Association of urinary bisphenol a concentration with heart disease: evidence from NHANES 2003/06.

addresses: Epidemiology and Public Health Group, Peninsula Medical School, University of Exeter, Exeter, United Kingdom. [email protected]: PMCID: PMC2800195types: Journal Article; Research Support, Non-U.S. Gov'tCopyright: © 2010 Melzer et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Bisphenol A (BPA) is a high production volume chemical widely used in food and drinks packaging. Associations have previously been reported between urinary BPA concentrations and heart disease, diabetes and liver enzymes in adult participants of the National Health and Nutrition Examination Survey (NHANES) 2003/04. We aimed to estimate associations between urinary BPA concentrations and health measures in NHANES 2005/06 and in data pooled across collection years

Does a modified STarT Back Tool predict outcome with a broader group of musculoskeletal patients than back pain? A secondary analysis of cohort data.

OBJECTIVES: The STarT Back Tool has good predictive performance for non-specific low back pain in primary care. We therefore aimed to investigate whether a modified STarT Back Tool predicted outcome with a broader group of musculoskeletal patients, and assessed the consequences of using existing risk-group cut-points across different pain regions. SETTING: Secondary analysis of prospective data from 2 cohorts: (1) outpatient musculoskeletal physiotherapy services (PhysioDirect trial n=1887) and (2) musculoskeletal primary-secondary care interface services (SAMBA study n=1082). PARTICIPANTS: Patients with back, neck, upper limb, lower limb or multisite pain with a completed modified STarT Back Tool (baseline) and 6-month physical health outcome (Short Form 36 (SF-36)). OUTCOMES: Area under the receiving operator curve (AUCs) tested discriminative abilities of the tool's baseline score for identifying poor 6-month outcome (SF-36 lower tertile Physical Component Score). Risk-group cut-points were tested using sensitivity and specificity for identifying poor outcome using (1) Youden's J statistic and (2) a clinically determined rule that specificity should not fall below 0.7 (false-positive rate <30%). RESULTS: In PhysioDirect and SAMBA, poor 6-month physical health was 18.5% and 28.2%, respectively. Modified STarT Back Tool score AUCs for predicting outcome in back pain were 0.72 and 0.79, neck 0.82 and 0.88, upper limb 0.79 and 0.86, lower limb 0.77 and 0.83, and multisite pain 0.83 and 0.82 in PhysioDirect and SAMBA, respectively. Differences between pain region AUCs were non-significant. Optimal cut-points to discriminate low-risk and medium-risk/high-risk groups depended on pain region and clinical services. CONCLUSIONS: A modified STarT Back Tool similarly predicts 6-month physical health outcome across 5 musculoskeletal pain regions. However, the use of consistent risk-group cut-points was not possible and resulted in poor sensitivity (too many with long-term disability being missed) or specificity (too many with good outcome inaccurately classified as 'at risk') for some pain regions. The draft tool is now being refined and validated within a new programme of research for a broader musculoskeletal population. TRIAL REGISTRATION NUMBER: ISRCTN55666618; Post results

Providing patients with direct access to musculoskeletal physiotherapy: the impact on general practice musculoskeletal workload and resource use. The STEMS-2 study.

OBJECTIVES: This study examined the real-world impact of patient direct access to NHS physiotherapy (self-referral) on (a) general practice consultations for musculoskeletal (MSK) conditions and (b) specified clinical management for patients with MSK conditions. DESIGN AND SETTING: Natural experiment in four general practices and the associated physiotherapy service. METHODS: Anonymised routinely collected data were obtained. MSK coded GP consultations, recorded fit notes, MSK-related prescription medication, X-rays and MRI requests, and referrals to secondary care for patients consulting with MSK conditions were identified and trends described across a 6-year period (June 2011 to June 2017). Joinpoint regression analysis was used to identify any significant changes in GP MSK consultation trends before and after the introduction of self-referral to physiotherapy. Physiotherapy service data examined access methods used by patients (GP referred, GP recommended self-referral, true self-referral) and the number of physiotherapy sessions. RESULTS: Direct access resulted in inconsistent impact on general practices. In one arm of the experiment a significant increase in GP consultations was observed and in one arm was stable. Exploratory examination of clinical management showed only requests for X-rays (arm 1) and possibly requests for MRI (arm 2) changed over time. Physiotherapy service referrals showed a low uptake of true self-referral (10% and 6%) in each arm respectively. CONCLUSION: This is the first study to examine the real-world impact of patient direct access to physiotherapy at general practice level. We found no consistent impact of patient direct access on GP MSK workload. Impact on some clinical management was observed but not consistently in the direction suggested by previous studies

Papers of Wilfred Hugh Hudspeth Index: Royal Society Collection

W.H.Hudspeth (1874-1952) son of Rev. Canon Francis Hudspeth and grandson of John Maule Hudspeth (1792-1837), graduated B.A. at Melbourne University and was called to the Tasmanian Bar in 1898. He practised for 30 years in partnership with N.E.Lewis and Tetley Gant. For many years he served on the Council of the Royal Society of Tasmania. His papers consist of notes on various aspects of the history of Tasmania and drafts of articles, written mainly between 1935 and 1951. Royal Society RS.

