Physical job demands in pregnancy and associated musculoskeletal health and employment outcomes: a systematic review.

OBJECTIVE: A decline in musculoskeletal health during pregnancy is an underappreciated adverse outcome of pregnancy that can have immediate and long-term health consequences. High physical job demands are known risk factors for nontraumatic musculoskeletal disorders in the general working population. Evidence from meta-analyses suggest that occupational lifting and prolonged standing during pregnancy may increase risk of adverse pregnancy outcomes. This systematic review examined associations between occupational lifting or postural load in pregnancy and associated musculoskeletal disorders and related sequalae. DATA SOURCES: Five electronic databases (Medline, Embase, CINAHL, NIOSHTIC-2, and Ergonomic Abstracts) were searched from 1990 to July 2022 for studies in any language. A Web of Science snowball search was performed in December 2022. Reference lists were manually reviewed. STUDY ELIGIBILITY CRITERIA: Eligible studies reported associations between occupational lifting or postural load and musculoskeletal health or sequelae (eg, employment outcomes) among pregnant and postpartum workers. METHODS: Data were extracted using a customized form to document study and sample characteristics; and details of exposures, outcomes, covariates, and analyses. Investigators independently assessed study quality for 7 risk-of-bias domains and overall utility, with discrepant ratings resolved through discussion. A narrative synthesis was conducted due to heterogeneity. RESULTS: Sixteen studies (11 cohort studies, 2 nested case-control studies, and 3 cross-sectional studies) from 8 countries were included (N=142,320 pregnant and N=1744 postpartum workers). Limited but consistent evidence with variable quality ratings, ranging from critical concern to high, suggests that pregnant workers exposed to heavy lifting (usually defined as ≥22 lbs or ≥10 kg) may be at increased risk of functionally limiting pelvic girdle pain and antenatal leave. Moreover, reports of dose-response relationships suggest graded risk levels according to lifting frequency, ranging from 21% to 45% for pelvic girdle pain and 58% to 202% for antenatal leave. Limited but consistent evidence also suggests that postural load increases the risk of employment cessation. CONCLUSION: Limited but consistent evidence suggests that pregnant workers exposed to heavy lifting and postural load are at increased risk of pelvic girdle pain and employment cessation. Job accommodations to reduce exposure levels may promote safe sustainable employment for pregnant workers.

Sex and race disparities in the association between work characteristics and vitamin D deficiency: findings from the National Health and Nutrition Examination Survey, 2005-2010.

OBJECTIVES: Vitamin D deficiency is highly prevalent worldwide; however, few large population-based studies have examined occupational risk factors. We examined associations between shift work, work schedule, hours worked, outdoor work, occupation and serum 25-hydroxyvitamin D (25(OH)D) levels in the US working population. METHODS: This cross-sectional study included 8601 workers from the 2005-2010 National Health and Nutrition Examination Survey (NHANES) cycles. NHANES occupational data were supplemented with measures of outdoor work from the Occupational Information Network. Serum 25(OH)D concentration in nanomoles per litre (nmol/L) was categorised as sufficient (≥75), insufficient (50-<75), moderately deficient (30-<50) and severely deficient (<30). Age-adjusted weighted multinomial and binary logistic regression were used to examine associations between work-related factors and vitamin D status with sex-race/ethnicity stratification. RESULTS: Shift workers had higher odds of severe vitamin D deficiency compared with day workers (OR: 1.64, 95% CI 1.22 to 2.19). Compared with those in white-collar occupations, those in natural resources were less likely to be deficient (OR: 0.31, 95% CI 0.19 to 0.52), while those in production were more likely to be deficient (OR: 2.25, 95% CI 1.48 to 3.43). Women working ≥40 hours/week compared with <40 hours/week were more likely to be moderately deficient (OR: 1.30, 95% CI 1.06 to 1.59). Black women working in sales were more likely to be deficient than those in management (OR: 1.53, 95% CI 1.03 to 2.27). Mexican American men working nights had the highest odds of deficiency (OR: 2.64, 95% CI 1.38 to 5.06). CONCLUSIONS: Work-related factors were associated with vitamin D status and there were race/ethnicity and sex differences. Targeted vitamin D screening and supplementation interventions may reduce these disparities.

