426 research outputs found

    Impact of facial conformation on canine health: Brachycephalic Obstructive Airway Syndrome

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    The domestic dog may be the most morphologically diverse terrestrial mammalian species known to man; pedigree dogs are artificially selected for extreme aesthetics dictated by formal Breed Standards, and breed-related disorders linked to conformation are ubiquitous and diverse. Brachycephaly–foreshortening of the facial skeleton–is a discrete mutation that has been selected for in many popular dog breeds e.g. the Bulldog, Pug, and French Bulldog. A chronic, debilitating respiratory syndrome, whereby soft tissue blocks the airways, predominantly affects dogs with this conformation, and thus is labelled Brachycephalic Obstructive Airway Syndrome (BOAS). Despite the name of the syndrome, scientific evidence quantitatively linking brachycephaly with BOAS is lacking, but it could aid efforts to select for healthier conformations. Here we show, in (1) an exploratory study of 700 dogs of diverse breeds and conformations, and (2) a confirmatory study of 154 brachycephalic dogs, that BOAS risk increases sharply in a non-linear manner as relative muzzle length shortens. BOAS only occurred in dogs whose muzzles comprised less than half their cranial lengths. Thicker neck girths also increased BOAS risk in both populations: a risk factor for human sleep apnoea and not previously realised in dogs; and obesity was found to further increase BOAS risk. This study provides evidence that breeding for brachycephaly leads to an increased risk of BOAS in dogs, with risk increasing as the morphology becomes more exaggerated. As such, dog breeders and buyers should be aware of this risk when selecting dogs, and breeding organisations should actively discourage exaggeration of this high-risk conformation in breed standards and the show ring

    Assessing feasibility and acceptability of web-based enhanced relapse prevention for bipolar disorder (ERPonline): a randomized controlled trial

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    Background: Interventions that teach people with Bipolar Disorder (BD) to recognise and respond to early warning signs of relapse are NICE recommended but implementation in clinical practice is poor. Objective: This study tests the feasibility and acceptability of a randomised controlled trial to evaluate an online enhanced relapse prevention intervention (ERPonline), and reports preliminary evidence of effectiveness. Methods: Single blind, parallel primarily online randomised controlled trial (n=96) over 48 weeks comparing ERPonline plus usual treatment to waitlist (WL) control plus usual treatment for people with BD recruited through National Health Services, voluntary organisations, and media. Randomisation was independent, minimised on number of previous episodes (<8,8-20,21+). Primary outcomes were feasibility and acceptability assessed by rates of study recruitment and retention, levels of intervention use, adverse events and participant feedback. Process and clinical outcomes were assessed by telephone and online and compared using linear models with intention-to-treat analysis. Results: Two hundred and eighty people registered interest online, from which ninety-six met inclusion criteria, consented and were randomised (49 to WL, 47 to ERPonline) over seventeen months, with 80% retention in telephone and online follow up, except week 48 online (76%). Acceptability was high for both ERPonline and trial methods. ERPonline cost approximately £19,340 to create, and £2176 per year to host and maintain the site. Qualitative data highlighted the importance of the relationship users have with online interventions and how this is created as an extension of the relationship with the humans perceived as offering and supporting its use. Differences between the group means suggested that access to ERPonline was associated with: a more positive model of bipolar disorder at 24 (10.70 (0.90-20.5 95%CIs)) and 48 weeks (13.1 (2.44-23.93 95%CIs)); increased monitoring of early warning signs of depression at 48 weeks (-1.39 (-2.61, -.163 95%CIs)) and of (hypo)mania at 24 (-1.72 (-2.98, -0.47 95%CIs)) and 48 weeks (-1.61 (-2.92, -0.30 95%CIs)), compared to WL. There was no evidence of impact of ERPonline on clinical outcomes or medication adherence, but relapse rates across both arms were very low (15%) and the sample remained high functioning throughout. One person died by suicide prior to randomisation. Five people in ERPonline and six in WL control reported ideas of suicide or self-harm during the study. None were deemed study related by an independent Trial Steering Committee. Conclusions: ERPonline offers a cheap accessible option for people seeking ongoing support following successful treatment. However, given high functioning and low relapse rates in this study, testing clinical effectiveness for this population would require very large sample sizes. Building in human support to use ERPonline should be considere

