WITHDRAWN: Antibiotics / anti-inflammatories for reducing acute inflammatory episodes in lymphoedema of the limbs.
Lymphoedema is a chronic, progressive condition and one area of debate is the optimum management for infective/inflammatory episodes (AIE's). To determine whether antibiotic/anti-inflammatory drugs given prophylactically reduce the number and severity of AIE's in patients with lymphoedema. We searched the Cochrane Breast Cancer Group register in September 2003, the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2003), CINAHL, MEDLINE, PASCAL, SIGLE, UnCover, reference lists produced by The British Lymphology Society, the National Research Register (NRR) and the International Society of Lymphology congress proceedings. Randomised controlled trials testing an antibiotic or anti-inflammatory drug against placebo (with or without physical therapies) were included. Eligibility for inclusion was confirmed by two blinded reviewers. The papers were screened independently using a checklist of criteria relating to quality. Both reviewers extracted data from the eligible studies using a data extraction form. Four studies (364 randomised patients) were included. Two studied the effects of intensive physical treatment plus selenium or placebo in preventing AIE's, and two studied the effects of Ivermectin, Diethylcarbamazine (DEC) (anti-filarial agents) and penicillin as prophylactic treatment for adeno lymphangitis(ADL) versus placebo.Both selenium trials reported no inflammatory episodes during the trial period in the treated group but one case of infection in the two placebo groups respectively. Seven additional cases of infection in trial one and 14 cases in trial two required treatment in the three month follow up period.One anti-filarial trial reported 127 ADL episodes for all groups during the treatment year (compared with 684 episodes during the pre-treatment year). There were 228 ADL episodes during the trial follow-up year but no findings were significant. No link was found between the grade of oedema and the frequency of ADL episodes. There was a significant link between increased episodes and the rainy season. Penicillin reduced the mean number of inflammatory episodes from 4.6 to 0.5 after treatment, which increased to 1.9 at the end of follow-up. The effectiveness of selenium in preventing AIE in lymphoedema remains inconclusive in the absence of properly conducted randomised-controlled trials. Anti-filarials do not appear to reduce ADL episodes in filarial lymphoedema. Penicillin appears to contribute to a significant reduction in ADL when combined with foot-care. The importance of foot-care should be recommended, which may also apply to care of the arm following breast cancer treatment. Properly conducted trials are needed to demonstrate any efficacy of these interventions.


Diagnostic accuracy of cannabinoid testing by liquid chromatography-tandem mass spectrometry in human hair.
To determine the diagnostic accuracy of Cannabinoids testing by LC-MS/MS in human hair and compare it with urine in civil heavy vehicle drivers. Current study was a diagnostic accuracy study done in "Armed Forces Institute of Pathology Rawalpindi, Pakistan" from February to November 2017. Urine and hair samples were collected by non-probability convenient sampling technique from 151 heavy vehicle drivers from Punjab. Hair and urine samples were collected from each subject. Separation of compounds was performed on Agilent Poroshell and analyzed using 6460 Triple Quadrapole LC-MS along-with software Mass hunter ©. Study population (151 civil heavy vehicle drivers) was divided into three main divisions There were 69 (46%) truck drivers,43 (28.5%) twenty-wheeler drivers and 39 (26%) bus drivers. Mean age of study participants was 36±10.82 years. Paired t-test was applied to check mean difference between the two tests' concentration (i.e urine and hair analysis for cannabis) which showed significant difference at p<0.001. Among the different factors of diagnostic accuracy in hair and urine specimens were: Sensitivity (96% and 62%), Specificity (93% and 95%) Positive Predictive Value (88% and 87%), Negative Predictive Value (97% and 82%) respectively. Overall diagnostic accuracy of Cannabinoids detection in hair was 94% while in urine it was 83%. ROC curve showed area under curve of 0.79 and 0.96 for urine and hair samples respectively. Current study signified hair as a substitute matrix owing to its non-invasive specimen collection, better diagnostic yield and wider detection period compared to urine.


Music interventions for acquired brain injury.
Acquired brain injury (ABI) can result in impairments in motor function, language, cognition, and sensory processing, and in emotional disturbances, which can severely reduce a survivor's quality of life. Music interventions have been used in rehabilitation to stimulate brain functions involved in movement, cognition, speech, emotions, and sensory perceptions. An update of the systematic review published in 2010 was needed to gauge the efficacy of music interventions in rehabilitation for people with ABI. To assess the effects of music interventions for functional outcomes in people with ABI. We expanded the criteria of our existing review to: 1) examine the efficacy of music interventions in addressing recovery in people with ABI including gait, upper extremity function, communication, mood and emotions, cognitive functioning, social skills, pain, behavioural outcomes, activities of daily living, and adverse events; 2) compare the efficacy of music interventions and standard care with a) standard care alone, b) standard care and placebo treatments, or c) standard care and other therapies; 3) compare the efficacy of different types of music interventions (music therapy delivered by trained music therapists versus music interventions delivered by other professionals). We searched the Cochrane Stroke Group Trials Register (January 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 6), MEDLINE (1946 to June 2015), Embase (1980 to June 2015), CINAHL (1982 to June 2015), PsycINFO (1806 to June 2015), LILACS (1982 to January 2016), and AMED (1985 to June 2015). We handsearched music therapy journals and conference proceedings, searched dissertation and specialist music databases, trials and research registers, reference lists, and contacted relevant experts and music therapy associations to identify unpublished research. We imposed no language restriction. We performed the original search in 2009. We included all randomised controlled trials and controlled clinical trials that compared music interventions and standard care with standard care alone or combined with other therapies. We examined studies that included people older than 16 years of age who had ABI of a non-degenerative nature and were participating in treatment programmes offered in hospital, outpatient, or community settings. We included studies in any language, published and unpublished. Two review authors independently extracted data and assessed the risk of bias of the included studies. We contacted trial researchers to obtain missing data or for additional information when necessary. Where possible, we presented results for continuous outcomes in meta-analyses using mean differences (MDs) and standardised mean differences (SMDs). We used post-test scores. In cases of significant baseline difference, we used change scores. We conducted a sensitivity analysis to assess the impact of the randomisation method. We identified 22 new studies for this update. The evidence for this update is based on 29 trials involving 775 participants. A music intervention known as rhythmic auditory stimulation may be beneficial for improving the following gait parameters after stroke. We found a reported increase in gait velocity of 11.34 metres per minute (95% confidence interval (CI) 8.40 to 14.28; 9 trials; 268 participants; P < 0.00001; moderate-quality evidence). Stride length of the affected side may also benefit, with a reported average of 0.12 metres more (95% CI 0.04 to 0.20; 5 trials; 129 participants; P = 0.003; moderate-quality evidence). We found a reported average improvement for general gait of 7.67 units on the Dynamic Gait Index (95% CI 5.67 to 9.67; 2 trials; 48 participants; P < 0.00001). There may also be an improvement in gait cadence, with a reported average increase of 10.77 steps per minute (95% CI 4.36 to 17.18; 7 trials; 223 participants; P = 0.001; low-quality evidence).Music interventions may be beneficial for improving the timing of upper extremity function after stroke as scored by a reduction of 1.08 seconds on the Wolf Motor Function Test (95% CI -1.69 to -0.47; 2 trials; 122 participants; very low-quality evidence).Music interventions may be beneficial for communication outcomes in people with aphasia following stroke. Overall, communication improved by 0.75 standard deviations in the intervention group, a moderate effect (95% CI 0.11 to 1.39; 3 trials; 67 participants; P = 0.02; very low-quality evidence). Naming was reported as improving by 9.79 units on the Aachen Aphasia Test (95% CI 1.37 to 18.21; 2 trials; 35 participants; P = 0.02). Music interventions may have a beneficial effect on speech repetition, reported as an average increase of 8.90 score on the Aachen Aphasia Test (95% CI 3.25 to 14.55; 2 trials; 35 participants; P = 0.002).There may be an improvement in quality of life following stroke using rhythmic auditory stimulation, reported at 0.89 standard deviations improvement on the Stroke Specific Quality of Life Scale, which is considered to be a large effect (95% CI 0.32 to 1.46; 2 trials; 53 participants; P = 0.002; low-quality evidence). We found no strong evidence for effects on memory and attention. Data were insufficient to examine the effect of music interventions on other outcomes.The majority of studies included in this review update presented a high risk of bias, therefore the quality of the evidence is low. Music interventions may be beneficial for gait, the timing of upper extremity function, communication outcomes, and quality of life after stroke. These results are encouraging, but more high-quality randomised controlled trials are needed on all outcomes before recommendations can be made for clinical practice.


A multisite study of long-term remission and relapse of type 2 diabetes mellitus following gastric bypass.
Gastric bypass has profound effects on glycemic control in adults with type 2 diabetes mellitus. The goal of this study was to examine the long-term rates and clinical predictors of diabetes remission and relapse among patients undergoing gastric bypass. We conducted a retrospective cohort study of adults with uncontrolled or medication-controlled type 2 diabetes who underwent gastric bypass from 1995 to 2008 in three integrated health care delivery systems in the USA. Remission and relapse events were defined by diabetes medication use and clinical laboratory measures of glycemic control. We identified 4,434 adults with uncontrolled or medication-controlled type 2 diabetes who had gastric bypass. Overall, 68.2 % (95 % confidence interval [CI], 66 and 70 %) experienced an initial complete diabetes remission within 5 years after surgery. Among these, 35.1 % (95 % CI, 32 and 38 %) redeveloped diabetes within 5 years. The median duration of remission was 8.3 years. Significant predictors of complete remission and relapse were poor preoperative glycemic control, insulin use, and longer diabetes duration. Weight trajectories after surgery were significantly different for never remitters, relapsers, and durable remitters (p = 0.03). Gastric bypass surgery is associated with durable remission of type 2 diabetes in many but not all severely obese diabetic adults, and about one third experience a relapse within 5 years of initial remission. More research is needed to understand the mechanisms of diabetes relapse, the optimal timing of surgery in effecting a durable remission, and the relationship between remission duration and incident microvascular and macrovascular events.


