Predicted 25-hydroxyvitamin D over the adult life and the risk of ovarian cancer.

The evidence from previous studies of serum 25-hydroxyvitamin D [25(OH)D] and ovarian cancer risk are not conclusive. However, 25(OH)D was generally only measured in late adulthood, which may not capture the etiologically relevant exposure periods. We investigated predicted 25(OH)D over the adult lifetime in relation to ovarian cancer risk in a population-based case-control study conducted from 2011 to 2016 in Montreal, Canada (490 cases, 896 controls). Predicted 25(OH)D was computed using previously validated regression models. Unconditional multivariable logistic regression models were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for average predicted 25(OH)D over the adult life and risk. In addition, the relative importance of different periods of past 25(OH)D exposure was explored using a weighted cumulative exposure (WCE) model. For each 20 nmol/L increase in average predicted 25(OH)D over the adult life, the aOR (95% CI) was 0.73 (0.55-0.96). In WCE analyses, the inverse association was strongest for exposures 5 to 20 years and 35 to 55 years prior to diagnosis, with aORs (95% CIs) of 0.82 (0.69-0.94) and 0.79 (0.66-1.02), respectively, for each 20 nmol/L increase in predicted 25(OH)D. These results support an inverse association between 25(OH)D in adulthood and ovarian cancer risk.

Effect of sleep disturbance on biomarkers related to the development of adverse health outcomes: A systematic review of the human literature.

Literature suggests that unrestricted and undisturbed sleep is vital for basic human function and performance; however, it is unclear as to what amount of sleep disturbance leads to dysregulation in biomarkers, which may underscore the development of adverse health effects. This systematic review aims to identify the amount of sleep disturbance that contributes to biomarker changes as a potential precursor to the development of adverse health effects. English-language comparative studies available in PubMed, Cochrane Central, EMBASE, and CINAHL databases from 1 January 1980 to 31 July 2021 were searched. Where possible, random-effects meta-analyses were used to examine the effect of sleep disturbances on adverse health effects. The risk of bias of individual studies was assessed using the Cochrane Risk of Bias Tool and the Risk of Bias of Nonrandomised Studies - of Exposures instruments and the certainty of the body of evidence for each outcome was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. The search identified 92 primary studies reporting on blood pressure, hypertension, heart rate, cardiac arrhythmia, cardiac output, waist circumference, cortisol, adrenaline, noradrenaline, immune system markers, glucose, insulin, cholesterol, and triglyceride levels. Although some meta-analyses suggested there may be an association between sleep disturbances and certain outcomes, the certainty in the evidence was very low due to concerns with risk of bias, inconsistency across exposures, populations, and imprecision in the estimates of effects. Further research is needed to explore the point at which types, levels and duration of sleep disturbances may begin to increase the risk of developing adverse health outcomes to inform and tailor health interventions.

Impact of Noise Exposure on Risk of Developing Stress-Related Metabolic Effects: A Systematic Review and Meta-Analysis.

Background: Exposure to noise can increase biological stress reactions, which may increase adverse health effects, including metabolic disorders; however, the certainty in the association between exposure to noise and metabolic outcomes has not been widely explored. The objective of this review is to evaluate the evidence between noise exposures and metabolic effects. Materials and Methods: A systematic review of English and comparative studies available in PubMed, Cochrane Central, EMBASE, and CINAHL databases between January 1, 1980 and December 29, 2021 was performed. Risk of Bias of Nonrandomized Studies of Exposures was used to assess risk of bias of individual studies and certainty of the body of evidence for each outcome was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: Fifty-six primary studies reporting on cortisol, cholesterol levels, waist circumference, glucose levels, and adrenaline and/or noradrenaline were identified. Although meta-analyses suggested that there may be an increase in waist circumference and adrenaline with increased noise exposure, the certainty in the evidence is very low. Overall, the certainty in the evidence of an effect of increased noise on all the outcomes were low to very low due to concerns with risk of bias, inconsistency across exposure sources, populations, and studies, and imprecision in the estimates of effects. Conclusions: The certainty of the evidence of increased noise on metabolic effects was low to very low, which likely reflects the inability to compare across the totality of the evidence for each outcome. The findings from this review may be used to inform policies involving noise reduction and mitigation strategies, and to direct further research in areas that currently have limited evidence available.

Impact of Noise Exposure on Risk of Developing Stress-Related Health Effects Related to the Cardiovascular System: A Systematic Review and Meta-Analysis.