Minimal metabolic pathway structure is consistent with associated biomolecular interactions

Pathways are a universal paradigm for functionally describing cellular processes. Even though advances in high-throughput data generation have transformed biology, the core of our biological understanding, and hence data interpretation, is still predicated on human-defined pathways. Here, we introduce an unbiased, pathway structure for genome-scale metabolic networks defined based on principles of parsimony that do not mimic canonical human-defined textbook pathways. Instead, these minimal pathways better describe multiple independent pathway-associated biomolecular interaction datasets suggesting a functional organization for metabolism based on parsimonious use of cellular components. We use the inherent predictive capability of these pathways to experimentally discover novel transcriptional regulatory interactions in Escherichia coli metabolism for three transcription factors, effectively doubling the known regulatory roles for Nac and MntR. This study suggests an underlying and fundamental principle in the evolutionary selection of pathway structures; namely, that pathways may be minimal, independent, and segregated

Responsiveness and Minimal Important Change for Pain and Disability Outcome Measures in Pregnancy-Related Low Back and Pelvic Girdle Pain.

BACKGROUND: Pregnancy-related low back pain and pelvic girdle pain (LBP/PGP) are common and negatively impact the lives of many pregnant women. Several patient-based outcome instruments measure treatment effect but there is no consensus about which measure to use with women who have these pain presentations. OBJECTIVE: The objective was to compare the responsiveness of 3 outcome measures in LBP/PGP: Oswestry Disability Index-version 2.0 (ODI), Pelvic Girdle Questionnaire (PGQ), and 0-10 numerical rating scale for pain severity (NRS); and to estimate a minimal important change (MIC) for these measures in pregnancy-related LBP/PGP. DESIGN: This was a methodology study using data from a pilot randomised trial (RCT). METHODS: Women (n = 124) with pregnancy-related LBP/PGP were recruited to a pilot RCT evaluating the benefit of adding acupuncture to standard care and 90 completed 8-weeks follow-up. Responsiveness was evaluated by examining correlation between change score and the external anchor (6-point global perceived effect scale) and by using receiver operating characteristic (ROC) curve analysis. MIC was estimated using anchor-based methods. RESULTS: All measures showed good responsiveness, with areas under ROC curve ranging from 0.77 to 0.90. The estimated MICs were 3.1, 11.0, 9.4, 13.3, and 1.3 for ODI, PGQ-total, PGQ-activity, PGQ-symptoms, and NRS, respectively. All the measures, apart from ODI, had MICs larger than the measurement error. LIMITATIONS: Lack of optimal "gold standard" or external criterion for assessing responsiveness and MIC was a limitation of this study. CONCLUSION: All 3 outcome measures demonstrated good responsiveness. MICs were derived for each instrument. The PGQ at 8 weeks post-randomisation was identified as an appropriate outcome measure for pregnancy-related LBP/PGP since it is specific to these pain presentations and assesses both activity limitations and symptoms. The NRS is an efficient, shorter alternative

Structure and function of a spectrin-like regulator of bacterial cytokinesis

© 2014 Macmillan Publishers Limited. All rights reserved. Bacterial cell division is facilitated by a molecular machine - the divisome - that assembles at mid-cell in dividing cells. The formation of the cytokinetic Z-ring by the tubulin homologue FtsZ is regulated by several factors, including the divisome component EzrA. Here we describe the structure of the 60-kDa cytoplasmic domain of EzrA, which comprises five linear repeats of an unusual triple helical bundle. The EzrA structure is bent into a semicircle, providing the protein with the potential to interact at both N- and C-termini with adjacent membrane-bound divisome components. We also identify at least two binding sites for FtsZ on EzrA and map regions of EzrA that are responsible for regulating FtsZ assembly. The individual repeats, and their linear organization, are homologous to the spectrin proteins that connect actin filaments to the membrane in eukaryotes, and we thus propose that EzrA is the founding member of the bacterial spectrin family

Stakeholder narratives on trypanosomiasis, their effect on policy and the scope for One Health

