Although long working hours are common in working populations, little is known about the effect of long working hours on mental health.
We examined the association between long working hours and the ...onset of depressive and anxiety symptoms in middle-aged employees. Participants were 2960 full-time employees aged 44 to 66 years (2248 men, 712 women) from the prospective Whitehall II cohort study of British civil servants. Working hours, anxiety and depressive symptoms, and covariates were measured at baseline (1997-1999) followed by two subsequent measurements of depressive and anxiety symptoms (2001 and 2002-2004).
In a prospective analysis of participants with no depressive (n=2549) or anxiety symptoms (n=2618) at baseline, Cox proportional hazard analysis adjusted for baseline covariates showed a 1.66-fold 95% confidence interval (CI) 1.06-2.61 risk of depressive symptoms and a 1.74-fold (95% CI 1.15-2.61) risk of anxiety symptoms among employees working more than 55 h/week compared with employees working 35-40 h/week. Sex-stratified analysis showed an excess risk of depression and anxiety associated with long working hours among women hazard ratios (HRs) 2.67 (95% CI 1.07-6.68) and 2.84 (95% CI 1.27-6.34) respectively but not men 1.30 (0.77-2.19) and 1.43 (0.89-2.30).
Working long hours is a risk factor for the development of depressive and anxiety symptoms in women.
It is well established that selected lifestyle factors are individually associated with lower risk of chronic diseases, but how combinations of these factors are associated with disease-free ...life-years is unknown.
To estimate the association between healthy lifestyle and the number of disease-free life-years.
A prospective multicohort study, including 12 European studies as part of the Individual-Participant-Data Meta-analysis in Working Populations Consortium, was performed. Participants included 116 043 people free of major noncommunicable disease at baseline from August 7, 1991, to May 31, 2006. Data analysis was conducted from May 22, 2018, to January 21, 2020.
Four baseline lifestyle factors (smoking, body mass index, physical activity, and alcohol consumption) were each allocated a score based on risk status: optimal (2 points), intermediate (1 point), or poor (0 points) resulting in an aggregated lifestyle score ranging from 0 (worst) to 8 (best). Sixteen lifestyle profiles were constructed from combinations of these risk factors.
The number of years between ages 40 and 75 years without chronic disease, including type 2 diabetes, coronary heart disease, stroke, cancer, asthma, and chronic obstructive pulmonary disease.
Of the 116 043 people included in the analysis, the mean (SD) age was 43.7 (10.1) years and 70 911 were women (61.1%). During 1.45 million person-years at risk (mean follow-up, 12.5 years; range, 4.9-18.6 years), 17 383 participants developed at least 1 chronic disease. There was a linear association between overall healthy lifestyle score and the number of disease-free years, such that a 1-point improvement in the score was associated with an increase of 0.96 (95% CI, 0.83-1.08) disease-free years in men and 0.89 (95% CI, 0.75-1.02) years in women. Comparing the best lifestyle score with the worst lifestyle score was associated with 9.9 (95% CI 6.7-13.1) additional years without chronic diseases in men and 9.4 (95% CI 5.4-13.3) additional years in women (P < .001 for dose-response). All of the 4 lifestyle profiles that were associated with the highest number of disease-free years included a body-mass index less than 25 (calculated as weight in kilograms divided by height in meters squared) and at least 2 of the following factors: never smoking, physical activity, and moderate alcohol consumption. Participants with 1 of these lifestyle profiles reached age 70.3 (95% CI, 69.9-70.8) to 71.4 (95% CI, 70.9-72.0) years disease free depending on the profile and sex.
In this multicohort analysis, various healthy lifestyle profiles appeared to be associated with gains in life-years without major chronic diseases.
