Solution of the structure of tetrameric human glucose 6-phosphate dehydrogenase by molecular replacement

Recombinant human glucose 6-phosphate dehydrogenase (G6PD) has been crystallized and its structure solved by molecular replacement. Crystals of the natural mutant R459L grow under similar conditions in space groups P212121 and C2221 with eight or four 515-residue molecules in the asymmetric unit, respectively. A non-crystallographic 222 tetramer was found in the C2221 crystal form using a 4 A resolution data set and a dimer of the large beta + alpha domains of the Leuconostoc mesenteroides enzyme as a search model. This tetramer was the only successful search model for the P212121 crystal form using data to 3 A. Crystals of the deletion mutant DeltaG6PD grow in space group F222 with a monomer in the asymmetric unit; 2.5 A resolution data have been collected. Comparison of the packing of tetramers in the three space groups suggests that the N-terminal tail of the enzyme prevents crystallization with exact 222 molecular symmetry.published_or_final_versio

Deformation velocity imaging using optical coherence tomography and its applications to the cornea

Optical coherence tomography (OCT) can monitor human donor corneas non-invasively during the de-swelling process following storage for corneal transplantation, but currently only resultant thickness as a function of time is extracted. To visualize and quantify the mechanism of de-swelling, we present a method exploiting the nanometer sensitivity of the Fourier phase in OCT data to image deformation velocities. The technique was demonstrated by non-invasively showing during de-swelling that osmotic flow through an intact epithelium is negligible and removing the endothelium approximately doubled the initial flow at that interface. The increased functional data further enabled the validation of a mathematical model of the cornea. Included is an efficient method of measuring high temporal resolution (1 minute demonstrated) corneal thickness, using automated collection and semi-automated graph search segmentation. These methods expand OCT capabilities to measure volume change processes for tissues and materials

Implementing neuroimaging and eye tracking methods to assess neurocognitive development of young infants in low- and middle-income countries

Infants and children in low- and middle-income countries (LMICs) are frequently exposed to a range of environmental risk factors which may negatively affect their neurocognitive development. The mechanisms by which factors such as undernutrition and poverty impact development and cognitive outcomes in early childhood are poorly understood. This lack of knowledge is due in part to a paucity of objective assessment tools which can be implemented across different cultural settings and in very young infants. Over the last decade, technological advances, particularly in neuroimaging, have opened new avenues for research into the developing human brain, allowing us to investigate novel biological associations. This paper presents functional near-infrared spectroscopy (fNIRS), electroencephalography (EEG) and eye tracking (ET) as objective, cross-cultural methods for studying infant neurocognitive development in LMICs, and specifically their implementation in rural Gambia, West Africa. These measures are currently included, as part of a broader battery of assessments, in the Brain Imaging for Global Health (BRIGHT) project, which is developing brain function for age curves in Gambian and UK infants from birth to 24 months of age. The BRIGHT project combines fNIRS, EEG and ET with behavioural, growth, health and sociodemographic measures. The implementation of these measures in rural Gambia are discussed, including methodological and technical challenges that needed to be addressed to ensure successful data acquisition. The aim is to provide guidance to other groups seeking to implement similar methods in their research in other LMICs to better understand associations between environmental risk and early neurocognitive development

Idiopathic eosinophilic parotitis in an eight-year-old boy: a case report

<p>Abstract</p> <p>Introduction</p> <p>A number of medical conditions, some of them recently reported, are associated with an increased production of eosinophils. We report the first case of eosinophilic parotitis in the literature.</p> <p>Case presentation</p> <p>The patient was an eight-year-old Caucasian boy who presented with a two-year history of recurring acute parotitis with no fever. He had had a total of five episodes with no response to antibiotics, but remission had been achieved with oral corticosteroid therapy. We performed allergy tests for inhalant and food allergens and for haptens, but the results were all negative. The results of echography ruled out sialodochitis. Instead, a swab from the parotid duct led to the detection of a high number of eosinophils.</p> <p>Conclusions</p> <p>This report is first in the literature to describe a case of eosinophilic parotitis, and we suggest that a cytological assessment, which is quite simple yet rarely used by physicians, be performed when patients with parotitis of uncertain origin are under evaluation.</p

The social value of a QALY : raising the bar or barring the raise?