Fabrication and characterization of DNA-loaded zein nanospheres.
Particulates incorporating DNA are promising vehicles for gene delivery, with the ability to protect DNA and provide for controlled, localized, and sustained release and transfection. Zein, a hydrophobic protein from corn, is biocompatible and has properties that make it a promising candidate material for particulate delivery, including its ability to form nanospheres through coacervation and its insolubility under physiological conditions, making it capable of sustained release of encapsulated compounds. Due to the promise of this natural biomaterial for drug delivery, the objective of this study was to formulate zein nanospheres encapsulating DNA as the therapeutic compound, and to characterize size, charge, sustained release, cell cytotoxicity and cellular internalization of these particles. Zein nanospheres encapsulating DNA were fabricated using a coacervation technique, without the use of harsh solvents or temperatures, resulting in the preservation of DNA integrity and particles with diameters that ranged from 157.8 ± 3.9 nm to 396.8 ± 16.1 nm, depending on zein to DNA ratio. DNA encapsulation efficiencies were maximized to 65.3 ± 1.9% with a maximum loading of 6.1 ± 0.2 mg DNA/g zein. The spheres protected encapsulated DNA from DNase I degradation and exhibited sustained plasmid release for at least 7 days, with minimal burst during the initial phase of release. Zein/DNA nanospheres demonstrated robust biocompatibility, cellular association, and internalization. This study represents the first report on the formation of zein particles encapsulating plasmid DNA, using simple fabrication techniques resulting in preservation of plasmid integrity and tunable sizes. DNA encapsulation efficiencies were maximized to acceptable levels at higher zein to DNA ratios, while loading was comparable to that of other hydrophilic compounds encapsulated in zein and that of DNA incorporated into PLGA nano- and microspheres. The hydrophobic nature of zein resulted in spheres capable of sustained release of plasmid DNA. Zein particles may be an excellent potential tool for the delivery of DNA with the ability to be fine-tuned for specific applications including oral gene delivery, intramuscular delivery, and in the fabrication of tissue engineering scaffolds.


Total fluoride intake and implications for dietary fluoride supplementation.
This paper reviews the history and validity of recommended "optimal" levels of systemic fluoride intake and the available information on levels of fluoride intake in young children from foods and beverages (including water), dentifrices, dietary fluoride supplements, mouthrinses, and gels. Most of the studies emphasize the substantial variation in ingestion among individuals. Often, a substantial proportion of individuals received fluoride well beyond the mean exposure reported in the study. Limitations in the existing data make it difficult to determine the total distribution of fluoride intake from all sources. Therefore, hypothetical combinations of possible daily fluoride intake from the three main sources (diet, dentifrices, and supplements) are presented for those aged 6, 12, 24, and 36 months, with associated mean intake per kg body weight. Findings suggest that some children exceed the "optimal" level of fluoride intake from single sources alone, while others can from a combination of sources. Moreover, if current recommended "optimal" levels, which have been derived on an empirical basis, are actually lower than what has been quoted in the literature, then more children could be ingesting excessive amounts of fluoride, which could increase their risk of developing objectionable dental fluorosis. The variation and complexity of fluoride ingestion from all sources should be considered in the evaluation of recommendations for use of dietary fluoride supplements.


Homocysteine induces mesangial cell apoptosis via activation of p38-mitogen-activated protein kinase.
Hyperhomocysteinemia is prevalent among patients with chronic kidney disease (CKD) and has been linked to progressive kidney and vascular diseases. Increased glomerular mesangial cell (MC) turnover, including proliferation and apoptosis, is a hallmark of CKD. Activation of p38-mitogen-activated protein kinase (p38-MAPK) has been linked to apoptosis in many cell lines. Accordingly, we studied the effect of homocysteine (Hcy) on MC p38-MAPK signalling and apoptosis. Hcy (50 microM/24 h) increased MC apoptosis as determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end labelling (TUNEL) and single-stranded DNA (ssDNA) analysis. In addition to increases in pro-caspase-3 protein and caspase-3 activity, cells exposed to Hcy manifested enhanced reactive oxygen species content. Hcy increased p38-MAPK activity (fivefold), with maximal effect at 50 microM and 20 min; p38-MAPK activation was attenuated by N-acetylcysteine (Nac) and catalase (Cat), further indicating that the effect was via oxidative stress. Confocal microscopy revealed activation and nuclear translocation of p38-MAPK that was attenuated by Cat. In addition, Hcy-induced apoptosis as determined by TUNEL and ssDNA assay was abrogated by Nac, Cat, and SB203580 (p38-MAPK inhibitor). We conclude that in MC, Hcy (i) activates p38-MAPK and increases p38MAPK nuclear translocation via an oxidative stress dependent mechanism and (ii) induces DNA damage and apoptosis that is dependent on oxidative stress and p38-MAPK activation.


N-Acetoxy-acetylaminofluorene reacts preferentially with a control region of intracellular SV40 chromosome.
Many chemical carcinogens or their metabolites react with DNA; thus it is of interest to determine what effect chromosomal structure has on these reactions. The chromosome of simian virus 40 (SV40) is well suited for such studies; like chromatin of eukaryotic cells, it is organized into nucleosomes. The nucleotide sequence of SV40 is known, together with much about the pattern of viral gene expression and DNA replication, and the structure of the viral chromosome. We have investigated the binding of the ultimate carcinogen, N-acetoxy-acetylaminofluorene (AAAF), to specific regions of the SV40 chromosome in situ in the intact infected cell. The results, reported here, indicate that a region containing regulatory functions on the intracellular SV40 chromosome has unique structural properties which render it more susceptible to attack by AAAF than the rest of the SV40 genome. The preferential binding of AAAF to regulatory regions of chromatin may have implications for the mechanism of action of this and similar carcinogens.


B-vitamins and bone health--a review of the current evidence.
Because of ongoing global ageing, there is a rapid worldwide increase in incidence of osteoporotic fractures and the resultant morbidity and mortality associated with these fractures are expected to create a substantial economic burden. Dietary modification is one effective approach for prevention of osteoporosis in the general population. Recently, B vitamins have been investigated for their possible roles in bone health in human studies. In this review, we provide different lines of evidence and potential mechanisms of individual B vitamin in influencing bone structure, bone quality, bone mass and fracture risk from published peer-reviewed articles. These data support a possible protective role of B vitamins, particularly, B2, B6, folate and B12, in bone health. However, results from the clinical trials have not been promising in supporting the efficacy of B vitamin supplementation in fracture reduction. Future research should continue to investigate the underlying mechanistic pathways and consider interventional studies using dietary regimens with vitamin B enriched foods to avoid potential adverse effects of high-dose vitamin B supplementation. In addition, observational and interventional studies conducted in Asia are limited and thus require more attention due to a steep rise of osteoporosis and hip fracture incidence projected in this part of the world.


MPO Promoter Polymorphism rs2333227 Enhances Malignant Phenotypes of Colorectal Cancer by Altering the Binding Affinity of AP-2α.
Myeloperoxidase (MPO) promoter SNPs rs2243828 (-764T>C) and rs2333227 (G-463A) program malignant phenotypes by regulating MPO transcriptional activity. In this study, we enrolled a total of 1,175 controls and 1,078 patients with colorectal cancer with comprehensive clinical and survival information to assess whether these SNPs could affect the susceptibility and development of colorectal cancer. The MPO rs2333227 TT genotype significantly increased the risk of colorectal cancer and decreased the overall survival time of patients. Colorectal cancer cells with the rs2333227 TT genotype exhibited enhanced proliferation, migration, and invasion capacity in vitro and in vivo Mechanistically, we found that MPO SNP rs2333227 C to T mutation altered the binding affinity of the transcription factors AP-2α to the rs2333227 mutation region, sequentially enhancing expression levels of MPO and activating further IL23A-MMP9 axis-mediated oncogenic signaling. Taken together, our findings indicate that MPO SNP rs2333227 serves as a marker of enhanced risk for development of colorectal cancer.Significance: MPO polymorphisms are a guide for high risk and poor prognosis in patients colorectal cancer. Cancer Res; 78(10); 2760-9. ©2018 AACR.


DNA polymerase mu interacts with a meiosis-specific RecA homolog Lim15 during meiosis in Coprinus cinereus.
Meiosis is a fundamental process in eukaryotes. Homologous chromosomes are paired and recombined during meiotic prophase I, which results in variation among the gametes. However, the mechanism of recombination between the maternal and paternal chromosome is unknown. In this study, we report on the identification of interaction between Coprinus cinereus DNA polymerase mu (CcPol mu) and CcLim15/Dmc1, a meiosis-specific RecA-like protein, during meiosis. Interaction between these two proteins was confirmed using a GST-pull down assay. A two-hybrid assay revealed that the N-terminus of CcPol mu, which includes the BRCT domain, is responsible for binding the C-terminus of CcLim15. Furthermore, co-immunoprecipitation experiments indicate that these two proteins also interact in the crude extract of the meiotic cell. A significant proportion of CcPol mu and CcLim15 is shown to co-localize in nuclei from the leptotene/zygotene stage to the early pachytene stage during meiotic prophase I. Moreover, CcLim15 enhances polymerase activity of CcPol mu early in the reaction. These results suggest that CcPol mu might be recruited by CcLim15 and elongate the D-loop structure during homologous recombination in meiosis.


Factors Associated with Interstitial Lung Disease in Patients with Polymyositis and Dermatomyositis: A Systematic Review and Meta-Analysis.
Interstitial lung disease (ILD) is an extramuscular manifestation that results in increased morbidity and mortality from polymyositis (PM) and dermatomyositis (DM). The aim of this study was to systematically evaluate risk factors associated with the development of ILD in PM/DM. Observational studies were identified from searching PubMed, Medline, Embase, and the Cochrane Library. Pooled odds ratios (ORs) or standardized mean differences (SMDs) and corresponding 95% confidence intervals (CIs) were obtained for the relationships between risk factors and ILD in PM/DM using either fixed- or random-effects models, whichever were appropriate. Heterogeneity tests, sensitivity analyses, and publication bias assessments were also performed. Twenty-three studies were selected for a meta-analysis that included 834 patients and 1245 control subjects. Risk factors that may have increased the risk of developing ILD in PM/DM patients included older age at diagnosis (SMD, 0.35; 95% CI, 0.18-0.52; P < 0.0001), arthritis/arthralgia (OR, 3.17; 95% CI, 1.99-5.04; P < 0.00001), fever (OR, 2.31; 95% CI, 1.42-3.76; P = 0.0007), presence of anti-Jo-1 antibodies (OR, 3.34; 95% CI, 2.16-5.16; P < 0.00001), elevated erythrocyte sedimentation rate (ESR; SMD, 0.48; 95% CI, 0.32-0.64; P < 0.00001), presence of anti-MDA5 antibodies (OR, 18.26; 95% CI, 9.66-34.51; P < 0.00001), and elevated C-reactive protein level (CRP; OR, 3.50; 95% CI, 1.48-8.28; P = 0.004). Meanwhile, malignancy (OR, 0.36; 95% CI, 0.18-0.72; P = 0.004) reduced the risk of developing ILD in PM/DM patients. Our meta-analysis results suggest that the association between PM/DM and ILD may be due to such risk factors as older age at diagnosis, arthritis/arthralgia, fever, presence of anti-Jo-1 antibodies, elevated ESR, presence of anti-MDA5 antibodies, and elevated CRP level, while malignancy was associated with a reduced risk of developing ILD. Thus, these variables may be used to guide screening processes for ILD in patients with PM/DM.