Covering: up to 2022A very large group of biosynthetically linked fungal secondary metabolites are formed
the key intermediate emodin and its corresponding anthrone. The group includes anthraquinones ...such as chrysophanol and cladofulvin, the grisandienes geodin and trypacidin, the diphenyl ether pestheic acid, benzophenones such as monodictyphenone and various xanthones including the prenylated shamixanthones, the agnestins and dimeric xanthones such as the ergochromes, cryptosporioptides and neosartorin. Such compounds exhibit a wide range of bioactivities and as such have been utilised in traditional medicine for centuries, as well as garnering more recent interest from the pharmaceutical sector. Additional interest comes from industries such as textiles and cosmetics due to their use as natural colourants. A variety of biosynthetic routes and mechanisms have been proposed for this family of compounds, being altered and updated as new biosynthetic methods develop and new results emerge. After nearly 100 years of such research, this review aims to provide a comprehensive overview of what is currently known about the biosynthesis of this important family, amalgamating the early chemical and biosynthetic studies with the more recent genetics-based advances and comparative bioinformatics.
Previous research has focused on overall associations between work stress and body mass index (BMI) ignoring the possibility that stress may cause some people to eat less and lose weight and others ...to eat more. Using longitudinal data, we studied whether work stress induced weight loss in lean individuals and weight gain in overweight individuals.
Prospective cohort study.
A total of 7965 British civil servants (5547 men and 2418 women) aged 35-55 at study entry (The Whitehall II study).
Work stress, indicated by the job strain model and measured as job control, job demands and job strain, was assessed at baseline and BMI at baseline and at 5-year follow-up.
In men, the effect of job strain on weight gain and weight loss was dependent on baseline BMI (P</=0.03). In the leanest quintile (BMI<22 kg/m(2)) at baseline, high job strain and low job control were associated with weight loss by follow-up, whereas among those in the highest BMI quintile (>27 kg/m(2)), these stress indicators were associated with subsequent weight gain. No corresponding interaction was seen among women.
Inconsistent findings reported by previous studies of stress and BMI have generally been interpreted to indicate the absence of an association. In light of our results, the possibility of differential effects of work stress should also be taken into account.
Maleidrides are a class of bioactive secondary metabolites unique to filamentous fungi, which contain one or more maleic anhydrides fused to a 7-, 8- or 9- membered carbocycle (named heptadrides, ...octadrides and nonadrides respectively). Herein structural and biosynthetic studies on the antifungal octadride, zopfiellin, and nonadrides scytalidin, deoxyscytalidin and castaneiolide are described. A combination of genome sequencing, bioinformatic analyses, gene disruptions, biotransformations, isotopic feeding studies, NMR and X-ray crystallography revealed that they share a common biosynthetic pathway, diverging only after the nonadride deoxyscytalidin. 5-Hydroxylation of deoxyscytalidin occurs prior to ring contraction in the zopfiellin pathway of
Diffractella curvata
. In
Scytalidium album
, 6-hydroxylation - confirmed as being catalysed by the α-ketoglutarate dependent oxidoreductase ScyL2 - converts deoxyscytalidin to scytalidin, in the final step in the scytalidin pathway. Feeding scytalidin to a zopfiellin PKS knockout strain led to the production of the nonadride castaneiolide and two novel ring-open maleidrides.
Deoxyscytalidin is a common biosynthetic intermediate to the nonadride scytalidin in the fungus
Scytalidium album
and in
Diffractella curvata
gives the octadride zopfiellin.
Covering: up to early 2022Maleidrides are a family of polyketide-based dimeric natural products isolated from fungi. Many maleidrides possess significant bioactivities, making them attractive ...pharmaceutical or agrochemical lead compounds. Their unusual biosynthetic pathways have fascinated scientists for decades, with recent advances in our bioinformatic and enzymatic understanding providing further insights into their construction. However, many intriguing questions remain, including exactly how the enzymatic dimerisation, which creates the diverse core structure of the maleidrides, is controlled. This review will explore the literature from the initial isolation of maleidride compounds in the 1930s, through the first full structural elucidation in the 1960s, to the most recent
,
, and
analyses.
