and clinical risk category? A comparative analysis.
To assess the degree of upgrading and increase in clinical risk category of transperineal template biopsy (TTB) compared with transrectal ultrasonography-guided prostate biopsy (TRUSB). Upgrading of TRUSB Gleason grade and sum after radical prostatectomy (RP) is well recognised. TTB may offer a more thorough mapping of the prostate than TRUSB, as well as a more accurate assessment of the tumour. In this retrospective cohort study of prospectively collected data, we compare the initial TRUSB and TTB Gleason grade and sum with the final assessment at RP. Following Ethics Committee approval, 431 laparoscopic and robotic RP specimens of two urologists, fellowship-trained in minimally invasive RP, were examined in the private sector between April 2009 and October 2013. Final RP Gleason grade and sum were compared with the initial prostate biopsy. All pathological assessments were performed by a dedicated uropathology unit, experienced in prostate pathology. Upgrading was defined either as an increase in the primary Gleason grade, or as identification of a higher grade tertiary pattern at final RP analysis. Increase in clinical risk category was defined as an increase from low- (Gleason ≤6), to either intermediate- (Gleason 7) or high-risk disease (Gleason 8-10); or as an increase from intermediate- to high-risk disease. The chi-squared test was used to compare categorical variables, while the Wilcoxon rank sum was used for continuous quantitative variables. The 431 RP specimens comprised 283 in which the prostate cancer was diagnosed at TRUSB and 148 diagnosed at TTB. There was no difference between TRUSB and TTB in mean prostate weight (46.4 vs 44.2 g), final RP pathological stage (pT2: 187 vs 102; pT3 97 vs 48; P = 0.65) or mean tumour volume (2.15 vs 2.14 mL). Overall, 33.22% of TRUSB and 30.41% of TTB were upgraded, which was not significantly different (P = 0.55). Similarly there was no difference in whether there was an increase to a higher Gleason sum (TRUSB 23.3% vs TTB 20.9%; P = 0.57). TTB was more reflective of the actual clinical risk category, with TRUSB more likely to show an increase in clinical risk (TRUSB 22.3% vs TTB 14.2%; P = 0.04). In this series, TTB more accurately predicted clinical risk category than TRUSB. TTB should be considered before active surveillance, to ensure that occult higher risk disease has not been under diagnosed. Upgrading and increase in clinical risk category was relatively common in each group highlighting the need for improved pretreatment staging accuracy.


Information storage capacity of incompletely connected associative memories.
In this paper, the memory capacity of incompletely connected associative memories is investigated. First, the capacity is derived for memories with fixed parameters. Optimization of the parameters yields a maximum capacity between 0.53 and 0.69 for hetero-association and half of it for autoassociation improving previously reported results. The maximum capacity grows with increasing connectivity of the memory and requires sparse input and output patterns. Further, parameters can be chosen in such a way that the information content per pattern asymptotically approaches 1 with growing size of the memory.


Social Stigma and Well-Being in a Sample of Schizophrenia Patients.
The present study analyzes the existing relationship between three variables related to social rejection (perception of overt and subtle discrimination and stigma consciousness) and the psychological and subjective well-being among people with schizophrenia. Likewise, we will analyze the relationship between two possible strategies to cope with stigma (active coping and avoidant coping) and well-being. A cross-sectional study was conducted in a sample of 50 people with schizophrenia recruited from the social care network for people with mental illness in the Community of Madrid. Results show, as expected, the existence of a negative association between the variables related to social rejection and psychological and subjective well-being. It was also found that avoidant coping is negatively related to well-being, while active coping is positively related, although in the latter case relations do not reach significance. In view of the implementation of interventions to improve the well-being of people with schizophrenia, our results suggest implementing strategies to reduce the perception of discrimination (especially subtle or indirect discrimination) and encouraging the use of active strategies to cope with stigma as opposed to avoidant-coping strategies.


Single-shot ADC imaging for fMRI.
It has been suggested that apparent diffusion coefficient (ADC) contrast can be sensitive to cerebral blood flow (CBF) changes during brain activation. However, current ADC imaging techniques have an inherently low temporal resolution due to the requirement of multiple acquisitions with different b-factors, as well as potential confounds from cross talk between the deoxyhemoglobin-induced background gradients and the externally applied diffusion-weighting gradients. In this report a new method is proposed and implemented that addresses these two limitations. Specifically, a single-shot pulse sequence that sequentially acquires one gradient-echo (GRE) and two diffusion-weighted spin-echo (SE) images was developed. In addition, the diffusion-weighting gradient waveform was numerically optimized to null the cross terms with the deoxyhemoglobin-induced background gradients to fully isolate the effect of diffusion weighting from that of oxygenation-level changes. The experimental results show that this new single-shot method can acquire ADC maps with sufficient signal-to-noise ratio (SNR), and establish its practical utility in functional MRI (fMRI) to complement the blood oxygenation level-dependent (BOLD) technique and provide differential sensitivity for different vasculatures to better localize neural activity originating from the small vessels.