Viral vectors for malaria vaccine development.
A workshop on viral vectors for malaria vaccine development, organized by the PATH Malaria Vaccine Initiative, was held in Bethesda, MD on October 20, 2005. Recent advancements in viral-vectored malaria vaccine development and emerging vector technologies were presented and discussed. Classic viral vectors such as poxvirus, adenovirus and alphavirus vectors have been successfully used to deliver malaria antigens. Some of the vaccine candidates have demonstrated their potential in inducing malaria-specific immunity in animal models and human trials. In addition, emerging viral-vector technologies, such as measles virus (MV), vesicular stomatitis virus (VSV) and yellow fever (YF) virus, may also be useful for malaria vaccine development. Studies in animal models suggest that each viral vector is unique in its ability to induce humoral and/or cellular immune responses. Those studies have also revealed that optimization of Plasmodium genes for mammalian expression is an important aspect of vaccine design. Codon-optimization, surface-trafficking, de-glycosylation and removal of toxic domains can lead to improved immunogenicity. Understanding the vector's ability to induce an immune response and the expression of malaria antigens in mammalian cells will be critical in designing the next generation of viral-vectored malaria vaccines.


A forward osmosis-membrane distillation hybrid process for direct sewer mining: system performance and limitations.
This study demonstrates the robustness and treatment capacity of a forward osmosis (FO)-membrane distillation (MD) hybrid system for small-scale decentralized sewer mining. A stable water flux was realized using a laboratory-scale FO-MD hybrid system operating continuously with raw sewage as the feed at water recovery up to 80%. The hybrid system also showed an excellent capacity for the removal of trace organic contaminants (TrOCs), with removal rates ranging from 91 to 98%. The results suggest that TrOC transport through the FO membrane is governed by "solute-membrane" interaction, whereas that through the MD membrane is strongly correlated to TrOC volatility. Concentrations of organic matter and TrOCs in the draw solution increased substantially as the water recovery increased. This accumulation of some contaminants in the draw solution is attributed to the difference in their rejection by the FO and MD systems. We demonstrate that granular activated carbon adsorption or ultraviolet oxidation could be used to prevent contaminant accumulation in the draw solution, resulting in near complete rejection (>99.5%) of TrOCs.


Mobilization of the genes for photosynthesis from Rhodopseudomonas capsulata by a promiscuous plasmid.
Plasmid pBLM2, a derivative of RP1 with enhanced chromosome mobilization activity in Rhodopseudomonas capsulata, was isolated by screening rare exconjugant clones for sex factor activity. pBLM2 mobilized all known genes affecting photosynthesis as well as chromosomal genes for streptomycin and rifampin resistance and tryptophan and cytochrome biosynthesis. Tight linkage was exhibited among the genes affecting photosynthesis. The frequency of successful transfer of chromosomal markers reached 6 X 10(-4) per donor cell. R-primes were occasionally formed during conjugation, and a number of R-primes bearing the genes for photosynthesis were isolated by screening R. capsulata exconjugants with complementation phenotypes for the ability to transmit plasmid-borne R. capsulata genes to Escherichia coli cells. These R-primes were unstable in R. capsulata, but stable in E. coli or Pseudomonas fluorescens. Complementation and recombination events that occurred upon introduction of R-primes into R. capsulata mutants with altered photosynthetic apparatuses could be visualized as variations in colony pigmentation. Each R-prime studied complemented all known types of mutation affecting the differentiation of the photosynthetic apparatus, and no other R. capsulata gene was identified on those plasmids. The R. capsulata genes borne on the R-primes were not functional in E. coli or P. fluorescens.


Incomplete inversion of the hippocampus--a common developmental anomaly.
Incomplete inversion of the hippocampus, an imperfect fetal development, has been described in patients with epilepsy or severe midline malformations. We studied this condition in a nonepileptic population without obvious developmental anomalies. We analyzed the coronal MR images of 50 women and 50 men who did not have epilepsy. Twenty of them were healthy volunteers and 80 were patients without obvious intracranial developmental anomalies, intracranial masses, hydrocephalus or any condition affecting the temporal lobes. If the entire hippocampus (the head could not be evaluated) were affected, the incomplete inversion was classified as total, otherwise as partial. Incomplete inversion of the hippocampus was found in 19/100 subjects (9 women, 10 men). It was unilateral, always on the left side, in 13 subjects (4 women, 9 men): 9 were of the total type, 4 were partial. It was bilateral in six subjects (five women, one man): four subjects had total types bilaterally, two had a combination of total and partial types. The collateral sulcus was vertically oriented in all subjects with a deviating hippocampal shape. We conclude that incomplete inversion of the hippocampus is not an unusual morphologic variety in a nonepileptic population without other obvious intracranial developmental anomalies.


Metabolic and Cardiovascular Responses on a Novel, Whole Body Exercise Device Compared to a Cycle Ergometer.
The purpose of this study was to compare the metabolic effects during a similar bout of exercise on a novel, whole body exercise device (Fish and Kangaroo Machine; FKM) and a cycle ergometer. Recreationally active men and women (n =13) completed two exercise sessions. The exercise protocol included intervals alternating between exercise (3-min) and rest (3-min) for a total duration of 39-min. The exercise intensity between the two modes was matched based on heart rate response. Heart rate, cardiac output, and stroke volume were measured using a wireless telemetry technique (Physioflow Enduro). Oxygen consumption (VO2) was measured via breath-by-breath automated analysis of expired respiratory gas (MGC Diagnostics Ultima). Capillary blood lactate was measured using a handheld meter (LactatePlus). While maintaining the heartrate response, stroke volume presented at a higher-level during rest periods, although not significant. There was also higher cardiac output at the end of the exercise bout with the FKM. VO2 was lower at the same heart rate and peak lactate was higher during FKM exercise. Cardiovascular recovery was improved following FKM exercise compared to cycling. The observed responses demonstrated that for a similar heart rate response, the FKM has an enhanced anaerobic metabolic component compared to cycling. These findings demonstrate the FKM may represent a novel exercise device comparable to cycling with unique anaerobic training potential.


Detection of Cyclooxygenase-2-Derived Oxygenation Products of the Endogenous Cannabinoid 2-Arachidonoylglycerol in Mouse Brain.
Cyclooxygenase-2 (COX-2) catalyzes the formation of prostaglandins, which are involved in immune regulation, vascular function, and synaptic signaling. COX-2 also inactivates the endogenous cannabinoid (eCB) 2-arachidonoylglycerol (2-AG) via oxygenation of its arachidonic acid backbone to form a variety of prostaglandin glyceryl esters (PG-Gs). Although this oxygenation reaction is readily observed in vitro and in intact cells, detection of COX-2-derived 2-AG oxygenation products has not been previously reported in neuronal tissue. Here we show that 2-AG is metabolized in the brain of transgenic COX-2-overexpressing mice and mice treated with lipopolysaccharide to form multiple species of PG-Gs that are detectable only when monoacylglycerol lipase is concomitantly blocked. Formation of these PG-Gs is prevented by acute pharmacological inhibition of COX-2. These data provide evidence that neuronal COX-2 is capable of oxygenating 2-AG to form a variety PG-Gs in vivo and support further investigation of the physiological functions of PG-Gs.


Safety and efficacy of inactivated African horse sickness (AHS) vaccine formulated with different adjuvants.
African horse sickness virus (AHSV) is a virus species in the genus Orbivirus of the family Reoviridae causing African Horse Sickness (AHS) in equids with a mortality of about 95% in naïve horses. AHS causes serious losses in developing countries where horses play a central role in draft power and transportation. There are nine AHSV serotypes inducing no or low cross-neutralizing antibodies. AHSV is spread by biting Culicoides midges. AHS is endemic in sub-Saharan Africa, and a serious threat outside Africa, since Culicoides species in moderate climate conditions are spreading the closely related bluetongue virus. AHS outbreaks will be devastating for the equestrian industry in developed countries. Live-attenuated vaccines (LAVs) are licensed, marketed and in use in Africa. Their application is controversial with regard to safety issues. LAVs are not allowed in AHS-free countries. We here studied inactivated AHSV with different adjuvants in guinea pigs and horses. Subcutaneous and intramuscular vaccination were studied in horses. Local reactions were observed after prime and boost vaccination. In general, neutralizing antibodies (nAbs) titres were very low after prime vaccination, whereas boost vaccination resulted in high nAb titres for some adjuvants. Vaccinated horses were selected based on local reactions and nAb titres to study efficacy. Unfortunately, not all vaccinated horses survived virulent AHSV infection. Further, most survivors temporarily developed clinical signs and viremia. Further, the current prototype inactivated AHS vaccine is not suitable as emergency vaccine, because onset of protection is slow and requires boost vaccinations. On the other hand, inactivated AHS vaccine is completely safe with respect to virus spread, and incorporation of the DIVA principle based on NS3/NS3a serology and exploring a vaccine production platform for other serotypes is feasible. A superior adjuvant increasing the protective response without causing local reactions will be required to develop payable and acceptable inactivated AHS vaccines.


A SEROLOGICAL DIFFERENTIATION OF HUMAN AND OTHER GROUPS OF HEMOLYTIC STREPTOCOCCI.
1. All except two of 106 strains of hemolytic streptococci isolated from man, other animals, milk, and cheese have been classified into five groups, which bear a definite relationship to the sources of the cultures. These broad groups may be subdivided into specific types by methods discussed elsewhere. The specific group classification is made possible by employing two special reagents: (a) extracts prepared by treatment of the bacteria with hot hydrochloric acid, and (b) serum of animals immunized with formalinized cultures. This differentiation is not detected by the agglutination reaction. The grouping agrees with that described by other investigators on the basis of cultural and biochemical characteristics. 2. The group-specific substance present in strains of Group A has been identified chemically as carbohydrate in nature. The chemical composition of the specific substances upon which the specificity of the other groups depends has not been determined. It seems not unlikely, however, that all of them may belong in the general class of carbohydrates, each being chemically distinct and serologically specific in the individual groups.


