Oesophageal foreign bodies in dogs: factors affecting success of endoscopic retrieval

Oesophageal foreign bodies are common in dogs. Endoscopic removal is a viable treatment option but few studies have assessed the clinical and radiographic features that would be useful in decision-making and prognosis

Effectiveness and safety of oral HIV preexposure prophylaxis for all populations.

ObjectivePreexposure prophylaxis (PrEP) offers a promising new approach to HIV prevention. This systematic review and meta-analysis evaluated the evidence for use of oral PrEP containing tenofovir disoproxil fumarate as an additional HIV prevention strategy in populations at substantial risk for HIV based on HIV acquisition, adverse events, drug resistance, sexual behavior, and reproductive health outcomes.DesignRigorous systematic review and meta-analysis.MethodsA comprehensive search strategy reviewed three electronic databases and conference abstracts through April 2015. Pooled effect estimates were calculated using random-effects meta-analysis.ResultsEighteen studies were included, comprising data from 39 articles and six conference abstracts. Across populations and PrEP regimens, PrEP significantly reduced the risk of HIV acquisition compared with placebo. Trials with PrEP use more than 70% demonstrated the highest PrEP effectiveness (risk ratio = 0.30, 95% confidence interval: 0.21-0.45, P < 0.001) compared with placebo. Trials with low PrEP use did not show a significantly protective effect. Adverse events were similar between PrEP and placebo groups. More cases of drug-resistant HIV infection were found among PrEP users who initiated PrEP while acutely HIV-infected, but incidence of acquiring drug-resistant HIV during PrEP use was low. Studies consistently found no association between PrEP use and changes in sexual risk behavior. PrEP was not associated with increased pregnancy-related adverse events or hormonal contraception effectiveness.ConclusionPrEP is protective against HIV infection across populations, presents few significant safety risks, and there is no evidence of behavioral risk compensation. The effective and cost-effective use of PrEP will require development of best practices for fostering uptake and adherence among people at substantial HIV risk

Community perceptions of paediatric severe anaemia in Uganda

BACKGROUND: Severe anaemia remains a major cause of morbidity and mortality among children in sub-Saharan Africa. There is limited research on the beliefs and knowledge for paediatric severe anaemia in the region. The effect of these local beliefs and knowledge on the healthcare seeking of paediatric severe anaemia remains unknown. OBJECTIVE: To describe community perceptions of paediatric severe anaemia in Uganda. METHODS: Sixteen in-depth interviews of caregivers of children treated for severe anaemia and six focus group discussions of community members were conducted in three regions of Uganda between October and November 2017. RESULTS: There was no common local name used to describe paediatric severe anaemia, but the disease was understood in context as 'having no blood'. Severe anaemia was identified to be a serious disease and the majority felt blood transfusion was the ideal treatment, but concomitant use of traditional and home remedies was also widespread. Participants articulated signs of severe pediatric anemia, such as palmar, conjunctival, and tongue pallor. Other signs described included jaundice, splenomegaly, difficulty in breathing and poor appetite. Poor feeding, malaria, splenomegaly and evil spirits were perceived to be the common causes of severe anaemia. Other causes included: human immunodeficiency virus (HIV), haemoglobinuria, fever, witchcraft, mosquito bites, and sickle cell. Splenomegaly and jaundice were perceived to be both signs and causes of severe anaemia. Severe anaemia was interpreted to be caused by evil spirits if it was either recurrent, led to sudden death, or manifested with cold extremities. CONCLUSION: The community in Uganda perceived paediatric severe anaemia as a serious disease. Their understanding of the signs and perceived causes of severe anaemia to a large extent aligned with known clinical signs and biological causes. Belief in evil spirits persists and may be one obstacle to seeking timely medical care for paediatric severe anaemia

Caregivers and community perceptions of blood transfusion for children with severe anaemia in Uganda

Objective To describe local perceptions of blood transfusion for children with severe anaemia in Uganda. Background Blood transfusion is a common emergency treatment for children with severe anaemia and saves millions of lives of African children. However, the perceptions of transfusion recipients have not been well studied. A better understanding of the perceived risk may improve transfusion care. Methods A qualitative study based on 16 in‐depth interviews of caregivers of transfused children, and six focus group discussions with community members was conducted in three regions of Uganda between October and November 2017. Results Caregivers of children and community members held blood transfusion in high regard and valued it as life‐saving. However, there were widespread perceived transfusion risks, including: Human immunodeficiency virus (HIV) transmission, too rapid blood infusion and blood incompatibility. Other concerns were: fatality, changes in behaviour, donor blood being ‘too strong’ and use of animal blood. In contrast, recent transfusion, older age, knowledge of HIV screening of blood for transfusion, faith in God and having a critically ill child were associated with less fear about transfusion. Respondents also emphasised challenges to transfusion services access including distance to hospitals, scarcity of blood and health workers' attitudes. Conclusion Perceptions of the community and caregivers of transfused children in Uganda about blood transfusion were complex: transfusion is considered life‐saving but there were strong perceived transfusion risks of HIV transmission and blood incompatibility. Addressing community perceptions and facilitating access to blood transfusion represent important strategies to improve paediatric transfusion care