Indoor air pollution and its impact on children under five years old in Bangladesh.
Indoor air concentrations of volatile organic compounds (VOCs), carbon monoxide (CO), carbon dioxide (CO2), nitrogen dioxide (NO2), and dust particles were measured for 49 biomass and 46 fossil fuel users in urban slums of Dhaka, Bangladesh. The health impacts of these pollutants were assessed on 65 and 51 children under five years old from families who use biomass and fossil fuel as main source of energy, respectively. Mean concentrations of CO were found to be significantly higher in biomass fuel users (P = 0.010), while geometric mean concentrations of benzene, xylene, toluene, hexane, total VOCs, and NO2 were significantly higher (P < 0.01) in the fossil fuel users. Symptoms such as redness of eyes, itching of skin, nasal discharge, cough, shortness of breath, chest tightness, wheezing, or whistling chest were found to be associated with the choice of biomass fuel, with the odds ratio ranging from 4.0 to 6.3. No significant association of use of biomass fuel with respiratory diseases, eczema, diarrhea, or viral fever was observed after adjustment for potential confounders. These results suggest a significant association between the biomass fuel-using population and respiratory symptoms. These symptoms may not be due to the pollutants only, as some other underlying causes may be present. The health of children under five years old in Bangladesh, especially those living in poor socioeconomic conditions, is considered to be worsening because of indoor air pollution. It is commonly suggested that biomass fuel should be replaced by fossil fuel, as pollution levels are believed to be higher with biomass fuel. Our findings, however, suggest that pollution can be higher with fossil fuels, and indicate that a switch in fuel from biomass to fossil does not necessarily improve the children's health. Awareness programs should therefore be undertaken to avoid the unnecessary use of gas. Clean fuels and clean stoves should also be ensured to reduce emissions of indoor air pollutants.


The coupling effects of some thiol and other sulfur-containing compounds on the circadian rhythm of cell division in photosynthetic mutants of Euglena.
Previous work has demonstrated a persisting, free-running, circadian rhythm of cell division in the P4ZUL photosynthetic mutant of the alga Euglena gracilis Klebs (Strain Z) Pringsheim grown organotrophically in continuous light or darkness at 19 degrees C following prior synchronization by a repetitive LD:10,14 light cycle. A similar circadian rhythmicity has been recently discovered in the W6ZHL heat-bleached and the Y9ZNalL naladixic acid-induced mutants of Euglena grown under comparable conditions. Over extended timespans, however, these mutants appear to gradually lose first their ability to display persisting overt rhythms, and then even their capability of being entrained by imposed LD cycles. These properties can be restored by the addition of certain sulfur-containing compounds to the medium including cysteine, methionine, dithiothreital, sodium monosulfide, sodium sulfite, and sodium thiosulfate, as well as thioglycolic [mercaptoacetic] acid. The implications of these findings toward biological clock mechanisms are discussed: It appears that some sort of coupling process is operating as opposed to the initiation of an underlying oscillation.


Effects of orthoses on upright functional skills of children and adolescents with cerebral palsy.
Most research details the influence of orthoses on impairments in children with cerebral palsy. The purpose of this study was to determine the effect of orthoses on multiple tests of function. The researchers used the Standardized Walking Obstacle Course (SWOC), Pediatric Balance Scale (PBS), performance on individualized goals related upright function, and self-reports of comfort and stability with and without orthoses to examine 28 children (5.4-19.1 years of age) with cerebral palsy. No significant differences were found in performance on the SWOC and PBS with and without orthoses. Only 18% of the children performed better on an individualized goal with their orthoses, but 48% of the children reported more feelings of comfort and stability while wearing orthoses. Results of this study bring into question the use of orthoses to improve functional balance and ambulation in children with cerebral palsy.


[Transurethral thermotherapy in prostatic adenoma].
Microwave thermotherapy is considered to be an alternative to conventional surgical treatment of benign prostatic hyperplasia (BPH). Our initial experience of the first six months shows this technique has achieved objective improvement of the symptoms and uroflowmetry, as well as a significant reduction of postmicturition residual urine. It carries a minimal morbidity, no mortality and has permitted recovery of micturition in over 90% of the patients with urinary retention.


