Inhibition of Small-Conductance Calcium-Activated Potassium Current (I K,Ca) Leads to Differential Atrial Electrophysiological Effects in a Horse Model of Persistent Atrial Fibrillation.
Small-conductance Ca2+-activated K+ (KCa2) channels have been proposed as a possible atrial-selective target to pharmacologically terminate atrial fibrillation (AF) and to maintain sinus rhythm. However, it has been hypothesized that the importance of the KCa2 current-and thereby the efficacy of small-conductance Ca2+-activated K+ current (I K,Ca) inhibition-might be negatively related to AF duration and the extent of AF-induced remodeling. To address the hypothesis of the efficacy of I K,Ca inhibition being dependent on AF duration, the anti-arrhythmic properties of the I K,Ca inhibitor NS8593 (5 mg/kg) and its influence on atrial conduction were studied using epicardial high-density contact mapping in horses with persistent AF. Eleven Standardbred mares with tachypacing-induced persistent AF (42 ± 5 days of AF) were studied in an open-chest experiment. Unipolar AF electrograms were recorded and isochronal high-density maps analyzed to allow for the reconstruction of wave patterns and changes in electrophysiological parameters, such as atrial conduction velocity and AF cycle length. Atrial anti-arrhythmic properties and adverse effects of NS8593 on ventricular electrophysiology were evaluated by continuous surface ECG monitoring. I K,Ca inhibition by NS8593 administered intravenously had divergent effects on right and left AF complexity and propagation properties in this equine model of persistent AF. Despite global prolongation of AF cycle length, a slowing of conduction in the right atrium led to increased anisotropy and electrical dissociation, thus increasing AF complexity. In contrast, there was no significant change in AF complexity in the LA, and cardioversion of AF was not achieved. Intra-atrial heterogeneity in response to I K,Ca inhibition by NS8593 was observed. The investigated dose of NS8593 increased the AF cycle length but was not sufficient to induce cardioversion. In terms of propagation properties during AF, I K,Ca inhibition by NS8593 led to divergent effects in the right and left atrium. This divergent behavior may have impeded the cardioversion success.


ABO and D typing and alloantibody screening in marrow samples: relevance to intraosseous blood transfusion.
Blood transfusion through the intraosseous route is gaining popularity in emergency medicine. Pretransfusion peripheral blood (PB) samples are usually not available in these patients, leading to discrepancies in blood group typing and a possible delay in transferring to group-specific blood products. The aim of this study was to assess the feasibility of ABO and D typing and red blood cell alloantibody screening in marrow (BM) samples. Direct and reverse ABO typing, D typing, and a two-cell alloantibody screen were performed in EDTA-anticoagulated BM samples with standard manual column agglutination techniques. EDTA-anticoagulated PB samples were used as controls. The mean age of the study subjects (n = 71) was 47 years (range, 1-82 years). All ABO groups and both D+ and D- types were represented. In all subjects, concordant results were observed for all analyses in BM and PB samples. In 15 (21%) of the samples, a discrepancy of one reaction strength step (1+) was observed in at least one of the analyses (Cohen's weighted κ = 0.993); this did not affect interpretation of the results. Blood group typing and alloantibody screening are feasible in BM samples, providing proof-of-concept that intraosseous samples for blood group serologic analyses can be collected from emergency patients before intraosseous blood transfusion. This will enable a timely transfer to group-specific blood products and enable conservation of the valuable universal-donor blood products.


Relationship between Automated Coronary Calcium Volumes and a Set of Manual Coronary Lumen Volume, Vessel Volume and Atheroma Volume in Japanese Diabetic Cohort.
A high degree of correlation exists between Coronary Artery Diseases (CAD) and calcification of the vessel wall. For Percutaneous Coronary Interventional (PCI) planning, it is essential to have an exact understanding of the extent to which calcium volume is correlated to the lumen, vessel, and atheroma volume regions in the coronary artery, which is unclear in recent studies. Four automated Coronary Calcium Volume (aCCV) measurement methods {threshold, Fuzzy c-Means (FCM), K-means, and Hidden Markov Random Field (HMRF)} and its correlation with three manual (experts) coronary parameters namely: Coronary Vessel Volume (mCVV), Coronary Lumen Volume (mCLV), and Coronary Atheroma Volume (mCAV), was determined in a Japanese diabetic cohort. Intravascular Ultrasound (IVUS) image dataset from 19 patients (around 40,090 frames) was collected using 40 MHz IVUS catheter (Atlantis® SR Pro, Boston Scientific®, pullback speed of 0.5 mm/sec). The methodology consisted of automatically computing the calcium volume in the entire IVUS coronary videos using FCM, K-means, and HMRF based pixel classification and comparing it against the previously published threshold-based method. The Coefficient of Correlation (CC) was then established between the four aCCV and three manually (experts) coronary parameters: mCVV, mCLV, and mCAV computed using iMAP software Boston Scientific®. Statistical tests (Two-tailed paired Student t-test, Wilcoxon signed rank test, Mann-Whitney test, Chi-square test, and Kolmogorov-Smirnov KS-test) were performed to demonstrate consistency, reliability, and accuracy of the proposed work. Correlation coefficient of: (a) automated threshold-based volume; (b) automated FCM based volume; (c) automated K-means based volume; and (d) automated HMRF based volume and corresponding three manually (expert's) coronary parameters (mCLV, mCVV, mCAV) were: (0.51, 0.40, 0.48), (0.52, 0.38, 0.49), (0.56, 0.45, 0.52), and (0.57, 0.42, 0.56), respectively. The CC between age and haemoglobin was 0.50. Automated coronary volume measurement using HMRF method is more accurate compared to threshold, FCM, and K-means-based method, since it is more strongly correlated with three expert's readings.


Detection and characterization of a clinical Escherichia coli ST3204 strain coproducing NDM-16 and MCR-1.
A plasmid-mediated colistin resistance gene, mcr-1, has been reported worldwide and has caused concern regarding a major therapeutic challenge. Alarmingly, mcr-1 has spread into clinical carbapenem-resistant Enterobacteriaceae isolates, resulting in extensively drug-resistant and even pan drug-resistant isolates that can cause untreatable infections. In this study, we report isolation of an extensively drug-resistant Escherichia coli strain EC1188 that coproduces NDM-16 and MCR-1 from a urine sample taken from a patient with craniocerebral injury. E. coli strain EC1188 was identified and subjected to genotyping, susceptibility testing and conjugation experiments. The genetic locations of blaNDM-16 and mcr-1 were established with southern blot hybridization. The complete genome sequence of this strain was obtained and the genetic characteristics of the mcr-1- and blaNDM-16-harboring plasmids were analyzed. In addition, comparative genetic analyses of mcr-1 and blaNDM-16 with closely related plasmids were also carried out. Whole-genome sequencing revealed that strain EC1188 possess various resistance genes and virulence genes. S1-pulsed-field gel electrophoresis and southern blot suggested that the blaNDM-16 and mcr-1 genes were located on an ~65 kb plasmid and an ~80 kb plasmid, respectively. Moreover, the two genes could successfully transfer their resistance phenotype to E. coli strain C600. Sequence analysis showed that these two plasmids possessed high sequence similarity to previously reported blaNDM-5-harboring and mcr-1-harboring plasmids in China. To the best of our knowledge, this is the first report to isolate an E. coli strain that coproduces NDM-16 and MCR-1. In addition, we characterized the blaNDM-16-harboring plasmid for the first time. Our study further emphasizes that the co-occurrence of the two prevalent transferrable resistance plasmids in a single isolate is highly significant because infections caused by MCR-1-producing carbapenem-resistant Enterobacteriaceae isolates are increasing each year. It is imperative to perform active surveillance to prevent further dissemination of MCR-1-producing CRE isolates.


'She might have what I have got': the potential utility of vignettes as an indirect measure of awareness in early-stage dementia.
In early-stage dementia, awareness at the meta-representational level involving a person's appraisal of his/her own condition and its implications has usually been assessed by interview, but contextual factors may influence responding. We examined the utility of an indirect, vignette-based method of eliciting awareness. Three vignettes describing early-stage dementia, established dementia and healthy ageing were used to elicit views of the problem and the kinds of advice that might be helpful for the characters depicted. Responses were obtained from 91 people with early-stage Alzheimer's, vascular or mixed dementia, 87 carers and 80 older controls. For the participants with dementia, awareness was assessed in separate in-depth interviews and rated on a five-point scale for comparison purposes. Participants with dementia were often able to correctly identify the problems described in the vignettes, although scoring lower than carers or controls. Participants with dementia were also able to offer advice for those depicted, although to a lesser extent than carers or controls. Ability to offer advice was greater where MMSE scores were higher. For participants with dementia, vignette scores were moderately correlated with ratings derived from interviews, and those showing limited or no awareness offered fewer items of advice than those showing some or good awareness. In addition, 29% of participants with dementia spontaneously pointed out similarities between their own condition and that of the person depicted. The vignette method may be useful where resources preclude the use of in-depth interviews, and may supplement in-depth interviews as part of a multi-dimensional assessment of awareness.


bHLH-O proteins are crucial for Drosophila neuroblast self-renewal and mediate Notch-induced overproliferation.
Drosophila larval neurogenesis is an excellent system for studying the balance between self-renewal and differentiation of a somatic stem cell (neuroblast). Neuroblasts (NBs) give rise to differentiated neurons and glia via intermediate precursors called GMCs or INPs. We show that E(spl)mγ, E(spl)mβ, E(spl)m8 and Deadpan (Dpn), members of the basic helix-loop-helix-Orange protein family, are expressed in NBs but not in differentiated cells. Double mutation for the E(spl) complex and dpn severely affects the ability of NBs to self-renew, causing premature termination of proliferation. Single mutations produce only minor defects, which points to functional redundancy between E(spl) proteins and Dpn. Expression of E(spl)mγ and m8, but not of dpn, depends on Notch signalling from the GMC/INP daughter to the NB. When Notch is abnormally activated in NB progeny cells, overproliferation defects are seen. We show that this depends on the abnormal induction of E(spl) genes. In fact E(spl) overexpression can partly mimic Notch-induced overproliferation. Therefore, E(spl) and Dpn act together to maintain the NB in a self-renewing state, a process in which they are assisted by Notch, which sustains expression of the E(spl) subset.


