196 research outputs found

    Autoantibodies targeting TLR and SMAD pathways define new subgroups in systemic lupus erythematosus

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    T.J.V. was awarded funding to from the George Koukis Foundation and an Arthritis Research UK Special Strategic Award. The study received support from the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and the Biomedical Research Centre based at Guy’s & St. Thomas’ National Health Service (NHS) Foundation Trust, in partnership with King’s College London. The TwinsUK study was funded by the Wellcome Trust; European Community’s Seventh Framework Programme (FP7/2007-2013)

    A study of patient attitudes towards decentralisation of HIV care in an urban clinic in South Africa

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    <p>Abstract</p> <p>Background</p> <p>In South Africa, limited human resources are a major constraint to achieving universal antiretroviral therapy (ART) coverage. Many of the public-sector HIV clinics operating within tertiary facilities, that were the first to provide ART in the country, have reached maximum patient capacity. Decentralization or "down-referral" (wherein ART patients deemed stable on therapy are referred to their closest Primary Health Clinics (PHCs) for treatment follow-up) is being used as a possible alternative of ART delivery care. This cross-sectional qualitative study investigates attitudes towards down-referral of ART delivery care among patients currently receiving care in a centralized tertiary HIV clinic.</p> <p>Methods</p> <p>Ten focus group discussions (FGDs) with 76 participants were conducted in early 2008 amongst ART patients initiated and receiving care for more than 3 months in the tertiary HIV clinic study site. Eligible individuals were invited to participate in FGDs involving 6-9 participants, and lasting approximately 1-2 hours. A trained moderator used a discussion topic guide to investigate the main issues of interest including: advantages and disadvantages of down-referral, potential motivating factors and challenges of down-referral, assistance needs from the transferring clinic as well as from PHCs.</p> <p>Results</p> <p>Advantages include closeness to patients' homes, transport and time savings. However, patients favour a centralized service for the following reasons: less stigma, patients established relationship with the centralized clinic, and availability of ancillary services. Most FGDs felt that for down-referral to occur there needed to be training of nurses in patient-provider communication.</p> <p>Conclusion</p> <p>Despite acknowledging the down-referral advantages of close proximity and lower transport costs, many participants expressed concerns about lack of trained HIV clinical staff, negative patient interactions with nurses, limited confidentiality and stigma. There was consensus that training of nurses and improved health systems at the local clinics were needed if successful down-referral was to take place.</p

    Enhanced tonic GABAA inhibition in typical absence epilepsy

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    The cellular mechanisms underlying typical absence seizures, which characterize various idiopathic generalized epilepsies, are not fully understood, but impaired GABAergic inhibition remains an attractive hypothesis. In contrast, we show here that extrasynaptic GABAA receptor–dependent ‘tonic’ inhibition is increased in thalamocortical neurons from diverse genetic and pharmacological models of absence seizures. Increased tonic inhibition is due to compromised GABA uptake by the GABA transporter GAT–1 in the genetic models tested, and GAT–1 is critical in governing seizure genesis. Extrasynaptic GABAA receptors are a requirement for seizures in two of the best characterized models of absence epilepsy, and the selective activation of thalamic extrasynaptic GABAA receptors is sufficient to elicit both electrographic and behavioural correlates of seizures in normal animals. These results identify an apparently common cellular pathology in typical absence seizures that may have epileptogenic significance, and highlight novel therapeutic targets for the treatment of absence epilepsy.peer-reviewe

    Funding Source and Research Report Quality in Nutrition Practice-Related Research

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    BACKGROUND: The source of funding is one of many possible causes of bias in scientific research. One method of detecting potential for bias is to evaluate the quality of research reports. Research exploring the relationship between funding source and nutrition-related research report quality is limited and in other disciplines the findings are mixed. OBJECTIVE: The purpose of this study is to determine whether types of funding sources of nutrition research are associated with differences in research report quality. DESIGN: A retrospective study of research reporting quality, research design and funding source was conducted on 2539 peer reviewed research articles from the American Dietetic Association's Evidence Analysis Library® database. RESULTS: Quality rating frequency distributions indicate 43.3% of research reports were rated as positive, 50.1% neutral, and 6.6% as negative. Multinomial logistic regression results showed that while both funding source and type of research design are significant predictors of quality ratings (χ2 = 118.99, p≤0.001), the model's usefulness in predicting overall research report quality is little better than chance. Compared to research reports with government funding, those not acknowledging any funding sources, followed by studies with University/hospital funding were more likely to receive neutral vs positive quality ratings, OR = 1.85, P <0.001 and OR = 1.54, P<0.001, respectively and those that did not report funding were more likely to receive negative quality ratings (OR = 4.97, P<0.001). After controlling for research design, industry funded research reports were no more likely to receive a neutral or negative quality rating than those funded by government sources. CONCLUSION: Research report quality cannot be accurately predicted from the funding source after controlling for research design. Continued vigilance to evaluate the quality of all research regardless of the funding source and to further understand other factors that affect quality ratings are warranted