Serial measurements of mesothelioma serum biomarkers in asbestos-exposed individuals: a prospective longitudinal cohort study.
Soluble mesothelin (SM) and megakaryocyte potentiating factor (MPF) are serum biomarkers of mesothelioma. This study aims to examine the longitudinal behavior of SM and MPF in controls to gain insight in the optimal use of these biomarkers in screening. Asbestos-exposed individuals, with no malignant disease at inclusion, were surveilled for 2 years with annual measurements of SM and MPF. Fixed thresholds were set at 2.10 nmol/L for SM and 13.10 ng/ml for MPF. Longitudinal biomarker analysis, using a random intercept model, estimated the association with age and glomerular filtration rate (GFR), and the intraclass correlation. The latter represents the proportion of total biomarker variance accounted for by the between-individual variance. A total of 215 participants were included, of whom 179 and 137 provided a second sample and third sample, respectively. Two participants with normal SM and MPF levels presented afterward with mesothelioma and lung cancer, respectively. Participants with elevated biomarker levels were typically older and had a lower GFR. During follow-up, biomarker levels significantly increased. Longitudinal analysis indicated that this was in part due to aging, while changes in GFR had a less pronounced effect on serial biomarker measurements. SM and MPF had a high intraclass correlation of 0.81 and 0.78, respectively, which implies that a single biomarker measurement and fixed threshold are suboptimal in screening. The longitudinal behavior of SM and MPF in controls indicates that a biomarker-based screening approach can benefit from the incorporation of serial measurements and individual-specific screening rules, adjusted for age and GFR. Large-scale validation remains nevertheless mandatory to elucidate whether such an approach can improve the early detection of mesothelioma.


Alcohol marketing in televised English professional football: a frequency analysis.
The aim of the study was to explore the frequency of alcohol marketing (both formal commercials and otherwise) in televised top-class English professional football matches. A purposive sample of six broadcasts (total = 1101 min) of televised top-class English club football matches were identified and recorded in full. A customized coding framework was used to identify and categorize all verbal and visual alcohol references in non-commercial broadcasting. The number and the duration of all formal alcohol commercials were also noted. A mean of 111 visual references and 2 verbal references to alcohol per hour of broadcast were identified. Nearly all visual references were to beer products and were primarily simple logos or branding. The majority of verbal alcohol references were related to title-sponsorship of competitions. A total of 17 formal alcohol commercials were identified, accounting for <1% of total broadcast time. Visual alcohol references in televised top-class English football matches are common with an average of nearly two per minute. Verbal references are rare and formal alcohol commercials account for <1% of broadcast time. Restriction of all alcohol sports sponsorship, as seen for tobacco, may be justified.


Recent considerations in recurrent cellulitis.
Cellulitis is a frequently diagnosed syndrome that causes considerable morbidity. For a subset of patients, recurrent bouts of infection impact their quality of life. Most cases are due to b-hemolytic streptococci or Staphylococcus aureus. Inclusion of interdigital space (toe web) or mucosal (anal) swab cultures may increase the ability to define pathogens among patients with lower extremity cellulitis. The pathogenesis of cellulitis is complex, and more work is needed so that novel therapies and vaccines can be developed to improve treatment and prevention of this disorder.


Kikuchi-Fujimoto Disease: part of the differential diagnosis of cervical lymphadenopathy in an HIV-positive patient.
A 38-year-old HIV-positive Nigerian woman presented with a three-week history of cervical lymphadenopathy, night sweats, weight loss and fever. Provisional diagnoses of tuberculosis and lymphoma were considered; however, a histological diagnosis of Kikuchi-Fujimoto Disease was reached. This rare benign disease has presenting features that mimic more serious conditions commonly occurring in HIV-positive patients. This case report emphasises the importance of Kikuchi-Fujimoto Disease in the differential diagnosis of cervical lymphadenopathy in HIV-positive patients.