Human Bile Contains Cholangiocyte Organoid-Initiating Cells Which Expand as Functional Cholangiocytes in Non-canonical Wnt Stimulating Conditions.
Diseases of the bile duct (cholangiopathies) remain a common indication for liver transplantation, while little progress has been made over the last decade in understanding the underlying pathophysiology. This is largely due to lack of proper in vitro model systems to study cholangiopathies. Recently, a culture method has been developed that allows for expansion of human bile duct epithelial cells grown as extrahepatic cholangiocyte organoids (ncECOs) in non-canonical Wnt-stimulating conditions. These ncECOs closely resemble cholangiocytes in culture and have shown to efficiently repopulate collagen scaffolds that could act as functional biliary tissue in mice. Thus far, initiation of ncECOs required tissue samples, thereby limiting broad patient-specific applications. Here, we report that bile fluid, which can be less invasively obtained and with low risk for the patients, is an alternative source for culturing ncECOs. Further characterization showed that bile-derived cholangiocyte organoids (ncBCOs) are highly similar to ncECOs obtained from bile duct tissue biopsies. Compared to the previously reported bile-cholangiocyte organoids cultured in canonical Wnt-stimulation conditions, ncBCOs have superior function of cholangiocyte ion channels and are able to respond to secretin and somatostatin. In conclusion, bile is a new, less invasive, source for patient-derived cholangiocyte organoids and makes their regenerative medicine applications more safe and feasible.


Sensitivity characterization of a time-domain fluorescence imager: eXplore Optix.
A key issue in the practical application of fluorescence imaging is the presence of a background signal detected during data acquisition when no target fluorescent material is present. Regardless of the technology employed, background signals cannot be completely eliminated, which limits the detection sensitivity of fluorescence imaging systems, especially for in vivo applications. We present a methodology to characterize the sensitivity of fluorescence imaging devices by taking the background effect into account through the fluorescent signal-to-background ratio (SBR). In an initial application of the methodology, tissuelike liquid phantoms with Cy5.5 fluorescent inclusions were investigated experimentally over a wide range of varying parameters, such as tissue absorption coefficient, scattering coefficient, fluorophore concentration, and inclusion location. By defining detectable and quantifiable SBR thresholds, empirical relations are established, and the sensitivity performance of Advanced Research Technologies's eXplore Optix using Cy5.5 is characterized.


Y-chromosome diversity in Native Mexicans reveals continental transition of genetic structure in the Americas.
The genetic characterization of Native Mexicans is important to understand multiethnic based features influencing the medical genetics of present Mexican populations, as well as to the reconstruct the peopling of the Americas. We describe the Y-chromosome genetic diversity of 197 Native Mexicans from 11 populations and 1,044 individuals from 44 Native American populations after combining with publicly available data. We found extensive heterogeneity among Native Mexican populations and ample segregation of Q-M242* (46%) and Q-M3 (54%) haplogroups within Mexico. The northernmost sampled populations falling outside Mesoamerica (Pima and Tarahumara) showed a clear differentiation with respect to the other populations, which is in agreement with previous results from mtDNA lineages. However, our results point toward a complex genetic makeup of Native Mexicans whose maternal and paternal lineages reveal different narratives of their population history, with sex-biased continental contributions and different admixture proportions. At a continental scale, we found that Arctic populations and the northernmost groups from North America cluster together, but we did not find a clear differentiation within Mesoamerica and the rest of the continent, which coupled with the fact that the majority of individuals from Central and South American samples are restricted to the Q-M3 branch, supports the notion that most Native Americans from Mesoamerica southwards are descendants from a single wave of migration. This observation is compatible with the idea that present day Mexico might have constituted an area of transition in the diversification of paternal lineages during the colonization of the Americas.


Powered robotic exoskeletons in post-stroke rehabilitation of gait: a scoping review.
Powered robotic exoskeletons are a potential intervention for gait rehabilitation in stroke to enable repetitive walking practice to maximize neural recovery. As this is a relatively new technology for stroke, a scoping review can help guide current research and propose recommendations for advancing the research development. The aim of this scoping review was to map the current literature surrounding the use of robotic exoskeletons for gait rehabilitation in adults post-stroke. Five databases (Pubmed, OVID MEDLINE, CINAHL, Embase, Cochrane Central Register of Clinical Trials) were searched for articles from inception to October 2015. Reference lists of included articles were reviewed to identify additional studies. Articles were included if they utilized a robotic exoskeleton as a gait training intervention for adult stroke survivors and reported walking outcome measures. Of 441 records identified, 11 studies, all published within the last five years, involving 216 participants met the inclusion criteria. The study designs ranged from pre-post clinical studies (n = 7) to controlled trials (n = 4); five of the studies utilized a robotic exoskeleton device unilaterally, while six used a bilateral design. Participants ranged from sub-acute (<7 weeks) to chronic (>6 months) stroke. Training periods ranged from single-session to 8-week interventions. Main walking outcome measures were gait speed, Timed Up and Go, 6-min Walk Test, and the Functional Ambulation Category. Meaningful improvement with exoskeleton-based gait training was more apparent in sub-acute stroke compared to chronic stroke. Two of the four controlled trials showed no greater improvement in any walking outcomes compared to a control group in chronic stroke. In conclusion, clinical trials demonstrate that powered robotic exoskeletons can be used safely as a gait training intervention for stroke. Preliminary findings suggest that exoskeletal gait training is equivalent to traditional therapy for chronic stroke patients, while sub-acute patients may experience added benefit from exoskeletal gait training. Efforts should be invested in designing rigorous, appropriately powered controlled trials before powered exoskeletons can be translated into a clinical tool for gait rehabilitation post-stroke.


Quantitative and qualitative analysis of ictal vocalization in focal epilepsy syndromes.
To investigate the frequency, localizing significance, and intensity characteristics of ictal vocalization in different focal epilepsy syndromes. Up to four consecutive focal seizures were evaluated in 277 patients with lesional focal epilepsy, excluding isolated auras and subclinical EEG seizure patterns. Vocalization was considered to be present if observed in at least one of the analyzed seizures and not being of speech quality. Intensity features of ictal vocalization were analyzed in a subsample of 17 patients with temporal and 19 with extratemporal epilepsy syndrome. Ictal vocalization was observed in 37% of the patients (102/277) with similar frequency amongst different focal epilepsy syndromes. Localizing significance was found for its co-occurrence with ictal automatisms, which identified patients with temporal seizure onset with a sensitivity of 92% and specificity of 70%. Quantitative analysis of vocalization intensity allowed to distinguish seizures of frontal from temporal lobe origin based on the intensity range (p = 0.0003), intensity variation (p < 0.0001), as well as the intensity increase rate at the beginning of the vocalization (p = 0.003), which were significantly higher in frontal lobe seizures. No significant difference was found for mean intensity and mean vocalization duration. Although ictal vocalization is similarly common in different focal epilepsies, it shows localizing significance when taken into account the co-occurring seizure semiology. It especially increases the localizing value of automatisms, predicting a temporal seizure onset with a sensitivity of 92% and specificity of 70%. Quantitative parameters of the intensity dynamic objectively distinguished frontal lobe seizures, establishing an observer independent tool for semiological seizure evaluation.


Reciprocal Interactions between Cadmium-Induced Cell Wall Responses and Oxidative Stress in Plants.
Cadmium (Cd) pollution renders many soils across the world unsuited or unsafe for food- or feed-orientated agriculture. The main mechanism of Cd phytotoxicity is the induction of oxidative stress, amongst others through the depletion of glutathione. Oxidative stress can damage lipids, proteins, and nucleic acids, leading to growth inhibition or even cell death. The plant cell has a variety of tools to defend itself against Cd stress. First and foremost, cell walls might prevent Cd from entering and damaging the protoplast. Both the primary and secondary cell wall have an array of defensive mechanisms that can be adapted to cope with Cd. Pectin, which contains most of the negative charges within the primary cell wall, can sequester Cd very effectively. In the secondary cell wall, lignification can serve to immobilize Cd and create a tougher barrier for entry. Changes in cell wall composition are, however, dependent on nutrients and conversely might affect their uptake. Additionally, the role of ascorbate (AsA) as most important apoplastic antioxidant is of considerable interest, due to the fact that oxidative stress is a major mechanism underlying Cd toxicity, and that AsA biosynthesis shares several links with cell wall construction. In this review, modifications of the plant cell wall in response to Cd exposure are discussed. Focus lies on pectin in the primary cell wall, lignification in the secondary cell wall and the importance of AsA in the apoplast. Regarding lignification, we attempt to answer the question whether increased lignification is merely a consequence of Cd toxicity, or rather an elicited defense response. We propose a model for lignification as defense response, with a central role for hydrogen peroxide as substrate and signaling molecule.


Broad-host-range vectors for delivery of TnphoA: use in genetic analysis of secreted virulence determinants of Vibrio cholerae.
Gene fusions between the cholera toxin structural genes and phoA, which encodes bacterial alkaline phosphatase, were identified after TnphoA mutagenesis of the cloned genes in Escherichia coli and were then mobilized into Vibrio cholerae. The activities of the hybrid proteins were detectable in V. cholerae and suggested that, like cholera toxin, they were secreted beyond the cytoplasm. To extend the utility of TnphoA to identify additional genetic export signals in V. cholerae and other gram-negative bacteria, TnphoA delivery vectors utilizing broad-host-range plasmids were developed. By using V. cholerae as a model system, insertion mutants carrying active phoA gene fusions were identified as colonies expressing alkaline phosphatase, which appeared blue on agar containing the indicator 5-bromo-4-chloro-3-indolyl phosphate. Since alkaline phosphatase is active only upon export from the cytoplasm, PhoA+ colonies resulting from the mutagenesis procedure were enriched for insertions in genes that encode secreted proteins. Insertion mutations were identified in the gene encoding a major outer membrane protein, OmpV, and in tcpA, which encodes a pilus (fimbrial) subunit. Mutant strains harboring chromosomal insertions isolated in this manner can be used to assess the role of the corresponding inactivated gene products on survival of V. cholerae in vivo. The expression of the hybrid proteins as determined by measuring alkaline phosphatase activity also allowed the convenient study of virulence gene expression.