Occupational physical demands and menstrual cycle irregularities in flight attendants and teachers.

OBJECTIVES: Flight attendants perform physically demanding work such as lifting baggage, pushing service carts and spending the workday on their feet. We examined if more frequent exposure to occupational physical demands could explain why previous studies have found that flight attendants have a higher reported prevalence of menstrual cycle irregularities than other workers. METHODS: We conducted a cross-sectional analysis of 694 flight attendants and 120 teachers aged 18-44 years from three US cities. Eligible participants were married, had not had a hysterectomy or tubal ligation, were not using hormonal contraception and were not recently pregnant. Participants reported menstrual cycle characteristics (cramps, pain, irregular cycles, flow, bleed length, cycle length) and occupational physical demands (standing, lifting, pushing/pulling, bending/twisting, overall effort). We used modified Poisson regression to examine associations between occupation (flight attendant, teacher) and menstrual irregularities; among flight attendants, we further examined associations between occupational physical demands and menstrual irregularities. RESULTS: All occupational physical demands were more commonly reported by flight attendants than teachers. Flight attendants reported more frequent menstrual cramps than teachers, and most occupational physical demands were associated with more frequent or painful menstrual cramps. Lifting heavy loads was also associated with irregular cycles. CONCLUSIONS: Occupational physical demands were associated with more frequent and worse menstrual pain among flight attendants. The physical demands experienced by these workers may contribute to the high burden of menstrual irregularities reported by flight attendants compared with other occupational groups, such as teachers.

Shiftwork, long working hours and markers of inflammation in a national US population-based sample of employed black and white men and women aged ≥45 years.

OBJECTIVES: Work schedule demands contribute to circadian disruption and may influence health via an inflammatory response. We examined the impact of shiftwork and long work hours on inflammation in a national US sample. METHODS: Participants included 12 487 employed black and white men and women aged ≥45 years enrolled in the REasons for Geographic and Racial Differences in Stroke Study who completed an occupational questionnaire (2011-2013) and clinical examination (2013-2016). Cross-sectional associations between shiftwork and work hours with log-transformed high-sensitivity C reactive protein (CRP) and white blood cell (WBC) count were examined by multiple linear regression analysis, overall and by race-sex subgroups. RESULTS: Overall, rotating shift workers had higher log-CRP concentration compared with day workers (ß=0.09, 95% CI:0.02 to 0.16) and findings for WBC were null. Black women had the highest geometric mean CRP (2.82 mg/L), while white men had the highest WBC (6.35×109/L). White men who worked afternoons had higher log-CRP compared with those who worked days (ß=0.20, 95% CI: 0.08 to 0.33). Black men engaged in shiftwork <10 years working ≥55 hours/week had higher log-CRP and log-WBC compared with those working days <55 hours/week (ß=0.33, 95% CI: 0.02 to 0.64 and ß=0.10, 95% CI: 0.003 to 0.19). Among shift workers, non-retired white women working forward and backward shift rotations had higher log-CRP compared with those working forward only (ß=0.49, 95% CI: 0.02 to 0.96). CONCLUSIONS: Shift workers had higher inflammatory markers compared with day workers and race-sex disparities should be examined further. These findings highlight a potential biological pathway linking work schedule demands and chronic disease.

Drusen in patient-derived hiPSC-RPE models of macular dystrophies.