Cognitive deficits in presumed minor head-injured patients.
To determine the frequency of cognitive deficits in ED patients with presumed minor head injury and to identify factors in the initial history and physical examination predictive of cognitive deficits in these patients. A prospective clinical study was performed over a nine-month period at a large community-based ED (60,000 patient annual census). Consecutive patients between 16 and 50 years of age who presented to the ED with a history of blunt trauma or a deceleration injury to the head and a Glasgow Coma Scale (GCS) score of 14 or 15 were included. Patients who were admitted to the hospital or who had an abnormal imaging study of the skull or brain also were excluded. Detailed history and physical examination findings were collected using a standardized data form. Cognitive testing was done at one week postinjury (Halstead-Reitan Neuropsychological Test Battery). Seventy patients were originally entered into the study, and 36 completed the follow-up. Those completing the study were more commonly employed and less likely to have used sensorium-altering drugs or ethanol. Of the 36 patients who completed the study, 42% had either mild or moderate cognitive deficits at one week postinjury. Abnormal cerebellar function during the initial visit was associated with the presence of cognitive deficits at follow-up (p = 0.004). However, only four of 15 (27%; 95% CI 8-55%) patients with a cognitive deficit had an abnormal cerebellar finding. Many patients with minor head injuries have cognitive deficits one week after injury. History and physical examination features are poor predictors of these deficits. Further studies are needed to evaluate the duration and final outcome of these cognitive deficits.


[The effect of benzylpenicillin and doxycycline on toxicity and antineoplastic action of cyclophosphamide and methotrexate in mice].
The effect of benzylpenicillin and doxycycline on toxicity and anticancer activity of cyclophosphamide and methotrexate in mice was studied. Benzylpenicillin applied both at once repeatedly enhances anticancer activity of cyclophosphamide against L 1210 leukemia within limited range of CP. Benzylpenicillin does not change anticancer activity of methotrexate, but doxycycline of both cyclophosphamide and methotrexate, against L 1210 leukemia in mice.


Dietary Intake is Positively Associated with Cognitive Function of a Chinese Older Adults Sample.
The relationship between cognitive function and dietary intake in older adults was under-studied in China. This study examined this relationship in a Chinese sample while controlling for the effects of sleep quality and socio demographic confounders. The sample consisted of 340 Chinese older adults (age > 60) who were randomly selected from Wuhan city in central China. Cognitive function was assessed by the Mini-mental State Examination [MMSE], sleep quality by the Pittsburgh Sleep Quality Index [PSQI], and dietary intake by frequencies of intake of meat products, fruits, fish/seafood/aquatic products, nuts and mushroom/algae over the past year. First, confirmatory factor analysis (CFA) was conducted to evaluate the measurement properties of cognitive function, dietary intake, and sleep quality. Second, structural equation modeling (SEM) was conducted to examine the relations of cognitive function, dietary intake, and sleep quality. Dietary intake was found to be positively related to cognitive function. Older age, lower education status, monthly income, and living alone or without a spouse were significantly associated with poorer cognitive function. SES status had an indirect effect on cognitive function via dietary intake. Dietary intake may be critical to maintain normal cognitive function of older adults in China.


[Effectiveness of medial ankle branches propeller "Tennis racket-like" flap in repair of heel-ankle tissue defects].
To investigate effectiveness of the medial ankle branches propeller "Tennis racket-like" flap in repair of heel-ankle tissue defect. Between June 2011 and June 2016, 50 patients with heel-ankle tissue defects were treated. There were 40 males and 10 females, with a median age of 35.6 years (range, 6-58 years). The defects were caused by trauma in 44 cases, scar deformity after trauma in 2 cases, chronic ulcer in 2 cases, and squamous cell carcinoma in 2 cases. The defects located at heel in 20 cases, ankle in 15 cases, and heel-ankle in 15 cases. The size of heel-ankle tissue defect ranged from 3.5 cm×2.0 cm to 13.0×10.0 cm. The course of disease ranged from 3 hours to 2 months (mean, 28 days). All wounds were repaired by the medial ankle branches propeller "Tennis racket-like" flap in a size of 3.8 cm×2.2 cm-13.4 cm×10.3 cm. The donor site was directly sutured in 5 cases or repaired by skin grafting in 45 cases. All flaps survived and wounds healed by first intention. Partial necrosis of skin grafting occurred in 1 case, and the wound recovered by change dressing. The other skin grafting survived and wounds healed by first intention. Forty-eight patients were followed up 12 months after operation. The appearance, sensory, and function of repaired heel-ankle flaps were satisfactory. For heel-ankle tissue defect repair, the medial ankle branches propeller "Tennis racket-like" flap has advantages of the high survival rate, reliable blood supply, and sensory recovery.