Background: : Exposure to acute noise can cause an increase in biological stress reactions, which provides biological plausibility for a potential association between sustained noise exposure and stress-related health effects. However, the certainty in the evidence for an association between exposures to noise on short- and long-term biomarkers of stress has not been widely explored. The objective of this review was to evaluate the strength of evidence between noise exposure and changes in the biological parameters known to contribute to the development of stress-related adverse cardiovascular responses. Materials and Methods: This systematic review comprises English language comparative studies available in PubMed, Cochrane Central, EMBASE, and CINAHL databases from January 1, 1980 to December 29, 2021. Where possible, random-effects meta-analyses were used to examine the effect of noise exposure from various sources on stress-related cardiovascular biomarkers. The risk of bias of individual studies was assessed using the risk of bias of nonrandomized studies of exposures instrument. The certainty of the body of evidence for each outcome was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. Results: : The search identified 133 primary studies reporting on blood pressure, hypertension, heart rate, cardiac arrhythmia, vascular resistance, and cardiac output. Meta-analyses of blood pressure, hypertension, and heart rate suggested there may be signals of increased risk in response to a higher noise threshold or incrementally higher levels of noise. Across all outcomes, the certainty of the evidence was very low due to concerns with the risk of bias, inconsistency across exposure sources, populations, and studies and imprecision in the estimates of effects. Conclusions: : This review identifies that exposure to higher levels of noise may increase the risk of some short- and long-term cardiovascular events; however, the certainty of the evidence was very low. This likely represents the inability to compare across the totality of the evidence for each outcome, underscoring the value of continued research in this area. Findings from this review may be used to inform policies of noise reduction or mitigation interventions.

Impact of Noise Exposure on Risk of Developing Stress-Related Obstetric Health Effects: A Systematic Review and Meta-Analysis.

Background: Exposure to noise can increase biological stress reactions and that could increase the risk of stress-related prenatal effects, including adverse obstetric outcomes; however, the association between exposure to noise and adverse obstetric outcomes has not been extensively explored. The objective of this review was to evaluate the evidence between noise exposures and adverse obstetric outcomes, specifically preeclampsia, gestational diabetes, and gestational hypertension. Materials and Methods: A systematic review of English language, comparative studies available in PubMed, Cochrane Central, EMBASE, and CINAHL databases between January 1, 1980 and December 29, 2021 was performed. Risk of bias for individual studies was assessed using the Risk of Bias Instrument for Nonrandomized Studies of Exposures, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the certainty of the body of evidence for each outcome. Results: Six studies reporting on preeclampsia, gestational diabetes, and gestational hypertension were identified. Although some studies suggested there may be signals of increased responses to increased noise exposure for preeclampsia and gestational hypertension, the certainty in the evidence of an effect of increased noise on all the outcomes was very low due to concerns with risk of bias, inconsistency across studies, and imprecision in the effect estimates. Conclusions: While the certainty of the evidence for noise exposure and adverse obstetric outcomes was very low, the findings from this review may be useful for directing further research in this area, as there is currently limited evidence available. These findings may also be useful for informing guidelines and policies involving noise exposure situations or environments.

Omega-3 Polyunsaturated Fatty Acids Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials.

Background Current evidence might support the use of omega-3 fatty acids (preferably docosahexaenoic acid and eicosapentaenoic acid) for lowering blood pressure (BP), but the strength and shape of the dose-response relationship remains unclear. Methods and Results This study included randomized controlled trials published before May 7, 2021, that involved participants aged ≥18 years, and examined an association between omega-3 fatty acids (docosahexaenoic acid, eicosapentaenoic acid, or both) and BP. A random-effects 1-stage cubic spline regression model was used to predict the average dose-response association between daily omega-3 fatty acid intake and changes in BP. We also conducted stratified analyses to examine differences by prespecified subgroups. Seventy-one trials were included, involving 4973 individuals with a combined docosahexaenoic acid+eicosapentaenoic acid dose of 2.8 g/d (interquartile range, 1.3 g/d to 3.6 g/d). A nonlinear association was found overall or in most subgroups, depicted as J-shaped dose-response curves. The optimal intake in both systolic BP and diastolic BP reductions (mm Hg) were obtained by moderate doses between 2 g/d (systolic BP, -2.61 [95% CI, -3.57 to -1.65]; diastolic BP, -1.64 [95% CI, -2.29 to -0.99]) and 3 g/d (systolic BP, -2.61 [95% CI, -3.52 to -1.69]; diastolic BP, -1.80 [95% CI, -2.38 to -1.23]). Subgroup studies revealed stronger and approximately linear dose-response relations among hypertensive, hyperlipidemic, and older populations. Conclusions This dose-response meta-analysis demonstrates that the optimal combined intake of omega-3 fatty acids for BP lowering is likely between 2 g/d and 3 g/d. Doses of omega-3 fatty acid intake above the recommended 3 g/d may be associated with additional benefits in lowering BP among groups at high risk for cardiovascular diseases.