Age-related macular degeneration (AMD) and related macular dystrophies (MDs) are a major cause of vision loss. However, the mechanisms underlying their progression remain ill-defined. This is partly due to the lack of disease models recapitulating the human pathology. Furthermore, in vivo studies have yielded limited understanding of the role of specific cell types in the eye vs. systemic influences (e.g., serum) on the disease pathology. Here, we use human induced pluripotent stem cell-retinal pigment epithelium (hiPSC-RPE) derived from patients with three dominant MDs, Sorsby's fundus dystrophy (SFD), Doyne honeycomb retinal dystrophy/malattia Leventinese (DHRD), and autosomal dominant radial drusen (ADRD), and demonstrate that dysfunction of RPE cells alone is sufficient for the initiation of sub-RPE lipoproteinaceous deposit (drusen) formation and extracellular matrix (ECM) alteration in these diseases. Consistent with clinical studies, sub-RPE basal deposits were present beneath both control (unaffected) and patient hiPSC-RPE cells. Importantly basal deposits in patient hiPSC-RPE cultures were more abundant and displayed a lipid- and protein-rich "drusen-like" composition. Furthermore, increased accumulation of COL4 was observed in ECM isolated from control vs. patient hiPSC-RPE cultures. Interestingly, RPE-specific up-regulation in the expression of several complement genes was also seen in patient hiPSC-RPE cultures of all three MDs (SFD, DHRD, and ADRD). Finally, although serum exposure was not necessary for drusen formation, COL4 accumulation in ECM, and complement pathway gene alteration, it impacted the composition of drusen-like deposits in patient hiPSC-RPE cultures. Together, the drusen model(s) of MDs described here provide fundamental insights into the unique biology of maculopathies affecting the RPE-ECM interface.

Influenza A Virus Protein PA-X Contributes to Viral Growth and Suppression of the Host Antiviral and Immune Responses.

UNLABELLED: Influenza virus infection causes global inhibition of host protein synthesis in infected cells. This host shutoff is thought to allow viruses to escape from the host antiviral response, which restricts virus replication and spread. Although the mechanism of host shutoff is unclear, a novel viral protein expressed by ribosomal frameshifting, PA-X, was found to play a major role in influenza virus-induced host shutoff. However, little is known about the impact of PA-X expression on currently circulating influenza A virus pathogenicity and the host antiviral response. In this study, we rescued a recombinant influenza A virus, A/California/04/09 (H1N1, Cal), containing mutations at the frameshift motif in the polymerase PA gene (Cal PA-XFS). Cal PA-XFS expressed significantly less PA-X than Cal wild type (WT). Cal WT, but not Cal PA-XFS, induced degradation of host ß-actin mRNA and suppressed host protein synthesis, supporting the idea that PA-X induces host shutoff via mRNA decay. Moreover, Cal WT inhibited beta interferon (IFN-ß) expression and replicated more rapidly than Cal PA-XFS in human respiratory cells. Mice infected with Cal PA-XFS had significantly lower levels of viral growth and greater expression of IFN-ß mRNA in their lungs than mice infected with Cal WT. Importantly, more antihemagglutinin and neutralizing antibodies were produced in Cal PA-XFS-infected mice than in Cal WT-infected mice, despite the lower level of virus replication in the lungs. Our data indicate that PA-X of the pandemic H1N1 virus has a strong impact on viral growth and the host innate and acquired immune responses to influenza virus. IMPORTANCE: Virus-induced host protein shutoff is considered to be a major factor allowing viruses to evade innate and acquired immune recognition. We provide evidence that the 2009 H1N1 influenza A virus protein PA-X plays a role in virus replication and inhibition of host antiviral response by means of its host protein synthesis shutoff activity both in vitro and in vivo. We also demonstrated that, while the growth of Cal PA-XFS was attenuated in the lungs of infected animals, this mutant induced a stronger humoral response than Cal WT. Our findings clearly highlight the importance of PA-X in counteracting the host innate and acquired immune responses to influenza virus, an important global pathogen. This work demonstrates that inhibition of PA-X expression in influenza virus vaccine strains may provide a novel way of safely attenuating viral growth while inducing a more robust immune response.

The Role of Occupational Status in the Association Between Job Strain and Ambulatory Blood Pressure During Working and Nonworking Days.