Patterns of alcohol and alcohol-flavoured non-alcoholic beverage advertisements over Japanese free-to-air television networks.
Alcohol use is a serious public health challenge worldwide. Japan has no government regulations or legal penalties against advertising alcoholic beverages on television (TV). Instead, advertisements depend on the Japanese alcohol industry's self-regulation on airtime (no advertisements from 5 am to 6 pm) and the content of alcoholic beverages, which must not tempt minors. However, many adolescents (10 to 19 years old) watch TV from 6 pm to 11 pm. The aim of this study was to describe the pattern in the advertising of alcoholic beverages and alcohol-flavoured non-alcoholic beverages (AFNAB) in Japan during the popular TV viewing time for adolescents. A secondary analysis of advertising airtime data from five free-to-air Japanese TV networks in the Greater Tokyo area that aired between 12 August and 3 November 2019, was performed. During the study period, 5215 advertisements for alcoholic beverages and AFNABs aired (1451.75 min). In total, 2303 advertisements (44.2%) were beer, low-malt beer, or beer-taste beverages, 277 (5.3%) were whisky, 2334 (44.8%) were local alcoholic beverages (shochu and seishu), and 301 (5.8%) were AFNAB. On average, more advertisements aired on weekends (67.6 advertisements) than on weekdays (59.3 advertisements) per day. Approximately 30% of advertisements for AFNABs were aired during the time restricted for alcohol advertising, although AFNABs are considered alcohol according to industry guidelines. During the popular television viewing time for young adolescents, about two to three times more advertisements were aired per hour than during the rest of the day, on both weekdays and weekends (p < 0.001). The number of alcohol advertisements aired at times when adolescents often watch TV is 2 to 3.2 times higher than that at other times of the day. Furthermore, despite the industry's self-imposed regulations, some alcoholic beverages are still advertised. Therefore, other methods to protect children and adolescents from exposure to advertisements for alcoholic beverages should be investigated and implemented.


Localization of the vasopressin V1a and V2 receptors within the renal cortical and medullary circulation.
Arginine vasopressin (AVP) is a potent vasoconstrictor that preferentially reduces renal medullary blood flow through the stimulation of the vasopressin V1a receptor (V1aR). Studies have also shown that the vasopressin V2 receptor (V2R) may modulate AVP-mediated vasoconstriction. At present, the distribution of the V1aR and V2R within the renal cortical and medullary microcirculation has not been determined. This study was designed to localize the transcriptional and translational sites of the V1aR and V2R in microdissected intrarenal vascular segments from both the cortex and medulla, specifically the interlobar, arcuate, and interlobular arteries; afferent and efferent arterioles; glomeruli; and single outer medullary vasa recta capillaries using reverse transcription-polymerase chain reaction and Western blot analyses. The results indicated that V1aR mRNA and proteins were present in the isolated cortical or medullary vasculature, but the V2R mRNA and proteins were not found. This study suggests that the vasoconstrictor action of AVP within the renal medulla is mediated through the V1aR and that the modulatory V2R-mediated vasodilation is probably through the release of paracrine hormones found within the renal interstitial or tubular cells.


An extreme entity in differential diagnosis of musculoskeletal involvement-fibrodysplasia ossificans progressiva: a case based review.
Çakan M, Aktay-Ayaz N, Karadağ ŞG, Keskindemirci G. An extreme entity in differential diagnosis of musculoskeletal involvement-fibrodysplasia ossificans progressiva: a case based review. Turk J Pediatr 2018; 60: 593-597. Fibrodysplasia ossificans progressiva is one of the most devastating disorder of mankind characterized by progressive heterotopic ossification. Apart from hallux valgus, other symptoms start to develop in the first decade of life. The initial symptoms are tumefactive lesions on the back that gives an impression of benign or malignant tumoral lesion. It may cause restricted motion of the neck and shoulders and magnetic resonance imaging of the lesions may be reported as myositis or myofasciitis and these children may be referred to rheumatologists. Currently there is no definitive treatment of the disease but the most important issue in these patients is `primum non nocere`, because any invasive procedure could potentially trigger a flare and heterotopic calcification. Herein, we present a young case of fibrodysplasia ossificans progressiva to remind the typical signs and symptoms of the disease to all clinicians caring for children.


Early Upper Paleolithic subsistence in the Levant: Zooarchaeology of the Ahmarian-Aurignacian sequence at Manot Cave, Israel.
The Early Upper Paleolithic period in the Levant is essential in the studies of the establishment of modern human communities outside Africa, and corresponding archaeological evidence may be used to shed light on human ecology, economy and demography. Specifically, cultural differences between two Early Upper Paleolithic entities, the Early Ahmarian and the Levantine Aurignacian, raise the question of differing adaptations. In this article we use archaeofaunal remains from the Early Upper Paleolithic sequence at Manot Cave (Western Galilee, Israel), to track human hunting patterns, carcass transport and processing within the Early Ahmarian (46-42 ka) and Levantine Aurignacian (38-34 ka) phases. We test two hypotheses: 1) the Ahmarian and Aurignacian represent adaptations to different environments; and 2) the two entities differ in mobility patterns and site use. Our multivariate taphonomic analysis showed subtle differences in depositional processes between the two phases and demonstrated a primarily anthropogenic complex. In both phases, human subsistence was based on two ungulate species, mountain gazelle (Gazella gazella) and Mesopotamian fallow deer (Dama mesopotamica), with some contribution from birds, tortoises and small mammals. Among the gazelles, it appears that female herds were targeted, and that hunting took place close to the cave. The results of the research show great similarity in environmental exploitation between the Ahmarian and Aurignacian phases concerning prey spectrum and choice, carcass transport and processing. These patterns occupy a middle position between the Middle Paleolithic and the late Epipaleolithic of the region. Despite this, there are also several significant differences between the phases such as increased exploitation of small game (especially birds) and faster accumulation and higher densities of material in the Aurignacian. This may indicate greater occupation intensity during the Aurignacian compared to the Ahmarian, and thus could explain the outstanding character of this entity in the Levant.


Virtual reality in neurosurgical education: part-task ventriculostomy simulation with dynamic visual and haptic feedback.
Mastery of the neurosurgical skill set involves many hours of supervised intraoperative training. Convergence of political, economic, and social forces has limited neurosurgical resident operative exposure. There is need to develop realistic neurosurgical simulations that reproduce the operative experience, unrestricted by time and patient safety constraints. Computer-based, virtual reality platforms offer just such a possibility. The combination of virtual reality with dynamic, three-dimensional stereoscopic visualization, and haptic feedback technologies makes realistic procedural simulation possible. Most neurosurgical procedures can be conceptualized and segmented into critical task components, which can be simulated independently or in conjunction with other modules to recreate the experience of a complex neurosurgical procedure. We use the ImmersiveTouch (ImmersiveTouch, Inc., Chicago, IL) virtual reality platform, developed at the University of Illinois at Chicago, to simulate the task of ventriculostomy catheter placement as a proof-of-concept. Computed tomographic data are used to create a virtual anatomic volume. Haptic feedback offers simulated resistance and relaxation with passage of a virtual three-dimensional ventriculostomy catheter through the brain parenchyma into the ventricle. A dynamic three-dimensional graphical interface renders changing visual perspective as the user's head moves. The simulation platform was found to have realistic visual, tactile, and handling characteristics, as assessed by neurosurgical faculty, residents, and medical students. We have developed a realistic, haptics-based virtual reality simulator for neurosurgical education. Our first module recreates a critical component of the ventriculostomy placement task. This approach to task simulation can be assembled in a modular manner to reproduce entire neurosurgical procedures.


Meditation as a potential therapy for autism: a review.
Autism is a chronic neurodevelopmental disorder of unknown cause that affects approximately 1-3 percent of children and four times more boys than girls. Its prevalence is global and its social impact is devastating. In autism, the brain is unable to process sensory information normally. Instead, simple stimuli from the outside world are experienced as overwhelmingly intense and strain the emotional centers of the brain. A stress response to the incoming information is initiated that destabilizes cognitive networks and short-circuits adequate behavioral output. As a result, the child is unable to respond adequately to stimulation and initiate social behavior towards family, friends, and peers. In addition, these children typically face immune-digestive disorders that heighten social fears, anxieties, and internal conflicts. While it is critical to treat the physical symptoms, it is equally vital to offer an evidence-based holistic solution that harmonizes both their emotional and physical well-being as they move from childhood into adult life. Here, we summarize evidence from clinical studies and neuroscience research that suggests that an approach built on yogic principles and meditative tools is worth pursuing. Desired outcomes include relief of clinical symptoms of the disease, greater relaxation, and facilitated expression of feelings and skills, as well as improved family and social quality of life.


Clinical needs of in-treatment pregnant women with co-occurring disorders: implications for primary care.
We investigated social vulnerability and behavioral health clinical profiles (symptom severity) of pregnant women with co-occurring disorders, defined as substance abuse, mental illness, and trauma at treatment entry compared to their nonpregnant counterparts and the role of interpersonal abuse in clinical presentation among pregnant women. Our objective was to provide primary health care providers with insight into the needs of pregnant patients with high behavioral health risks to serve them better during the critical window of opportunity for long-term impact. We conducted cross-sectional secondary analysis of baseline data from women enrolled in treatment programs in the Women, Co-occurring Disorders and Violence Study from nine sites across the United States. We used analysis of variance and Cochran-Mantel-Haenszel statistical analyses to compare means and frequencies of social vulnerability indicators and baseline Addiction Severity Index, Brief Symptom Inventory of mental health, and Posttraumatic Stress Diagnostic Scale scores between 152 pregnant and 2,577 nonpregnant women, and between pregnant women with and without current interpersonal abuse. Compared to nonpregnant women, pregnant women evidenced more social vulnerability but better behavioral health clinical profiles at treatment entry. Current interpersonal abuse was associated with increased mental health and trauma symptomatology but not with alcohol or drug abuse severity among pregnant women. The prenatal period is an important time for screening and intervention for factors such as social vulnerability and co-occurring disorders, known to affect pregnancy and infant outcomes; social and behavioral health services are particularly essential among pregnant women with co-occurring disorders.