Investigating the relationship between melatonin patterns and methylation in circadian genes among day shift and night shift workers.

OBJECTIVES: Mechanisms underlying the carcinogenicity of night shift work remain uncertain. One compelling yet understudied cancer mechanism may involve altered DNA methylation in circadian genes due to melatonin secretion patterns. The objective of this study was to explore the relationship between melatonin secretion patterns and circadian gene methylation among day and night shift workers. METHODS: Female healthcare employees (n=38 day workers, n=36 night shift workers) for whom we had urinary 6-sulfatoxymelatonin secretion data from a previous study were recontacted. New blood samples were collected and used to measure methylation levels at 1150 CpG loci across 22 circadian genes using the Illumina Infinium MethylationEPIC beadchip. Linear regression was used to examine the association between melatonin (acrophase and mesor) and M values for each CpG site (false discovery rate, q=0.2), while testing for effect modification by shift work status. RESULTS: Among night shift workers, a higher mesor (24 hours of mean production of melatonin) was associated with increased methylation in the body of RORA (q=0.02) and decreased methylation in the putative promoter region of MTNR1A (q=0.03). Later acrophase (ie, time of peak concentration) was associated with increased methylation in the putative promoter region of MTNR1A (q=0.20) and decreased methylation in the body of PER3 (q=0.20). No associations were identified among day workers. CONCLUSIONS: In conclusion, patterns in melatonin secretion were associated with differential circadian gene methylation among night shift workers. Melatonin and alteration of DNA methylation in circadian genes may be one pathway towards increased cancer risk, although larger-scale studies examining multiple time points are needed.

Modeling the relationship between shift work and cardiometabolic risk through circadian disruption, sleep and stress pathways.

The purpose of this study is to elucidate the multiple pathways linking shift work exposure to cardiometabolic risk (CMR) through the intermediates of circadian disruption, sleep disturbances, and stress. A cross-sectional study was conducted at Kingston Health Sciences Center that included female hospital workers, 160 who worked a day-only schedule and 168 who worked rotating days and nights. Participants completed questionnaires, a clinical exam, and wore accelerometers to collect sleep data for 8 days. Participants also collected urine samples at each void during a 24-h collection period, on the day shift for day-only workers and the night shift for rotating shift workers, for cortisol and melatonin measures. We adapted and tested a conceptual model proposed by Knutsson and Boggild for circadian disruption, sleep, and stress mechanistic pathways linking shift work to CMR using structural equation modeling techniques. Status as a rotating shift worker was associated with increased circadian disruption of cortisol and melatonin production compared to day-only workers (P < .001). Increased circadian disruption was associated with an increased CMR (P = .01). Rotating shift work was associated with sleep disturbances (P = .002) and increased job stress (P < .001), but neither was associated with CMR. We conclude that rotating shift work is associated indirectly with increased CMR. This association is mediated by circadian disruption as indicated by attenuated melatonin and cortisol, and flatter cortisol curves.

DNA methylation of circadian genes and markers of cardiometabolic risk in female hospital workers: An exploratory study.

Night shift work has been linked to increased risk of cardiovascular disease (CVD); however, the underlying mechanisms remain unclear. A compelling yet understudied mechanism involves differential DNA methylation of circadian genes. To investigate the relevance of this mechanism, we conducted an exploratory cross-sectional study of 74 female hospital personnel (38 day workers, 36 night shift workers). Sociodemographic, lifestyle, and health characteristics as well as shift work status and history were determined through self-report. Fasting blood samples were collected to measure markers of cardiometabolic risk and DNA was extracted to measure DNA methylation of 1150 cytosine-guanine (CpG) sites across 22 circadian genes. Associations between methylation levels at individual CpG sites (ß-values) and markers of cardiometabolic risk were analyzed while considering effect modification by shift work status. The false discovery rate was applied to account for multiple comparisons (q ≤ 0.20). Two CpG sites [cg06758649 (CRY1) and cg06899802 (CSNK1A1)] were differentially associated with waist circumference and body mass index by shift work status, and eight CpG sites [cg26103512 (CSNK1D), cg03941313 (CSNK1E), cg18217763 (CSNK1E), cg16682686 (DEC1), cg12061096 (RORA), cg10133825 (RORA), cg19652148 (RORA), and cg22904654 (RORA)] were differentially associated with LDL cholesterol concentration by shift work status (all q ≤ 0.20). Our findings suggest that the relationship between DNA methylation of circadian genes and cardiometabolic risk differs by day and night shift worker status, which may contribute to mechanisms of increased risk of CVD observed among night shift workers.