An overview of heart failure in low- and middle-income countries.
Heart failure (HF) is a global public health concern with disproportionate socioeconomic, morbidity and mortality burden on low- and middle-income countries (LMICs). This review summarises contemporary data on the demographic and clinical characteristics, aetiologies, treatment, economic burden and outcomes of HF in LMICs. Patients with HF in LMICs are younger than those from high-income countries (HICs) and present at advanced stages of the disease. Hypertension, ischaemic heart disease (IHD), cardiomyopathy (CMO), and rheumatic heart disease (RHD) are the leading causes of HF in LMICs. The contribution of infectious diseases to HF remains prominent in many LMICs. Most health facilities in LMICs lack adequate diagnostic tools for HF, and the use of evidence-based medical and device therapies is suboptimal. Further, HF in LMICs is associated with prolonged hospital stay and high in-hospital and one-year mortality. Finally, HF has profound economic impact on individual patients who, mostly, have no health insurance, and on societies where patients are young, comprising those who have the greatest potential to contribute to economic productivity.


High impact running improves learning.
Regular physical exercise improves cognitive functions and lowers the risk for age-related cognitive decline. Since little is known about the nature and the timing of the underlying mechanisms, we probed whether exercise also has immediate beneficial effects on cognition. Learning performance was assessed directly after high impact anaerobic sprints, low impact aerobic running, or a period of rest in 27 healthy subjects in a randomized cross-over design. Dependent variables comprised learning speed as well as immediate (1 week) and long-term (>8 months) overall success in acquiring a novel vocabulary. Peripheral levels of brain-derived neurotrophic factor (BDNF) and catecholamines (dopamine, epinephrine, norepinephrine) were assessed prior to and after the interventions as well as after learning. We found that vocabulary learning was 20 percent faster after intense physical exercise as compared to the other two conditions. This condition also elicited the strongest increases in BDNF and catecholamine levels. More sustained BDNF levels during learning after intense exercise were related to better short-term learning success, whereas absolute dopamine and epinephrine levels were related to better intermediate (dopamine) and long-term (epinephrine) retentions of the novel vocabulary. Thus, BDNF and two of the catecholamines seem to be mediators by which physical exercise improves learning.


Ventilatory Ratio Threshold for Unassisted Breathing: A Retrospective Exploratory Analysis.
The ventilatory ratio (VR) is a simple index of ventilatory efficiency and dead space. Because increased dead space and high ventilatory demands impose a limitation to unassisted ventilation, and may predispose patients to injurious strong efforts during assisted ventilation, evaluation of the VR could provide helpful information during weaning. We hypothesize that there is a threshold of VR associated with tolerance of unassisted breathing. In a retrospective analysis, we included subjects ventilated in a control mode for at least 24 h, who were successfully liberated from mechanical ventilation, without use of noninvasive ventilation, and discharged alive from the ICU. We focused on the successful weaning attempts (the last, if more than one was performed) and evaluated the VR at the beginning and at the end of the assisted ventilation period. We examined 2,000 medical records and included in our analysis 572 subjects (age: 68 y, R5-95 = 25-85, 68% male) with main admission diagnosis of respiratory failure (23%), sepsis (11%), brain injury (34%), and postoperative (14%). The VR at the beginning and the end of the assisted ventilation period was 1.5 (R5-95 = 1-2.1) and 1.4 (R5-95 = 1-2), respectively. The median duration of assisted ventilation in subjects with a VR ≥ 2 at the beginning of the assisted ventilation period was 3 d (R5-95 = 0-14 d), significantly longer than in those with a VR < 2, 0.5 d (R5-95 = 0-8 d, P < .001). Successful liberation from assisted ventilation was associated with a VR < 2. A VR > 2 was associated with longer duration of weaning. The VR could be used as an additional tool to facilitate the decision-making process during weaning.


Early Cord Metabolite Index and Outcome in Perinatal Asphyxia and Hypoxic-Ischaemic Encephalopathy.
A 1H-NMR-derived metabolomic index based on early umbilical cord blood alterations of succinate, glycerol, 3-hydroxybutyrate and O-phosphocholine has shown potential for the prediction of hypoxic-ischaemic encephalopathy (HIE) severity. To evaluate whether this metabolite score can predict 3-year neurodevelopmental outcome in infants with perinatal asphyxia and HIE, compared with current standard biochemical and clinical markers. From September 2009 to June 2011, infants at risk of perinatal asphyxia were recruited from a single maternity hospital. Cord blood was drawn and biobanked at delivery. Neonates were monitored for development of encephalopathy both clinically and electrographically. Neurodevelopmental outcome was assessed at 36-42 months using the Bayley Scales of Infant and Toddler Development, ed. III (BSID-III). Death and cerebral palsy were also considered as abnormal end points. Thirty-one infants had both metabolomic analysis and neurodevelopmental outcome at 36-42 months. No child had a severely abnormal BSID-III result. The metabolite index significantly correlated with outcome (ρ2 = 0.30, p < 0.01), which is robust to predict both severe outcome (area under the receiver operating characteristic curve: 0.92, p < 0.01) and intact survival (0.80, p = 0.01). There was no correlation between the index score and performance in the individual BSID-III subscales (cognitive, language, motor). The metabolite index outperformed other standard biochemical markers at birth for prediction of outcome at 3 years, but was not superior to EEG or the Sarnat score.


Peripheral Neuropathy in Children With Chronic Kidney Disease: Are We Looking Enough?
Peripheral neuropathy in chronic kidney disease (CKD) is the most common neurological complication. We aimed to look at the prevalence and patterns of neuropathy in children with CKD. This cross-sectional study was conducted over 1 year in children with CKD, stage III and above. Nerve conduction studies (NCS) were performed as per standard protocols using surface electrodes on the muscles and by supramaximal stimulation of the corresponding nerves. Presence of electrophysiological abnormalities in the absence of clinical symptoms or signs was considered as subclinical neuropathy. Nearly 45 children were evaluated. The majority were males (n = 39, 86.7%). The mean age was 7.9 ± 3 years (range 2-14). The mean estimated glomerular filtration rate (GFR) at enrolment was 23.3 ± 14.6 mL/min/1.73 m2 (range 5-67). The majority of children were in stage III (n = 19, 42%), followed by stages V (n = 15, 33%) and IV (n = 11, 25%). There was no evidence of clinical neuropathy; 13 children (29%) showed subclinical neuropathy. All the nerves had an axonal pattern of involvement. Motor polyneuropathy was most common type of peripheral neuropathy. The commonest nerves involved were tibial and common peroneal nerves. There were no biochemical or clinical predictors of neuropathy in our cohort. The prevalence of subclinical neuropathy is high in children with CKD, stage III and above. Axonal motor polyneuropathy is the predominant pattern. Electrophysiological assessment of nerve function should be routinely done in children with advanced stages of CKD to prevent chronic complications.


Promoting E2F1-mediated apoptosis in oestrogen receptor-α-negative breast cancer cells.
Because oestrogen receptor α (ERα) regulates E2F1 expression to mediate tamoxifen resistance in ERα-positive breast cancer cells, we aimed to define the possible roles of ERα and E2F1 in promoting the resistance of ERα-negative breast cancer cells to 4-hydroxy-tamoxifen (4OHT). This study utilised conventional techniques to demonstrate the effects of 4OHT on the expression of ERα and E2F1 and also examined the individual and combined effects of 4OHT with dipyridamole (DIPY) and 3-O-(3,4,5-trimethoxybenzoyl)-(-)-catechin (TMCG) on the oestrogen-negative MDA-MB-231 breast cancer cell line using viability assays, Hoechst staining, MALDI-TOF mass spectroscopy, and confocal microscopy. Despite the ERα-negative status of the MDA-MB-231 cells, we observed that 4OHT efficiently up-regulated ERα in these cells and that this upregulation promoted E2F1-mediated cell growth. Because E2F1 plays a dual role in cell growth/apoptosis, we designed a therapy incorporating TMCG/DIPY to take advantage of the elevated E2F1 expression in these 4OHT-treated cells. 4OHT enhances the toxicity of TMCG/DIPY in these ERα-negative breast cancer cells. Because TMCG/DIPY treatment modulates the methylation status/stability of E2F1, the results demonstrate that therapies targeting the epigenetic machinery of cancer cells in the presence of overexpressed E2F1 may result in efficient E2F1-mediated cell death.


Effect of nasal balloon autoinflation in children with otitis media with effusion in primary care: an open randomized controlled trial.
Otitis media with effusion is a common problem that lacks an evidence-based nonsurgical treatment option. We assessed the clinical effectiveness of treatment with a nasal balloon device in a primary care setting. We conducted an open, pragmatic randomized controlled trial set in 43 family practices in the United Kingdom. Children aged 4-11 years with a recent history of ear symptoms and otitis media with effusion in 1 or both ears, confirmed by tympanometry, were allocated to receive either autoinflation 3 times daily for 1-3 months plus usual care or usual care alone. Clearance of middle-ear fluid at 1 and 3 months was assessed by experts masked to allocation. Of 320 children enrolled, those receiving autoinflation were more likely than controls to have normal tympanograms at 1 month (47.3% [62/131] v. 35.6% [47/132]; adjusted relative risk [RR] 1.36, 95% confidence interval [CI] 0.99 to 1.88) and at 3 months (49.6% [62/125] v. 38.3% [46/120]; adjusted RR 1.37, 95% CI 1.03 to 1.83; number needed to treat = 9). Autoinflation produced greater improvements in ear-related quality of life (adjusted between-group difference in change from baseline in OMQ-14 [an ear-related measure of quality of life] score -0.42, 95% CI -0.63 to -0.22). Compliance was 89% at 1 month and 80% at 3 months. Adverse events were mild, infrequent and comparable between groups. Autoinflation in children aged 4-11 years with otitis media with effusion is feasible in primary care and effective both in clearing effusions and improving symptoms and ear-related child and parent quality of life. ISRCTN, No. 55208702.


