Explore the vast range of titles available.

Evidence suggests that there are social inequalities in multimorbidity, with a recent review indicating that area levels of deprivation are consistently associated with greater levels of multimorbidity. Definitions of multimorbidity, the most common of which is the co-occurrence of more than one long term condition, can include long term physical conditions, mental health conditions or both. The most commonly used measure of deprivation in England and Wales is the Index of Multiple Deprivation (IMD), an index of seven different deprivation domains. It is unclear which features of IMD may be mediating associations with multimorbidity. Thus, there may be associations because of the individual characteristics of those living in deprived areas, characteristics of the areas themselves or overlap in definitions. Data from over 25,000 participants (aged 16+) of Understanding Society (Wave 10, 1/2018–3/2020) were used to understand the most salient features of multimorbidity associated with IMD and whether physical or mental conditions are differentially associated with the seven domains of IMD. 24% of participants report multimorbidity. There is an increased prevalence of multimorbidity composed of only long-term physical conditions in the most deprived decile of deprivation (22%, 95% CI[19,25]) compared to the least deprived decile (16%, 95% CI[14,18]). Mental health symptoms but not reporting of conditions vary by decile of IMD. Associations with multimorbidity are limited to the health, income, education and employment domains of IMD. We conclude that multimorbidity represents a substantial population burden, particularly in the most deprived areas in England and Wales.

The COVID-19 pandemic in the UK and subsequent lockdown may have affected the mental health of the population. This study examines whether there was an increase in the prevalence and incidence of common mental disorders (CMD) in the UK adult population during the first months of lockdown and whether changes in CMD were associated with stressors related to the pandemic and lockdown. Longitudinal data from the UK Household Longitudinal Study waves 10-11: 2019-2020 and waves 1-4 of the COVID-19 monthly surveys in April ( = 17 761) to July 2020 ( = 13 754), a representative sample of UK adult population, were analysed. CMD was measured using the 12-item General Health Questionnaire (GHQ-12) (cut-off >2). Changes in CMD were analysed in relation to COVID-19 and social stressors. Around 29% of adults without CMD less than a year earlier had a CMD in April 2020. However, by July 2020, monthly incidence of CMD had reduced to 9%. Most employment, financial and psychological 'shocks' were at their highest levels in April and reduced steadily in later months. Despite the lifting of some lockdown conditions by July, stressors related to loneliness, unemployment, financial problems and domestic work continued to influence CMD. Some COVID-19 policy responses such as furloughing may have been effective in mitigating the increase in CMD for some groups of employees. Despite some reduction in levels of pandemic and lockdown-related stressors by the middle of 2020, loneliness and financial stressors remained key determinants of incidence in CMD among the UK adult population.

Background There has been a steady increase in the number of studies aiming to identify DNA methylation differences associated with complex phenotypes. Many of the challenges of epigenetic epidemiology regarding study design and interpretation have been discussed in detail, however there are analytical concerns that are outstanding and require further exploration. In this study we seek to address three analytical issues. First, we quantify the multiple testing burden and propose a standard statistical significance threshold for identifying DNA methylation sites that are associated with an outcome. Second, we establish whether linear regression, the chosen statistical tool for the majority of studies, is appropriate and whether it is biased by the underlying distribution of DNA methylation data. Finally, we assess the sample size required for adequately powered DNA methylation association studies. Results We quantified DNA methylation in the Understanding Society cohort ( n  = 1175), a large population based study, using the Illumina EPIC array to assess the statistical properties of DNA methylation association analyses. By simulating null DNA methylation studies, we generated the distribution of p -values expected by chance and calculated the 5% family-wise error for EPIC array studies to be 9 × 10 − 8 . Next, we tested whether the assumptions of linear regression are violated by DNA methylation data and found that the majority of sites do not satisfy the assumption of normal residuals. Nevertheless, we found no evidence that this bias influences analyses by increasing the likelihood of affected sites to be false positives. Finally, we performed power calculations for EPIC based DNA methylation studies, demonstrating that existing studies with data on ~ 1000 samples are adequately powered to detect small differences at the majority of sites. Conclusion We propose that a significance threshold of P  < 9 × 10 − 8 adequately controls the false positive rate for EPIC array DNA methylation studies. Moreover, our results indicate that linear regression is a valid statistical methodology for DNA methylation studies, despite the fact that the data do not always satisfy the assumptions of this test. These findings have implications for epidemiological-based studies of DNA methylation and provide a framework for the interpretation of findings from current and future studies.

