Health disparities by occupation, modified by education: a cross-sectional population study

<p>Abstract</p> <p>Background</p> <p>Socio-economic disparities in health status are frequently reported in research. By comparison with education and income, occupational status has been less extensively studied in relation to health status or the occurrence of specific chronic diseases. The aim of this study was to investigate health disparities in the working population based on occupational position and how they were modified by education.</p> <p>Methods</p> <p>Our data were derived from the National Survey of General Practice that comprised 104 practices in the Netherlands. 136,189 working people aged 25–64 participated in the study. Occupational position was assessed by the International Socio-Economic Index of occupational position (ISEI). Health outcomes were self-perceived health status and physician-diagnosed diseases. Odds ratios were estimated using multivariate logistic regression analysis.</p> <p>Results</p> <p>The lowest occupational position was observed to be associated with poor health in men (OR = 1.6, 95% CI 1,5 to 1.7) and women (OR = 1.3, 95% CI 1.2 to 1.4). The risk of poor health gradually decreased in relation to higher occupational positions. People with the lowest occupational positions were more likely to suffer from depression, diabetes, ischaemic heart disease, arthritis, muscle pain, neck and back pain and tension headache, in comparison to people with the highest occupational position (OR 1.2 to 1.6). A lower educational level induced an additional risk of poor health and disease. We found that gender modified the effects on poor health when both occupational position and education were combined in the analysis.</p> <p>Conclusion</p> <p>A low occupational position was consistently associated working people with poor health and physician-diagnosed morbidity. However a low educational level was not. Occupational position and education had a combined effect on self-perceived health, which supports the recent call to improve the conceptual framework of health disparities.</p

Genetic variants associated with longitudinal changes in brain structure across the lifespan

Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging

Sediment source fingerprinting: benchmarking recent outputs, remaining challenges and emerging themes

Abstract: Purpose: This review of sediment source fingerprinting assesses the current state-of-the-art, remaining challenges and emerging themes. It combines inputs from international scientists either with track records in the approach or with expertise relevant to progressing the science. Methods: Web of Science and Google Scholar were used to review published papers spanning the period 2013–2019, inclusive, to confirm publication trends in quantities of papers by study area country and the types of tracers used. The most recent (2018–2019, inclusive) papers were also benchmarked using a methodological decision-tree published in 2017. Scope: Areas requiring further research and international consensus on methodological detail are reviewed, and these comprise spatial variability in tracers and corresponding sampling implications for end-members, temporal variability in tracers and sampling implications for end-members and target sediment, tracer conservation and knowledge-based pre-selection, the physico-chemical basis for source discrimination and dissemination of fingerprinting results to stakeholders. Emerging themes are also discussed: novel tracers, concentration-dependence for biomarkers, combining sediment fingerprinting and age-dating, applications to sediment-bound pollutants, incorporation of supportive spatial information to augment discrimination and modelling, aeolian sediment source fingerprinting, integration with process-based models and development of open-access software tools for data processing. Conclusions: The popularity of sediment source fingerprinting continues on an upward trend globally, but with this growth comes issues surrounding lack of standardisation and procedural diversity. Nonetheless, the last 2 years have also evidenced growing uptake of critical requirements for robust applications and this review is intended to signpost investigators, both old and new, towards these benchmarks and remaining research challenges for, and emerging options for different applications of, the fingerprinting approach

Balancing repair and tolerance of DNA damage caused by alkylating agents

Alkylating agents constitute a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER) and mismatch repair (MMR), respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for a favourable response of an organism to alkylating agents. Furthermore, the response of an individual to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity

Systematic review of methods used in meta-analyses where a primary outcome is an adverse or unintended event

addresses: Peninsula College of Medicine and Dentistry, St Luke's Campus, University of Exeter, Exeter, UK. [email protected]: PMCID: PMC3528446types: Journal Article; Research Support, Non-U.S. Gov't© 2012 Warren et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Adverse consequences of medical interventions are a source of concern, but clinical trials may lack power to detect elevated rates of such events, while observational studies have inherent limitations. Meta-analysis allows the combination of individual studies, which can increase power and provide stronger evidence relating to adverse events. However, meta-analysis of adverse events has associated methodological challenges. The aim of this study was to systematically identify and review the methodology used in meta-analyses where a primary outcome is an adverse or unintended event, following a therapeutic intervention