Exploring the impact of night shift work on methylation of circadian genes.

Night shift work is associated with increased breast cancer risk, but the molecular mechanisms are not well-understood. The objective of this study was to explore the relationship between night shift work parameters (current status, duration/years, and intensity) and methylation in circadian genes as a potential mechanism underlying the carcinogenic effects of night shift work. A cross-sectional study was conducted among 74 female healthcare employees (n = 38 day workers, n = 36 night shift workers). The Illumina Infinium MethylationEPIC beadchip was applied to DNA extracted from blood samples to measure methylation using a candidate gene approach at 1150 CpG loci across 22 circadian genes. Linear regression models were used to examine the association between night shift work parameters and continuous methylation measurements (ß-values) for each CpG site. The false-discovery rate (q = 0.2) was used to account for multiple comparisons. Compared to day workers, current night shift workers demonstrated hypermethylation in the 5'UTR region of CSNK1E (q = 0.15). Individuals that worked night shifts for ≥10 years exhibited hypomethylation in the gene body of NR1D1 (q = 0.08) compared to those that worked <10 years. Hypermethylation in the gene body of ARNTL was also apparent in those who worked ≥3 consecutive night shifts a week (q = 0.18). These findings suggest that night shift work is associated with differential methylation in core circadian genes, including CSNK1E, NR1D1 and ARNTL. Future, larger-scale studies with long-term follow-up and detailed night shift work assessment are needed to confirm and expand on these findings.

Systematic review support received and needed by researchers: a survey of libraries supporting Ontario medical schools.

Introduction: Finding efficient ways to meet the growing demand for library systematic review support is imperative for facilitating the production of high-quality research. The objectives of this study were threefold: 1) to ascertain the systematic review support provided by health sciences libraries at Ontario medical schools and their affiliated hospitals, 2) to determine the perceived educational needs by researchers at these institutions, and 3) to assess the potential usefulness of freely available, online educational modules for researchers that discuss all stages of the systematic review process. Methods: We conducted a cross-sectional survey in June and July of 2020. Data was analyzed and presented using median and interquartile range (IQR) for continuous measures, and in proportions for categorical measures. Results: 13 of 19 libraries invited provided usable data. Most libraries spent more time supporting systematic reviews via collaboration and participation than by providing educational support. The perceived needs of library users were contrary to the perceived gaps in researcher support provided by the library/institution. All libraries reported they would find freely available, online educational modules useful for training researchers. Discussion: The next steps for our inter-professional research team will be to develop freely available, online education modules that introduce researchers to all stages of the systematic review process. These modules cannot replace the value that direct support from librarians, biostatisticians or methodology experts can provide, however, they may offer a more efficient way for libraries to familiarize researchers and trainees with best practices and universally accepted reporting guidelines for performing a high-quality review.

Outdoor light at night at residences and breast cancer risk in Canada.

Experimental and epidemiologic studies suggest that light at night (LAN) exposure disrupts circadian rhythm, and this disruption may increase breast cancer risk. We investigated the potential association between residential outdoor LAN and breast cancer risk. A population-based case-control study was conducted in Vancouver, British Columbia and Kingston, Ontario, Canada with incident breast cancer cases, and controls frequency matched by age in the same region. This analysis was restricted to 844 cases and 905 controls who provided lifetime residential histories. Using time-weighted average duration at each home 5-20 years prior to study entry, two measures of cumulative average outdoor LAN were calculated using two satellite data sources. Logistic regression was used to estimate the relationship between outdoor LAN and breast cancer risk, considering interactions for menopausal status and night shift work. We found no association between residential outdoor LAN and breast cancer for either measure of LAN [OR comparing highest vs. lowest tertile (DNB) = 0.95, 95% CI 0.70-1.27]. We also found no association when considering interactions for menopausal status and past/current night work status. These findings were robust to changes to years of residential data considered, residential mobility, and longer exposure windows. Our findings are consistent with studies reporting that outdoor LAN has a small effect or no effect on breast cancer risk.