    Mice with reduced DAT levels recreate seasonal-induced switching between states in bipolar disorder.

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    Developing novel therapeutics for bipolar disorder (BD) has been hampered by limited mechanistic knowledge how sufferers switch between mania and depression-how the same brain can switch between extreme states-described as the "holy grail" of BD research. Strong evidence implicates seasonally-induced switching between states, with mania associated with summer-onset, depression with winter-onset. Determining mechanisms of and sensitivity to such switching is required. C57BL/6J and dopamine transporter hypomorphic (DAT-HY 50% expression) mice performed a battery of psychiatry-relevant behavioral tasks following 2-week housing in chambers under seasonally relevant photoperiod extremes. Summer-like and winter-like photoperiod exposure induced mania-relevant and depression-relevant behaviors respectively in mice. This behavioral switch paralleled neurotransmitter switching from dopamine to somatostatin in hypothalamic neurons (receiving direct input from the photoperiod-processing center, the suprachiasmatic nucleus). Mice with reduced DAT expression exhibited hypersensitivity to these summer-like and winter-like photoperiods, including more extreme mania-relevant (including reward sensitivity during reinforcement learning), and depression-relevant (including punishment-sensitivity and loss-sensitivity during reinforcement learning) behaviors. DAT mRNA levels switched in wildtype littermate mice across photoperiods, an effect not replicated in DAT hypomorphic mice. This inability to adjust DAT levels to match photoperiod-induced neurotransmitter switching as a homeostatic control likely contributes to the susceptibility of DAT hypormophic mice to these switching photoperiods. These data reveal the potential contribution of photoperiod-induced neuroplasticity within an identified circuit of the hypothalamus, linked with reduced DAT function, underlying switching between states in BD. Further investigations of the circuit will likely identify novel therapeutic targets to block switching between states

    Dissection of genetic associations with language-related traits in population-based cohorts

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    Recent advances in the field of language-related disorders have led to the identification of candidate genes for specific language impairment (SLI) and dyslexia. Replication studies have been conducted in independent samples including population-based cohorts, which can be characterised for a large number of relevant cognitive measures. The availability of a wide range of phenotypes allows us to not only identify the most suitable traits for replication of genetic association but also to refine the associated cognitive trait. In addition, it is possible to test for pleiotropic effects across multiple phenotypes which could explain the extensive comorbidity observed across SLI, dyslexia and other neurodevelopmental disorders. The availability of genome-wide genotype data for such cohorts will facilitate this kind of analysis but important issues, such as multiple test corrections, have to be taken into account considering that small effect sizes are expected to underlie such associations

    Modeling visual-based pitch, lift and speed control strategies in hoverflies

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    <div><p>To avoid crashing onto the floor, a free falling fly needs to trigger its wingbeats quickly and control the orientation of its thrust accurately and swiftly to stabilize its pitch and hence its speed. Behavioural data have suggested that the vertical optic flow produced by the fall and crossing the visual field plays a key role in this anti-crash response. Free fall behavior analyses have also suggested that flying insect may not rely on graviception to stabilize their flight. Based on these two assumptions, we have developed a model which accounts for hoverflies´ position and pitch orientation recorded in 3D with a fast stereo camera during experimental free falls. Our dynamic model shows that optic flow-based control combined with closed-loop control of the pitch suffice to stabilize the flight properly. In addition, our model sheds a new light on the visual-based feedback control of fly´s pitch, lift and thrust. Since graviceptive cues are possibly not used by flying insects, the use of a vertical reference to control the pitch is discussed, based on the results obtained on a complete dynamic model of a virtual fly falling in a textured corridor. This model would provide a useful tool for understanding more clearly how insects may or not estimate their absolute attitude.</p></div
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