Implementing school malaria surveys in Kenya: towards a national surveillance system.
To design and implement surveys of malaria infection and coverage of malaria control interventions among school children in Kenya in order to contribute towards a nationwide assessment of malaria. The country was stratified into distinct malaria transmission zones based on a malaria risk map and 480 schools were visited between October 2008 and March 2010. Surveys were conducted in two phases: an initial opportunistic phase whereby schools were selected for other research purposes; and a second phase whereby schools were purposively selected to provide adequate spatial representation across the country. Consent for participation was based on passive, opt-out consent rather than written, opt-in consent because of the routine, low-risk nature of the survey. All children were diagnosed for Plasmodium infection using rapid diagnostic tests, assessed for anaemia and were interviewed about mosquito net usage, recent history of illness, and socio-economic and household indicators. Children's responses were entered electronically in the school and data transmitted nightly to Nairobi using a mobile phone modem connection. RDT positive results were corrected by microscopy and all results were adjusted for clustering using random effect regression modelling. 49,975 children in 480 schools were sampled, at an estimated cost of US$ 1,116 per school. The overall prevalence of malaria and anaemia was 4.3% and 14.1%, respectively, and 19.0% of children reported using an insecticide-treated net (ITN). The prevalence of infection showed marked variation across the country, with prevalence being highest in Western and Nyanza provinces, and lowest in Central, North Eastern and Eastern provinces. Nationally, 2.3% of schools had reported ITN use >60%, and low reported ITN use was a particular problem in Western and Nyanza provinces. Few schools reported having malaria health education materials or ongoing malaria control activities. School malaria surveys provide a rapid, cheap and sustainable approach to malaria surveillance which can complement household surveys, and in Kenya, show that large areas of the country do not merit any direct school-based control, but school-based interventions, coupled with strengthened community-based strategies, are warranted in western and coastal Kenya. The results also provide detailed baseline data to inform evaluation of school-based malaria control in Kenya.


The association between smoking and hypertension in a population-based sample of Vietnamese men.
The association between tobacco smoking and blood pressure in epidemiological studies remains unclear despite experimental evidence that smoking elevates blood pressure. This study examined the association between smoking and hypertension in a population-based sample of Vietnamese men. The study utilized a population-based sample of men (n = 910) from a survey of risk factors of noncommunicable diseases in Vietnam. Measurements including behavioural risk factors, body composition, and blood pressure were performed according to internationally standardized protocols. Poisson regression was used to obtain prevalence ratios and 95% confidence intervals (CIs). All analyses were performed using complex survey methods. There were significant trends of increasing prevalence of hypertension with increasing years (P = 0.05) and pack-years (P = 0.03) of smoking after adjusting for age, BMI, and alcohol intake. Relative to never-smokers, the risk of hypertension for those who had smoked for 30 years or more and those who had smoked 20 pack-years or more were 1.52 (95% CI 0.95-2.44) and 1.34 (95% CI 0.94-1.91), respectively. Overall, however, current smokers were not at higher risk of hypertension than never-smokers (prevalence ratio = 1.08, 95% CI 0.70-1.68), and ex-smokers were more likely to be hypertensive than either never-smokers (prevalence ratio = 1.81, 95% CI 1.07-3.06) or current smokers (prevalence ratio = 1.67, 95% CI 1.25-2.23), similarly adjusted. In this population-based sample, hypertension was associated with smoking in a dose-response manner when characterized as number of years of smoking and lifetime cigarette consumption, but was not associated with current smoking status.


A zero altered Poisson random forest model for genomic-enabled prediction.
In genomic selection choosing the statistical machine learning model is of paramount importance. In this paper, we present an application of a zero altered random forest model with two versions (ZAP_RF and ZAPC_RF) to deal with excess zeros in count response variables. The proposed model was compared with the conventional random forest (RF) model and with the conventional Generalized Poisson Ridge regression (GPR) using two real datasets, and we found that, in terms of prediction performance, the proposed zero inflated random forest model outperformed the conventional RF and GPR models.


Evolution. The benefits of allocating sex.
Organisms allocate resources to male and female offspring in a process called sex allocation. In a Perspective, Stuart West and colleagues discuss what sex allocation tells us about evolution by natural selection and how sex allocation can be applied to understanding the mating structure of parasitic protozoans.


Serotonin hyperpolarizes cholinergic low-threshold burst neurons in the rat laterodorsal tegmental nucleus in vitro.
Serotonergic suppression of cholinergic neuronal activity implicated in the regulation of rapid eye movement sleep and its associated phenomenon, pontogeniculooccipital waves, has long been postulated, but no direct proof has been available. In this study, intracellular and whole-cell patch-clamp recording techniques were combined with enzyme histochemistry to examine the intrinsic electrophysiological properties and response to serotonin (5-HT) of identified cholinergic rat laterodorsal tegmental nucleus neurons in vitro. Sixty-five percent of the recorded neurons demonstrated a prominent low-threshold burst, and of these, 83% were cholinergic. In current-clamp recordings 64% of the bursting cholinergic neurons tested responded to the application of 5-HT with a membrane hyperpolarization and decrease in input resistance. This effect was mimicked by application of the selective 5-HT type 1 receptor agonist carboxamidotryptamine maleate. Whole-cell patch-clamp recordings revealed that the hyperpolarizing response was mediated by an inwardly rectifying K+ current. Application of 5-HT decreased excitability and markedly modulated the discharge pattern of cholinergic bursting neurons: during a 5-HT-induced hyperpolarization these neurons exhibited no rebound burst after hyperpolarizing current input and a burst in response to depolarizing current input. In the absence of 5-HT, the relatively depolarized cholinergic bursting neurons responded to an identical hyperpolarizing current input with a burst and did not produce a burst after depolarizing current input. These data provide a cellular and molecular basis for the hypothesis that 5-HT modulates rapid eye movement sleep phenomenology by altering the firing pattern of bursting cholinergic neurons.


Spontaneous terminal ileitis resembling Crohn disease in captive tamarins.
Five tamarins (four Saguinus mystax and one S. labiatus) died with wasting syndrome characterized by chronic diarrhea at the Center for Reproduction and Conservation of Non-Human Primates in Iquitos, Peru. At necropsy, the terminal ileum of all affected tamarins was found to be markedly thickened. Histologically, the terminal ileal mucosa was completely ulcerated, and effaced by debris and mononuclear inflammatory cells. The submucosa and serosa were thickened by fibroplasia, mononuclear cell infiltrates and variable edema. No infectious agent was observed. The lesions were similar to those described previously for Crohn disease. This is to our knowledge the first report of terminal ileitis resembling Crohn disease in non-human primates.


Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women.
The effect of raloxifene, a selective estrogen-receptor modulator, on coronary heart disease (CHD) and breast cancer is not established. We randomly assigned 10,101 postmenopausal women (mean age, 67.5 years) with CHD or multiple risk factors for CHD to 60 mg of raloxifene daily or placebo and followed them for a median of 5.6 years. The two primary outcomes were coronary events (i.e., death from coronary causes, myocardial infarction, or hospitalization for an acute coronary syndrome) and invasive breast cancer. As compared with placebo, raloxifene had no significant effect on the risk of primary coronary events (533 vs. 553 events; hazard ratio, 0.95; 95 percent confidence interval, 0.84 to 1.07), and it reduced the risk of invasive breast cancer (40 vs. 70 events; hazard ratio, 0.56; 95 percent confidence interval, 0.38 to 0.83; absolute risk reduction, 1.2 invasive breast cancers per 1000 women treated for one year); the benefit was primarily due to a reduced risk of estrogen-receptor-positive invasive breast cancers. There was no significant difference in the rates of death from any cause or total stroke according to group assignment, but raloxifene was associated with an increased risk of fatal stroke (59 vs. 39 events; hazard ratio, 1.49; 95 percent confidence interval, 1.00 to 2.24; absolute risk increase, 0.7 per 1000 woman-years) and venous thromboembolism (103 vs. 71 events; hazard ratio, 1.44; 95 percent confidence interval, 1.06 to 1.95; absolute risk increase, 1.2 per 1000 woman-years). Raloxifene reduced the risk of clinical vertebral fractures (64 vs. 97 events; hazard ratio, 0.65; 95 percent confidence interval, 0.47 to 0.89; absolute risk reduction, 1.3 per 1000). Raloxifene did not significantly affect the risk of CHD. The benefits of raloxifene in reducing the risks of invasive breast cancer and vertebral fracture should be weighed against the increased risks of venous thromboembolism and fatal stroke. (ClinicalTrials.gov number, NCT00190593 [ClinicalTrials.gov].).


Dendritic growth of arcuate neuroendocrine neurons following orchidectomy in adult rats.
Recent studies have shown that changes in dendritic architecture are an important component of functional plasticity in the adult central nervous system. In the present study, we determined whether gonadectomy induces changes in dendritic architecture in the arcuate nucleus, a target tissue for gonadal hormones. A combination of retrograde labeling with systemically injected Fluoro-Gold and intracellular injection of neurons in a fixed-slice preparation was used to examine the morphology of neuroendocrine neurons in the rat arcuate nucleus. Intracellullary filled arcuate neuroendocrine neurons (8-21 neurons per brain) from intact (n = 5) and orchidectomized (n = 5) animals were reconstructed with the aid of a computer microscope. A quantitative analysis revealed that orchidectomy had no effect on the number and distribution of Fluoro-Gold-labeled neuroendocrine neurons in the rat arcuate nucleus. The morphology of arcuate neuroendocrine neurons in intact animals was relatively simple, with the majority of neurons (79%) having only two primary dendrites and few dendritic spines. Compared with intact controls, arcuate neuroendocrine neurons in the orchidectomized group had significantly larger somatic profile areas and exhibited significant increases in dendrite length, dendrite volume, terminal branch number, and spines per unit length of dendrite. The increase in terminal branch number in orchidectomized animals was due primarily to the appearance of short branches that gave a striking, claw-like appearance to many of the distal dendrites. These results provide evidence for hormonal regulation of dendritic morphology of arcuate neuroendocrine neurons in adult mammals.


Tibetan Medicated-Bath Therapy may Improve Adjuvant Arthritis in Rat.
Tibetan medicated-bath therapy has been applied to patients with rheumatoid arthritis for centuries. However, the detailed action mechanism of Tibetan medicated-bath therapy on the morphology and function of joints remains unknown. We designed our investigation to evaluate the efficacy of Tibetan medicated-bath therapy on adjuvant arthritis (AA) of rats in comparison with water-bath and dexamethasone administration. AA was induced by intradermal injection of Mycobacterium butyricum suspended in sterile mineral oil. The control animals were similarly injected with sterile vehicle. Eight days after injection, rats were treated with fresh-water bath, Tibetan medicated-bath (40 degrees C, 15 min) or intramuscular injection with dexamethasone for 21 consecutive days after which we evaluated the severity of arthritis visually and microscopically and measured serum interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha levels. While arthritis did not significantly change after water-bath treatment, the Tibetan medicated-bath and dexamethasone groups showed diminished joint swelling and alleviation of, inflammatory cell infiltration and the destruction of bone and cartilage. Serum IL-6 and TNF-alpha levels significantly decreased. Our results demonstrated that Tibetan medicated-bath therapy exerted a reliable effect on rat adjuvant arthritis, which may be involved in the inflammatory cytokines, IL-6 and TNF-alpha. Our data provide evidence for clinical use of Tibetan-medicated bath therapy for arthritis patients.


