The antibody loci of the domestic goat (Capra hircus)

The domestic goat (Capra hircus) is an important ruminant species both as a source of antibody-based reagents for research and biomedical applications and as an economically important animal for agriculture, particularly for developing nations that maintain most of the global goat population. Characterization of the loci encoding the goat immune repertoire would be highly beneficial for both vaccine and immune reagent development. However, in goat and other species whose reference genomes were generated using short-read sequencing technologies, the immune loci are poorly assembled as a result of their repetitive nature. Our recent construction of a long-read goat genome assembly (ARS1) has facilitated characterization of all three antibody loci with high confidence and comparative analysis to cattle. We observed broad similarity of goat and cattle antibody-encoding loci but with notable differences that likely influence formation of the functional antibody repertoire. The goat heavy-chain locus is restricted to only four functional and nearly identical IGHV genes, in contrast to the ten observed in cattle. Repertoire analysis indicates that light-chain usage is more balanced in goats, with greater representation of kappa light chains (~ 20-30%) compared to that in cattle (~ 5%). The present study represents the first characterization of the goat antibody loci and will help inform future investigations of their antibody responses to disease and vaccination

A Systematic Review on the Efficacy of Iontophoresis as a Treatment for Lateral Epicondylitis

Background and purpose: It is still inconclusive which method of iontophoresis delivers the most medication deepest through the skin, and therefore most effective in treating lateral epicondylitis. The purpose of this systematic review is to analyze the efficacy of treatments for lateral epicondylitis using iontophoresis. Method: The review included articles from peer-reviewed journals with sufficient data related to the purpose and focus of the study. Inclusion criteria included randomized control trials, cohort studies, case studies, systematic reviews, meta-analyses, and pilot studies published since 2000. Results: Fourteen relevant studies were identified. Twelve were experimental in vivo studies, two were review studies. All studies were published 2002 through 2015, providing a robust overview of treatments over the last 15 years. Discussion and conclusion: Among studies in this systemic review, pooled data from RCTs pointed to minimal intermediate- to long-term clinical benefit for the nonsurgical treatment of lateral epicondylitis. Of drug treatments, the most frequently used in iontophoresis are dexamethasone and lidocaine. Studies of iontophoresis with dexamethasone show evidence that the combination of treatments may be effective in reducing pain; there is evidence supporting the iontophoretic administration of dexamethasone as an alternative to other medication and oral therapy. Based on this review, it is not conclusive that iontophoresis be recommended as a treatment approach for the management of epicondylitis, however iontophoresis should not be ruled out in treating epicondylitis as it is a dose-response modality. More research and review of research is needed on the use of iontophoresis in managing epicondylitis

Equity, gender and health: New directions for global men’s health promotion

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154916/1/hpja337_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154916/2/hpja337.pd

The crystal structure of superoxide dismutase from Plasmodium falciparum

Background: Superoxide dismutases (SODs) are important enzymes in defence against oxidative stress. In Plasmodium falciparum, they may be expected to have special significance since part of the parasite life cycle is spent in red blood cells where the formation of reactive oxygen species is likely to be promoted by the products of haemoglobin breakdown. Thus, inhibitors of P. falciparum SODs have potential as anti-malarial compounds. As a step towards their development we have determined the crystal structure of the parasite's cytosolic iron superoxide dismutase. Results: The cytosolic iron superoxide dismutase from P. falciparum (PfFeSOD) has been overexpressed in E. coli in a catalytically active form. Its crystal structure has been solved by molecular replacement and refined against data extending to 2.5 angstrom resolution. The structure reveals a two-domain organisation and an iron centre in which the metal is coordinated by three histidines, an aspartate and a solvent molecule. Consistent with ultracentrifugation analysis the enzyme is a dimer in which a hydrogen bonding lattice links the two active centres. Conclusion: The tertiary structure of PfFeSOD is very similar to those of a number of other iron-and manganese-dependent superoxide dismutases, moreover the active site residues are conserved suggesting a common mechanism of action. Comparison of the dimer interfaces of PfFeSOD with the human manganese-dependent superoxide dismutase reveals a number of differences, which may underpin the design of parasite-selective superoxide dismutase inhibitors

The evolution of the natural killer complex; a comparison between mammals using new high-quality genome assemblies and targeted annotation.