Effect of Fluorinated Ligand on Structural, Electronic and DNA-binding Properties of Copper Paddlewheel Complex: Synthesis, Structure and Properties.
This paper presents synthesis, structural description and properties of a binuclear paddlewheel copper(II) carboxylate complex with formula [(py)Cu(μ-L)4Cu(py)], where py = pyridine and L = 4-fluorophenylacetate. Structural characteristics, electronic absorption and DNA-binding properties of the synthesized complex have been compared to those of the non-fluorinated analogues (where F is replaced by H, -CH3 and -OCH3) already reported and the modifications successfully ascribed to fluorine. The complex exhibits typical paddlewheel structure and there are two crystallographically independent molecules in the unit cell. The electronic absorption spectrum of complex is also different and the mode and extent of DNA-binding ability of complex are significantly altered owing to the presence of suitably substituted fluorine. The effect of fluorine is clearly manifested in the modified properties of synthesized complex.


A Scalable Chemical Approach for the Synthesis of a Highly Tolerant and Efficient Oil Absorbent.
In the past, bio-inspired extreme water repellent property has been strategically embedded on commercially available sponges for developing selective oil absorbents. However, most of the reported materials lack physical and chemical durability, limiting their applicability at practically harsh settings. Herein, a stable dispersion of polymeric nanocomplexes was exploited to achieve a chemically reactive coating on the highly compressible melamine foam. A superhydrophobic melamine foam (SMF) was achieved after post-covalent modification of the reactive coating through 1,4-conjugate addition reaction at ambient conditions. The durability of the embedded extreme water repellent property in the as-modified melamine foam has been elaborately demonstrated through exposing it to severe physical manipulations, chemically harsh aqueous media including pH 1, pH 12, surfactant contaminated water, river water, seawater and prolonged UV irradiation. Thus, the highly tolerant SMF was utilized as an efficient oil absorbent wherein oils of varying densities could be selectively recovered from an oil/water interface with high (e.g., 137 g g-1 for chloroform and 83 g g-1 for diesel) oil absorption capacity. Moreover, the selective oil absorption capacity of the as-synthesized material remained unaffected at practically relevant severe chemical and physical settings, and the extreme water repellency of the material remained unaltered even after repetitive (at least 50 cycles) use for oil/water separation.


Radioactivity concentrations in soil and dose assessment for Samsun city centre, Turkey.
In this study, natural gamma radioactivity levels were determined in the soil samples of the Samsun city centre by using the gamma ray spectrometry method. The analysis carried out with the high-purity germanium gamma spectrometry system has shown that average activity concentrations of (238)U, (232)Th, (40)K and (137)Cs were 19±2, 22±4, 521±23 and 15±1 Bq kg(-1), respectively. From the gamma analysis of soil samples, the average value of the absorbed gamma dose rates in air and the average value of the external annual effective dose rates were calculated as 45±4 nGy h(-1) and 55±5 µSv y(-1), respectively. The external hazard index has also been calculated and it has been found that the radiation hazard in Samsun is insignificant.


Helminth fauna of a Japanese golden eagle, Aquila chrysaetos japonica.
A Japanese golden eagle, Aquila chrysaetos japonica, was found dead in Nagano Prefecture PB 399-8200, Japan, and subjected to necropsy. The necropsy revealed that the entire length of the intestine was filled with several masses of intestinal parasites. The recovered helminths were identified as one digenean trematode species, Neodiplostomum reflexum; two species of nematodes, Synhimantus sp. and larvae of Porrocaecum sp.; and a single species of Acanthocephala, Centrorhynchus sp. Digenea and acanthocephalans were found in massive numbers, obliterating the intestinal lumen, which suggests that the bird died as a result of the parasitic intestinal obstruction. The same type of helminths as those observed in this case was previously recorded in crested serpent eagles (Spilornis cheela perplexus) in Japan, but the present study emphasizes the presence of the four species in the Japanese golden eagle as a new host record. To the authors' knowledge, this is the first report of N. reflexum in Japan.


Brief report: the impact of subcortical band heterotopia and associated complications on the neuropsychological functioning of a 13-year-old child.
Motor impairment in children with Asperger syndrome (AS) or high functioning autism (HFA) has been reported previously. This study presents results of a quantitative assessment of neuromotor skills in 14-22 year old HFA/AS. Sixteen HFA/AS and 16 IQ-matched controls were assessed by the Zurich Neuromotor Assessment (ZNA). The HFA/AS group showed strongest impairments of dynamic balance skills and diadochokinesis. Motor abilities were associated with degree of social withdrawal in the full sample and severity of current autistic symptoms in the HFA/AS group. Similar motor patterns as in younger children were found in the older adolescents. The association of autistic symptoms with motor performance points towards an essential role of motor impairment in autism spectrum disorders.