Comparison of a mindful eating intervention to a diabetes self-management intervention among adults with type 2 diabetes: a randomized controlled trial.
Mindful eating may be an effective intervention for increasing awareness of hunger and satiety cues, improving eating regulation and dietary patterns, reducing symptoms of depression and anxiety, and promoting weight loss. Diabetes self-management education (DSME), which addresses knowledge, self-efficacy, and outcome expectations for improving food choices, also may be an effective intervention for diabetes self-care. Yet few studies have compared the impact of mindful eating to a DSME-based treatment approach on patient outcomes. Adults 35 to 65 years old with type 2 diabetes for ≥1 year not requiring insulin therapy were recruited from the community and randomly assigned to treatment group. The impact of a group-based 3-month mindful eating intervention (MB-EAT-D; n = 27) to a group-based 3-month DSME "Smart Choices" (SC) intervention (n = 25) postintervention and at 3-month follow-up was evaluated. Repeated-measures ANOVA with contrast analysis compared change in outcomes across time. There was no significant difference between groups in weight change. Significant improvement in depressive symptoms, outcome expectations, nutrition and eating-related self-efficacy, and cognitive control and disinhibition of control regarding eating behaviors occurred for both groups (all p < .0125) at 3-month follow-up. The SC group had greater increase in nutrition knowledge and self-efficacy than the MB-EAT-D group (all p < .05) at 3-month follow-up. MB-EAT-D had significant increase in mindfulness, whereas the SC group had significant increase in fruit and vegetable consumption at study end (all p < .0125). Both SC and MB-EAT-D were effective treatments for diabetes self-management. The availability of mindful eating and DSME-based approaches offers patients greater choices in meeting their self-care needs.


Airglow events visible to the naked eye.
During IR photographic airglow observations covering several years, three naked-eye events have been recorded. Two of these are moving, luminous acoustic gravity wave groups of some 10-15-km wavelength, which occur near high lunar tide in the atmosphere. The events appear quickly, endure 0.5-1 h, then fade. Visible photos of two events appear enhanced while little enhancement is present in the IR photos, although the structures are well correlated. If these events are due to OH, we suggest that some unrecognized mechanism, perhaps a gravity wave interaction, enhances the visible transitions of the OH over the IR transitions. If the events are due to an unrecognized continuum emitter, perhaps NO, its emission must occur at the same height as the OH. Spectra seem to be the only reasonable approach to solving this problem.


Effects of residence and race on burden of travel for care: cross sectional analysis of the 2001 US National Household Travel Survey.
Travel burden is a key element in conceptualizing geographic access to health care. Prior research has shown that both rural and minority populations bear disproportionate travel burdens. However, many studies are limited to specific types of patient or specific locales. The purpose of our study was to quantify geographic and race-based differences in distance traveled and time spent in travel for medical/dental care using representative national data. Data were drawn from 2001 National Household Travel Survey (NHTS), a nationally representative, cross-sectional household survey conducted by the US Department of Transportation. Participants recorded all travel on a designated day; the overall response rate was 41%. Analyses were restricted to households reporting at least one trip for medical and/or dental care; 3,914 trips made by 2,432 households. Dependent variables in the analysis were road miles traveled, minutes spent traveling, and high travel burden, defined as more than 30 miles or 30 minutes per trip. Independent variables of interest were rural residence and race. Characteristics of the individual, the trip, and the community were controlled in multivariate analyses. The average trip for care in the US in 2001 entailed 10.2 road miles (16.4 kilometers) and 22.0 minutes of travel. Rural residents traveled further than urban residents in unadjusted analysis (17.5 versus 8.3 miles; 28.2 versus 13.4 km). Rural trips took 31.4% longer than urban trips (27.2 versus 20.7 minutes). Distance traveled did not vary by race. African Americans spent more time in travel than whites (29.1 versus 20.6 minutes); other minorities did not differ. In adjusted analyses, rural residence (odds ratio, OR, 2.67, 95% confidence interval, CI 1.39 5.1.5) was associated with a trip of 30 road miles or more; rural residence (OR, 1.80, CI 1.09 2.99) and African American race/ethnicity (OR 3.04. 95% CI 2.0 4.62) were associated with a trip lasting 30 minutes or longer. Rural residents and African Americans experience higher travel burdens than urban residents or whites when seeking medical/dental care.


Effect of indomethacin on ultraviolet radiation-induced recurrent herpes simplex virus disease in guinea-pigs.
Exposure to u.v. radiation increases the local level of prostaglandins which may play a role in u.v. radiation-induced herpes simplex virus (HSV) recurrences. We used the guinea-pig model of u.v. radiation-induced recurrent genital HSV-2 disease for examining the effects of indomethacin, a prostaglandin inhibitor, on u.v.-induced recurrences. In the first experiment, performed 100 days after HSV-2 inoculation, treatment with indomethacin for 5 days begun 24 h before u.v.-irradiation decreased the proportion of animals developing HSV disease recurrences from 11/13 (84.6%) to 2/13 (15.4%) (P < 0.001). In the second experiment, performed 135 days after HSV-2 inoculation, treatment with indomethacin for 5 days begun 24 h before u.v.-irradiation decreased the number of animals developing recurrences from 12/21 (57.1%) to 5/21 (23.8%) (P < 0.05). Five days of indomethacin treatment begun 4 h after u.v.-irradiation, however, did not reduce the percentage of animals developing disease recurrences but did decrease the mean number of days with recurrent lesions in animals that developed recurrences. Our data suggest that indomethacin may modify u.v. radiation-induced recurrent lesions by decreasing viral reactivation when given before u.v. radiation exposure or by reducing prostaglandin-induced immunosuppression when given before or after exposure. Future studies are needed for evaluating indomethacin prophylaxis for recurrent HSV disease when prolonged u.v. radiation exposure is anticipated.


Contact dermatitis.
Contact dermatitis is a common inflammatory skin disorder caused by exposure to various antigens and irritants. It is associated with significant morbidity, and it is one of the most common reasons for worker's compensation claims for skin disease. Based on the mechanism by which contact allergy develops, several types are recognized, including allergic contact dermatitis, irritant contact dermatitis, contact photo-dermatitis and contact urticaria. The clinical presentation of contact dermatitis, regardless of the mechanism, ranges from localized vesicles and bullae on erythematous skin in acute stages to erythematous lichenified plaques in chronic stages. Diagnosis is suggested by the localization of the eruption and the history of exposure to an offending agent. Treatment includes removal of the offending agent in conjunction with use of anti-inflammatory steroid creams, antihistamines and, in severe cases, oral corticosteroids.


Effect of Silicon Rate and Host Resistance on Blast, Scald, and Yield of Upland Rice.
Blast-resistant, partially resistant, and susceptible cultivars of rice were planted in soil amended with Si at 0, 500, or 1,000 kg/ha at two locations in eastern Colombia to assess differential responses to leaf blast, neck blast, and leaf scald, and to examine the quantity and quality of grains harvested. Leaf and neck blast on partially resistant and susceptible cultivars were reduced by Si as the rate of Si was increased. Depending on the location, the level of severity of leaf and neck blast on partially resistant cultivars, when fertilized with Si at 500 or 1,000 kg/ha, was lowered to that of resistant cultivars without Si. At both locations, yields were increased by as much as 42%, depending on the cultivar, by Si applied at 1,000 kg/ha. In general, high rates of Si reduced the number of broken grains harvested. Grain discoloration, regardless of cultivar or location, was reduced by as much as 70% at the high rate of Si. The application of Si to complement host resistance to blast and scald appears to be an effective strategy for disease management in rice and provides the added benefit of improving the quantity and quality of rice yields.


Oral Contraceptive Use does not Negatively Affect Body Composition and Strength Adaptations in Trained Women.
The purpose was to analyze the influence of oral contraceptive use on body composition and strength levels in trained women. Twenty-three resistance-trained women participated in this study (age=27.4±3.4 years; fat mass=28.0±5.0%; BMI=22.9±2.7 kg∙m-2). Subjects performed an 8-week non-linear resistance-training program. Participants were assigned to either a group that consumed oral contraceptives (n=12, OC) or to a group that did not consume (n=11, NOC). Changes in body composition were measured by dual energy X-ray absorptiometry. Strength performance was assessed via the one maximum repetition (1RM) test in the squat and bench press, and muscular power was evaluated using the countermovement jump (CMJ) test. Fat free mass increased significantly in OC but no changes were seen in NOC. There were no changes in fat mass for either OC or NOC. Significant changes were found in bench press 1RM for both OC and NOC; similarly, increases in squat 1RM were reported in OC and NOC. Alternatively, no significant changes were found in CMJ in both OC and NOC. No significant between-group differences were detected in any of the studied variables. The use of oral contraceptives during resistance training did not negatively affect body composition or strength levels in trained women.


Variability of the coat protein gene of Citrus psorosis virus in Campania, southern Italy.
Variability of the Coat protein (CP) gene of Citrus psorosis virus (CPsV) was assessed serologically, and by sequence analyses of two genomic regions located in the 3' (region C) and 5' (region V) halves of the gene. Analysis of 53 psorosis field sources from Campania, Italy, with 23 monoclonal antibodies revealed nine serogroups and at least ten different epitopes. Sequence analysis of 19 of these sources showed limited nucleotide diversity of the CP gene in the population. Diversity was slightly higher in region V than in region C. Phylogenetic analysis of the V and C regions of the CP showed that the Campania sources of CPsV were clearly separated from the CPsV-4 isolate from Florida. For C region, most of the CPsV sources clustered together, whereas two clusters were observed for region V. The ratio between nonsynonymous and synonymous substitutions for regions C (0.083) and V (0.345) indicated negative selective pressure for amino acid changes, more intense in the C region. No correlation was found between serogroups and specific aminoacid sequences, field location or citrus cultivar.