Natural killer (NK) cells are a diverse population of lymphocytes with a range of biological roles including essential immune functions. NK cell diversity is in part created by the differential expression of cell surface receptors which modulate activation and function, including multiple subfamilies of C-type lectin receptors encoded within the NK complex (NKC). Little is known about the gene content of the NKC beyond rodent and primate lineages, other than it appears to be extremely variable between mammalian groups. We compared the NKC structure between mammalian species using new high-quality draft genome assemblies for cattle and goat; re-annotated sheep, pig, and horse genome assemblies; and the published human, rat, and mouse lemur NKC. The major NKC genes are largely in the equivalent positions in all eight species, with significant independent expansions and deletions between species, allowing us to propose a model for NKC evolution during mammalian radiation. The ruminant species, cattle and goats, have independently evolved a second KLRC locus flanked by KLRA and KLRJ, and a novel KLRH-like gene has acquired an activating tail. This novel gene has duplicated several times within cattle, while other activating receptor genes have been selectively disrupted. Targeted genome enrichment in cattle identified varying levels of allelic polymorphism between the NKC genes concentrated in the predicted extracellular ligand-binding domains. This novel recombination and allelic polymorphism is consistent with NKC evolution under balancing selection, suggesting that this diversity influences individual immune responses and may impact on differential outcomes of pathogen infection and vaccination

Brain hubs defined in the group do not overlap with regions of high inter-individual variability

Connector \u27hubs\u27 are brain regions with links to multiple networks. These regions are hypothesized to play a critical role in brain function. While hubs are often identified based on group-average functional magnetic resonance imaging (fMRI) data, there is considerable inter-subject variation in the functional connectivity profiles of the brain, especially in association regions where hubs tend to be located. Here we investigated how group hubs are related to locations of inter-individual variability. To answer this question, we examined inter-individual variation at group-level hubs in both the Midnight Scan Club and Human Connectome Project datasets. The top group hubs defined based on the participation coefficient did not overlap strongly with the most prominent regions of inter-individual variation (termed \u27variants\u27 in prior work). These hubs have relatively strong similarity across participants and consistent cross-network profiles, similar to what was seen for many other areas of cortex. Consistency across participants was further improved when these hubs were allowed to shift slightly in local position. Thus, our results demonstrate that the top group hubs defined with the participation coefficient are generally consistent across people, suggesting they may represent conserved cross-network bridges. More caution is warranted with alternative hub measures, such as community density (which are based on spatial proximity to network borders) and intermediate hub regions which show higher correspondence to locations of individual variability

Seasonal patterns of oral antihistamine and intranasal corticosteroid purchases from Australian community pharmacies : a retrospective observational study

Acknowledgments The abstract of this paper was presented at the Respiratory Effectiveness Group 2016 Annual Summit as a poster presentation with interim findings. The poster’s abstract was published in “Poster Abstracts” in The Journal of Thoracic Disease (Vol. 8, Supplement 5, 5 July 2016). http://jtd.amegroups.com/article/view/8504.Peer reviewedPublisher PD

KINEMATIC ANALYSIS OF MEN BOBSLED PUSH STARTS

The purpose of this study was to provide a descriptive analysis of selected kinematic variables associated with the push start for brakemen in the two-man bobsled. Eleven male bobsledders served as subjects for this study. The subjects were videotaped at 120 Hz during competition at the Lake Placid, NY bobsled track as they were competing for positions on the men’s 2004 National Bobsled Team. Selected groups of variables measured at specific events in this study included step length, frequency, and foot contact time; COM velocity; and trunk, knee, and elbow angles. A relationship of 0.63 was determined between start time and finish time; an exploratory correlational analysis between start time and COM velocity at 2nd step take-off (TO) was -0.63. Start time is of critical importance in determining final race time