The LOXL2 gene encodes a new lysyl oxidase-like protein and is expressed at high levels in reproductive tissues.
We have reported in this paper the complete cDNA sequence, gene structure, and tissue-specific expression of LOXL2, a new amine oxidase and a member of an emerging family of human lysyl oxidases. The predicted amino acid sequence, from several overlapping cDNA clones isolated from placenta and spleen cDNA libraries, shared extensive sequence homology with the conserved copper-binding and catalytic domains of both lysyl oxidase (LOX) and the lysyl oxidase-like (LOXL) protein. These conserved domains are encoded by five consecutive exons within the LOX, LOXL, and LOXL2 genes that also maintained exon-intron structure conservation. In contrast, six exons encoding the amino-terminal domains diverged both in sequence and structure. Exon 1 of the LOXL2 gene does not encode a signal sequence that is present in LOX and LOXL, suggesting a different processing and intracellular localization for this new protein. Expression of the LOXL2 gene was detected in almost all tissues with the highest steady state mRNA levels in the reproductive tissues, placenta, uterus and prostate. In situ hybridization identified placental syncytial and cytotrophoblasts responsible for the synthesis of LOXL2 mRNA and demonstrated a spatial and temporal expression pattern unique to the LOXL2 gene.


Long-term (52-week) safety and efficacy of Sacubitril/valsartan in Asian patients with hypertension.
Sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor-neprilysin inhibitor, demonstrated significant reductions in office and 24 h ambulatory blood pressure (BP) over 8 weeks in Asian patients with hypertension. This 52-week extension to the 8-week core study was aimed at evaluating the long-term safety, tolerability and efficacy of sacubitril/valsartan. Patients who completed an 8-week randomized study (the core study) were enrolled in this 52-week open-label study and received sacubitril/valsartan 200 mg QD. The sacubitril/valsartan dose was uptitrated to 400 mg QD if BP was uncontrolled (>140/90 mm Hg) after 4 weeks. Subsequently, in patients with uncontrolled BP, treatment was intensified every 4 weeks with amlodipine 5-10 mg followed by hydrochlorothiazide 6.25-25 mg. Of the 341 patients enrolled, 7 (2.1%) discontinued the study drug due to adverse events (AEs). The incidence of AEs and serious AEs were 63.9 and 3.8%, respectively, and no deaths were reported in this study. The most frequent AEs were nasopharyngitis (18.2%) and dizziness (8.8%). Events that were potentially indicative of low BP were infrequent. One patient reported mild transient angioedema (lasting 2.5 h) that resolved without treatment but led to study drug discontinuation. The sacubitril/valsartan-based regimen provided clinically significant mean sitting systolic BP (msSBP) and mean sitting diastolic BP (msDBP) reductions from baseline (-24.7/-16.2 mm Hg). The overall BP control, msSBP and msDBP response rates were 75.3, 90.6 and 87.6%, respectively. Long-term use of sacubitril/valsartan was generally safe and well-tolerated in patients with hypertension and provided significant BP reductions from baseline.


Three-year clinical evaluation of a self-cured posterior composite resin.
A study was conducted to determine whether the wear resistance of a posterior composite could be improved by maximizing filler particle-to-particle contacts. This was expected to reduce stress concentrations on the resin matrix and thus reduce occlusal wear. A self-curing quartz-filled composite with this design, P-10, was used to restore 90 Class I and II cavity preparations in adult teeth. Restorations were recalled after baseline at six months, one year, two years, and three years to measure wear by direct and indirect evaluation methods. There was no apparent advantage for this material compared with other previously evaluated posterior composites. The average cumulative wear for P-10 after three years was 145 microns. In addition, the restorations were evaluated for color-matching, interfacial staining, secondary caries, marginal adaptation, surface texture, and postoperative sensitivity. This material was not significantly different in those ways from other posterior composite products except in terms of more rapid color change, because it is self-cured.