OBJECTIVES: The objectives of this study were to determine whether job strain is more strongly associated with higher ambulatory blood pressure (ABP) among blue-collar workers compared with white-collar workers, to examine whether this pattern generalizes across working and nonworking days and across sex, and to examine whether this pattern is accounted for by psychosocial factors or health behaviors during daily life. METHODS: A total of 480 healthy workers (mean age = 43 years, 53% female) in the Adult Health and Behavior Project-Phase 2 completed ABP monitoring during 3 working days and 1 nonworking day. Job strain was operationalized as high psychological demand (> sample median) combined with low decision latitude (

Biomechanical and organisational stressors and associations with employment withdrawal among pregnant workers: evidence and implications.

The distribution of exposure to biomechanical and organisational job stressors (BOJS) and associations with employment withdrawal (antenatal leave, unemployment) was examined in a case-control study of 1114 pregnant workers in California. We performed descriptive and multivariate logistic and multinomial regression analyses. At pregnancy onset, 57% were exposed to one or more biomechanical stressors, including frequent bending, heavy lifting and prolonged standing. One-third were simultaneously exposed to BOJS. Exposure to biomechanical stressors declined as pregnancy progressed and cessation often (41%) coincided with employment withdrawal (antenatal leave and unemployment). In multivariate modelling, whether we adjusted for or considered organisational stressors as coincident exposures, results showed that pregnant workers exposed to biomechanical stressors had increased employment withdrawal compared to the unexposed. Work schedule accommodations moderate this association. Paid antenatal leave, available to few US women, was an important strategy for mitigating exposure to BOJS. Implications for science and policy are discussed. Practitioner Summary: This case-control study showed that exposure to biomechanical stressors decline throughout pregnancy. Antenatal leave was an important strategy used for mitigating exposure among sampled California women with access to paid benefits. Employment withdrawal among workers exposed to BJOS may be reduced by proactive administrative and engineering efforts applied early in pregnancy.

Miscarriage among flight attendants.

BACKGROUND: Cosmic radiation and circadian disruption are potential reproductive hazards for flight attendants. METHODS: Flight attendants from 3 US airlines in 3 cities were interviewed for pregnancy histories and lifestyle, medical, and occupational covariates. We assessed cosmic radiation and circadian disruption from company records of 2 million individual flights. Using Cox regression models, we compared respondents (1) by levels of flight exposures and (2) to teachers from the same cities, to evaluate whether these exposures were associated with miscarriage. RESULTS: Of 2654 women interviewed (2273 flight attendants and 381 teachers), 958 pregnancies among 764 women met study criteria. A hypothetical pregnant flight attendant with median first-trimester exposures flew 130 hours in 53 flight segments, crossed 34 time zones, and flew 15 hours during her home-base sleep hours (10 pm-8 am), incurring 0.13 mGy absorbed dose (0.36 mSv effective dose) of cosmic radiation. About 2% of flight attendant pregnancies were likely exposed to a solar particle event, but doses varied widely. Analyses suggested that cosmic radiation exposure of 0.1 mGy or more may be associated with increased risk of miscarriage in weeks 9-13 (odds ratio = 1.7 [95% confidence interval = 0.95-3.2]). Risk of a first-trimester miscarriage with 15 hours or more of flying during home-base sleep hours was increased (1.5 [1.1-2.2]), as was risk with high physical job demands (2.5 [1.5-4.2]). Miscarriage risk was not increased among flight attendants compared with teachers. CONCLUSIONS: Miscarriage was associated with flight attendant work during sleep hours and high physical job demands and may be associated with cosmic radiation exposure.

Methods and feasibility of collecting occupational data for a large population-based cohort study in the United States: the reasons for geographic and racial differences in stroke study.