Background: Since the inception of the National Institute for Health and Clinical Excellence (NICE) in England, there have been questions about the empirical basis for the cost-per-QALY threshold used by NICE and whether QALYs gained by different beneficiaries of health care should be weighted equally. The Social Value of a QALY (SVQ) project, reported in this paper, was commissioned to address these two questions. The results of SVQ were released during a time of considerable debate about the NICE threshold, and authors with differing perspectives have drawn on the SVQ results to support their cases. As these discussions continue, and given the selective use of results by those involved, it is important, therefore, not only to present a summary overview of SVQ, but also for those who conducted the research to contribute to the debate as to its implications for NICE. Discussion: The issue of the threshold was addressed in two ways: first, by combining, via a set of models, the current UK Value of a Prevented Fatality (used in transport policy) with data on fatality age, life expectancy and age-related quality of life; and, second, via a survey designed to test the feasibility of combining respondents’ answers to willingness to pay and health state utility questions to arrive at values of a QALY. Modelling resulted in values of £10,000-£70,000 per QALY. Via survey research, most methods of aggregating the data resulted in values of a QALY of £18,000-£40,000, although others resulted in implausibly high values. An additional survey, addressing the issue of weighting QALYs, used two methods, one indicating that QALYs should not be weighted and the other that greater weight could be given to QALYs gained by some groups. Summary: Although we conducted only a feasibility study and a modelling exercise, neither present compelling evidence for moving the NICE threshold up or down. Some preliminary evidence would indicate it could be moved up for some types of QALY and down for others. While many members of the public appear to be open to the possibility of using somewhat different QALY weights for different groups of beneficiaries, we do not yet have any secure evidence base for introducing such a system

The Prevalence and Characteristics of Performance-Enhancing Drug Use Among Bodybuilding Athletes in the South of Iran, Bushehr

Background: Several reports have implied progressive increase of performance-enhancing drug (PED) use among Iranian athletes. More importantly, most of the previous research in the Iranian population had mainly focused on the anabolic steroid abuse, and ignored other agents. Objectives: The aim of this study was to investigate the prevalence and characteristics of PED use among bodybuilding athletes in Bushehr, south of Iran. Methods: Four hundred and fifty three male bodybuilding athletes were recruited from Bushehr gyms between February and May of 2015. Men were eligible to participate in the survey if they had regularly participated in the strength-training exercise (minimum of 1 year and 4 hour/week). Data were collected via a face-to-face interview. The survey consisted of three separate parts including demographic data, exercise pattern and PED use. Results: According to this study, 234 (51.7%) of bodybuilding athletes had used PEDs. The PED users reported an average of 3.80 � 4.52 agents’ use in their programs and they had used PEDs for the average of 3.24 � 3.99 years. The most prevalent agents which had been abused by the athletes were anabolic steroids (used by 185 athletes (79.4% of athletes). Furthermore, 110 (47%) of athletes reported stimulant agents’ use during their routines. The most prevalent motivation for using PEDs was increasing muscle mass that was reported by 164 (70.1%) of PED users. In addition, sexual and dermatologic effects were the most prevalent adverse effects reported by the PED user athletes (114 (49.4%) and 103 (44.2%), respectively). Conclusions: This study showed the high rate of PED use among recreational and professional Iranian bodybuilding athletes that can expose them to the serious side effects of these agents

In ovo exposure to o,p -DDE affects sexual development but not sexual differentiation in Japanese medaka (Oryzias latipes).