Dominant role of cAMP in regulation of microvessel permeability.
We reported previously that increasing cAMP levels in endothelial cells attenuated ATP-induced increases in hydraulic conductivity (L(p)), and that the activation of cGMP-dependent pathways was a necessary step to increase L(p) in response to inflammatory mediators. The aim of the present study was to evaluate the role of basal levels of cAMP in microvessel permeability under resting conditions and to evaluate the cross talk between cAMP- and cGMP-dependent signaling mechanisms in regulation of microvessel permeability under stimulated conditions, using individually perfused microvessels from frog and rat mesenteries. We found that reducing cAMP levels by inhibition of adenylate cyclase or inhibiting cAMP-dependent protein kinase through the use of H-89 increased basal L(p) in both frog and rat mesenteric venular microvessels. We also found that 8-bromocAMP (8-BrcAMP, 0.2 and 2 mM) was sufficient to attenuate or abolish the increases in L(p) due to exposure of frog mesenteric venular microvessels to 8-BrcGMP (2 mM) and ATP (10 microM). Similarly, in rat mesenteric venular microvessels, application of 8-BrcAMP (2 mM) abolished the increases in L(p) due to exposure to 8-BrcGMP alone (2 mM) or with the combination of bradykinin (1 nM). In addition, application of erythro-9-(2-hydroxy-3-nonyl)adenine, an inhibitor of cGMP-stimulated phosphodiesterase, significantly attenuated both 8-BrcGMP- and bradykinin-induced increases in L(p). These results demonstrate that basal levels of cAMP are critical to maintaining normal permeability under resting conditions, and that increased levels of cAMP are capable of overcoming the activation of cGMP-dependent pathways, therefore preventing increases in microvessel permeability. The balance between endothelial concentrations of these two opposing cyclic nucleotides controls microvessel permeability, and cAMP levels play a dominant role.


A review of undergraduate interprofessional simulation-based education (IPSE).
Interprofessional simulation-based education (IPSE) is becoming an increasingly popular educational strategy worldwide within undergraduate healthcare curricular. The purpose of the literature review was to examine qualitative, quantitative and mixed/multi-method research studies featuring undergraduate IPSE. A literature review was conducted using CINAHL, MEDLINE, and PsycINFO databases from January 1999 to September 2011 and pre-set criteria. The criteria used to screen all 120 abstracts included: (a) the article pertained to both simulation and undergraduate IPE and (b) the article reported a research study. Eighteen articles which met the pre-set criteria were included in the literature review. All studies featured outcome measures; many were purposely designed and lacked psychometric development and evaluation. Key IPSE drivers included capacity planning, preparedness for disaster management and improving patient care through the evaluation of teambuilding, teamwork skills or communicating within inter-disciplinary teams. Studies evaluated/explored either student or teacher perspectives of learning within the context of IPSE or both. The IPSE learning processes varied considerably in relation to duration, fidelity and professions involved. The scenarios ranged from managing adults admitted to hospital settings, mass casualty/mock disaster patient management to the use of training wards. The majority of the articles identified common IPSE outcomes relating to increased confidence, knowledge, leadership, teamwork, and communication skills. Based on the findings of this review, the authors suggest that further multi-site, longitudinal research studies are required to provide evidence of the transferability of skills developed during IPSE and their overall impact on both undergraduate education and healthcare.


British container breeding mosquitoes: the impact of urbanisation and climate change on community composition and phenology.
The proliferation of artificial container habitats in urban areas has benefitted urban adaptable mosquito species globally. In areas where mosquitoes transmit viruses and parasites, it can promote vector population productivity and fuel mosquito-borne disease outbreaks. In Britain, storage of water in garden water butts is increasing, potentially expanding mosquito larval habitats and influencing population dynamics and mosquito-human contact. Here we show that the community composition, abundance and phenology of mosquitoes breeding in experimental water butt containers were influenced by urbanisation. Mosquitoes in urban containers were less species-rich but present in significantly higher densities (100.4±21.3) per container than those in rural containers (77.7±15.1). Urban containers were dominated by Culex pipiens (a potential vector of West Nile Virus [WNV]) and appear to be increasingly exploited by Anopheles plumbeus (a human-biting potential WNV and malaria vector). Culex phenology was influenced by urban land use type, with peaks in larval abundances occurring earlier in urban than rural containers. Among other factors, this was associated with an urban heat island effect which raised urban air and water temperatures by 0.9°C and 1.2°C respectively. Further increases in domestic water storage, particularly in urban areas, in combination with climate changes will likely alter mosquito population dynamics in the UK.


Comparison of three generic vancomycin products using liquid chromatography-mass spectrometry and an online tool.
Three different generic vancomycin products were compared using liquid chromatography-mass spectrometry (LC-MS) and open-access metabolomic tools. Single-lot samples of vancomycin hydrochloride from three different manufacturers (Hospira, APP Pharmaceuticals, and Pfizer) were reconstituted and injected into a high-resolution LC-MS system. The mass spectral fingerprints were compared for similarity of nonvancomycin B components using the XCMS Online system through Scripps University. Significance was defined as a p of ≤0.01 and a fold change of ≥1.5. The concentration of vancomycin B in each product was also measured using LC-MS on days 0, 1, 2, 4, 7, 10, and 14. Qualitative comparisons of the products using the XCMS Online interface indicated the presence of significant differences among the products at the time of reconstitution; however, these variations seemed to converge after 14 days of storage. The concentration profiles of vancomycin B during refrigerated storage did not differ significantly among the three products. XCMS Online analyses revealed that the Pfizer and Hospira products were the most similar to each other. While there were no significant differences found in the concentration of vancomycin B among Pfizer, APP, and Hospira products, there were differences in their initial mass spectral analysis after reconstitution. Liquid chromatography-tandem mass spectrometry profiles of the ions or isotopes present in the three products showed significant differences in impurities such as crystalline degradation product (CDP)-1 and CDP intermediate. After 14 days of refrigerated storage, the differences among the products converged, and fewer distinct features could be detected.


Vacuum ultraviolet 6-m monochromator.
A description is given of the design and construction of the Adelaide 6.65-m VUV monochromator. The instrument has an off-plane Eagle mounting and can be used in the first order over a wavelength range from central image to 460 nm. Digital encoders are used to monitor the angular rotation and linear displacement of the grating to provide servocontrolled wavelength and focusing adjustments which are electronically (rather than mechanically) coupled and operated through a programmable calculator. The monochromator is designed for high resolution studies of photoabsorption in atmospheric gases, and its performance is illustrated by reference to absorption studies in portions of the Schumann-Runge band system of molecular oxygen.


Regions of open water and melting sea ice drive new particle formation in North East Greenland.
Atmospheric new particle formation (NPF) and growth significantly influences the indirect aerosol-cloud effect within the polar climate system. In this work, the aerosol population is categorised via cluster analysis of aerosol number size distributions (9-915 nm, 65 bins) taken at Villum Research Station, Station Nord (VRS) in North Greenland during a 7 year record (2010-2016). Data are clustered at daily averaged resolution; in total, we classified six categories, five of which clearly describe the ultrafine aerosol population, one of which is linked to nucleation events (up to 39% during summer). Air mass trajectory analyses tie these frequent nucleation events to biogenic precursors released by open water and melting sea ice regions. NPF events in the studied regions seem not to be related to bird colonies from coastal zones. Our results show a negative correlation (r = -0.89) between NPF events and sea ice extent, suggesting the impact of ultrafine Arctic aerosols is likely to increase in the future, given the likely increased sea ice melting. Understanding the composition and the sources of Arctic aerosols requires further integrated studies with joint multi-component ocean-atmosphere observation and modelling.


Limitations of climatic data for inferring species boundaries: insights from speckled rattlesnakes.
Phenotypes, DNA, and measures of ecological differences are widely used in species delimitation. Although rarely defined in such studies, ecological divergence is almost always approximated using multivariate climatic data associated with sets of specimens (i.e., the "climatic niche"); the justification for this approach is that species-specific climatic envelopes act as surrogates for physiological tolerances. Using identical statistical procedures, we evaluated the usefulness and validity of the climate-as-proxy assumption by comparing performance of genetic (nDNA SNPs and mitochondrial DNA), phenotypic, and climatic data for objective species delimitation in the speckled rattlesnake (Crotalus mitchellii) complex. Ordination and clustering patterns were largely congruent among intrinsic (heritable) traits (nDNA, mtDNA, phenotype), and discordance is explained by biological processes (e.g., ontogeny, hybridization). In contrast, climatic data did not produce biologically meaningful clusters that were congruent with any intrinsic dataset, but rather corresponded to regional differences in atmospheric circulation and climate, indicating an absence of inherent taxonomic signal in these data. Surrogating climate for physiological tolerances adds artificial weight to evidence of species boundaries, as these data are irrelevant for that purpose. Based on the evidence from congruent clustering of intrinsic datasets, we recommend that three subspecies of C. mitchellii be recognized as species: C. angelensis, C. mitchellii, and C. Pyrrhus.


An anatomical signature for literacy.
Language is a uniquely human ability that evolved at some point in the roughly 6,000,000 years since human and chimpanzee lines diverged. Even in the most linguistically impoverished environments, children naturally develop sophisticated language systems. In contrast, reading is a learnt skill that does not develop without intensive tuition and practice. Learning to read is likely to involve ontogenic structural brain changes, but these are nearly impossible to isolate in children owing to concurrent biological, environmental and social maturational changes. In Colombia, guerrillas are re-integrating into mainstream society and learning to read for the first time as adults. This presents a unique opportunity to investigate how literacy changes the brain, without the maturational complications present in children. Here we compare structural brain scans from those who learnt to read as adults (late-literates) with those from a carefully matched set of illiterates. Late-literates had more white matter in the splenium of the corpus callosum and more grey matter in bilateral angular, dorsal occipital, middle temporal, left supramarginal and superior temporal gyri. The importance of these brain regions for skilled reading was investigated in early literates, who learnt to read as children. We found anatomical connections linking the left and right angular and dorsal occipital gyri through the area of the corpus callosum where white matter was higher in late-literates than in illiterates; that reading, relative to object naming, increased the interhemispheric functional connectivity between the left and right angular gyri; and that activation in the left angular gyrus exerts top-down modulation on information flow from the left dorsal occipital gyrus to the left supramarginal gyrus. These findings demonstrate how the regions identified in late-literates interact during reading, relative to object naming, in early literates.