Model potential study of non-valence correlation-bound anions of (C60)n clusters: the role of electric field-induced charge transfer.
A polarization model which accounts for electric field-induced charge transfer between fullerene molecules is introduced. Application of this model to the C60 dimer and trimer shows that intermolecular charge transfer makes a significant contribution to the polarizabilities of these clusters. This polarization model is incorporated into a one-electron Hamiltonian for describing non-valence correlation-bound anions, allowing us to further demonstrate that intermolecular charge transfer also results in increased stability of these anion states.


Mycotoxins and antifungal drug interactions: implications in the treatment of illnesses due to indoor chronic toxigenic mold exposures.
Chronic exposure to toxigenic molds in water-damaged buildings is an indoor environmental health problem to which escalating health and property insurance costs are raising a statewide concern in recent times. This paper reviews the structural and functional properties of mycotoxins produced by toxigenic molds and their interactive health implications with antifungal drugs. Fundamental bases of pathophysiological, neurodevelopmental, and cellular mechanisms of mycotoxic effects are evaluated. It is most likely that the interactions of mycotoxins with antifungal drugs may, at least in part, contribute to the observable persistent illnesses, antifungal drug resistance, and allergic reactions in patients exposed to chronic toxigenic molds. Safe dose level of mycotoxin in humans is not clear. Hence, the safety regulations in place at the moment remain inconclusive, precautionary, and arbitrary. Since some of the antifungal drugs are derived from molds, and since they have structural and functional groups similar to those of mycotoxins, the knowledge of their interactions are important in enhancing preventive measures.


Systematic Review of Occupational Therapy and Adult Cancer Rehabilitation: Part 1. Impact of Physical Activity and Symptom Management Interventions.
This article is the first part of a systematic review of evidence for the effectiveness of cancer rehabilitation interventions within the scope of occupational therapy that address the activity and participation needs of adult cancer survivors. This article focuses on the importance of physical activity and symptom management. Strong evidence supports the use of exercise for cancer-related fatigue and indicates that lymphedema is not exacerbated by exercise. Moderate evidence supports the use of yoga to relieve anxiety and depression and indicates that exercise as a whole may contribute to a return to precancer levels of sexual activity. The results of this review support inclusion of occupational therapy in cancer rehabilitation and reveal a significant need for more research to explore ways occupational therapy can positively influence the outcomes of cancer survivors. Part 2 of the review also appears in this issue.


Probing the ethanol-induced chain interdigitations in gel-state bilayers of mixed-chain phosphatidylcholines.
Using high-resolution differential scanning calorimetry (DSC), we have studied the effects of ethanol concentrations, [EtOH], on the main phase transition temperatures (T[m]) of the following mixed-chain phosphatidylcholines (PCs): C(15):C(17)PC, C(17):C(15)PC, and C(12):C(20)PC. These lipids have a common molecular weight; however, their apparent acyl chain-length differences between the sn-1 and sn-2 acyl chains, delta C, are distinctively different. The delta C values for these three mixed-chain PCs are, respectively, 0.5, 3.5, and 6.5 C-C bond lengths. DSC results show that the T(m) profiles for C(15):C(17)PC and C(17):C(15)PC bilayers in the plot of T(m) versus [EtOH] are V-shaped biphasic curves, with the minimum T(m) occurring at 50 and 73 mg/ml of ethanol, respectively. In contrast, the C(12):C(20)PC bilayer exhibits a nearly linear decrease in T(m) with increasing [EtOH]. In addition, x-ray diffraction experiments were also performed to assess the structural changes of these three mixed-chain PCs in the gel-state bilayers, at 20 degrees C, in response to high concentrations of ethanol. X-ray diffraction data indicate that, in the absence of ethanol, these three lamellar lipids are all packed in the normal (L beta') gel phase in aqueous media. In the presence of 120 mg/ml of ethanol, however, the C(15):C(17)PC and C(17):C(15)PC lamellae are packed in the fully interdigitated (L beta[I]) gel phase. The V-shaped T(m) curves detected calorimetrically for these two lipids in response to [EtOH] can thus be explained by the ethanol-induced L beta' --> L beta[I] isothermal phase transition. Interestingly, the results of x-ray diffraction study reveal, for the first time, that an ethanol-induced L beta' --> L(MI) (mixed interdigitated phase) isothermal phase transition occurs in the gel-state bilayer of highly asymmetrical C(12):C(20)PC. Therefore, the chain asymmetry is recognized to play an important role in the ethanol-induced chain interdigitation at T < T(m).


Familial associations with EEG variants in manic-depressive disease.
Electroencephalographic (EEG) studies of 60 patients with bipolar manic-depressive disease disclosed an incidence of small sharp spikes plus a few other variations in 47% of the sample. In women these EEG features were significantly associated with a history of mental illness in the patient's mother or the maternal side of the family and an absence of mental disorder in the fathers. The reverse was true of women probands without these EEG characteristics. In the men small sharp spikes did not relate to parental psychopathology but half of the sisters of men with these EEG characteristics were found to be mentally ill. On the basis of these observations and previous work, we hypothesize that the small sharp spike EEG pattern might be an inherited characteristic related in some way to the familal transmission of manic-depressive disease.


Prevalence, management and outcome of early adenocarcinoma (pT1) of the esophago-gastric junction. Comparison between early cancer in Barrett's esophagus (type I) and early cancer of the cardia (type II).
The study compares, in true adenocarcinoma of the cardia and in adenocarcinoma in Barrett's esophagus, the prevalence of early cancers and their outcome in those patients suitable for resection surgery. From 1980 to 1993, 26 of 350 (7.4%) resected adenocarcinomas of the esophago-gastric junction were pathologically staged as early cancer or pT1. The prevalence of early cancer was 3.7% (11/294) for true cancer of the cardia and 27% (15/56) for cancer in Barrett's esophagus (P < 0.001). Ten of the 15 latter cancers were diagnosed during endoscopic surveillance for benign Barrett's esophagus. Among early cancers, there were four mucosal and 22 submucosal tumours; of the latter, eight had lymph node metastasis and seven neoplastic permeation of lympho-hematic vessels. The most frequently used surgical procedure was esophago-gastric resection and gastric pull-up. Postoperative morbidity was 15.4%, and hospital mortality 3.8%. Excluding postoperative deaths, the overall 5-year survival rate was 79% for early cancer of the cardia and 83% for early cancer in Barrett's esophagus (log rank test = 0.0214, P = 0.88). Overall, the survival rate was 100% in the absence of lymph node metastasis and 43% in the presence of node metastasis (log rank test = 15.811, P = 0.0001). Only one of five patients with both node metastasis and vessel infiltration survived longer than 5 years. In conclusion, the prevalence of early cancer was significantly greater for cancer in Barrett's esophagus than for true cancer of the cardia. Prognosis of the two types of tumour after resection surgery was the same and depended on lymph node status and neoplastic permeation of lympho-hematic vessels.


Implications of hormonal influences on sexual behavior for demographic models of reproduction.
In exploring the implications of hormonal influences on sexual behavior for reproduction, we have focused on androgens because of the convincing evidence for androgenic effects on female sexual motivation. We have been guided by the simple idea, based on clinical findings among hyperandrogenic women, that higher testosterone levels will increase female sexual motivation which in turn will result in increased coital frequency. However, careful consideration of the evidence fails to confirm such a role for testosterone in sexual behavior among normal women at any point in the reproductive span. While some amount of testosterone appears to be important in maintaining female sexual motivation, there is little evidence that variation in testosterone within the normal range is associated with variation in sexual motivation. Reported associations between testosterone and sexual behavior among married women cannot be interpreted as resulting from androgenic effects on sexual motivation. Thus we are left with the task of explaining why testosterone does not appear to play the same role in libido among hyperandrogenic and normal women. As mentioned earlier, some of the difference may attributable to the much higher levels of testosterone among hyperandrogenic women. Sherwin points out that the levels of sexual motivation decline with declining testosterone levels even while testosterone is well above normally occurring levels. It is possible that the brain is simply not sensitive to the variation in testosterone levels found in normal women. Other evidence suggests that the presence of intact ovaries may be equally important. A recent study of androgen replacement in naturally post-menopausal women failed to find a dramatic effect of testosterone on sexual motivation and behavior, despite levels similar to those in studies on surgically menopausal women, pointing to the importance of other factors associated with the presence of ovaries. A similar point can be made with regard to hyperandrogenism related to endogenous sources of testosterone, as in the case of PCOS. High levels of testosterone effectively disrupt ovarian function and interfere with other ovarian processes. Among hyperandrogenic women sexual behavior appears to be related to the direct effects of androgens on motivation, while the indirect effects of estrogen and progesterone are essentially eliminated. Among normal women, on the other hand, there is little evidence for such a dominating role of a direct androgenic effect on sexual behavior. Instead, other ovarian hormones, including estrogen and progesterone may also play a demonstrable role, despite the lack of strong evidence at this point.(ABSTRACT TRUNCATED AT 400 WORDS)


The genus Hatschekia (Copepoda: Hatschekiidae) from pufferfishes (Tetraodontiformes: Tetraodontidae) off the Ryukyu Islands, Japan, with descriptions of four new species and a redescription of H. pholas.
Four new species of the genus Hatschekia Poche, 1902 (Copepoda: Siphonostomatoida: Hatschekiidae) are described based on female specimens collected from pufferfishes (Tetraodontiformes: Tetraodontidae) caught in coastal waters off the Ryukyu Islands, Japan: H. longiabdominalis sp. n. on Arothron hispidus (Linnaeus), H. geniculata sp. n. on A. hispidus (type host) and A. stellatus (Bloch et Schneider), H. ellipsocorpa sp. n. on A. mappa (Lesson), and H. boonah sp. n. on A. nigropunctatus (Bloch et Schneider) (type host) and A. meleagris (Schneider). Hatschekia longiabdominalis sp. n. and H. boonah sp. n. differ from all other congeners by sharing an unusual, projected abdomen and a fusiform trunk with posterior lobes; these two species are differentiated from each other by the shape of the dorsal chitinous frame on the cephalothorax. Hatschekia geniculata sp. n. can be distinguished by the combination of the following morphological characters: a rhomboidal cephalothorax with a pair of lateral conical protrusions, a cylindrical trunk with posterior lobes and a bent abdomen with a dorsal protrusion. Hatschekia ellipsocorpa sp. n. resembles H. pholas (Wilson, 1906) but can be distinguished from the latter by the possession of one distal and one inner setae on the terminal endopodal segment of legs 1 and 2. Hatschekiapholas is also redescribed based on female specimens from the tetraodontid A. stellatus. At present, 44 nominal species of the genus have been reported from Japan, including four new species described in this paper; 38 of them have been described originally from Japan.


