Building health: an epidemiological study of "sick building syndrome" in the Whitehall II study

Objectives: Sick building syndrome (SBS) is described as a group of symptoms attributed to the physical environment of specific buildings. Isolating particular environmental features responsible for the symptoms has proved difficult. This study explores the role and significance of the physical and psychosocial work environment in explaining SBS. Methods: Cross sectional data on the physical environment of a selection of buildings were added to individual data from the Whitehall II study—an ongoing health survey of office based civil servants. A self-report questionnaire was used to capture 10 symptoms of the SBS and psychosocial work stress. In total, 4052 participants aged 42–62 years working in 44 buildings were included in this study. Results: No significant relation was found between most aspects of the physical work environment and symptom prevalence, adjusted for age, sex, and employment grade. Positive (non-significant) relations were found only with airborne bacteria, inhalable dust, dry bulb temperature, relative humidity, and having some control over the local physical environment. Greater effects were found with features of the psychosocial work environment including high job demands and low support. Only psychosocial work characteristics and control over the physical environment were independently associated with symptoms in the multivariate analysis. Conclusions: The physical environment of office buildings appears to be less important than features of the psychosocial work environment in explaining differences in the prevalence of symptoms

Reasons for non participation in the Valuing Active Life in Dementia (VALID) randomised controlled trial of a dyadic occupational therapy intervention: an interview study

Objectives There is currently little known about why people decline to participate in dyadic, psychosocial dementia research. This interview study aims to explore the reasons why people declined to participate in the Valuing Active Life in Dementia (VALID) research trial. Methods Ten family carers of people with dementia, who were part of a dyad that had declined to take part in the randomised controlled trial, participated in qualitative telephone interviews to explore their reasons for declining. Inductive thematic analysis was used to identify themes. Findings Two themes with related sub-themes were identified. 1) Protectiveness; protecting the person with dementia, themselves as carers, and their current lifestyle. 2) ‘It’s not for us’; the time commitment, and the possible unsuitability of the intervention, was seen to outweigh the perceived benefit of taking part. People with dementia were not always involved in the decision making process, with carers stating the decision not to participate was made in the usual way as all their decisions. No apparent differences between the spousal and child carers were apparent in the small sample. Conclusions Recruitment to randomised controlled trials can be considered difficult or unfair because some participants will miss out on the desired intervention. However, this study shows that concern about the time and inconvenience of being involved in the trial can put people off research participation. Identifying possible reasons for declining research participation contributes to the design of future trials and recruitment strategies, so that the potential benefit is considered relative to the time and effort involved. Offering research opportunities to people with dementia and their families at the right stage of the dementia trajectory for their needs, facilitating personalised recruitment strategies with finely tailored researcher communication skills should help maximise recruitment, reduce attrition and deliver a more successful trial

Reasons for nonparticipation in the Valuing Active Life in Dementia randomised controlled trial of a dyadic occupational therapy intervention: An interview study

Objectives: There is currently little known about why people decline to participate in dyadic, psychosocial dementia research. This interview study aims to explore the reasons why people declined to participate in the Valuing Active Life in Dementia research trial. / Methods: Ten family carers of people with dementia, who were part of a dyad that had declined to take part in the randomised controlled trial, participated in qualitative telephone interviews to explore their reasons for declining. Inductive thematic analysis was used to identify themes. / Findings: Two themes with related sub-themes were identified: (1) Protectiveness – protecting the person with dementia, themselves as carers and their current lifestyle; (2) ‘It’s not for us’ – the time commitment, and the possible unsuitability of the intervention, was seen to outweigh the perceived benefit of taking part. People with dementia were not always involved in the decision-making process, with carers stating the decision not to participate was made in the usual way as all their decisions. No apparent differences between the spousal and the child carers were apparent in the small sample. / Conclusion: Recruitment to randomised controlled trials can be considered difficult or unfair because some participants will miss out on the desired intervention. However, this study shows that concern about the time and inconvenience of being involved in the trial can put people off research participation. Identifying possible reasons for declining research participation contributes to the design of future trials and recruitment strategies, so that the potential benefit is considered relative to the time and effort involved. Offering research opportunities to people with dementia and their families at the right stage of the dementia trajectory for their needs, facilitating personalised recruitment strategies with finely tailored researcher communication skills should help maximise recruitment, reduce attrition and deliver a more successful trial

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

Can favourable psychosocial working conditions in midlife moderate the risk of work exit for chronically ill workers? A 20-year follow-up of the Whitehall II study

OBJECTIVES: To investigate if favourable psychosocial working conditions can reduce the risk of work exit and specifically for workers with chronic disease. METHODS: Men and women (32%) aged 35-55, working and having no chronic disease at baseline of the Whitehall II study of London-based civil servants were selected (n=9040). We observed participants' exit from work through retirement, health-related exit and unemployment, new diagnosis of chronic disease (ie, coronary heart disease, diabetes, stroke and cancer) and their psychosocial working conditions in midlife. Using cause-specific Cox models, we examined the association of chronic disease and favourable psychosocial working conditions and their interaction, with the three types of work exit. We adjusted for gender, occupational grade, educational level, remaining in civil service, spouse's employment status and mental health. RESULTS: Chronic disease significantly increased the risk of any type of work exit (HR 1.27) and specifically the risk of health-related exit (HR 2.42). High skill discretion in midlife reduced the risk of any type of work exit (HR 0.90), retirement (HR 0.91) and health-related exit (HR 0.68). High work social support in midlife decreased the risk of health-related exit (HR 0.79) and unemployment (HR 0.71). Favourable psychosocial working conditions in midlife did not attenuate the association between chronic disease and work exit significantly. CONCLUSIONS: The chronically ill have increased risks of work exit, especially through health-related exit routes. Chronic disease is an obstacle to extended working lives. Favourable working conditions directly relate to reduced risks of work exit

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

ImpRess: an Implementation Readiness checklist developed using a systematic review of randomised controlled trials assessing cognitive stimulation for dementia

Background Research reporting results of clinical trials, psychosocial or technological interventions frequently omit critical details needed to inform implementation in practice. The aim of this article is to develop an Implementation Readiness (ImpRess) checklist, that includes criteria deemed useful in measuring readiness for implementation and apply it to trials of cognitive stimulation in dementia, providing a systematic review of their readiness for widespread implementation. Methods Five electronic databases were searched. After initial screening of papers, two reviewers assessed quality and scored the included studies based on the ImpRess checklist specifically developed for this review. Results Twenty studies met the inclusion criteria. As determined by the ImpRess checklist, scores ranged from 11 to 29 out of 52. According to the checklist the most comprehensive and ready to implement version of cognitive stimulation was Cognitive Stimulation Therapy. Conclusions Reports of interventions rarely include consideration of implementation in practice. Contrary to the growing number of reporting guidelines, crucial items within the ImpRess checklist have been frequently overlooked. This study was able to show that the ImpRess checklist was feasible in practice and reliable. The checklist may be useful in evaluating readiness for implementation for other manualised interventions