Background This paper explores the framings of trypanosomiasis, a widespread and potentially fatal zoonotic disease transmitted by tsetse flies (Glossina species) affecting both humans and livestock. This is a country case study focusing on the political economy of knowledge in Zambia. It is a pertinent time to examine this issue as human population growth and other factors have led to migration into tsetse-inhabited areas with little historical influence from livestock. Disease transmission in new human-wildlife interfaces such as these is a greater risk, and opinions on the best way to manage this are deeply divided. Methods A qualitative case study method was used to examine the narratives on trypanosomiasis in the Zambian policy context through a series of key informant interviews. Interviewees included key actors from international organisations, research organisations and local activists from a variety of perspectives acknowledging the need to explore the relationships between the human, animal and environmental sectors. Principal Findings Diverse framings are held by key actors looking from, variously, the perspectives of wildlife and environmental protection, agricultural development, poverty alleviation, and veterinary and public health. From these viewpoints, four narratives about trypanosomiasis policy were identified, focused around four different beliefs: that trypanosomiasis is protecting the environment, is causing poverty, is not a major problem, and finally, that it is a Zambian rather than international issue to contend with. Within these narratives there are also conflicting views on the best control methods to use and different reasoning behind the pathways of response. These are based on apparently incompatible priorities of people, land, animals, the economy and the environment. The extent to which a One Health approach has been embraced and the potential usefulness of this as a way of reconciling the aims of these framings and narratives is considered throughout the paper. Conclusions/Significance While there has historically been a lack of One Health working in this context, the complex, interacting factors that impact the disease show the need for cross-sector, interdisciplinary decision making to stop rival narratives leading to competing actions. Additional recommendations include implementing: surveillance to assess under-reporting of disease and consequential under-estimation of disease risk; evidence-based decision making; increased and structurally managed funding across countries; and focus on interactions between disease drivers, disease incidence at the community level, and poverty and equity impacts

Keele Aches and Pains Study Protocol: validity, acceptability and feasibility of the Keele STarT MSK Tool for subgrouping musculoskeletal patients in primary care

Musculoskeletal conditions represent a considerable burden worldwide, and are predominantly managed in primary care. Evidence suggests that many musculoskeletal conditions share similar prognostic factors. Systematically assessing patient’s prognosis, and matching treatments based on prognostic subgroups (stratified care), has been shown to be clinically and cost effective. This study (Keele Aches and Pains Study: KAPS) aims to refine and examine the validity of a brief questionnaire (Keele STarT MSK Tool), designed to enable risk-stratification of primary care patients with the five most common musculoskeletal pain presentations. We will also describe the subgroups of patients, and explore the acceptability and feasibility of using the tool, and how the tool is best implemented in clinical practice. The study design is mixed methods: a prospective, quantitative observational cohort study with a linked qualitative focus group and interview study. Patients who have consulted their General Practitioner or Healthcare Practitioner (GP/HCP) about a relevant musculoskeletal condition will be recruited from General practice. Participating patients will complete a baseline questionnaire (shortly after consultation), plus questionnaires 2 and 6 months later. A sub-sample of patients, along with participating GPs and HCPs, will be invited to take part in qualitative focus groups and interviews. The Keele STarT MSK Tool will be refined based on face, discriminant, construct and predictive validity at baseline and 2 months, and validated using data from 6 month follow-up. Patient and clinician perspectives about using the tool will be explored. This study will provide a validated prognostic tool (the Keele STarT MSK Tool) with established cut-points to stratify patients with the five most common musculoskeletal presentations into low, medium and high risk subgroups. The qualitative analysis of patient and healthcare perspectives will inform how to embed the tool into clinical practice using established general practice IT systems and clinician support packages

Insights into the Influence of Specific Splicing Events on the Structural Organization of LRRK2

Leucine-rich repeat kinase 2 (LRRK2) is a large protein of unclear function. Rare mutations in the LRRK2 gene cause familial Parkinson's disease (PD) and inflammatory bowel disease. Genome-wide association studies (GWAS) have revealed significant association of the abovementioned diseases at the LRRK2 locus. Cell and systems biology research has led to potential roles that LRRK2 may have in PD pathogenesis, especially the kinase domain (KIN). Previous human expression studies showed evidence of mRNA expression and splicing patterns that may contribute to our understanding of the function of LRRK2. In this work, we investigate and identified significant regional differences in LRRK2 expression at the mRNA level, including a number of splicing events in the Ras of complex protein (Roc) and C-terminal of Roc domain (COR) of LRRK2, in the substantia nigra (SN) and occipital cortex (OCTX). Our findings indicate that the predominant form of LRRK2 mRNA is full length, with shorter isoforms present at a lower copy number. Our molecular modelling study suggests that splicing events in the ROC/COR domains will have major consequences on the enzymatic function and dimer formation of LRRK2. The implications of these are highly relevant to the broader effort to understand the biology and physiological functions of LRRK2, and to better characterize the role(s) of LRRK2 in the underlying mechanism leading to PD