Postponing the morning dose of AEDs: effect on the epileptiform EEG activity.
The effects of postponing the morning dose of antiepileptic drugs (AEDs) before undergoing an electroencephalogram (EEG) on the likelihood of recording interictal epileptiform activity (IEA) in patients with epilepsy are unclear. This was a prospective study on patients undergoing video-EEG monitoring. The 3-h recordings used for evaluation started at 08:00 am. Each subject received the usual AED dosage at 08:00 am on the first full day of recording but not until 11:00 am on the following day. IEA (spikes, sharp waves, and spike and wave complexes) was counted at 1-h intervals on each day and compared. Each subject served as his/her own control. The measureable serum drug levels were obtained at 10:00 am on both days. Fifty patients (age 32 ± 11.7 years, 22 women) were enrolled. Forty-seven had focal epilepsy, and three had generalized epilepsy. Six were on monotherapy, and 44 were on polytherapy. The number of IEAs w/wo medication was similar throughout each hour. Twenty-five patients had IEA on the 1st day, and 28 had IEA on the 2nd day. Twenty-one had IEA on both days, while 18 had none on either day. Seven of the 25 without IEA on the 1st day had IEA on the 2nd day, and 4 of the 25 with IEA had no IEA on the 2nd day. Age, gender, epilepsy type, disease duration, seizure frequency, and AED type did not influence IEA. Delaying the morning dose of AEDs prior to an EEG tracing was not associated with increased IEA in patients with epilepsy.


Parentage testing implications of male fertility after allogeneic bone marrow transplantation.
Fertility is expected to be reduced after the extensive chemotherapy and/or radiotherapy that is needed for conditioning prior to bone marrow transplantation. However, a male patient can be fertile, and in very rare situations such as reported here, this may confuse subsequent paternity testing. The patient, initially excluded as the biological father by red cell types but not by HLA, was subsequently included after the history of his previous marrow transplant was revealed, a review of the HLA results and further RFLP testing on buccal mucosal cells. This case points to the need for good history taking before performing paternity testing.


The regulatory subunit of protein kinase CK2 is a specific A-Raf activator.
Two protein kinases that are involved in proliferation and oncogenesis but so far were thought to be functionally independent are Raf and CK2. The Raf signaling pathway is known to play a critical role in such fundamental biological processes as cellular proliferation and differentiation. Abnormal activation of this pathway is potentially oncogenic. Protein kinase CK2 exhibits enhanced levels in solid human tumors and proliferating tissue. In a two-hybrid screen of a mouse-embryo cDNA library we detected an interaction between A-Raf and CK2beta subunit. This binding was specific, as no interaction between CK2beta and B-Raf or c-Raf-1 was observed. Regions critical for this interaction were localized between residues 550 and 569 in the A-Raf kinase domain. A-Raf kinase activity was enhanced 10-fold upon coexpression with CK2beta in Sf9 cells. The alpha subunit of CK2 abolishes this effect. This is the first demonstration of both a direct Raf-isoform-specific activation and a regulatory role for CK2beta independent of the CK2alpha subunit. The present data thus link two different protein kinases that were thought to work separately in the cell.


The effects of alginate and non-alginate wound dressings on blood coagulation and platelet activation.
Alginates are used as haemostats in wound dressings. They act as calcium ion (Ca) donors as they contain mannuronic (M) or guluronic (G) groups with a high Ca content. This study compared the effects of calcium and zinc containing alginates and non-alginate dressings on blood coagulation and platelet activation to determine which was the best haemostat. We showed that alginate materials activated coagulation more than non-alginate materials. The extent of coagulation activation was affected differently by the alginate M or G group composition. It was demonstrated that alginates containing zinc ions had the greatest potentiating effect on prothrombotic coagulation and platelet activation.


Singlet molecular oxygen by direct excitation.
Direct excitation at 1064 nm and detection of singlet molecular oxygen at 1270 nm is made possible by the availability of powerful YAG-lasers and sensitive NIR photomultipliers. Singlet oxygen was generated in condensed phase at 77 K by direct excitation at 1064 nm (without the use of sensitizers). Several luminescing species were observed by time resolved luminescence spectroscopy and luminescence lifetime measurements, including the single molecule (1)Delta(g)and (1)Sigma(g)(+)states as well as luminescence from the [(1)Delta(g)](2) simultaneous transition. As an application we propose a novel method for obtaining quantitative non-intrusive mapping of the 2-D oxygen concentrations and pressure at cryogenic temperatures, which is of importance in aircraft design for high altitudes.