Primary extradural meningiomas: a report on nine cases and review of the literature from the era of computerized tomography scanning.
Primary meningiomas arising outside the intracranial compartment (primary extradural meningiomas [PEMs]) are rare tumors. To develop a better understanding of these tumors and to establish a comprehensive classification scheme for them, the authors analyzed a series of patients treated at the M. D. Anderson Cancer Center (MDACC) and reviewed all cases reported in the English-language literature since the inception of the use of computerized tomography (CT) scanning. Clinical records, results of radiographic studies, and histological slides were reviewed for all cases of PEM at MDACC. Demographic features, symptoms, tumor location, histological grade, and patient outcome were assessed in all cases. A comprehensive literature search identified 168 PEMs in 142 patients reported during the CT era. These reports were also analyzed for common features. Tumors for both data sets were classified as purely extracalvarial (Type I), purely calvarial (Type II), and calvarial with extracalvarial extension (Type III). Type II and Type III tumors were further categorized as convexity (C) or skull base (B) lesions. The incidence of PEMs at MDACC was 1.6%, which was consistent with the rate reported in the literature. In both data sets, the male/female ratio was nearly 1:1. The most common presenting symptom was a gradually expanding mass. The age of patients at diagnosis of PEM was bimodal, peaking during the second decade and during the fifth to seventh decades. In all MDACC cases and in 90% of those reported in the literature the PEMs were located in the head and neck. The majority of tumors originated in the skull (70%). In the MDACC series and in the literature review, the majority (67% and 89%, respectively) of tumors were histologically benign. Although fewer PEMs were malignant or atypical (33% at MDACC and 11% in the literature), their incidence was higher than that observed for primary intracranial meningiomas. Distant metastasis was not a common feature reported for patients with PEMs (6% in the literature). Outcome data were available in 96 of the cases culled from the CT-era literature. The combination of the MDACC data and the data obtained from the literature demonstrated that patients with benign Type IIB or Type IIIB lesions were more likely to experience recurrence than patients with benign Type IIC or Type IIIC tumors (26% compared with 0%, p < 0.05). The more aggressive atypical and malignant tumors were associated with a statistically significant higher death rate (29%) relative to benign tumors (4.8% death rate, p < 0.004). Defining a tumor as a PEM is dependent on the tumor's relation to the dura mater and the extent and direction of its growth. Classification of PEMs as calvarial or extracalvarial and as convexity or skull base lesions correlates well with clinical outcome.


Activation of endoplasmic reticulum stress response by enhanced polyamine catabolism is important in the mediation of cisplatin-induced acute kidney injury.
Cisplatin-induced nephrotoxicity limits its use in many cancer patients. The expression of enzymes involved in polyamine catabolism, spermidine/spermine N1-acetyltransferase (SSAT) and spermine oxidase (SMOX) increase in the kidneys of mice treated with cisplatin. We hypothesized that enhanced polyamine catabolism contributes to tissue damage in cisplatin acute kidney injury (AKI). Using gene knockout and chemical inhibitors, the role of polyamine catabolism in cisplatin AKI was examined. Deficiency of SSAT, SMOX or neutralization of the toxic products of polyamine degradation, H2O2 and aminopropanal, significantly diminished the severity of cisplatin AKI. In vitro studies demonstrated that the induction of SSAT and elevated polyamine catabolism in cells increases the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) and enhances the expression of binding immunoglobulin protein BiP/GRP78) and CCAAT-enhancer-binding protein homologous protein (CHOP/GADD153). The increased expression of these endoplasmic reticulum stress response (ERSR) markers was accompanied by the activation of caspase-3. These results suggest that enhanced polyamine degradation in cisplatin AKI may lead to tubular damage through the induction of ERSR and the consequent onset of apoptosis. In support of the above, we show that the ablation of the SSAT or SMOX gene, as well as the neutralization of polyamine catabolism products modulate the onset of ERSR (e.g. lower BiP and CHOP) and apoptosis (e.g. reduced activated caspase-3). These studies indicate that enhanced polyamine catabolism and its toxic products are important mediators of ERSR and critical to the pathogenesis of cisplatin AKI.


Danish nationwide registers for public health and health-related research.
The Nordic countries have a strong tradition of using nationwide social and health registers for research purposes. The aim of the current paper is to provide an overview of the Danish population-based registers in public health and health-related research, and to discuss their strengths and limitations. Danish registers on somatic and psychiatric hospital contacts as well as care provided by general practitioners were reviewed. The availability of demographic, individual-level variables of relevance for health-related research was summarized. Since 1968, every person living in Denmark has a unique identifier. This identifier is listed in Danish registers enabling linkage of information from a range of registers on an individual level. The nationwide coverage of all patient contacts at somatic and psychiatric hospitals, consultations with general practitioners, purchases of prescribed medications, and a complete follow-up with respect to causes of death support public health studies surveying trends of prevalence and incidence. Historical data on psychiatric and somatic hospitalizations since 1969 and 1977, respectively, allow an in-depth assessment of the burden of disease and time trends. Demographic characteristics of individuals and family units, together with information on education, employment, income, place of residence and migration, are provided by social registers. Register data are fully representative of the entire population with no loss to follow-up. Nationwide coverage also ensures a large sample to investigate events and conditions with low base rates. Clinical observations are limited and often only available for select patient populations. However, the opportunities available for public health research through linkage of register data with the increasing number of nationwide clinical databases, bio-banks and surveys entail promising perspectives for future research.


Global ecotypes in the ubiquitous marine clade SAR86.
SAR86 is an abundant and ubiquitous heterotroph in the surface ocean that plays a central role in the function of marine ecosystems. We hypothesized that despite its ubiquity, different SAR86 subgroups may be endemic to specific ocean regions and functionally specialized for unique marine environments. However, the global biogeographical distributions of SAR86 genes, and the manner in which these distributions correlate with marine environments, have not been investigated. We quantified SAR86 gene content across globally distributed metagenomic samples and modeled these gene distributions as a function of 51 environmental variables. We identified five distinct clusters of genes within the SAR86 pangenome, each with a unique geographic distribution associated with specific environmental characteristics. Gene clusters are characterized by the strong taxonomic enrichment of distinct SAR86 genomes and partial assemblies, as well as differential enrichment of certain functional groups, suggesting differing functional and ecological roles of SAR86 ecotypes. We then leveraged our models and high-resolution, remote sensing-derived environmental data to predict the distributions of SAR86 gene clusters across the world's oceans, creating global maps of SAR86 ecotype distributions. Our results reveal that SAR86 exhibits previously unknown, complex biogeography, and provide a framework for exploring geographic distributions of genetic diversity from other microbial clades.


Disability and disability benefit seeking in chronic low back pain.
Numerous studies suggest psychosocial factors contribute to functional disability in patients with chronic low back pain (CLBP). However, less is known about the association of psychosocial factors, such as depression, with seeking medical disability benefits and their prevalence in benefit seekers compared with patients already receiving such payments. To determine if characteristics of disability benefit seekers differ from patients receiving disability benefits and if both differ from patients not dependent on such payments. Questionnaire data on pain, health-related quality of life, depression, social support, substance abuse, adverse childhood experiences and disability seeking were obtained from CLBP respondents recruited at 10 primary care clinics throughout Texas. A multinomial logistic regression model was computed using variables significantly associated with disability status and pain severity in univariate models. There were 213 participants. In full models, compared with those not on disability benefits, only depression symptoms were significantly associated with seeking disability benefits (odds ratio [OR] = 1.13; 95% confidence interval [CI] 1.01-1.26) and only duration of pain was significantly associated with being on such benefits (OR = 1.05; 95% CI 1.01-1.09). Patient characteristics differ between disability benefit seekers and those established on disability benefit payments. Depression may be a modifiable correlate of disability benefit seeking that if treated may reduce the number of patients who eventually come to depend on disability benefits. Additional data collection involving other pain syndromes is warranted to determine if these results are unique to CLBP or apply to other painful conditions.


Transmission of HTLV-III infection from human plasma to chimpanzees: an animal model for AIDS.
Two of three chimpanzees given plasma from patients with acquired immune deficiency syndrome (AIDS) or pre-AIDS showed serum antibodies to type III human T-cell leukemia virus (HTLV-III) 10 to 12 weeks after transfusion. One animal also developed lymphadenopathy, transient depression of the ratio of T4 to T8 lymphocytes, and impaired blastogenic responses. No opportunistic infections occurred. Adenopathy persisted for 32 weeks, and antibody to HTLV-III persisted for at least 48 weeks. This transmission of HTLV-III by lymphocyte-poor plasma confirms the potential risk of such plasma or plasma derivatives to recipients. The susceptibility of the chimpanzee to HTLV-III infection and the ability to simulate the human lymphadenopathy syndrome in this animal makes it a valuable model for further study of AIDS.


Positive selection on mitochondrial M7 lineages among the Gelong people in Hainan.
Selections on human mitochondrial variations are difficult to examine. In this study, we found possible signs of selection on mitochondrial M7 lineages among the Gelong people who migrated from Guizhou to Hainan (the hottest province in China) throughout the last 1000 years. The genetic structure of the Gelong people shows an obvious sex-biased population admixture pattern with only 4.9% paternal contribution but 30.7% maternal contribution from indigenous Hlai people. According to frequency spectrum tests for deviation from neutrality and mismatch tests of demographic expansion, part of the maternal mitochondrial M7 lineages among the Gelong came from the Hlai had spread quickly and therefore might have undergone positive selection. In the future, whole mitochondrial genome sequencing might reveal the functional advantage of the M7 lineages.


Prolonged aerobic exercise: physiological studies in rat gastrocnemius with additional observations on the effects of acute mitochondrial blockade.
Protracted low frequency (1 and 5 Hz) stimulation of rat gastrocnemius in vivo leads to fatigue and fall out of glycolytic fibres with the development of a stable twitch response with continuation of the stimulus train. This model was used to examine the physiological effects of acute mitochondrial blockade on oxidative fibre function with the injection of a mitochondrial uncoupler (dinitrophenol) and a site I inhibitor (diphenyleneiodonium) intraarterially after a stable twitch response had developed. Dinitrophenol leads to progressive failure of contractility, closely followed by action potential failure and electrically silent contracture: external work accelerated this sequence but it also developed in resting muscle suggesting that DNP lead to active ATP hydrolysis and a more severe energy depletion than that encountered in human disease states. Diphenyleneiodonium also leads to progressive twitch tension and action potential failure but contracture was late and inconstant, considerable recovery in twitch parameters was seen with rest and restimulation lead to pathological fatiguability of twitch tension. This model has some similarity to human mitochondriopathies with pathological fatiguability. This acute model should allow ready testing of any therapeutic approaches which bypass respiratory chain blocks.


