Trypanosomosis in The Gambia: prevalence in working horses and donkeys detected by whole genome amplification and PCR, and evidence for interactions between trypanosome species

<p>Abstract</p> <p>Background</p> <p>The Gambia has an increasing population of <it>equidae </it>largely used for agriculture and transportation. A review of cases at The Gambian Horse and Donkey Trust (GHDT) indicated that a common reason for presentation is a poorly defined medical condition often attributed to trypanosomosis. There are few reports describing the prevalence or the range of clinical signs associated with infection with different species of trypanosomes in horses and donkeys, but given the importance of these animals, the role of trypanosomosis requires investigation.</p> <p>Results</p> <p>In total 241 animals from the Central River Division in The Gambia (183 horses and 58 donkeys) were screened using Whole Genome Amplification (WGA) followed by trypanosome species identification using polymerase chain reaction (PCR). The results indicated overall trypanosome prevalence of 91%; with an infection rate of 31% for <it>Trypanosoma congolense </it>Savannah, 87% for <it>Trypanosoma vivax </it>and 18% for <it>Trypanosoma brucei </it>sp. Multiple species were present in 43% of infections. Microscopy had a good specificity (100%) and positive predictive value (100%) for trypanosome detection, but the sensitivity (20%) and negative predictive value (10.5%) were low relative to PCR-based diagnosis.</p> <p>Infection with <it>T congolense </it>showed the greatest negative effect on packed cell volume (PCV), while infection with <it>T. brucei </it>sp also had a significant, although lesser, negative effect on PCV. In addition, cases positive by microscopy were associated with significantly lower PCV. However, concurrent infection with <it>T. vivax </it>appeared to cause less effect on PCV, compared to animals infected with <it>T. congolense </it>alone.</p> <p>Conclusion</p> <p>The prevalence of Trypanosomosis was high in both horses and donkeys. Infection with <it>T. congolense </it>appeared to have the greatest clinical significance, while <it>T. vivax </it>infection may be of limited clinical significance in this population. Indeed, there is evidence of <it>T. vivax </it>co-infection ameliorating the pathology caused by <it>T. congolense</it>. WGA and PCR allowed a more comprehensive analysis of field infections with the detection of infections below the threshold of microscopy, and provided indications of interactions between parasite species that would otherwise remain undetected. The study raises important questions about the epidemiology of trypanosome infection in relation to disease that require a full scale longitudinal analysis.</p

‘A silent epidemic of grief’: a survey of bereavement care provision in the UK and Ireland during the COVID-19 pandemic

Objectives: To investigate the experiences and views of practitioners in the UK and Ireland concerning changes in bereavement care during the COVID-19 pandemic. Design: Online survey using a snowball sampling approach. Setting: Practitioners working in hospitals, hospices, care homes and community settings across the UK and Ireland. Participants: Health and social care professionals involved in bereavement support. Interventions: Brief online survey distributed widely across health and social care organisations. Results: 805 respondents working in hospice, community, and hospital settings across the UK and Ireland completed the survey between 3 August and 4 September 2020. Changes to bereavement care practice were reported in: the use of telephone, video and other forms of remote support (90%); supporting people bereaved from non-COVID conditions (76%), from COVID-19 (65%) and people bereaved before the pandemic (61%); funeral arrangements (61%); identifying bereaved people who might need support (56%); managing complex forms of grief (48%) and access to specialist services (41%). Free-text responses demonstrated the complexities and scale of the impact on health and social care services, practitioners and their relationships with bereaved families, and on bereaved people. Conclusions: The pandemic has created major challenges for the support of bereaved people: increased needs for bereavement care, transition to remote forms of support and the stresses experienced by practitioners, among others. The extent to which services are able to adapt, meet the escalating level of need and help to prevent a ‘tsunami of grief’ remains to be seen. The pandemic has highlighted the need for bereavement care to be considered an integral part of health and social care provision

Combining Active and Passive Airborne Remote Sensing to Quantify NO2 and Ox Production near Bakersfield, CA

Aims: The objective of this study is to demonstrate the integrated use of passive and active remote sensing instruments to quantify the rate of NOx emissions, and investigate the Ox production rates from an urban area.Place and Duration of Study: A research flight on June 15, 2010 was conducted over Bakersfield, CA and nearby areas with oil and natural gas production. Methodology: Three remote sensing instruments, namely the University of Colorado AMAX-DOAS, NOAA TOPAZ lidar, and NCAS Doppler lidar were deployed aboard the NOAA Twin Otter during summer 2010. Production rates of nitrogen dioxide (NO2) and Ox&lsquo;(background corrected O3 + NO2) were quantified using the horizontal flux divergence approach by flying closed loops near Bakersfield, CA. By making concurrent measurements of the trace gases as well as the wind fields, we have reduced the uncertainty due to wind field in production rates.Results: We find that the entire region is a source for both NO2 and Ox&rsquo;. NO2 production is highest over the city (1.35 kg hr-1 km-2 NO2), and about 30 times lower at background sites (0.04 kg hr-1 km-2 NO2). NOx emissions as represented in the CARB 2010 emission inventory agreewell with our measurements over Bakersfield city (within 30%). However, emissions upwind of the city are significantly underestimated. The Ox&rsquo; production is less variable, found ubiquitous, and accounts for 7.4 kg hr-1 km-2 Ox&rsquo; at background sites. Interestingly, the maximum of 17.1 kg hr-1 km-2 Ox&rsquo;production was observed upwind of the city. A plausible explanation for the efficient Ox&rsquo; production upwind of Bakersfield, CA are favorable volatile organic compound (VOC) to NOx ratios for Ox&rsquo; production, that are affected by emissions from large oil and natural gas operations in that area. Conclusion: The NO2 and O3 source fluxes vary significantly, and allow us to separate and map NOx emissions and Ox production rates in the Central Valley. The data is probed over spatial scales that link closely with those predicted by atmospheric models, and provide innovative means to test and improve atmospheric models that are used to manage air resources. Emissions from oil and natural gas operations are a source for O3 air pollution, and deserve further study to better characterize effects on public health.</p