BACKGROUND: Coronary heart disease and stroke are major contributors to preventable mortality. Evidence links work conditions to these diseases; however, occupational data are perceived to be difficult to collect for large population-based cohorts. We report methodological details and the feasibility of conducting an occupational ancillary study for a large U.S. prospective cohort being followed longitudinally for cardiovascular disease and stroke. METHODS: Current and historical occupational information were collected from active participants of the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study. A survey was designed to gather quality occupational data among this national cohort of black and white men and women aged 45 years and older (enrolled 2003-2007). Trained staff conducted Computer-Assisted Telephone Interviews (CATI). After a brief pilot period, interviewers received additional training in the collection of narrative industry and occupation data before administering the survey to remaining cohort members. Trained coders used a computer-assisted coding system to assign U.S. Census codes for industry and occupation. All data were double coded; discrepant codes were independently resolved. RESULTS: Over a 2-year period, 17,648 participants provided consent and completed the occupational survey (87% response rate). A total of 20,427 jobs were assigned Census codes. Inter-rater reliability was 80% for industry and 74% for occupation. Less than 0.5% of the industry and occupation data were uncodable, compared with 12% during the pilot period. Concordance between the current and longest-held jobs was moderately high. The median time to collect employment status plus narrative and descriptive job information by CATI was 1.6 to 2.3 minutes per job. Median time to assign Census codes was 1.3 minutes per rater. CONCLUSIONS: The feasibility of conducting high-quality occupational data collection and coding for a large heterogeneous population-based sample was demonstrated. We found that training for interview staff was important in ensuring that narrative responses for industry and occupation were adequately specified for coding. Estimates of survey administration time and coding from digital records provide an objective basis for planning future studies. The social and environmental conditions of work are important understudied risk factors that can be feasibly integrated into large population-based health studies.

Clinical guidelines for occupational lifting in pregnancy: evidence summary and provisional recommendations.

Empirically based lifting criteria established by the National Institute for Occupational Safety and Health (NIOSH) to reduce the risk of overexertion injuries in the general US working population were evaluated for application to pregnant workers. This report proposes criteria to guide decisions by medical providers about permissible weights for lifting tasks performed at work over the course of an uncomplicated pregnancy. Our evaluation included an extensive review of the literature linking occupational lifting to maternal and fetal health. Although it has been 29 years since the American Medical Association's Council on Scientific Affairs published its report on the Effects of Pregnancy on Work Performance, these guidelines continue to influence clinical decisions and workplace policies. Provisional clinical guidelines derived from the NIOSH lifting criteria that account for recent evidence for maternal and fetal health are presented and aim to improve the standard of care for pregnant workers.

Retirement and cognitive aging in a racially diverse sample of older Americans.

BACKGROUND: Retirement represents a crucial transitional period for many adults with possible consequences for cognitive aging. We examined trajectories of cognitive change before and after retirement in Black and White adults. METHODS: Longitudinal examination of up to 10 years (mean = 7.1 ± 2.2 years) using data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study-a national, longitudinal study of Black and White adults ≥45 years of age. Data were from 2226 members of the REGARDS study who retired around the time when an occupational ancillary survey was administered. Cognitive function was an average of z-scores for tests of verbal fluency, memory, and global function. RESULTS: Cognitive functioning was stable before retirement (Estimate = 0.05, p = 0.322), followed by a significant decline after retirement (Estimate = -0.15, p < 0.001). The decline was particularly pronounced in White (Estimate = -0.19, p < 0.001) compared with Black (Estimate = -0.07, p = 0.077) participants, twice as large in men (Estimate = -0.20, p < 0.001) compared with women (Estimate = -0.11, p < 0.001), highest among White men (Estimate = -0.22, p < 0.001) and lowest in Black women (Estimate = -0.04, p = 0.457). Greater post-retirement cognitive decline was also observed among participants who attended college (Estimate = -0.14, p = 0.016). While greater work complexity (Estimate = 0.92, p < 0.05) and higher income (Estimate = 1.03, p < 0.05) were related to better cognitive function at retirement, neither was significantly related to cognitive change after retirement. CONCLUSION: Cognitive functioning may decline at an accelerated rate immediately post-retirement, more so in White adults and men than Black adults and women. Lifelong structural inequalities including occupational segregation and other social determinants of cognitive health may obscure the role of retirement in cognitive aging.