Despite being banned in many countries, dichlorodiphenyltrichloroethane (DDT) and its metabolites dichlorodiphenyldichloroethylene (DDE) and dichlorodiphenyldichloroethane (DDD) continue to be found in fish tissues at concentrations of concern. Like o,p -DDT, o,p -DDE is estrogenic and is believed to exert its effects through binding to the estrogen receptor. The limited toxicologic data for o,p -DDE suggest that it decreases fecundity and fertility of fishes. We conducted an egg injection study using the d-rR strain of medaka and environmentally relevant concentrations of o,p -DDE to examine its effects on sexual differentiation and development. The gonads of exposed fish showed no evidence of sex reversal or intersex. However, other gonad abnormalities occurred in exposed individuals. Females exhibited few vitellogenic oocytes and increased atresia. Male testes appeared morphologically normal but were very small. Gonadosomatic index values for both sexes were lower for exposed fish. Our observations of abnormal female and very small male gonads after in ovo o,p -DDE exposure may be indicative of effects on early endocrine processes important for normal ovarian and testicular development

PROPEL: implementation of an evidence based pelvic floor muscle training intervention for women with pelvic organ prolapse: a realist evaluation and outcomes study protocol

Abstract Background Pelvic Organ Prolapse (POP) is estimated to affect 41%–50% of women aged over 40. Findings from the multi-centre randomised controlled “Pelvic Organ Prolapse PhysiotherapY” (POPPY) trial showed that individualised pelvic floor muscle training (PFMT) was effective in reducing symptoms of prolapse, improved quality of life and showed clear potential to be cost-effective. However, provision of PFMT for prolapse continues to vary across the UK, with limited numbers of women’s health physiotherapists specialising in its delivery. Implementation of this robust evidence from the POPPY trial will require attention to different models of delivery (e.g. staff skill mix) to fit with differing care environments. Methods A Realist Evaluation (RE) of implementation and outcomes of PFMT delivery in contrasting NHS settings will be conducted using multiple case study sites. Involving substantial local stakeholder engagement will permit a detailed exploration of how local sites make decisions on how to deliver PFMT and how these lead to service change. The RE will track how implementation is working; identify what influences outcomes; and, guided by the RE-AIM framework, will collect robust outcomes data. This will require mixed methods data collection and analysis. Qualitative data will be collected at four time-points across each site to understand local contexts and decisions regarding options for intervention delivery and to monitor implementation, uptake, adherence and outcomes. Patient outcome data will be collected at baseline, six months and one year follow-up for 120 women. Primary outcome will be the Pelvic Organ Prolapse Symptom Score (POP-SS). An economic evaluation will assess the costs and benefits associated with different delivery models taking account of further health care resource use by the women. Cost data will be combined with the primary outcome in a cost effectiveness analysis, and the EQ-5D-5L data in a cost utility analysis for each of the different models of delivery. Discussion Study of the implementation of varying models of service delivery of PFMT across contrasting sites combined with outcomes data and a cost effectiveness analysis will provide insight into the implementation and value of different models of PFMT service delivery and the cost benefits to the NHS in the longer term

'Reaching the hard to reach' - lessons learned from the VCS (voluntary and community Sector). A qualitative study.

Background The notion 'hard to reach' is a contested and ambiguous term that is commonly used within the spheres of social care and health, especially in discourse around health and social inequalities. There is a need to address health inequalities and to engage in services the marginalized and socially excluded sectors of society. Methods This paper describes a pilot study involving interviews with representatives from eight Voluntary and Community Sector (VCS) organisations . The purpose of the study was to explore the notion of 'hard to reach' and perceptions of the barriers and facilitators to accessing services for 'hard to reach' groups from a voluntary and community sector perspective. Results The 'hard to reach' may include drug users, people living with HIV, people from sexual minority communities, asylum seekers, refugees, people from black and ethnic minority communities, and homeless people although defining the notion of the 'hard to reach' is not straight forward. It may be that certain groups resist engaging in treatment services and are deemed hard to reach by a particular service or from a societal stance. There are a number of potential barriers for people who may try and access services, including people having bad experiences in the past; location and opening times of services and how services are funded and managed. A number of areas of commonality are found in terms of how access to services for 'hard to reach' individuals and groups could be improved including: respectful treatment of service users, establishing trust with service users, offering service flexibility, partnership working with other organisations and harnessing service user involvement. Conclusions: If health services are to engage with groups that are deemed 'hard to reach' and marginalised from mainstream health services, the experiences and practices for engagement from within the VCS may serve as useful lessons for service improvement for statutory health services