Improving transitional patient safety: research protocol of the Transitional Incident Prevention Programme

Introduction: Patient transitions between primary and hospital care include referral, discharge, and simultaneous care by the outpatient clinic and the general practitioner (GP). Research on referrals and discharge shows that safety incidents in these transitions are common. We developed the multifaceted Transitional Incident Prevention Programme (TIPP), which aims to improve transitional patient safety preventing future incidents. With this study, we aim to evaluate the effectiveness of the TIPP programme on transitional patient safety, and to evaluate its implementation and the acceptance in GP-practices and hospitals. Methods: The TIPP intervention study is a controlled before and after study combined with qualitative methods. The study will be conducted in both rural and urban settings including three hospitals, together with referring primary care practices. The TIPP intervention is aimed at three aspects of transitional safety: 1) Healthcare process, 2) Transitional patient safety culture, and 3) Patient participation. Together with the participating hospital departments, GPs and patients, we will develop a tailored improvement programme, taking into account the different context of each setting. Discussion: The purpose of this protocol paper is to present and discuss the research design and methodology of the TIPP intervention. Trial registration: Dutch trial register NTR481

Role of solution conformation and flexibility of short peptide ligands that bind to the p56(lck) SH2 domain

A general approach in drug design is making ligands more rigid in order to avoid loss in conformational entropy (ΔSconf) upon receptor binding. We hypothesized that in the high affinity binding of pYEEI peptide ligands to the p56lck SH2 domain this loss in ΔSconf might be diminished due to preorganization of the fourfold negatively charged pYEEI peptide in the bound, extended, conformation. A thermodynamic analysis was performed on the peptides Ac-pYEEI-NH2, Ac-pYAAI-NH2 and Ac-pYGGI-NH2 using surface plasmon resonance (SPR) competition experiments to assay affinity constants at different temperatures. To study the effect of solution conformation and flexibility a computational conformation analysis was performed from which low energy conformations in solution were calculated, and Sconf estimated. It was found that the calculated low energy conformations for especially the pYE moiety in solution resemble that in the bound state. In the calculated minimum energy conformation in solution isoleucine is bent towards the pY aromatic ring, the occurrence of such conformation is experimentally confirmed by NMR. The estimated values for Sconf of the EE- and AA-peptide were similar, suggesting no predominant role of preorganization of the solution conformation due to electrostatic repulsion. Apparently the thermodynamics obey the same entropy-enthalpy compensation relationship, which also was found to hold for other peptides and peptidomimetics binding to p60src family SH2 domains. The implications of the results for drug design are discussed

Effects of oxatomide and derivatives on high affinity IgE receptor-activated signal transduction pathways in rat basophilic leukemia cells: Role of protein tyrosine hyperphosphorylation and inhibition of extracellular calcium influx

The antiallergic drug oxatomide and analogs inhibit mediator release from a rat basophilic leukemia (RBL-2H3) cell line, which is frequently used as a mast cell model. By investigating a series of derivatives of oxatomide with different inhibiting activities on exocytosis, we aimed to evaluate the role of their effects on the early steps of the signal transduction cascade in the inhibition of exocytosis. The active compounds induced hyperphosphorylation of tyrosine residues both in stimulated as well as in resting cells. Furthermore, some elevation of the inositol 1,4,5-trisphosphate (IP3) formation upon antigen activation was observed for the active derivatives. Ca2+ fluxes were also studied. The inhibition of the antigen-induced Ca-45(2+) influx correlated with the effects of the drugs on exocytosis. Furthermore, the inhibitory activity on antigen- and thapsigargin-mediated exocytosis correlated well. Adherence of the cells to fibronectin, stimulating cellular integrin receptors, was synergistic to antigen activation of the RBL cells. However, oxatomide did lack any effect on integrin-mediated processes, as the IC50 value for exocytosis was identical for fibronectin-adhered cells and standard cultured cells. We conclude that oxatomide and its analogs inhibit exocytosis, mainly by inhibiting Ca2+ influx over score operated Ca2+ (SOC) channels. The drugs have a direct effect on the store operated Ca2+ channels or affect the direct regulation of these channels. (C) 1998 Elsevier Science Inc