Promoting Community and Population Health in Public Health and Medicine: A Stepwise Guide to Initiating and Conducting Community-engaged Research

Various methods, approaches, and strategies designed to understand and reduce health disparities, increase health equity, and promote community and population health have emerged within public health and medicine. One such approach is community-engaged research. While the literature describing the theory, principles, and rationale underlying community engagement is broad, few models or frameworks exist to guide its implementation. We abstracted, analyzed, and interpreted data from existing project documentation including proposal documents, project-specific logic models, research team and partnership meeting notes, and other materials from 24 funded community-engaged research projects conducted over the past 17 years. We developed a 15-step process designed to guide the community-engaged research process. The process includes steps such as: networking and partnership establishment and expansion; building and maintaining trust; identifying health priorities; conducting background research, prioritizing “what to take on”; building consensus, identifying research goals, and developing research questions; developing a conceptual model; formulating a study design; developing an analysis plan; implementing the study; collecting and analyzing data; reviewing and interpreting results; and disseminating and translating findings broadly through multiple channels. Here, we outline and describe each of these steps

Dimensions and Global Twist of Single-Layer DNA Origami Measured by Small-Angle X-ray Scattering

The rational design of complementary DNA sequences can be used to create nanostructures that self-assemble with nanometer precision. DNA nanostructures have been imaged by atomic force microscopy and electron microscopy. Small-angle X-ray scattering (SAXS) provides complementary structural information on the ensemble-averaged state of DNA nanostructures in solution. Here we demonstrate that SAXS can distinguish between different single-layer DNA origami tiles that look identical when immobilized on a mica surface and imaged with atomic force microscopy. We use SAXS to quantify the magnitude of global twist of DNA origami tiles with different crossover periodicities: these measurements highlight the extreme structural sensitivity of single-layer origami to the location of strand crossovers. We also use SAXS to quantify the distance between pairs of gold nanoparticles tethered to specific locations on a DNA origami tile and use this method to measure the overall dimensions and geometry of the DNA nanostructure in solution. Finally, we use indirect Fourier methods, which have long been used for the interpretation of SAXS data from biomolecules, to measure the distance between DNA helix pairs in a DNA origami nanotube. Together, these results provide important methodological advances in the use of SAXS to analyze DNA nanostructures in solution and insights into the structures of single-layer DNA origami

Acute camptocormia induced by olanzapine: a case report

<p>Abstract</p> <p>Introduction</p> <p>Camptocormia refers to an abnormal posture with flexion of the thoraco-lumbar spine which increases during walking and resolves in supine position. This symptom is an increasingly recognized feature of parkinsonian and dystonic disorders, but may also be caused by neuromuscular diseases. There is recent evidence that both central and peripheral mechanisms may be involved in the pathogenesis of camptocormia. We report a case of acute onset of camptocormia, a rare side effect induced by olanzapine, a second-generation atypical anti-psychotic drug with fewer extra-pyramidal side-effects, increasingly used as first line therapy for schizophrenia, delusional disorders and bipolar disorder.</p> <p>Case presentation</p> <p>A 73-year-old Caucasian woman with no history of neuromuscular disorder, treated for chronic delusional disorder for the last ten years, received two injections of long-acting haloperidol. She was then referred for fatigue. Physical examination showed a frank parkinsonism without other abnormalities. Routine laboratory tests showed normal results, notably concerning creatine kinase level. Fatigue was attributed to haloperidol which was substituted for olanzapine. Our patient left the hospital after five days without complaint. She was admitted again three days later with acute back pain. Examination showed camptocormia and tenderness in paraspinal muscles. Creatine kinase level was elevated (2986 UI/L). Magnetic resonance imaging showed necrosis and edema in paraspinal muscles. Olanzapine was discontinued. Pain resolved quickly and muscle enzymes were normalized within ten days. Risperidone was later introduced without significant side-effect. The camptocormic posture had disappeared when the patient was seen as an out-patient one year later.</p> <p>Conclusions</p> <p>Camptocormia is a heterogeneous syndrome of various causes. We believe that our case illustrates the need to search for paraspinal muscle damage, including drug-induced rhabdomyolysis, in patients presenting with acute-onset bent spine syndrome. Although rare, the occurrence of camptocormia induced by olanzapine must be considered.</p