Job complexity and hazardous working conditions: How do they explain educational gradient in mortality?

Although education's protective effects on health have been well recognized, specific mechanisms through which higher education is associated with better health are still debated. Occupation, although strongly shaped by education, has rarely been examined as a mediating mechanism. Education attainment is patterned by race in the United States, and the same education does not lead to similar occupations for members of different racial/ethnic groups. Therefore, examining the link from education to jobs to mortality can illuminate potential mechanisms that create racial health disparities. Using a large U.S. national cohort of Black and White men and women, we examined if 2 occupational characteristics, substantive complexity of work and hazardous working conditions, mediate the effect of education on mortality. Data on occupation were collected between 2011 and 2013, and mortality follow-up data up to March 2018 were included in this analysis. The race- and gender-stratified analyses showed that among White men, the association between higher education and lower mortality was mediated by lower hazard on the job. Among Black men and White women, higher complexity of work explained the association between higher education and lower mortality. Among Black women, neither job characteristic mediated the association. These results suggest that occupational characteristics help explain health inequalities not only by education but also by race and gender. Investigating occupation explicitly in the causal chain of health disparities will help us better understand the mechanism of and potential solutions for health inequalities. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Racial differences in sleep duration intersect with sex, socioeconomic status, and U.S. geographic region: The REGARDS study.

OBJECTIVES: Short and long sleep duration are associated with poor health outcomes and are most prevalent among racial/ethnic minorities. Few studies have investigated the intersection of other sociodemographic characteristics with race/ethnicity on sleep duration prevalence. DESIGN: Longitudinal retrospective analysis of continental U.S. cohort, the REasons for Geographic And Racial Differences in Stroke (REGARDS) PARTICIPANTS: Black (n = 7,547) and white (n = 12,341) adults, 56% women, ≥45 years MEASUREMENTS: At baseline (2003-07), participants reported age, sex, race, education, income, marital status, U.S. region, and employment status. The weighted average of reported sleep duration on weekdays and weekends, assessed at follow-up (2008-10), was categorized as <6, 6.0-6.99, 7.0-7.99 [reference], 8.0-8.99, and ≥9 h. Multinomial logistic regression models examined the independent and multivariable associations of sociodemographic factors with sleep duration. Interactions terms between race with education, income, region, and sex were examined. RESULTS: Average sleep duration was 7.0 h (SD=1.3). Prevalence of short (<6 h) and long (≥9 h) sleep duration was 11.4% (n = 2,260) and 7.0% (n = 1,395), respectively. In the multivariable model, interactions terms race*income, race*sex, and race*region were significant (P < .05). Relative to white adults, black adults, were most likely to have short sleep duration. The magnitude of that likelihood increased across greater levels of household income, but with greatest odds among black adults living outside of the Southeast and Appalachian United States, particularly for men (≥$75k; black men OR = 5.47, 95%CI: 3.94,7.54; black women OR = 4.28, 95%CI: 3.08, 5.96). CONCLUSIONS: Race in the context of socioeconomic, sex, and regional factors should be examined as key modifiers of sleep duration.

Occupation as socioeconomic status or environmental exposure? A survey of practice among population-based cardiovascular studies in the United States.

Decisions about how occupation is used in epidemiologic research can affect conclusions about the importance of socioeconomic and environmental factors in explaining disparities for outcomes such as cardiovascular disease. A review of practices in the collection and use of occupational data was conducted among population-based cardiovascular studies in the United States. Studies were identified for review from the National Heart, Lung, and Blood Institute website and the biomedical database, Computer Retrieval of Information on Scientific Projects, by use of selected criteria. Data collection instruments and study publications were retrieved and reviewed for 30 of 33 studies (91%). Most of the studies (83%) collected at least descriptive occupational data, and more than half (60%) collected data on workplace hazards. The reviewed studies produced 80 publications in which occupational data were used in analyses, most often as an indicator of socioeconomic status. Authors rarely acknowledged known conceptual and empirical links among socioeconomic status, employment stability, and working conditions. Underutilization of data on workplace conditions was found. Existing data could be used more effectively to examine the contribution of work-related social and environmental conditions to the development of modifiable cardiovascular disease through multiple pathways.