The house sparrow (Passer domesticus) as a sentinel for St. Louis encephalitis virus.
Birds are the primary hosts for St. Louis encephalitis (SLE) virus in most of North America. Because the increased prevalence of antibody in House Sparrows (Passer domesticus) has been related to human cases, this species has been frequently used as a sentinel of SLE virus activity in urban areas. This study investigated the susceptibility of House Sparrows to two strains of SLE virus, measured antibody profiles, and evaluated the use of House Sparrows in an urban surveillance system. House Sparrows were susceptible to both strains of SLE virus inoculated, although not equally, and produced viremias sufficient to infect vector mosquitoes. Both hemagglutination-inhibiting (HI) and neutralizing (N) antibody developed rapidly and to high titers within 2 weeks after inoculation. Detectable humoral antibody began to disappear by 3 months, but persisted for 2 years in 27% for HI and 36% for N antibody of the surviving birds. However, all of the surviving birds were resistant to reinfection with SLE virus at 2 years after inoculation. The titer of HI antibody appeared to be useful in determining recent exposure to SLE virus. The experimental data on HI antibody development and persistence was related to field serologic data from House Sparrows. The monthly prevalences of SLE antibody for independent samples of sera from House Sparrows collected in Memphis, Tennessee, in 1980 were similar. SLE amplification in the House Sparrow population was delayed until September. The Memphis arbovirus surveillance system detected the amplification quickly, and responded with increased adult mosquito control in the focal areas. Urban surveillance of SLE utilizing House Sparrows as sentinels is discussed.


Motogenic and morphogenic activity of epithelial receptor tyrosine kinases.
Receptor tyrosine kinases play essential roles in morphogenesis and differentiation of epithelia. Here we examined various tyrosine kinase receptors, which are preferentially expressed in epithelia (c-met, c-ros, c-neu, and the keratin growth factor [KGF] receptor), for their capacity to induce cell motility and branching morphogenesis of epithelial cells. We exchanged the ligand-binding domain of these receptors by the ectodomain of trkA and could thus control signaling by the new ligand, NGF. We demonstrate here that the tyrosine kinases of c-met, c-ros, c-neu, the KGF receptor, and trkA, but not the insulin receptor, induced scattering and increased motility of kidney epithelial cells in tissue culture. Mutational analysis suggests that SHC binding is essential for scattering and increased cell motility induced by trkA. The induction of motility in epithelial cells is thus an important feature of various receptor tyrosine kinases, which in vivo play a role in embryogenesis and metastasis. In contrast, only the c-met receptor promoted branching morphogenesis of kidney epithelial cells in three-dimensional matrices, which resemble the formation of tubular epithelia in development. Interestingly, the ability of c-met to induce morphogenesis could be transferred to trkA, when in a novel receptor hybrid COOH-terminal sequences of c-met (including Y14 to Y16) were fused to the trkA kinase domain. These data demonstrate that tubulogenesis of epithelia is a restricted activity of tyrosine kinases, as yet only demonstrated for the c-met receptor. We predict the existence of specific substrates that mediate this morphogenesis signal.


Improved serotonergic neurotransmission by genistein pretreatment regulates symptoms of obsessive-compulsive disorder in streptozotocin-induced diabetic mice.
Background Initial evidences have shown that diabetes mellitus occurs concomitantly with obsessive-compulsive disorder (OCD) symptomatology. Serotonergic psychiatric therapy posits that serotonin is a central character in the management of OCD. Hence, it is worth investigating novel chemical entities affecting the serotonergic system for targeting OCD. An isoflavonoid phytoestrogen, genistein, has been recognized as of great pharmacological value especially for protecting neurodegeneration, depression (serotonin regulation), and diabetes. The effectiveness of genistein pretreatment on the symptoms of OCD in streptozotocin-induced diabetic mice is investigated in this study. We also evaluate the probable involvement of the serotonergic system. Methods Groups of diabetic mice were treated with genistein at the dose of 5.0 and 10.0 mg/kg (intraperitoneal, twice daily, 14 days), and symptoms of OCD were assessed by the marble-burying behavior, in comparison with the standard drug fluoxetine. Neurochemical assessment of the serotonergic ratio 5-hydroxyindole-3-methoxyphenylacetic acid/5-hydroxytryptamine (5-HIAA/5-HT) in the cortical region of the brain was performed using HPLC (high-pressure liquid chromatography). Results Chronic treatment with genistein significantly recovered [F(6, 35)=53.00, p<0.0001, R2=0.9008] the symptoms of OCD as assessed by marble burying behavior in normal and diabetic mice. Locomotor performance was not influenced by the diabetic condition or any associated treatment. The turnover of serotonin neurotransmission (5-HIAA/5-HT) was significantly boosted in the diabetic condition; genistein treatment dragged it [F(6, 35)=35.75, p<0.0001, R2=0.8597] toward the respective control. Conclusions Genistein supplementation might be a potential therapeutic line for the management and/or prevention of diabetes-associated OCD symptomatology.


A Comparative Evaluation of Sorption, Solubility, and Compressive Strength of Three Different Glass Ionomer Cements in Artificial Saliva: An in vitro Study.
To evaluate and compare the sorption, solubility, and compressive strength of three different glass ionomer cements in artificial saliva - type IX glass ionomer cement, silver-reinforced glass ionomer cement, and zirconia-reinforced glass ionomer cement, so as to determine the material of choice for stress-bearing areas. A total of 90 cylindrical specimens (4 mm diameter and 6 mm height) were prepared for each material following the manufacturer's instructions. After subjecting the specimens to thermocycling, 45 specimens were immersed in artificial saliva for 24 hours for compressive strength testing under a universal testing machine, and the other 45 were evaluated for sorption and solubility, by first weighing them by a precision weighing scale (W1), then immersing them in artificial saliva for 28 days and weighing them (W2), and finally dehydrating in an oven for 24 hours and weighing them (W3). Group III (zirconomer) shows the highest compressive strength followed by group II (Miracle Mix) and least compressive strength is seen in group I (glass ionomer cement type IX-Extra) with statistically significant differences between the groups. The sorption and solubility values in artificial saliva were highest for glass ionomer cement type IX - Extra-GC (group I) followed by zirconomer-Shofu (group III), and the least value was seen for Miracle Mix-GC (group II). Zirconia-reinforced glass ionomer cement is a promising dental material and can be used as a restoration in stress-bearing areas due to its high strength and low solubility and sorption rate. It may be a substitute for silver-reinforced glass ionomer cement due to the added advantage of esthetics. This study provides vital information to pediatric dental surgeons on relatively new restorative materials as physical and mechanical properties of the new material are compared with conventional materials to determine the best suited material in terms of durability, strength and dimensional stability. This study will boost confidence among dental surgeons in terms of handling characteristics, cost effectiveness and success rate. This study will help clinically and scientifically; pediatric dental surgeons to use this material in stress-bearing areas in pediatric patients. Bhatia HP, Singh S, Sood S, Sharma N. A Comparative Evaluation of Sorption, Solubility, and Com-pressive Strength of Three Different Glass Ionomer Cements in Artificial Saliva: An in vitro Study. Int J Clin Pediatr Dent 2017;10(1):49-54.


Dietary krill oil enhances neurocognitive functions and modulates proteomic changes in brain tissues of d-galactose induced aging mice.
The effects of dietary krill oil on neurocognitive functions and proteomic changes in brain tissues of d-galactose-induced aging mice were evaluated. Dietary krill oil enhanced the neurocognitive functions of aging mice with a significant (P < 0.05) decrease in escape latency and an increase in the number of times of crossing over the hidden platform during the Morris water maze test. Krill oil was also found to protect against oxidative damage, lipid peroxidation and neurodegenerative diseases. Oxidative stress biomarkers of aging mice administered with krill oil showed significant (P < 0.05) improvement with an increase in serum superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels; there were insignificant changes in the serum malondialdehyde (MDA) level. In terms of proteomic changes, krill oil resulted in upregulation of the Celsr3 and Ppp1r1b gene expression, which contribute to brain development, learning and memory behavior processes. In particular, the Ppp1r1b gene is associated with the inhibition of dopamine releases, which decreases the motivation for learning.


Collagen/Beta-Tricalcium Phosphate Based Synthetic Bone Grafts via Dehydrothermal Processing.
Millions of patients worldwide remain inadequately treated for bone defects related to factors such as disease or trauma. The drawbacks of metallic implant and autograft/allograft use have steered therapeutic approaches towards tissue engineering solutions involving tissue regeneration scaffolds. This study proposes a composite scaffold with properties tailored to address the macro- and microenvironmental conditions deemed necessary for successful regeneration of bone in defect areas. The biodegradable scaffold composed of porous beta-tricalcium phosphate particles and collagen type I fibers is prepared from a mixture of collagen type-I and β-tricalcium phosphate (β-TCP) particles via lyophilization, followed by dehydrothermal (DHT) processing. The effects of both sterilization via gamma radiation and the use of DHT processing to achieve cross-linking were investigated. The impact of the chosen fabrication methods on scaffold microstructure and β-TCP particle-collagen fiber combinations were analyzed using X-ray diffractometry (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and microcomputerized tomography (µ-CT). Electron spinning resonance (ESR) analysis was used to investigate free radicals formation following sterilization. Results revealed that the highly porous (65% porosity at an average of 100 µm pore size), mechanically adequate, and biocompatible scaffolds can be utilized for bone defect repairs.