Efficient differentiation of human induced pluripotent stem cells generates cardiac cells that provide protection following myocardial infarction in the rat.
Induced pluripotent stem (iPS) cells are being used increasingly to complement their embryonic counterparts to understand and develop the therapeutic potential of pluripotent cells. Our objectives were to identify an efficient cardiac differentiation protocol for human iPS cells as monolayers, and demonstrate that the resulting cardiac progenitors could provide a therapeutic benefit in a rodent model of myocardial infarction. Herein, we describe a 14-day protocol for efficient cardiac differentiation of human iPS cells as a monolayer, which routinely yielded a mixed population in which over 50% were cardiomyocytes, endothelium, or smooth muscle cells. When differentiating, cardiac progenitors from day 6 of this protocol were injected into the peri-infarct region of the rat heart; after coronary artery ligation and reperfusion, we were able to show that human iPS cell-derived cardiac progenitor cells engrafted, differentiated into cardiomyocytes and smooth muscle, and persisted for at least 10 weeks postinfarct. Hearts injected with iPS-derived cells showed a nonsignificant trend toward protection from decline in function after myocardial infarction, as assessed by magnetic resonance imaging at 10 weeks, such that the ejection fraction at 10 weeks in iPS treated hearts was 62%±4%, compared to that of control infarcted hearts at 45%±9% (P<0.2). In conclusion, we demonstrated efficient cardiac differentiation of human iPS cells that gave rise to progenitors that were retained within the infarcted rat heart, and reduced remodeling of the heart after ischemic damage.


Autoantibodies to beta 2-adrenergic receptors: a possible cause of adrenergic hyporesponsiveness in allergic rhinitis and asthma.
Autoantibodies to beta 2-adrenergic receptors have been identified in the serum of one patient with allergic rhinitis ("hay fever") and two patients with asthma. The antibodies precipitate solubilized dog lung beta receptors in an indirect immunoprecipitation assay and inhibit the specific binding of iodine-125-labeled iodohydroxybenzylpindolol to membrane-associated receptors from dog lung, calf lung, and human placenta. Ligand binding to canine heart beta 1 receptors is not affected by the antibodies.


Autoimmunity and asbestos exposure.
Despite a body of evidence supporting an association between asbestos exposure and autoantibodies indicative of systemic autoimmunity, such as antinuclear antibodies (ANA), a strong epidemiological link has never been made to specific autoimmune diseases. This is in contrast with another silicate dust, crystalline silica, for which there is considerable evidence linking exposure to diseases such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Instead, the asbestos literature is heavily focused on cancer, including mesothelioma and pulmonary carcinoma. Possible contributing factors to the absence of a stronger epidemiological association between asbestos and autoimmune disease include (a) a lack of statistical power due to relatively small or diffuse exposure cohorts, (b) exposure misclassification, (c) latency of clinical disease, (d) mild or subclinical entities that remain undetected or masked by other pathologies, or (e) effects that are specific to certain fiber types, so that analyses on mixed exposures do not reach statistical significance. This review summarizes epidemiological, animal model, and in vitro data related to asbestos exposures and autoimmunity. These combined data help build toward a better understanding of the fiber-associated factors contributing to immune dysfunction that may raise the risk of autoimmunity and the possible contribution to asbestos-related pulmonary disease.


Measurement of paraben concentrations in human breast tissue at serial locations across the breast from axilla to sternum.
The concentrations of five esters of p-hydroxybenzoic acid (parabens) were measured using HPLC-MS/MS at four serial locations across the human breast from axilla to sternum using human breast tissue collected from 40 mastectomies for primary breast cancer in England between 2005 and 2008. One or more paraben esters were quantifiable in 158/160 (99%) of the tissue samples and in 96/160 (60%) all five esters were measured. Variation was notable with respect to individual paraben esters, location within one breast and similar locations in different breasts. Overall median values in nanograms per gram tissue for the 160 tissue samples were highest for n-propylparaben [16.8 (range 0-2052.7)] and methylparaben [16.6 (range 0-5102.9)]; levels were lower for n-butylparaben [5.8 (range 0-95.4)], ethylparaben [3.4 (range 0-499.7)] and isobutylparaben 2.1 (range 0-802.9). The overall median value for total paraben was 85.5 ng g(-1) tissue (range 0-5134.5). The source of the paraben cannot be identified, but paraben was measured in the 7/40 patients who reported never having used underarm cosmetics in their lifetime. No correlations were found between paraben concentrations and age of patient (37-91 years), length of breast feeding (0-23 months), tumour location or tumour oestrogen receptor content. In view of the disproportionate incidence of breast cancer in the upper outer quadrant, paraben concentrations were compared across the four regions of the breast: n-propylparaben was found at significantly higher levels in the axilla than mid (P = 0.004 Wilcoxon matched pairs) or medial (P = 0.021 Wilcoxon matched pairs) regions (P = 0.010 Friedman ANOVA).


Biophysical assessment of single cell cytotoxicity: diesel exhaust particle-treated human aortic endothelial cells.
Exposure to diesel exhaust particles (DEPs), a major source of traffic-related air pollution, has become a serious health concern due to its adverse influences on human health including cardiovascular and respiratory disorders. To elucidate the relationship between biophysical properties (cell topography, cytoskeleton organizations, and cell mechanics) and functions of endothelial cells exposed to DEPs, atomic force microscope (AFM) was applied to analyze the toxic effects of DEPs on a model cell line from human aortic endothelial cells (HAECs). Fluorescence microscopy and flow cytometry were also applied to further explore DEP-induced cytotoxicity in HAECs. Results revealed that DEPs could negatively impair cell viability and alter membrane nanostructures and cytoskeleton components in a dosage- and a time-dependent manner; and analyses suggested that DEPs-induced hyperpolarization in HAECs appeared in a time-dependent manner, implying DEP treatment would lead to vasodilation, which could be supported by down-regulation of cell biophysical properties (e.g., cell elasticity). These findings are consistent with the conclusion that DEP exposure triggers important biochemical and biophysical changes that would negatively impact the pathological development of cardiovascular diseases. For example, DEP intervention would be one cause of vasodilation, which will expand understanding of biophysical aspects associated with DEP cytotoxicity in HAECs.


In vitro activation of human chondrocytes and synoviocytes by a human interleukin-1-like factor.
Monocytes have been shown to secrete factors which stimulate the destruction of cartilage. Since one of the monocyte products, interleukin-1 (IL-1), has been shown to stimulate the release of collagenase and prostaglandin E from synoviocytes, we have investigated whether IL-1 is also responsible for chondrocyte activation. Purified preparations of IL-1 derived from human blood monocytes stimulated the production of prostaglandin E and plasminogen activator by human articular chondrocytes. After Sephadex G-75 chromatography, the lymphocyte-activating and the chondrocyte-activating activities of IL-1 eluted together in the regions corresponding to the void volume and to Kav = 0.2-0.3 (Mr 30,000-45,000) and Kav = 0.5-0.65 (Mr 12,000-17,000). The major peak of stimulating activity was the 12,000-17,000 dalton peak. Upon further analysis of the 12,000-17,000 dalton peak by isoelectric focusing, the major peak of lymphocyte-activating factor activity was recovered at a pI of 6.3 with a minor peak at 4.6-5.3. Similar patterns of activity were observed when the fractions were assayed for the stimulation of the production of prostaglandin E and plasminogen activator by human chondrocytes and of prostaglandin E by human synoviocytes. Treatment of the partially purified lymphocyte activating factor with phenylglyoxal reduced the thymocyte-stimulating activity 99% and the chondrocyte-stimulating activity 100%. These results suggest that IL-1 may stimulate the degradation of connective tissues during inflammation.


Long-term exposure of mouse pancreatic islets to oleate or palmitate results in reduced glucose-induced somatostatin and oversecretion of glucagon.
Long-term exposure to NEFAs leads to inhibition of glucose-induced insulin secretion. We tested whether the release of somatostatin and glucagon, the two other major islet hormones, is also affected. Mouse pancreatic islets were cultured for 72 h at 4.5 or 15 mmol/l glucose with or without 0.5 mmol/l oleate or palmitate. The release of glucagon and somatostatin during subsequent 1 h incubations at 1 or 20 mmol/l glucose as well as the islet content of the two hormones were determined. Lipid-induced changes in islet cell ultrastructure were assessed by electron microscopy. Culture at 15 mmol/l glucose increased islet glucagon content by approximately 50% relative to that observed following culture at 4.5 mmol/l glucose. Inclusion of oleate or palmitate reduced islet glucagon content by 25% (at 4.5 mmol/l glucose) to 50% (at 15 mmol/l glucose). Long-term exposure to the NEFA increased glucagon secretion at 1 mmol/l glucose by 50% (when islets had been cultured at 15 mmol/l glucose) to 100% (with 4.5 mmol/l glucose in the culture medium) and abolished the inhibitory effect of 20 mmol/l glucose on glucagon secretion. Somatostatin content was unaffected by glucose and lipids, but glucose-induced somatostatin secretion was reduced by approximately 50% following long-term exposure to either of the NEFA, regardless of whether the culture medium contained 4.5 or 15 mmol/l glucose. Ultrastructural evidence of lipid deposition was seen in <10% of non-beta cells but in >80% of the beta cells. Long-term exposure to high glucose and/or NEFA affects the release of somatostatin and glucagon. The effects on glucagon secretion are very pronounced and in type 2 diabetes in vivo may aggravate the hyperglycaemic effects due to lack of insulin.


Myasthenia gravis AChR antibodies inhibit function of rapsyn-clustered AChRs.
Direct inhibition of acetylcholine receptor (AChR) function by autoantibodies (Abs) is considered a rare pathogenic mechanism in myasthenia gravis (MG), but is usually studied on AChRs expressed in cell lines, rather than tightly clustered by the intracellular scaffolding protein, rapsyn, as at the intact neuromuscular junction. We hypothesised that clustered AChRs would provide a better target for investigating the functional effects of AChR-Abs. Acetylcholine-induced currents were measured using whole-cell patch clamping and a fast perfusion system to assess fast (<2 min) functional effects of the serum samples. The sensitivity, specificity and rapidity of the system were first demonstrated by applying maternal AChR-Ab positive plasmas known to inhibit fetal AChR function in TE671 cells. Eleven previously untested AChR-Ab positive MG sera, 10 AChR-Ab negative MG sera and 5 healthy control sera were then applied to unclustered and rapsyn-clustered human adult AChRs in CN21 cells. The maternal AChR-Ab positive plasmas reduced fetal AChR currents, but not adult AChR currents, by >80% within 100 s. Only 2/11 AChR-Ab positive sera inhibited AChR currents in unclustered AChRs, but 6/11 AChR-Ab positive sera compared with none of the 10 AChR-Ab negative sera (p=0.0020) inhibited rapsyn-clustered AChR currents, and current inhibition by the AChR-Ab positive sera was greater when the AChRs were clustered (p=0.0385). None of the sera had detectable effects on desensitisation or recovery from desensitisation. These results show that antibodies can inhibit AChR function rapidly and demonstrate the importance of clustering in exploring pathogenic disease mechanisms of MG Abs.