    Accuracy of responses from postal surveys about continuing medical education and information behavior: experiences from a survey among German diabetologists

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    BACKGROUND: Postal surveys are a popular instrument for studies about continuing medical education habits. But little is known about the accuracy of responses in such surveys. The objective of this study was to quantify the magnitude of inaccurate responses in a postal survey among physicians. METHODS: A sub-analysis of a questionnaire about continuing medical education habits and information management was performed. The five variables used for the quantitative analysis are based on a question about the knowledge of a fictitious technical term and on inconsistencies in contingency tables of answers to logically connected questions. RESULTS: Response rate was 52%. Non-response bias is possible but seems not very likely since an association between demographic variables and inconsistent responses could not be found. About 10% of responses were inaccurate according to the definition. CONCLUSION: It was shown that a sub-analysis of a questionnaire makes a quantification of inaccurate responses in postal surveys possible. This sub-analysis revealed that a notable portion of responses in a postal survey about continuing medical education habits and information management was inaccurate

    Measurement of D-s(+) and D-s(*+) production in B meson decays and from continuum e(+)e(-) annihilation at √s=10.6 GeV

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    This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APSNew measurements of Ds+ and Ds*+ meson production rates from B decays and from qq̅ continuum events near the Υ(4S) resonance are presented. Using 20.8 fb-1 of data on the Υ(4S) resonance and 2.6 fb-1 off-resonance, we find the inclusive branching fractions B(B⃗Ds+X)=(10.93±0.19±0.58±2.73)% and B(B⃗Ds*+X)=(7.9±0.8±0.7±2.0)%, where the first error is statistical, the second is systematic, and the third is due to the Ds+→φπ+ branching fraction uncertainty. The production cross sections σ(e+e-→Ds+X)×B(Ds+→φπ+)=7.55±0.20±0.34pb and σ(e+e-→Ds*±X)×B(Ds+→φπ+)=5.8±0.7±0.5pb are measured at center-of-mass energies about 40 MeV below the Υ(4S) mass. The branching fractions ΣB(B⃗Ds(*)+D(*))=(5.07±0.14±0.30±1.27)% and ΣB(B⃗Ds*+D(*))=(4.1±0.2±0.4±1.0)% are determined from the Ds(*)+ momentum spectra. The mass difference m(Ds+)-m(D+)=98.4±0.1±0.3MeV/c2 is also measured.This work was supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the Swiss NSF, A. P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation

    CLC-2 single nucleotide polymorphisms (SNPs) as potential modifiers of cystic fibrosis disease severity

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    BACKGROUND: Cystic fibrosis (CF) lung disease manifest by impaired chloride secretion leads to eventual respiratory failure. Candidate genes that may modify CF lung disease severity include alternative chloride channels. The objectives of this study are to identify single nucleotide polymorphisms (SNPs) in the airway epithelial chloride channel, CLC-2, and correlate these polymorphisms with CF lung disease. METHODS: The CLC-2 promoter, intron 1 and exon 20 were examined for SNPs in adult CF dF508/dF508 homozygotes with mild and severe lung disease (forced expiratory volume at one second (FEV1) > 70% and < 40%). RESULTS: PCR amplification of genomic CLC-2 and sequence analysis revealed 1 polymorphism in the hClC -2 promoter, 4 in intron 1, and none in exon 20. Fisher's analysis within this data set, did not demonstrate a significant relationship between the severity of lung disease and SNPs in the CLC-2 gene. CONCLUSIONS: CLC-2 is not a key modifier gene of CF lung phenotype. Further studies evaluating other phenotypes associated with CF may be useful in the future to assess the ability of CLC-2 to modify CF disease severity

    Beak and feather disease virus in wild and captive parrots: an analysis of geographic and taxonomic distribution and methodological trends