The relationship between night work, chronotype, and cardiometabolic risk factors in female hospital employees.

Night work has emerged as a risk factor for many chronic diseases, including obesity, diabetes, and cardiovascular disease. While night work is linked to a number of cardiometabolic indices, few studies have explored how different parameters, such as cumulative night work and intensity of night work, may influence cardiometabolic risk. Fewer studies have also explored the relationship while considering chronotype, a potential modifier between shift-induced circadian disruption and cardiometabolic outcomes. The main objective is to determine the association between night work parameters and cardiometabolic risk factors. The secondary objective is to assess how the association between night work parameters and cardiometabolic risk factors differs by chronotype. A cross-sectional study was conducted with 325 full- and part-time female hospital employees (168 rotating night workers, 157 day workers). Night work status, cumulative night work duration, and night work intensity were determined through self-report, and cardiometabolic risk factors were assessed through clinical exams. Chronotype was determined using the Munich Chronotype Questionniare (MCTQ). Multiple linear regression was used to examine the association between night work parameters and cardiometabolic risk factors. Current night work, cumulative night work, and night work intensity are associated with a number of cardiometabolic indices, including higher waist circumference, body mass index, fasting glucose, blood pressure, and cardiometabolic risk score. When stratified by chronotype, night work parameters are associated with a number of cardiometabolic risk factors in the evening-oriented chronotype subgroup. There is no difference in cardiometabolic risk factors in morning-oriented chronotypes when comparing night work parameters, with the exception of LDL cholesterol. These results suggest that night work parameters are associated with cardiometabolic risk, and night workers with an evening-oriented chronotype may be more susceptible to the adverse cardiometabolic impacts of night work. Future studies should consider chronotype when examining the relationship between night work and cardiometabolic risk.

Working Time Society consensus statements: Individual differences in shift work tolerance and recommendations for research and practice.

There is no standard definition of shift work universally, and no validated report of complete biological adjustment to shift work in workers. Similarly, the evidence for shift work tolerance is limited due to a small number of studies and a narrow range of outcome measures. This paper discusses evidence to date regarding individual differences in shift work tolerance and highlights areas for future research and recommendations for workplace practice. The few factors that are consistently associated with perceived or actual shift work tolerance are young age, low scores of morningness or being a late chronotype, low scores of languidity and neuroticism, high scores on extraversion, internal locus of control and flexibility and male sex. An important first step is to differentiate between factors that are potentially modifiable, such as those that are determined by lifestyle choices, and those factors specific to the working time arrangement. Identifying determinants of shift work tolerance and the ability to adjust to shift work, whether they are innate and/or acquired mechanisms, is important so workers who are less likely to tolerate shift work well can be self-identified and supported with appropriate harm/risk minimization strategies. This paper also identifies important areas for future research with the goal of increasing the evidence base on which we can develop evidence-based harm mitigation strategies for shift workers.

Investigating Cortisol Production and Pattern as Mediators in the Relationship Between Shift Work and Cardiometabolic Risk.

BACKGROUND: Shift work is a risk factor for many diseases, including cardiovascular disease. Although the biological pathways are still unclear, it is hypothesized that cortisol disruption during night work is an intermediate. The objective of this study is to determine whether total cortisol production and cortisol pattern mediate the relationship between current shift work and cardiometabolic risk (CMR) among female hospital employees. METHODS: A cross-sectional study was conducted among 326 female employees (166 rotating shift workers, 160 day workers), recruited from a hospital in Southeastern Ontario, Canada, during 2011 to 2014. Participants completed a baseline interview, questionnaire, and clinical exam. Urine samples were collected over two 24-hour periods and used to analyze creatinine-adjusted cortisol, which was then used to calculate total cortisol production (AUCG), and pattern (AUCI). Mediation analysis was performed to test the mediating effect of cortisol in the relationship between shift work and a continuous CMR score. RESULTS: Current shift work is associated with a 0.52 higher CMR score (95% CI: 0.15, 0.89), a lower cortisol output (AUCG), and a flatter pattern (AUCI) over a 2-day period. AUCG is a partial mediator in the relationship between shift work and CMR, whereas AUCI is not. AUCG is also associated with CMR while controlling for shift work, suggesting that lower total cortisol production is also linked to CMR in non-shift workers. CONCLUSIONS: Total cortisol production is a partial mediator in the relationship between rotating shift work and CMR among female hospital employees, whereas cortisol pattern is not a mediator.