Paeonol protects endotoxin-induced acute kidney injury: potential mechanism of inhibiting TLR4-NF-κB signal pathway.
In order to determine the therapeutic effect and mechanism of paeonol on acute kidney injury induced by endotoxin, an acute kidney injury model was established by intraperitoneal administration of lipopolysaccharide in mice in vivo and on LPS-induced dendritic cells in vitro. Renal tissues were used for histologic examination. Concentrations of blood urea nitrogen and serum creatinine were detected, inflammatory cytokines were determined by ELISA. The relative proteins' expression of TLR4-NF-κB signal pathway was assessed by Western blot, the localization and expression of phospho-NF-κB p65 in kidney was monitored by immunohistochemistry. Treatment of paeonol successfully cuts histopathological scores and dilutes the concentrations of blood urea nitrogen and serum creatinine as index of renal injury severity. In addition, paeonol reduces pro-inflammatory cytokines and increases anti-inflammatory cytokines stimulated by LPS in a dose-dependent manner. Paeonol also inhibits the expression of phosphorylated NF-κB p65, IκBα and IKKβ, and restrains NF-κB p65 DNA-binding activity. Paeonol treatment also attenuates the effects of LPS on dendritic cells, with significant inhibition of pro-inflammatory cytokines release, then TLR4 expression and NF-κB signal pathway have been suppressed. These results indicated that paeonol has protective effects on endotoxin-induced kidney injury. The mechanisms underlying such effects are associated with its successfully attenuate inflammatory and suppresses TLR4 and NF-κB signal pathway. Therefore, paeonol has great potential to be a novel and natural product agent for treating AKI or septic-AKI.


Whole genome sequencing versus traditional genotyping for investigation of a Mycobacterium tuberculosis outbreak: a longitudinal molecular epidemiological study.
Understanding Mycobacterium tuberculosis (Mtb) transmission is essential to guide efficient tuberculosis control strategies. Traditional strain typing lacks sufficient discriminatory power to resolve large outbreaks. Here, we tested the potential of using next generation genome sequencing for identification of outbreak-related transmission chains. During long-term (1997 to 2010) prospective population-based molecular epidemiological surveillance comprising a total of 2,301 patients, we identified a large outbreak caused by an Mtb strain of the Haarlem lineage. The main performance outcome measure of whole genome sequencing (WGS) analyses was the degree of correlation of the WGS analyses with contact tracing data and the spatio-temporal distribution of the outbreak cases. WGS analyses of the 86 isolates revealed 85 single nucleotide polymorphisms (SNPs), subdividing the outbreak into seven genome clusters (two to 24 isolates each), plus 36 unique SNP profiles. WGS results showed that the first outbreak isolates detected in 1997 were falsely clustered by classical genotyping. In 1998, one clone (termed "Hamburg clone") started expanding, apparently independently from differences in the social environment of early cases. Genome-based clustering patterns were in better accordance with contact tracing data and the geographical distribution of the cases than clustering patterns based on classical genotyping. A maximum of three SNPs were identified in eight confirmed human-to-human transmission chains, involving 31 patients. We estimated the Mtb genome evolutionary rate at 0.4 mutations per genome per year. This rate suggests that Mtb grows in its natural host with a doubling time of approximately 22 h (400 generations per year). Based on the genome variation discovered, emergence of the Hamburg clone was dated back to a period between 1993 and 1997, hence shortly before the discovery of the outbreak through epidemiological surveillance. Our findings suggest that WGS is superior to conventional genotyping for Mtb pathogen tracing and investigating micro-epidemics. WGS provides a measure of Mtb genome evolution over time in its natural host context.


[HIV risk practices and access to prevention in a men's prison in Burkina Faso].
The aim of this survey was to assess the HIV risk practices of male prisoners and their access to prevention. This descriptive study took place at the House of Detention and Corrections in Ouagadougou from June through August 2012. In all, 165 prisoners (median age: 28 years, range: 18-65) were interviewed. A low proportion of the prisoners (16%) had accurate knowledge of the modes of HIV transmission. Before imprisonment, their sex lives featured multiple partners, occasional sex, and low condom use. Seven (4%) prisoners reported homosexual relations while in prison. The conditions of incarceration and the denial of homosexual practices at Ouagadougou aggravate prisoners' vulnerability to HIV/AIDS.


[Somatotypes of male and female competitive Ju-Jutsuka].
31 men and 10 women of the German national cadre or cadres of the federal states (average age 22.3+/-6.1 years), who practised the still relatively new martial arts sports Ju-Jutsu for 8.9+/-4.3 years with 6.2+/-3.6 h training/week, were investigated by means of kinanthropometric methods and compared to 31 male and 10 female hobby martial arts athletes (average age 29.2+/-7.0 years), who practised Jeet Kune Do, Ju-Jutsu or Wing Chun since 8.2+/-7.8 years with 4.1+/-1.7 training hours/week. In the somatochart after Parnell the fighters were placed more endomesomorphic than the hobby sportsmen. In Conrad's chessboard sample graphics the fighters concentrate on the leptomorph half including the metromorph corridor. Remarkable above all is here a placement of the weight class average values toward the pyknomorph hyperplastic quadrant. Also in Knussmann's body build typognosis the weight classes reveal a clear tendency from the coordinates -13/0.5 to -8.3/6.5 in the superleptomorph area. The body fat percentage varies from 17.4 % (male competitors) to 21.8 % (male non-competitors) and 21.2 % (female competitors) to 23.6 % (female non-competitors), which appears still optimizable in comparison to other martial arts collectives.


Pediatric renal transplantation: a single center experience.
Renal transplantation is the treatment of choice for children with end-stage renal disease. The aim of this study was to evaluate retrospectively of our 37 pediatric renal allograft recipients, including 20 boys and 17 girls from July 2007 to August 2012. The overall mean age at transplantation was 12.16 ± 4.25 years. Three patients (8.1%) were transplanted preemptively; two were ABO-incompatible transplantations. The majority of recipients received living donor grafts (81%). The mean duration of follow-up was 25.10 ± 14.95 months. Seven acute rejection episodes were observed in 6 patients (16.2%). Eleven recipients developed serious viral infections: cytomegalovirus (n = 8), parvovirus (n = 2), BK virus (polyoma hominis 1) (n = 2), or Ebstein-Barr virus (n = 1). Three patients died; one from posttransplant lymphoproliferative disease, one from primary disease recurrence with infection, and one from sepsis. In conclusion, kidney transplantation is the treatment of choice for end-stage renal disease. Infection was the major concern after this procedure.


The Metadata Coverage Index (MCI): A standardized metric for quantifying database metadata richness.
Variability in the extent of the descriptions of data ('metadata') held in public repositories forces users to assess the quality of records individually, which rapidly becomes impractical. The scoring of records on the richness of their description provides a simple, objective proxy measure for quality that enables filtering that supports downstream analysis. Pivotally, such descriptions should spur on improvements. Here, we introduce such a measure - the 'Metadata Coverage Index' (MCI): the percentage of available fields actually filled in a record or description. MCI scores can be calculated across a database, for individual records or for their component parts (e.g., fields of interest). There are many potential uses for this simple metric: for example; to filter, rank or search for records; to assess the metadata availability of an ad hoc collection; to determine the frequency with which fields in a particular record type are filled, especially with respect to standards compliance; to assess the utility of specific tools and resources, and of data capture practice more generally; to prioritize records for further curation; to serve as performance metrics of funded projects; or to quantify the value added by curation. Here we demonstrate the utility of MCI scores using metadata from the Genomes Online Database (GOLD), including records compliant with the 'Minimum Information about a Genome Sequence' (MIGS) standard developed by the Genomic Standards Consortium. We discuss challenges and address the further application of MCI scores; to show improvements in annotation quality over time, to inform the work of standards bodies and repository providers on the usability and popularity of their products, and to assess and credit the work of curators. Such an index provides a step towards putting metadata capture practices and in the future, standards compliance, into a quantitative and objective framework.


Safety and efficacy of pyronaridine-artesunate in uncomplicated acute malaria: an integrated analysis of individual patient data from six randomized clinical trials.
Pyronaridine-artesunate (PA) is indicated for the treatment of acute uncomplicated Plasmodium falciparum and Plasmodium vivax malaria. Individual patient data on safety outcomes were integrated from six randomized clinical trials conducted in Africa and Asia in patients with microscopically confirmed P. falciparum (five studies) or P. vivax (one study) malaria. Efficacy against P. falciparum was evaluated across three Phase III clinical trials. The safety population included 2,815 patients randomized to PA, 1,254 to comparators: mefloquine + artesunate (MQ + AS), artemether-lumefantrine (AL), or chloroquine. All treatments were generally well tolerated. Adverse events occurred in 57.2% (1,611/2,815) of patients with PA versus 51.5% (646/1,254) for comparators, most commonly (PA; comparators): headache (10.6%; 9.9%), cough (5.9%; 5.6%) and anaemia (4.5%; 2.9%). Serious averse events were uncommon for all treatments (0-0.7%). Transient increases in alanine aminotransferase and aspartate aminotransferase were observed with PA but did not lead to any clinical sequelae. For P. falciparum malaria, day-28 PCR-corrected adequate clinical and parasitological response with PA was 93.6% ([1,921/2,052] 95% CI 92.6, 94.7) in the intent-to-treat population and 98.5% ([1,852/1,880] 95% CI 98.0, 99.1) in the per-protocol population. Median parasite clearance time was 24.1 h with PA, 31.9 h with MQ + AS, and 24.0 h with AL. Median fever clearance time was 15.5 h with PA, 15.8 h with MQ + AS, and 14.0 h with AL. By day 42, P. falciparum gametocytes had declined to near zero for all treatments. Pyronaridine-artesunate was well tolerated with no safety concerns with the exception of mostly mild transient rises in transaminases. Efficacy was high and met the requirements for use as first-line therapy. Pyronaridine-artesunate should be considered for inclusion in malaria treatment programmes. Clinicaltrials.gov: NCT00331136; NCT00403260; NCT00422084; NCT00440999; NCT00541385; NCT01594931.