High dose genistein in Sanfilippo syndrome: A randomised controlled trial

From Wiley via Jisc Publications RouterHistory: received 2021-02-09, rev-recd 2021-05-25, accepted 2021-05-27, pub-electronic 2021-06-13Article version: VoRPublication status: PublishedFunder: UK MPS SocietyFunder: National MPS society; Id: http://dx.doi.org/10.13039/100013927Funder: GEM AppealAbstract: The aim of this study was to evaluate the efficacy of high dose genistein aglycone in Sanfilippo syndrome (mucopolysaccharidosis type III). High doses of genistein aglycone have been shown to correct neuropathology and hyperactive behaviour in mice, but efficacy in humans is uncertain. This was a single centre, double‐blinded, randomised, placebo‐controlled study with open‐label extension phase. Randomised participants received either 160 mg/kg/day genistein aglycone or placebo for 12 months; subsequently all participants received genistein for 12 months. The primary outcome measure was the change in heparan sulfate concentration in cerebrospinal fluid (CSF), with secondary outcome measures including heparan sulfate in plasma and urine, total glycosaminoglycans in urine, cognitive and adaptive behaviour scores, quality of life measures and actigraphy. Twenty‐one participants were randomised and 20 completed the placebo‐controlled phase. After 12 months of treatment, the CSF heparan sulfate concentration was 5.5% lower in the genistein group (adjusted for baseline values), but this was not statistically significant (P = .26), and CSF heparan sulfate increased in both groups during the open‐label extension phase. Reduction of urinary glycosaminoglycans was significantly greater in the genistein group (32.1% lower than placebo after 12 months, P = .0495). Other biochemical and clinical parameters showed no significant differences between groups. High dose genistein aglycone (160 mg/kg/day) was not associated with clinically meaningful reductions in CSF heparan sulfate and no evidence of clinical efficacy was detected. However, there was a statistically significant reduction in urine glycosaminoglycans. These data do not support the use of genistein aglycone therapy in mucopolysaccharidosis type III. High dose genistein aglycone does not lead to clinically meaningful reductions in biomarkers or improvement in neuropsychological outcomes in mucopolysaccharidosis type III

Psychosocial factors associated with outcomes of sports injury rehabilitation in competitive athletes: a mixed studies systematic review.

The prime focus of research on sports injury has been on physical factors. This is despite our understanding that when an athlete sustains an injury it has psychosocial as well as physical impacts. Psychosocial factors have been suggested as prognostic influences on the outcomes of rehabilitation. The aim of this work was to address the question: are psychosocial factors associated with sports injury rehabilitation outcomes in competitive athletes?Mixed studies systematic review (PROSPERO reg.CRD42014008667).Electronic database and bibliographic searching was undertaken from the earliest entry until 1 June 2015. Studies that included injured competitive athletes, psychosocial factors and a sports injury rehabilitation outcome were reviewed by the authors. A quality appraisal of the studies was undertaken to establish the risk of reporting bias.25 studies were evaluated that included 942 injured competitive athletes were appraised and synthesised. Twenty studies had not been included in previous reviews. The mean methodological quality of the studies was 59% (moderate risk of reporting bias). Convergent thematic analysis uncovered three core themes across the studies: (1) emotion associated with rehabilitation outcomes; (2) cognitions associated with rehabilitation outcomes; and (3) behaviours associated with rehabilitation outcomes. Injury and performance-related fears, anxiety and confidence were associated with rehabilitation outcomes. There is gender-related, age-related and injury-related bias in the reviewed literature.Psychosocial factors were associated with a range of sports injury rehabilitation outcomes. Practitioners need to recognise that an injured athlete's thoughts, feelings and actions may influence the outcome of rehabilitation

A genome-wide association study identifies risk alleles in plasminogen and P4HA2 associated with giant cell arteritis

Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than 50 years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a well-powered study cohort. After imputation, 1,844,133 genetic variants were analysed in 2,134 cases and 9,125 unaffected controls from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest associated region (independent signals: rs9268905, P = 1.94E-54, per-allele OR = 1.79; and rs9275592, P = 1.14E-40, OR = 2.08). Additionally, PLG and P4HA2 were identified as GCA risk genes at the genome-wide level of significance (rs4252134, P = 1.23E-10, OR = 1.28; and rs128738, P = 4.60E-09, OR = 1.32, respectively). Interestingly, we observed that the association peaks overlapped with different regulatory elements related to cell types and tissues involved in the pathophysiology of GCA. PLG and P4HA2 are involved in vascular remodelling and angiogenesis, suggesting a high relevance of these processes for the pathogenic mechanisms underlying this type of vasculitis

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead