A Lifecourse Approach to Long-Term Sickness Absence-A Cohort Study

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Health Effects of Noise Exposure in Children.

The final publication is available at Springer via http://dx.doi.10.1007/s40572-015-0044-1.Environmental noise exposure, such as road traffic noise and aircraft noise, is associated with a range of health outcomes in children. Children demonstrate annoyance responses to noise, and noise is also related to lower well-being and stress responses, such as increased levels of adrenaline and noradrenaline. Noise does not cause more serious mental health problems, but there is growing evidence for an association with increased hyperactivity symptoms. Studies also suggest that noise might cause changes in cardiovascular functioning, and there is some limited evidence for an effect on low birth weight. There is robust evidence for an effect of school noise exposure on children's cognitive skills such as reading and memory, as well as on standardised academic test scores. Environmental noise does not usually reach levels that are likely to affect children's hearing; however, increasing use of personal electronic devices may leave some children exposed to harmful levels of noise

Forced residential mobility and social support: impacts on psychiatric disorders among Somali migrants

This study was funded by London Region NHS R&D Projectreference no: RCC01924; Prof Bhui is the PI

The MemProtMD database : a resource for membrane-embedded protein structures and their lipid interactions

Integral membrane proteins fulfil important roles in many crucial biological processes, including cell signalling, molecular transport and bioenergetic processes. Advancements in experimental techniques are revealing high resolution structures for an increasing number of membrane proteins. Yet, these structures are rarely resolved in complex with membrane lipids. In 2015, the MemProtMD pipeline was developed to allow the automated lipid bilayer assembly around new membrane protein structures, released from the Protein Data Bank (PDB). To make these data available to the scientific community, a web database (http://memprotmd.bioch.ox.ac.uk) has been developed. Simulations and the results of subsequent analysis can be viewed using a web browser, including interactive 3D visualizations of the assembled bilayer and 2D visualizations of lipid contact data and membrane protein topology. In addition, ensemble analyses are performed to detail conserved lipid interaction information across proteins, families and for the entire database of 3506 PDB entries. Proteins may be searched using keywords, PDB or Uniprot identifier, or browsed using classification systems, such as Pfam, Gene Ontology annotation, mpstruc or the Transporter Classification Database. All files required to run further molecular simulations of proteins in the database are provided

The energetics of protein-lipid interactions as viewed by molecular simulations

Membranes are formed from a bilayer containing diverse lipid species with which membrane proteins interact. Thus, integral membrane proteins are embedded in a bilayer, where they interact with lipids from their surroundings, whilst peripheral membrane proteins bind to lipids at the surface of membranes. Lipid interactions can influence the function of membrane proteins, either directly or allosterically. Both experimental (structural) and computational approaches can reveal lipid binding sites on membrane proteins. It is therefore important to understand the free energies of these interactions. This affords a more complete view of the engagement of a particular protein with the biological membrane surrounding it. Here, we describe a number of computational approaches currently in use for this purpose, including recent advances using both free energy and unbiased simulation methods. In particular we focus on interactions of integral membrane proteins with cholesterol, and with anionic lipids such as phosphatidylinositol 4,5-bisphosphate and cardiolipin. Peripheral membrane proteins are exemplified via interactions of PH domains with phosphoinositide-containing membranes. We summarise the current state of the field and provide an outlook on likely future directions of investigation

Structure and dynamics of the E. coli chemotaxis core signaling complex by cryo-electron tomography and molecular simulations

To enable the processing of chemical gradients, chemotactic bacteria possess large arrays of transmembrane chemoreceptors, the histidine kinase CheA, and the adaptor protein CheW, organized as coupled core-signaling units (CSU). Despite decades of study, important questions surrounding the molecular mechanisms of sensory signal transduction remain unresolved, owing especially to the lack of a high-resolution CSU structure. Here, we use cryo-electron tomography and sub-tomogram averaging to determine a structure of the Escherichia coli CSU at sub-nanometer resolution. Based on our experimental data, we use molecular simulations to construct an atomistic model of the CSU, enabling a detailed characterization of CheA conformational dynamics in its native structural context. We identify multiple, distinct conformations of the critical P4 domain as well as asymmetries in the localization of the P3 bundle, offering several novel insights into the CheA signaling mechanism