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    Psittacine beak and feather disease (PBFD) has emerged in recent years as a major threat to wild parrot populations and is an increasing concern to aviculturists and managers of captive populations. Pathological and serological tests for screening for the presence of beak and feather disease virus (BFDV) are a critical component of efforts to manage the disease and of epidemiological studies. Since the disease was first reported in the mid-1970s, screening for BFDV has been conducted in numerous wild and captive populations. However, at present, there is no current and readily accessible synthesis of screening efforts and their results. Here, we consolidate information collected from 83 PBFD- and BFDV-based publications on the primary screening methods being used and identify important knowledge gaps regarding potential global disease hotspots. We present trends in research intensity in this field and critically discuss advances in screening techniques and their applications to both aviculture and to the management of threatened wild populations. Finally, we provide an overview of estimates of BFDV prevalence in captive and wild flocks alongside a complete list of all psittacine species in which the virus has been confirmed. Our evaluation highlights the need for standardised diagnostic tests and more emphasis on studies of wild populations, particularly in view of the intrinsic connection between global trade in companion birds and the spread of novel BFDV strains into wild populations. Increased emphasis should be placed on the screening of captive and wild parrot populations within their countries of origin across the Americas, Africa and Asia

    A dual role of transient receptor potential melastatin 2 channel in cytotoxicity induced by silica nanoparticles

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    Silica nanoparticles (NPs) have remarkable applications. However, accumulating evidence suggests NPs can cause cellular toxicity by inducing ROS production and increasing intracellular Ca2+ ([Ca2+]i), but the underlying molecular mechanism is largely unknown. Transient receptor potential melastatin 2 (TRPM2) channel is known to be a cellular redox potential sensor that provides an important pathway for increasing the [Ca2+]i under oxidative stress. In this study, we examined the role of TRPM2 channel in silica NPs-induced oxidative stress and cell death. By quantitation of cell viability, ROS production, [Ca2+]i, and protein identification, we showed that TRPM2 channel is required for ROS production and Ca2+ increase induced by silica NPs through regulating NADPH oxidase activity in HEK293 cells. Strikingly, HEK293 cells expressing low levels of TRPM2 were more susceptible to silica NPs than those expressing high levels of TRPM2. Macrophages from young mice showed significantly lower TRPM2 expression than those from senescent mice and had significantly lower viability after silica NPs exposure than those from senescent ones. Taken together, these findings demonstrate for the first time that TRPM2 channel acts as an oxidative stress sensor that plays a dual role in silica NPs-induced cytotoxicity by differentially regulating the NADPH oxidase activity and ROS generation

    Protective effect of geranylgeranylacetone, an inducer of heat shock protein 70, against drug-induced lung injury/fibrosis in an animal model

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    <p>Abstract</p> <p>Background</p> <p>To determine whether oral administration of geranylgeranylacetone (GGA), a nontoxic anti-ulcer drug that is an inducer of heat shock protein (HSP) 70, protects against drug-induced lung injury/fibrosis <it>in vivo</it>.</p> <p>Methods</p> <p>We used a bleomycin (BLM)-induced lung fibrosis model in which mice were treated with oral 600 mg/kg of GGA before and after BLM administration. Inflammation and fibrosis were evaluated by histological scoring, hydroxyproline content in the lung and inflammatory cell count, and quantification by ELISA of macrophage inflammatory protein-2 (MIP-2) in bronchoalveolar lavage fluid. Apoptosis was evaluated by the TUNEL method. The induction of HSP70 in the lung was examined with western blot analysis and its localization was determined by immunohistochemistry.</p> <p>Results</p> <p>We confirmed the presence of inflammation and fibrosis in the BLM-induced lung injury model and induction of HSP70 by oral administration of GGA. GGA prevented apoptosis of cellular constituents of lung tissue, such as epithelial cells, most likely related to the <it>de novo </it>induction of HSP70 in the lungs. GGA-treated mice also showed less fibrosis of the lungs, associated with the findings of suppression of both production of MIP-2 and inflammatory cell accumulation in the injured lung, compared with vehicle-treated mice.</p> <p>Conclusion</p> <p>GGA had a protective effect on drug-induced lung injury/fibrosis. Disease-modifying antirheumatic drugs such as methotrexate, which are indispensable for the treatment of rheumatoid arthritis, often cause interstitial lung diseases, an adverse event that currently cannot be prevented. Clinical use of GGA for drug-induced pulmonary fibrosis might be considered in the future.</p
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