Sleep is an essential human function but its regulation is poorly understood. Using accelerometer data from 85,670 UK Biobank participants, we perform a genome-wide association study of 8 derived sleep traits representing sleep quality, quantity and timing, and validate our findings in 5,819 individuals. We identify 47 genetic associations at P  < 5 × 10 −8 , of which 20 reach a stricter threshold of P  < 8 × 10 −10 . These include 26 novel associations with measures of sleep quality and 10 with nocturnal sleep duration. The majority of identified variants associate with a single sleep trait, except for variants previously associated with restless legs syndrome. For sleep duration we identify a missense variant (p.Tyr727Cys) in PDE11A as the likely causal variant. As a group, sleep quality loci are enriched for serotonin processing genes. Although accelerometer-derived measures of sleep are imperfect and may be affected by restless legs syndrome, these findings provide new biological insights into sleep compared to previous efforts based on self-report sleep measures. Quality, quantity and timing of sleep are important factors for overall human health. Here, the authors perform GWAS for sleep traits estimated using wearable accelerometers and identify 47 genetic associations, including 26 novel associations for measures of sleep quality and 10 for nocturnal sleep duration.

Debates around the benefits of flexible work arrangements for employee well-being are limited by a lack of empirical analyses on whether flexible working enables employees with work or family stressors to cope with their levels of stress. This study examines whether the availability and use of different flexible work arrangements are associated with lower allostatic load (an index of chronic stress-related biomarkers) in a large representative study of UK adults. Male and female employees who made use of reduced hours working arrangements had lower levels of allostatic load. Among women caring for two or more children aged under 15, there was a difference of almost one unit of the allostatic load index (an additional biomarker risk) between women who used reduced hours flexible work and those without such arrangements. Reduced hours flexible work arrangements could enable women who combine work and family roles to reduce their levels of chronic stress.

Room temperatures ionic liquids are considered as miraculous solvents for biological system. Due to their inimitable properties and large variety of applications, they have been widely used in enzyme catalysis and protein stability and separation. The related information present in the current review is helpful to the researchers working in the field of biotechnology and biochemistry to design or choose an ionic liquid that can serve as a noble and selective solvent for any particular enzymatic reaction, protein preservation and other protein based applications. We have extensively analyzed the methods used for studying the protein–IL interaction which is useful in providing information about structural and conformational dynamics of protein. This can be helpful to develop and understanding about the effect of ionic liquids on stability and activity of proteins. In addition, the affect of physico-chemical properties of ionic liquids, viz. hydrogen bond capacity and hydrophobicity on protein stability are discussed.

Exosomes of endosomal origin are one class of extracellular vesicles that are important in intercellular communication. Exosomes are released by all cells in our body and their cargo consisting of lipids, proteins and nucleic acids has a footprint reflective of their parental origin. The exosomal cargo has the power to modulate the physiology of recipient cells in the vicinity of the releasing cells or cells at a distance. Harnessing the potential of exosomes relies upon the purity of exosome preparation. Hence, many methods for isolation have been developed and we provide a succinct summary of several methods. In spite of the seclusion imposed by the blood–brain barrier, cells in the CNS are not immune from exosomal intrusive influences. Both neurons and glia release exosomes, often in an activity-dependent manner. A brief description of exosomes released by different cells in the brain and their role in maintaining CNS homeostasis is provided. The hallmark of several neurodegenerative diseases is the accumulation of protein aggregates. Recent studies implicate exosomes’ intercellular communicator role in the spread of misfolded proteins aiding the propagation of pathology. In this review, we discuss the potential contributions made by exosomes in progression of Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Understanding contributions made by exosomes in pathogenesis of neurodegeneration opens the field for employing exosomes as therapeutic agents for drug delivery to brain since exosomes do cross the blood–brain barrier.