Modifying Effects of the HFE Polymorphisms on the Association between Lead Burden and Cognitive Decline

Background: As iron and lead promote oxidative damage, and hemochromatosis (HFE) gene polymorphisms increase body iron burden, HFE variant alleles may modify the lead burden and cognitive decline relationship. Objective: Our goal was to assess the modifying effects of HFE variants on the lead burden and cognitive decline relation in older adults. Methods: We measured tibia and patella lead using K-X-ray fluorescence (1991–1999) among participants of the Normative Aging Study, a longitudinal study of community-dwelling men from greater Boston. We assessed cognitive function with the Mini-Mental State Examination (MMSE) twice (1993–1998 and 1995–2000) and genotyped participants for HFE polymorphisms. We estimated the adjusted mean differences in lead-associated annual cognitive decline across HFE genotype groups (n = 358). Results: Higher tibia lead was associated with steeper cognitive decline among participants with at least one HFE variant allele compared with men with only wild-type alleles (p interaction = 0.03), such that a 15 μg/g increase in tibia lead was associated with a 0.2 point annual decrement in MMSE score among HFE variant allele carriers. This difference in scores among men with at least one variant allele was comparable to the difference in baseline MMSE scores that we observed among men who were 4 years apart in age. Moreover, the deleterious association between tibia lead and cognitive decline appeared progressively worse in participants with increasingly more copies of HFE variant alleles (p-trend = 0.008). Results for patella lead were similar. Conclusion: Our findings suggest that HFE polymorphisms greatly enhance susceptibility to lead-related cognitive impairment in a pattern consistent with allelelic dose

UK Parliament Environment, Food and Rural Affairs Select Committee Flooding Inquiry: Written Evidence from Dr Kate Smith et al. (FLO0043)

This submission presents the research conducted within the Energy and Environment Institute at the University of Hull. Our work demonstrates that hazards represented by flooding have multiple dimensions, and that solutions to them need to take these complex inter-relationships into account. The research described below covers both the physical and social impacts of flooding; the recommendations that follow from our work are based on our understanding that flood risk management needs to expand across land-water boundaries at the full range of spatial, temporal and societal scales. Responding to each of the terms of reference in turn, our data shows that the response to flooding needs to start changing now in order to ensure the resilience of our communities, businesses and infrastructure in the future

A KIR B centromeric region present in Africans but not Europeans protects pregnant women from pre-eclampsia.

In sub-Saharan Africans, maternal mortality is unacceptably high, with >400 deaths per 100,000 births compared with <10 deaths per 100,000 births in Europeans. One-third of the deaths are caused by pre-eclampsia, a syndrome arising from defective placentation. Controlling placentation are maternal natural killer (NK) cells that use killer-cell immunoglobulin-like receptor (KIR) to recognize the fetal HLA-C molecules on invading trophoblast. We analyzed genetic polymorphisms of maternal KIR and fetal HLA-C in 484 normal and 254 pre-eclamptic pregnancies at Mulago Hospital, Kampala, Uganda. The combination of maternal KIR AA genotypes and fetal HLA-C alleles encoding the C2 epitope associates with pre-eclampsia [P = 0.0318, odds ratio (OR) = 1.49]. The KIR genes associated with protection are located in centromeric KIR B regions that are unique to sub-Saharan African populations and contain the KIR2DS5 and KIR2DL1 genes (P = 0.0095, OR = 0.59). By contrast, telomeric KIR B genes protect Europeans against pre-eclampsia. Thus, different KIR B regions protect sub-Saharan Africans and Europeans from pre-eclampsia, whereas in both populations, the KIR AA genotype is a risk factor for the syndrome. These results emphasize the importance of undertaking genetic studies of pregnancy disorders in African populations with the potential to provide biological insights not available from studies restricted to European populations.This work was supported by the Wellcome Trust (090108/Z/09/Z, 085992/Z/08/Z, 089821/Z/09/Z), the British Heart Foundation (PG/ 09/077/27964), the Centre for Trophoblast Research at the University of Cambridge, a Wellcome Trust Uganda PhD Fellowship in Infection and Immunity held by Annettee Nakimuli, funded by a Wellcome Trust Strategic Award (084344), the US National Institutes of Health (AI017892), and the UK Medical Research Council (G0901682).This is the accepted manuscript of a paper published in PNAS (A Nakimuli, O Chazara, SE Hiby, L Farrell, S Tukwasibwe, J Jayaraman, JA Traherne, J Trowsdale, F Colucci, Emma Lougee, RW Vaughan, AM Elliott, J Byamugishaa, P Kaleebu, F Mirembe, N Nemat-Gorgani, P Parham, PJ Norman, A Moffett, PNAS 2015, 112, 845-850