Moderate alcoholic beverage intake and early nuclear and cortical lens opacities.
To study the relationship between alcoholic beverage intake and early lens opacities. 556 Boston-area women aged 53-74 years were sampled from the Nurses' Health Study cohort. Degree of opacity was assessed by eye examinations including lens photography. After multivariate adjustment, the odds of a nuclear opacity grade > or =2.3 increased by 30% (OR=1.3, 95% CI: 1.10-1.54) per 10-g increase in total alcohol intake. Furthermore, after control for intake of other alcoholic beverages, the odds of a higher nuclear opacity grade increased by 13% (OR=1.13, 95% CI: 1.02-1.26) for every two additional hard-alcoholic drinks consumed per week, and by 17% (OR=1.17, 95% CI: 1.03-1.33) for every two additional glasses of wine consumed per week. The odds of a cortical opacity grade > or =0.4 decreased by 12% (OR=0.88, 95% CI: 0.79-0.98) for every two additional glasses of wine consumed per week, but intake of other alcoholic beverages was unrelated to cortical opacity. Consumption of alcoholic beverages, particularly hard liquor and wine, was positively related to nuclear opacity. Wine drinking was inversely related to cortical opacity.


Pharmacological characterization of dopamine systems in the nucleus accumbens core and shell.
Recent anatomical data suggest that the nucleus accumbens can be parcellated into a core region, related to the caudate-putamen, and a shell region, associated with the limbic system. We have used pharmacological methods to characterize the dopamine innervations of the nucleus accumbens core and shell in the rat. Concentrations of both dopamine and serotonin were significantly greater in the nucleus accumbens shell than the nucleus accumbens core. Metabolite: amine ratios suggested that both dopamine and serotonin utilization are greater in the core. However, dopamine turnover (as determined by measuring the rate of decline of dopamine after alpha-methyl-p-tyrosine treatment) was not significantly different in the two accumbal sectors. Dopamine concentrations in the two nucleus accumbens sectors were decreased to an equivalent degree at both 4 and 18 h after reserpine administration. In contrast, serotonin concentrations were decreased to a significantly greater degree in the nucleus accumbens core than nucleus accumbens shell at 4 h, but not 18 h, after reserpine administration. Administration of haloperidol increased dopamine utilization in both nucleus accumbens sectors, but augmented utilization to a significantly greater degree in the nucleus accumbens core. Clozapine increased dopamine utilization to an equivalent degree in both nucleus accumbens regions. Short duration immobilization stress selectively increased dopamine utilization in the nucleus accumbens shell. These data indicate that there are significant differences between the nucleus accumbens core and nucleus accumbens shell in basal dopamine metabolism, and indicate that the core and shell dopamine innervations can be distinguished on the basis of response to both pharmacological and environmental challenges.(ABSTRACT TRUNCATED AT 250 WORDS)


Coupling interactions in electromagnetic scattering from finite array of cavities with stratified dielectric coating.
The coupling interactions in electromagnetic scattering from a finite array of two-dimensional identical cavities engraved in a perfectly electric conducting screen covered with stratified dielectric coating are presented using an algorithm based on the hybrid finite element-boundary integral method. The solution to the scattering from a finite array of cavities is approximated using the array factor method, which does not take into account the coupling between the cavities, and is compared to the recently developed finite element-boundary element method to demonstrate the importance of the inclusion of the coupling effect. Dependence of the coupling interactions between the cavities on various parameters such as separation periods, incident angle of the plane-wave excitation, and permittivity and thickness of the dielectric coating is demonstrated quantitatively through several numerical examples.


Sweating the small stuff: Glycoproteins in human sweat and their unexplored potential for microbial adhesion.
There is increasing evidence that secretory fluids such as tears, saliva and milk play an important role in protecting the human body from infection via a washing mechanism involving glycan-mediated adhesion of potential pathogens to secretory glycoproteins. Interaction of sweat with bacteria is well established as the cause of sweat-associated malodor. However, the role of sweat glycoproteins in microbial attachment has received little, if any, research interest in the past. In this review, we demonstrate how recent published studies involving high-throughput proteomic analysis have inadvertently, and fortuitously, exposed an abundance of glycoproteins in sweat, many of which have also been identified in other secretory fluids. We bring together research demonstrating microbial adhesion to these secretory glycoproteins in tears, saliva and milk and suggest a similar role of the sweat glycoproteins in mediating microbial attachment to sweat and/or skin. The contribution of glycan-mediated microbial adhesion to sweat glycoproteins, and the associated impact on sweat derived malodor and pathogenic skin infections are unchartered new research areas that we are beginning to explore.


Direct anastomotic visualization in stapled Billroth II gastrectomy.
An alternative technique of performing a posterior gastroenterostomy using the EEA stapler during the Billroth II procedure is presented. It avoids overlooking bleeding points or defection the anastomosis, thus decreasing the likelihood of postoperative complications. The classic sequence of dissection is modified, but it should not alter the results.