Common Mental Disorders

Common mental disorders (CMDs) comprise different types of depression and anxiety. They cause marked emotional distress and interfere with daily function,but do not usually affect insight or cognition. Although usually less disabling than major psychiatric disorders, their higher prevalence means the cumulative cost of CMDs to society is great. The revised Clinical Interview Schedule (CIS-R) has been used on each Adult Psychiatric Morbidity Survey (APMS) in the series to assess six types of CMD: depression, generalised anxiety disorder (GAD), panic disorder, phobias, obsessive compulsive disorder (OCD), and CMD not otherwise specified (CMD-NOS). Many people meet the criteria for more than one CMD. The CIS-R is also used to produce a score that reflects overall severity of CMD symptoms. • Since 2000, there has been a slight but steady increase in the proportion of women with CMD symptoms (as indicated by a CIS-R score of 12 or more), but overall stability at this level among men. The increase in prevalence was evident mostly at the more severe end of the scale (CIS-R score 18 or more). • Since the last survey (2007), increases in CMD have also been evident among late midlife men and women (aged 55 to 64), and approached significance in young women (aged 16 to 24). • The gap in rates of CMD symptoms between young men and women appears to have grown. In 1993, 16 to 24 year old women (19.2%) were twice as likely as 16 to 24 year old men (8.4%) to have symptoms of CMD (CIS-R score 12 or more). In 2014, CMD symptoms were about three times more common in women of that age (26.0%) than men (9.1%). • CMDs were more prevalent in certain groups of the population. These included Black women, adults under the age of 60 who lived alone, women who lived in large households, adults not in employment, those in receipt of benefits and those who smoked cigarettes. These associations are in keeping with increased social disadvantage and poverty being associated with higher risk of CMD. Most people identified by the CIS-R with a CMD also perceived themselves to have a CMD. This was not the case for most of the other disorders assessed in the APMS. • While most of these people had been diagnosed with a mental disorder by a professional, the disorders they reported having been diagnosed with tended to be ‘depression’ or ‘panic attacks’. However, the disorder most commonly identified by the CIS-R was GAD. This difference may reflect the language and terminology used by people when discussing their mental health with a professional

Negative Aspects of Close Relationships as Risk Factors for Cognitive Aging

The extent to which social relationships influence cognitive aging is unclear. In this study, we investigated the association of midlife quality of close relationships with subsequent cognitive decline. Participants in the Whitehall II Study (n = 5,873; ages 45-69 years at first cognitive assessment) underwent executive function and memory tests 3 times over a period of 10 years (1997-1999 to 2007-2009). Midlife negative and positive aspects of close relationships were assessed twice using the Close Persons Questionnaire during the 8 years preceding cognitive assessment. Negative aspects of close relationships, but not positive aspects, were associated with accelerated cognitive aging. Participants in the top third of reported negative aspects of close relationships experienced a faster 10-year change in executive function (-0.04 standard deviation, 95% confidence interval: -0.08, -0.01) than those in the bottom third, which was comparable with 1 extra year of cognitive decline for participants aged 60 years after adjustment for sociodemographic and health status. Longitudinal analysis found no evidence of reverse causality. This study highlights the importance of differentiating aspects of social relationships to evaluate their unique associations with cognitive aging

Structural basis of proton-coupled potassium transport in the KUP family

Potassium homeostasis is vital for all organisms, but is challenging in single-celled organisms like bacteria and yeast and immobile organisms like plants that constantly need to adapt to changing external conditions. KUP transporters facilitate potassium uptake by the co-transport of protons. Here, we uncover the molecular basis for transport in this widely distributed family. We identify the potassium importer KimA from Bacillus subtilis as a member of the KUP family, demonstrate that it functions as a K+/H+ symporter and report a 3.7 Å cryo-EM structure of the KimA homodimer in an inward-occluded, trans-inhibited conformation. By introducing point mutations, we identify key residues for potassium and proton binding, which are conserved among other KUP proteins

A Synthesis of the Evidence for Managing Stress at Work: A Review of the Reviews Reporting on Anxiety, Depression, and Absenteeism

Background. Psychosocial stressors in the workplace are a cause of anxiety and depressive illnesses, suicide and family disruption. Methods. The present review synthesizes the evidence from existing systematic reviews published between 1990 and July 2011. We assessed the effectiveness of individual, organisational and mixed interventions on two outcomes: mental health and absenteeism. Results. In total, 23 systematic reviews included 499 primary studies; there were 11 meta-analyses and 12 narrative reviews. Meta-analytic studies found a greater effect size of individual interventions on individual outcomes. Organisational interventions showed mixed evidence of benefit. Organisational programmes for physical activity showed a reduction in absenteeism. The findings from the meta-analytic reviews were consistent with the findings from the narrative reviews. Specifically, cognitive-behavioural programmes produced larger effects at the individual level compared with other interventions. Some interventions appeared to lead to deterioration in mental health and absenteeism outcomes.Gaps in the literature include studies of organisational outcomes like absenteeism, the influence of specific occupations and size of organisations, and studies of the comparative effectiveness of primary, secondary and tertiary prevention. Conclusions. Individual interventions (like CBT) improve individuals' mental health. Physical activity as an organisational intervention reduces absenteeism. Research needs to target gaps in the evidence