Sexual Selection, Agonistic Signaling, and the Effect of Beards on Recognition of Men's Anger Displays.
The beard is arguably one of the most obvious signals of masculinity in humans. Almost 150 years ago, Darwin suggested that beards evolved to communicate formidability to other males, but no studies have investigated whether beards enhance recognition of threatening expressions, such as anger. We found that the presence of a beard increased the speed and accuracy with which participants recognized displays of anger but not happiness (Experiment 1, N = 219). This effect was not due to negative evaluations shared by beardedness and anger or to negative stereotypes associated with beardedness, as beards did not facilitate recognition of another negative expression, sadness (Experiment 2, N = 90), and beards increased the rated prosociality of happy faces in addition to the rated masculinity and aggressiveness of angry faces (Experiment 3, N = 445). A computer-based emotion classifier reproduced the influence of beards on emotion recognition (Experiment 4). The results suggest that beards may alter perceived facial structure, facilitating rapid judgments of anger in ways that conform to evolutionary theory.


Arrhythmic risk biomarkers for the assessment of drug cardiotoxicity: from experiments to computer simulations.
In this paper, we illustrate how advanced computational modelling and simulation can be used to investigate drug-induced effects on cardiac electrophysiology and on specific biomarkers of pro-arrhythmic risk. To do so, we first perform a thorough literature review of proposed arrhythmic risk biomarkers from the ionic to the electrocardiogram levels. The review highlights the variety of proposed biomarkers, the complexity of the mechanisms of drug-induced pro-arrhythmia and the existence of significant animal species differences in drug-induced effects on cardiac electrophysiology. Predicting drug-induced pro-arrhythmic risk solely using experiments is challenging both preclinically and clinically, as attested by the rise in the cost of releasing new compounds to the market. Computational modelling and simulation has significantly contributed to the understanding of cardiac electrophysiology and arrhythmias over the last 40 years. In the second part of this paper, we illustrate how state-of-the-art open source computational modelling and simulation tools can be used to simulate multi-scale effects of drug-induced ion channel block in ventricular electrophysiology at the cellular, tissue and whole ventricular levels for different animal species. We believe that the use of computational modelling and simulation in combination with experimental techniques could be a powerful tool for the assessment of drug safety pharmacology.


Boron/nitrogen co-doped helically unzipped multiwalled carbon nanotubes as efficient electrocatalyst for oxygen reduction.
Bamboo structured nitrogen doped multiwalled carbon nanotubes have been helically unzipped, and nitrogen doped graphene oxide nanoribbons (CNx-GONRs) with a multifaceted microstructure have been obtained. CNx-GONRs have then been codoped with nitrogen and boron by simultaneous thermal annealing in ammonia and boron oxide atmospheres, respectively. The effects of the codoping time and temperature on the concentration of the dopants and their functional groups have been extensively investigated. X-ray photoelectron spectroscopy results indicate that pyridinic and BC3 are the main nitrogen and boron functional groups, respectively, in the codoped samples. The oxygen reduction reaction (ORR) properties of the samples have been measured in an alkaline electrolyte and compared with the state-of-the-art Pt/C (20%) electrocatalyst. The results show that the nitrogen/boron codoped graphene nanoribbons with helically unzipped structures (CNx/CBx-GNRs) can compete with the Pt/C (20%) electrocatalyst in all of the key ORR properties: onset potential, exchange current density, four electron pathway selectivity, kinetic current density, and stability. The development of such graphene nanoribbon-based electrocatalyst could be a harbinger of precious metal-free carbon-based nanomaterials for ORR applications.


A model of tuberculosis transmission and intervention strategies in an urban residential area.
The model herein aims to explore the dynamics of the spread of tuberculosis (TB) in an informal settlement or township. The population is divided into households of various sizes and also based on commuting status. The model dynamics distinguishes between three distinct social patterns: the exposure of commuters during travel, random diurnal interaction and familial exposure at night. Following the general SLIR models, the population is further segmented into susceptible (S), exposed/latently infected (L), active/infectious (I), and recovered (R) individuals. During the daytime, commuters travel on public transport, while non-commuters randomly interact in the community to mimic chance encounters with infectious persons. At night, each family interacts and sleeps together in the home. The risk of exposure to TB is based on the proximity, duration, and frequency of encounters with infectious persons. The model is applied to a hypothetical population to explore the effects of different intervention strategies including vaccination, wearing of masks during the commute, prophylactic treatment of latent infections and more effective case-finding and treatment. The most important findings of the model are: (1) members of larger families are responsible for more disease transmissions than those from smaller families, (2) daily commutes on public transport provide ideal conditions for transmission of the disease, (3) improved diagnosis and treatment has the greatest impact on the spread of the disease, and (4) detecting TB at the first clinic visit, when patients are still smear negative, is key.


An update on oxidative stress-mediated organ pathophysiology.
Exposure to environmental pollutants and drugs can result in pathophysiological situations in the body. Research in this area is essential as the knowledge on cellular survival and death would help in designing effective therapeutic strategies that are needed for the maintenance of the normal physiological functions of the body. In this regard, naturally occurring bio-molecules can be considered as potential therapeutic targets as they are normally available in commonly consumed foodstuffs and are thought to have minimum side effects. This review article describes the detailed mechanisms of oxidative stress-mediated organ pathophysiology and the ultimate fate of the cells either to survive or to undergo necrotic or apoptotic death. The mechanisms underlying the beneficial role of a number of naturally occurring bioactive molecules in oxidative stress-mediated organ pathophysiology have also been included in the review. The review provides useful information about the recent progress in understanding the mechanism(s) of various types of organ pathophysiology, the complex cross-talk between these pathways, as well as their modulation in stressed conditions. Additionally, it suggests possible therapeutic applications of a number of naturally occurring bioactive molecules in conditions involving oxidative stress.


Variability of lower extremity joint kinematics during backward walking in a virtual environment.
Backward walking (BW) shows significant differences with forward walking (FW) and these differences are potentially useful in rehabilitation. However the lack of visual cues makes BW risky. The purpose of this study was to investigate the effect of visual cues provided by a virtual environment on FW and BW on gait variability. Each subject underwent four conditions of treadmill walking at self-selected pace. The subjects walked backwards in three conditions and forwards in the fourth condition. A virtual corridor was displayed to the subjects in the FW condition (forward optic flow) and two of the backward conditions (forward and backward optic flow). The third BW condition was a control condition (no visual cues). Gait variability measures of the hip, knee and ankle range of motion and the stride interval were analyzed. Magnitude of variability was evaluated with the coefficient of variation and structure of variability with approximate entropy. Significant differences were demonstrated between the FW and the BW gait characteristics as well as in gait variability (for both magnitude and structure of variability). No significant differences were found between the three BW conditions as a result of the direction of visual cues. In order to get optimal benefit of BW in the aged and the diseased, optical flow of visual feedback may need to be manipulated in a different manner than FW. Future studies will explore other parameters of visual cues like the velocity of optic flow and appearance of obstacles to obtain the best visual cue configuration for rehabilitation.


Novel mutations in DLL3, a somitogenesis gene encoding a ligand for the Notch signalling pathway, cause a consistent pattern of abnormal vertebral segmentation in spondylocostal dysostosis.
The spondylocostal dysostoses (SCD) are a group of disorders characterised by multiple vertebral segmentation defects and rib anomalies. SCD can either be sporadic or familial, and can be inherited in either autosomal dominant or recessive modes. We have previously shown that recessive forms of SCD can be caused by mutations in the delta-like 3 gene, DLL3. Here, we have sequenced DLL3 in a series of SCD cases and identified 12 mutations in a further 10 families. These include 10 novel mutations in exons 4-8, comprising nonsense, missense, frameshift, splicing, and in frame insertion mutations that are predicted to result in either the truncation of the mature protein in the extracellular domain, or affect highly conserved amino acid residues in the epidermal growth factor-like repeats of the protein. The affected cases represent diverse ethnic backgrounds and six come from traditionally consanguineous communities. In all affected subjects, the radiological phenotype is abnormal segmentation throughout the entire vertebral column with smooth outlines to the vertebral bodies in childhood, for which we suggest the term "pebble beach sign". This is a very consistent phenotype-genotype correlation and we suggest the designation SCD type 1 for the AR form caused by mutations in the DLL3 gene.


Season and Weather Effects on Travel-Related Mood and Travel Satisfaction.
This study examines the effects of season and weather on mood (valence and activation) and travel satisfaction (measured by the Satisfaction with Travel Scale). Analyses are presented of 562 time-sampled morning commutes to work made by 363 randomly sampled people in three different Swedish cities asking them to use smartphones to report their mood in their home before and directly after the commutes. These reports as well as satisfaction with the commute obtained in summer and winter are linked to weather data and analyzed by means of fixed-effects regression analyses. The results reveal main effects of weather (temperature and precipitation) on mood and travel satisfaction (temperature, sunshine, precipitation, and wind speed). The effects of weather on mood and travel satisfaction differ depending on travel mode. Temperature leads to a more positive mood, wind leads to higher activation for public transport users, and sunshine leads to a more negative mood for cyclists and pedestrians. Sunshine and higher temperatures make travel more relaxed although not for cycling and walking, and rain and snow lead to a higher cognitive assessed quality of travel.


The effects of fescue toxicosis on beef cattle productivity.
Consumption of tall fescue forage infested with the endophytic fungus Acremonium coenophialum can result in a condition termed "fescue toxicosis," which is characterized by decreased weight gains, milk production, conception, and serum prolactin and an inability to dissipate body heat by beef cattle. These decreases in productivity have been estimated to cost beef producers more than $600 million annually. The unthrifty appearance of cattle consuming endophyte-infected tall fescue (E+) is most evident during periods of environmental heat or cold stress, suggesting an interaction with environmental conditions. Without temperature stress, cows consumed similar amounts of E+ and endophyte-free tall fescue (E-). But, when temperatures exceeded 32 degrees C, cows that grazed E+ consumed less forage than cows that grazed E-. After removal of E+ from the diet of steers, compensatory growth was observed, indicating no long-term negative effects of E+. A decrease in serum prolactin but apparently little change in other hormones has been measured after consumption of E+. Under periods of heat stress, animals had reduced ability to dissipate body heat, and blood flow to peripheral (rib skin), core-body (duodenum colon), and brain (cerebellum) tissues was decreased. Due to the depressive effects of E+ on prolactin and heat dissipation, dopamine antagonist therapy has been used in an attempt to rectify these changes. Dopamine antagonists have increased serum prolactin but there is limited evidence to suggest an improvement in heat dissipation. Experiments to elucidate the effects of E+ on alpha-1 and -2 adrenergic receptors may also offer insights into developing strategies to overcome the negative effects of E+ consumption. Preliminary results suggest that injections of an alpha-1 adrenergic antagonist (prazosin) in rats fed E+ under 32 degrees C conditions increased DM intake and reduced rectal temperature.