The correlation between objective and self-reported measures of physical activity varies between studies. We examined this association and whether it differed by demographic factors or socioeconomic ...status (SES). Data were from 3,975 Whitehall II (United Kingdom, 2012-2013) participants aged 60-83 years, who completed a physical activity questionnaire and wore an accelerometer on their wrist for 9 days. There was a moderate correlation between questionnaire- and accelerometer-assessed physical activity (Spearman's r = 0.33, 95% confidence interval: 0.30, 0.36). The correlations were higher in high-SES groups than in low-SES groups (P 's = 0.02), as defined by education (r = 0.38 vs. r = 0.30) or occupational position (r = 0.37 vs. r = 0.29), but did not differ by age, sex, or marital status. Of the self-reported physical activity, 68.3% came from mild activities, 25% from moderate activities, and only 6.7% from vigorous activities, but their correlations with accelerometer-assessed total physical activity were comparable (range of r 's, 0.21-0.25). Self-reported physical activity from more energetic activities was more strongly associated with accelerometer data (for sports, r = 0.22; for gardening, r = 0.16; for housework, r = 0.09). High-SES persons reported more energetic activities, producing stronger accelerometer associations in these groups. Future studies should identify the aspects of physical activity that are most critical for health; this involves better understanding of the instruments being used.
The cycloaspeptides are bioactive pentapeptides produced by various filamentous fungi, which have garnered interest from the agricultural industry due to the reported insecticidal activity of the ...minor metabolite, cycloaspeptide E. Genome sequencing, bioinformatics and heterologous expression confirmed that the cycloaspeptide gene cluster contains a minimal 5-module nonribosomal peptide synthetase (NRPS) and a new type of
-acting
-methyltransferase (
-MeT). Deletion of the
-MeT encoding gene and subsequent feeding studies determined that two modules of the NRPS preferentially accept and incorporate
-methylated amino acids. This discovery allowed the development of a system with unprecedented control over substrate supply and thus output, both increasing yields of specific metabolites and allowing the production of novel fluorinated analogues. Furthermore, the biosynthetic pathway to ditryptophenaline, another fungal nonribosomal peptide, was shown to be similar, in that methylated phenylalanine is accepted by the ditryptophenaline NRPS. Again, this allowed the directed biosynthesis of a fluorinated analogue, through the feeding of a mutant strain. These discoveries represent a new paradigm for the production of
-methylated cyclic peptides
the selective incorporation of
-methylated free amino acids.
This trial tested the hypothesis that combined androgen suppression (CAS) and whole-pelvic (WP) radiotherapy (RT) followed by a boost to the prostate improves progression-free survival (PFS) by 10% ...compared with CAS and prostate-only (PO) RT. This trial also tested the hypothesis that neoadjuvant and concurrent hormonal therapy (NCHT) improves PFS compared with adjuvant hormonal therapy (AHT) by 10%.
Eligibility included localized prostate cancer with an elevated prostate-specific antigen (PSA) < or = 100 ng/mL and an estimated risk of lymph node (LN) involvement of 15%. Between April 1, 1995, and June 1, 1999, 1,323 patients were accrued. Patients were randomly assigned to WP + NCHT, PO + NCHT, WP + AHT, or PO + AHT. Failure for PFS was defined as the first occurrence of local, regional, or distant disease; PSA failure; or death for any cause.
With a median follow-up of 59.5 months, WP RT was associated with a 4-year PFS of 54% compared with 47% in patients treated with PO RT (P =.022). Patients treated with NCHT experienced a 4-year PFS of 52% versus 49% for AHT (P =.56). When comparing all four arms, there was a progression-free difference among WP RT + NCHT, PO RT + NCHT, WP RT + AHT, and PO RT + AHT (60% v 44% v 49% v 50%, respectively; P =.008). No survival advantage has yet been seen.
WP RT + NCHT improves PFS compared with PO RT and NCHT or PO RT and AHT, and compared with WP RT + AHT in patients with a risk of LN involvement of 15%.
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