The Role of Occupation in Explaining Cognitive Functioning in Later Life: Education and Occupational Complexity in a U.S. National Sample of Black and White Men and Women.

OBJECTIVE: Positive associations between education and late-life cognition have been widely reported. This study examines whether occupational complexity mediates the relationship between education and late-life cognition, and whether the magnitude of mediation differs by race, gender, or education level. METHODS: Data were from a population-based cohort of non-Hispanic Blacks and Whites aged ≥45 years (n = 7,357). Education was categorized as less than high school, high school, some college, and college or higher. Using linear regression, we estimated the direct effect of each successive increase in education on cognitive functioning and indirect effects via substantive complexity of work. RESULTS: Occupational complexity significantly mediated 11%-22% of the cognitive gain associated with higher levels of education. The pattern of mediation varied between White men and all other race-gender groups: among White men, the higher the education, the greater the mediation effect by occupational complexity. Among Black men and women of both races, the higher the education, the smaller the mediation effect. DISCUSSION: Higher levels of education may provide opportunity for intellectually engaging environments throughout adulthood in the form of complex work, which may protect late-life cognition. However, this protective effect of occupational complexity may not occur equally across race-gender subgroups.

Environmental stress impairs photoreceptor outer segment (POS) phagocytosis and degradation and induces autofluorescent material accumulation in hiPSC-RPE cells.

Retinal pigment epithelium (RPE) cell dysfunction is central to the pathogenesis of age-related macular degeneration (AMD), a leading cause of adult blindness. Aging, the single biggest risk factor for AMD development, favors increase in RPE autofluorescent material due to accumulation of POS-digestion by-products through lysosomal dysfunction and impaired POS degradation. Apart from aging, environmental agents affect lysosomal function in multiple model systems and are implicated in AMD. Iron (Fe) overload and cigarette smoke exposure are the two environmental factors that are known to affect the lysosomal pathway and impact RPE cell health. However, the impact of Fe and cigarette smoke, on POS processing and its consequence for autofluorescent material accumulation in human RPE cells are yet to be established. Human induced pluripotent stem cell (hiPSC)-derived RPE, which phagocytoses and degrades POS in culture and can be derived from control individuals (no history/susceptibility for retinal disease), provides a model system to investigate the singular effect of excess Fe and/or cigarette smoke on POS processing by RPE cells. Using at least three distinct control hiPSC lines, we show that, compared to untreated hiPSC-RPE cells, POS uptake is reduced in both Fe (ferric ammonium citrate or FAC) and FAC + CSE (cigarette smoke extract)-treated hiPSC-RPE cells. Furthermore, exposure of hiPSC-RPE cultures to FAC + CSE leads to reduced levels of active cathepsin-D (CTSD), a lysosomal enzyme involved in POS processing, and causes delayed degradation of POS. Notably, delayed degradation of POS over time (2 weeks) in hiPSC-RPE cells exposed to Fe and CSE was sufficient to increase autofluorescent material build-up in these cells. Given that inefficient POS processing-mediated autofluorescent material accumulation in RPE cells has already been linked to AMD development, our results implicate a causative role of environmental agents, like Fe and cigarette smoke, in AMD.

Prevalence of workplace discrimination and mistreatment in a national sample of older U.S. workers: The REGARDS cohort study.