This study investigates the association between protected characteristics and inequalities in mental health care in the UK. Multinomial regression was used to model the association between protected characteristics and self-reported distress. Data was extracted from waves 6–10 (2014–2019) of the UK Household Longitudinal Study. Two risk categories were constructed: “undiagnosed distress” referred to a General Health Questionnaire-12 (GHQ-12) score above “caseness” along with no history of mental health diagnosis; “diagnosis without self-report symptoms” referred to a GHQ-12 score consistently below “caseness” within the study time frame but having received a mental health diagnosis. Compared to people without a disability, people with a disability are at considerably greater risk of both undiagnosed distress (Relative risk ratios (RRR) 2.76; Confidence Interval (CI): 2.55, 2.99) and diagnosis without self-reported symptoms (RRR 3.61; CI: 2.80, 4.66). Likewise, women were more likely than men to report undiagnosed distress (RRR = 1.49; CI: 1.38,1.61) or a diagnosis without self-reported symptoms (RRR = 1.38; CI: 1.08, 1.76. Lesbian, gay, and bisexual people are at greater risk of undiagnosed distress compared with heterosexual people (RRR 1.42; CI: 1.19, 1.70). Adults aged 16–24 years were at greatest risk compared to all other age groups. People from a minority ethnic background had a reduced risk of diagnosis without self-report symptoms compared with people from a White ethnic background (RRR 0.34; CI: 0.20, 0.61). Education, employment and income variables moderated some of these associations. This is the first study to examine diagnosis without self-report symptoms alongside undiagnosed distress. Findings suggest that addressing inequality in mental health care requires increased understanding of the needs and strengths within different groups and to provide appropriate forms of social, medical or psychosocial intervention rather than a singular focus on increasing detection, diagnosis and treatment. People with a disability appear to be at greatest disadvantage, requiring greater attention in policy and practice.

Background Interindividual genetic variability is well characterised, but we still lack a complete catalogue of loci displaying variable and stable epigenetic patterns. Results Here, we report a catalogue of stable and variable interindividual DNA methylation sites in human whole blood by analysing the DNA methylation patterns in 3642 individuals from a representative cohort for the British population using the IlluminaEPIC array. Our results show that 34,972 CpGs display variable methylation levels (VMPs) and 41,216 CpGs display stable methylation. Human whole blood is a widely used tissue in epigenetic research, particularly in Epigenome-Wide Association Studies, due to its accessibility and its ability to provide insights into systemic biological processes and disease mechanisms. This catalogue is a useful resource for interpretation of results when associating epigenetic signals to phenotypes. VMPs are highly enriched in CpG shores, enhancers and intergenic regions and approximately half of the VMPs are under genetic control. Our results also showed that trans mQTL-mCpG pairs (that is a SNP and CpG located > 500bp apart) are often located in the same TAD or connected by chromatin loops. A subset of these VMPs (784) are classified as putative epialleles and there is a link between some of these epialleles located in regulatory regions and gene expression. Conclusions Our study provides of a comprehensive and reliable catalogue of CpG sites displaying variable interindividual DNA methylation across the human epigenome.

Background The Horvath epigenetic clock is widely used. It predicts age quite well from 353 CpG sites in the DNA methylation profile in unknown samples and has been used to calculate “age acceleration” in various tissues and environments. Results The model systematically underestimates age in tissues from older people. This is seen in all examined tissues but most strongly in the cerebellum and is consistently observed in multiple datasets. Age acceleration is thus age-dependent, and this can lead to spurious associations. The current literature includes examples of association tests with age acceleration calculated in a wide variety of ways. Conclusions The concept of an epigenetic clock is compelling, but caution should be taken in interpreting associations with age acceleration. Association tests of age acceleration should include age as a covariate.