Outcomes following oesophagectomy in patients with oesophageal cancer: a secondary analysis of the ICNARC Case Mix Programme Database

Introduction: This report describes the case mix and outcomes of patients with oesophageal cancer admitted to adult critical care units following elective oesophageal surgery in England, Wales and Northern Ireland. Methods: Admissions to critical care following elective oesophageal surgery for malignancy were identified using data from the Intensive Care National Audit and Research Centre (ICNARC) Case Mix Programme Database. Information on admissions between December 1995 and September 2007 were extracted and the association between in-hospital mortality and patient characteristics on admission to critical care was assessed using multiple logistic regression analysis. The performance of three prognostic models (Simplified Acute Physiology Score (SAPS) II, Acute Physiology and Chronic Health Evaluation (APACHE) II and the ICNARC physiology score) was also evaluated. Results: Between 1995 and 2007, there were 7227 admissions to 181 critical care units following oesophageal surgery for malignancy. Overall mortality in critical care was 4.4% and in-hospital mortality was 11%, although both declined steadily over time. Eight hundred and seventy-three (12.2%) patients were readmitted to critical care, most commonly for respiratory complications (49%) and surgical complications (25%). Readmitted patients had a critical care unit mortality of 24.7% and in-hospital mortality of 33.9%. Overall in-hospital mortality was associated with patient age, and various physiological measurements on admission to critical care (partial pressure of arterial oxygen (PaO2):fraction of inspired oxygen (FiO2) ratio, lowest arterial pH, mechanical ventilation, serum albumin, urea and creatinine). The three prognostic models evaluated performed poorly in measures of discrimination, calibration and goodness of fit. Conclusions: Surgery for oesophageal malignancy continues to be associated with significant morbidity and mortality. Age and organ dysfunction in the early postoperative period are associated with an increased risk of death. Postoperative serum albumin is confirmed as an additional prognostic factor. More work is required to determine how this knowledge may improve clinical management

Stable isotopes used to infer trophic position of green turtles (Chelonia mydas) from Dry Tortugas National Park, Gulf of Mexico, United States

Evaluating resource use patterns for imperiled species is critical for understanding what supports their populations. Here we established stable isotope (δ13C, δ15N) values for the endangered green sea turtle (Chelonia mydas) population found within the boundaries of Dry Tortugas National Park (DRTO), south Florida, USA. There is little gene flow between turtles sampled at DRTO and in other rookeries in Florida, underscoring the need to study this distinct population. Between 2008 and 2015 we collected multiple sample types (skin [homogenized epidermis/dermis], whole blood, red blood cells, plasma, carapace) from 151 unique green turtles, including 43 nesting females and 108 in-water captures; some individuals were resampled multiple times across years to evaluate consistency of isotope signatures. Isotopic ratios ranged from -27.3 to -5.4 for δ13C and 3.7 to 10.6 for δ15N. Using linear mixed models, we evaluated covariates (sample type, turtle size and year) that best explained the isotope patterns observed in turtle tissues. Predictions from the top model for δ13C indicated a slight decrease over time and for δ15N a slight increase in the middle sampling years (2010–2012); results indicated that turtle size appeared to be the driver behind the range in δ13C and δ15N observed in turtle skin. We found a pattern in stable carbon isotope values that are indicative of an ontogenetic change from an omnivorous diet in smaller turtles to a seagrass-based diet in larger turtles. When we compared the stable carbon and nitrogen isotope values of the samples collected from turtles with that of seagrasses found in DRTO, we found that turtles \u3e 65 cm SCL had similar stable carbon isotope values to the seagrass species present. Results of this study suggest stable isotope analysis coupled with data for available resources can be useful for tracking and detecting future changes in green turtle resource shifts in DRTO