Although workplace discrimination and mistreatment (WDM) has recently drawn widespread media attention, our understanding of the prevalence of these phenomena remains limited. In the current study, we generated national prevalence estimates of WDM from a community-based cohort of employed black and white men and women aged ≥48 years. Measures of WDM in the current job were obtained by computer-assisted telephone interview (2011-2013) involving dichotomous responses (yes or no) to five questions and deriving a composite measure of discrimination (yes to at least one). Prevalence estimates and age- and region-adjusted prevalence ratios were derived with use of SUDAAN software to account for the complex sample design. Analyses were stratified by race and sex subgroups. This sample represents over 40 million U.S. workers aged ≥48 years. The prevalence of workplace discrimination ranged from a high of 25% for black women to a low of 11% for white men. Blacks reported a 60% higher rate of discrimination compared to whites; women reported a 53% higher prevalence of discrimination, compared with men. The prevalence of workplace mistreatment ranged from 13% for black women to 8% for white men. Women reported a 52% higher prevalence of mistreatment compared to men, while differences by race were not significant. Mistreatment was 4-8 times more prevalent among those reporting discrimination than among those reporting none. Subgroup differences in mistreatment were confined to the wage-employed. Findings suggest that middle age and older wage-employed blacks and women experience the highest prevalence of WDM; moreover, discrimination is strongly associated with mistreatment. This study contributes to our understanding of at-risk segments of the U.S. labor market and the need for targeted interventions to reduce WDM.

Characterization of Human iPSC-RPE on a Prosthetic Bruch's Membrane Manufactured From Silk Fibroin.

Purpose: RPE cell transplantation as a potential treatment for AMD has been extensively investigated; however, in AMD, ultrastructural damage affects both the RPE and its underlying matrix support, the Bruch's membrane (BrM). An RPE monolayer supported by a surrogate scaffold could thus provide a more effective approach to cell-based therapy for AMD. Toward this goal, we aimed to establish a functional human induced pluripotent stem cell-derived (hiPSC)-RPE monolayer on a Bombyx mori silk fibroin (BMSF) scaffold. Methods: RPE differentiated from five distinct hiPSC lines were cultured on BMSF membrane coated with extracellular matrix (ECM, COL1), and either regular tissue culture plastic or Transwell coated with ECM (LAM-TCP). Morphologic, gene and protein expression, and functional characteristics of the hiPSC-RPE cultured on different membranes were compared in longitudinal experiments spanning 1 day to ≥3 months. Results: The hiPSC-RPE monolayers on ECM-coated BMSF and TCP could be maintained in culture for ≥3 months and displayed RPE-characteristic morphology, pigmentation, polarity, and expression of RPE signature genes and proteins. Furthermore, hiPSC-RPE on both ECM-coated BMSF and TCP displayed robust expression and secretion of several basement membrane proteins. Importantly, hiPSC-RPE cells on COL1-BMSF and LAM-TCP showed similar efficacy in the phagocytosis and degradation of photoreceptor outer segments. Conclusions: A biomaterial scaffold manufactured from silk fibroin supports the maturation and long-term survival of a functional hiPSC-RPE monolayer. This has significant implications for both in vitro disease modeling and in vivo cell replacement therapy.

Physical and Organizational Job Stressors in Pregnancy and Associations With Primary Cesarean Deliveries.

OBJECTIVE: The aim of this study was to assess the relationship between exposure to physical and organizational job stressors during pregnancy and cesarean delivery. METHODS: We sampled 580 employed women in California who participated in a nested population-based case-control study of birth outcomes. Adjusted multivariate regression analyses estimated associations between heavy lifting, frequent bending, high noise, extreme temperature, prolonged standing and organizational stressors (shift work, inflexible schedules, effort-reward ratio), and primary cesarean (vs vaginal) delivery, controlling for covariates. RESULTS: Women occupationally exposed had higher odds of cesarean. Those exposed to daily manual lifting more than 15 pounds [adjusted odds ratio = 2.54; 95% confidence interval (95% CI) 1.21 to 5.32] and at least four physical job stressors (adjusted odds ratio = 3.49; 95% CI 1.21 to 10.09) had significantly elevated odds of cesarean delivery. Exposed morbid women experienced greater risk; risk was lower among those with schedule flexibility. CONCLUSION: Associations were found between modifiable exposure to physical job stressors during pregnancy and cesarean delivery.