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Hispanic/Latinos in the U.S. bear an excess burden of type 2 diabetes (T2D) . In type 1 diabetes and insulin-treated T2D, continuous glucose monitoring (CGM) is an established technology to guide therapy, yet CGM use and studies are rare in people with/at-risk of non-insulin treated T2D and ethnic minorities. In this study, CGM was used to assess breakfast glycemic response in free-living adults with or at risk of non-insulin treated T2D. For 9-14 days, 35 Hispanic/Latino adults (28 female, median HbA1c 6.0% [IQR 5.5%, 6.8%]) wore blinded Abbott Freestyle Libre CGM and logged food via the MyFitnessPal app. Start and peak time of glycemic responses associated with a glucose rise ≥20 mg/dL between 5-a.m. were manually annotated. Median variation between annotated and logged time was 39 [20, 78] minutes. Participants were stratified using HbA1c into at risk for T2D, pre-T2D, and T2D. Median starting glucose (SG) ; maximum glucose rise (Max GR) ; time-to-peak (TTP) ; and incremental area under the curve over 2, 3, and 4 hours (iAUC2hr, iAUC3hr, iAUC4hr) were computed (Table 1) . The T2D group had significantly higher post-breakfast glycemic measures than the at-risk group for all measures. The T2D group also had higher measures than pre-T2D for all but Max GR. Increases in response from at-risk to pre- to T2D in Hispanic/Latino adults suggest post-breakfast glycemic profiles may potentially be used to monitor diabetes progression. Disclosure A.Pai: Employee; Apple. R.F.Santiago: Research Support; Abbott. W.C.Bevier: Research Support; Abbott Diabetes. N.M.Glantz: Research Support; Abbott. S.Barua: None. A.Sabharwal: None. D.Kerr: Advisory Panel; Abbott Diabetes, Novo Nordisk A/S, Sanofi, Consultant; Evidation Health, Research Support; Novo Nordisk A/S, Stock/Shareholder; Glooko, Inc., Hi.Health. Funding Elsevier Foundation

Background Approximately 2.38 million janitors are employed in the U.S. While high physical workload may explain a lost-work days rate 2.7 times greater than other occupations, little is known about the association between janitors' physical workload, mental workload, and stress. Objective The objective of this study was to assess the associations between physical (ergonomic) and mental workload exposures and stress outcomes among janitors. Methods Questionnaire data, focused on ergonomic workload, mental workload and stress, were collected from Minnesota janitors for a one-year period. Physical workload was assessed with Borg Scales and Rapid Entire Body Assessments (REBA). Mental workload assessment utilized the NASA Task Load Index (TLX). Stress assessments utilized single-item ordinal stress scale (SISS) and Perceived Stress Scale-4 (PSS-4) measures. Descriptive and multivariable analyses, including bias adjustment, were conducted. Results Odds ratios (OR) and 95% confidence intervals (CI) for ergonomic workload (task frequency) effects on SISS were: REBA (1.18 OR, 1.02-1.37 CI); Borg (1.25 OR, 1.00-1.56 CI); combined REBA and Borg (1.10 OR, 1.01-1.20 CI). Mental workload was associated with higher PSS-4 levels (0.15 Mean Difference, 0.08-0.22 CI) and a 3% increased risk for each one-unit increase in the SISS scale (1.03 OR, 1.02-1.05 CI). Conclusions This research demonstrated a moderate effect of physical and mental workloads on stress among janitors.

Reducing or eliminating persistent disparities in lung cancer incidence and survival has been challenging because our current understanding of lung cancer biology is derived primarily from populations of European descent. Here we show results from a targeted sequencing panel using NCI-MD Case Control Study patient samples and reveal a significantly higher prevalence of PTPRT and JAK2 mutations in lung adenocarcinomas among African Americans compared with European Americans. This increase in mutation frequency was validated with independent WES data from the NCI-MD Case Control Study and TCGA. We find that patients carrying these mutations have a concomitant increase in IL-6/STAT3 signaling and miR-21 expression. Together, these findings suggest the identification of these potentially actionable mutations could have clinical significance for targeted therapy and the enrollment of minority populations in clinical trials., Lung cancer etiology has largely been studied in homogenous populations of European descent. Here, targeted sequencing in African American lung adenocarcinomas finds significantly higher prevalence of PTPRTand JAK2 mutations, validated independently by whole exome sequencing, highlighting potentially clinically actionable mutations in this population.

Background: Black cigarette smokers experience a disproportionate burden of non-small cell lung cancer (NSCLC) compared to other racial and ethnic groups, despite starting to smoke later in life, smoking less frequently, and smoking fewer cigarettes per day compared with White smokers. Research has shown that these disparities in NSCLC are wider in rural areas. Objective: To examine differences in smoking behaviors between Black and White individuals living in non-metropolitan areas and metropolitan areas. Methods: Using harmonized data from the Tobacco Use Supplement to the Current Population Survey (TUS-CPS) years 2010–2011, 2014–2015, and 2018–2019, we compared smoking behaviors between Black and White current and former smokers by metropolitan status (i.e., whether an individual lives in a densely populated area or not) and by both metropolitan status and sex. Results: Smoking prevalence was higher among White participants living in non-metropolitan versus Black participants. Further, in non-metropolitan areas, Black individuals reported smoking fewer cigarettes per day, fewer years of smoking, and a later age of initiation compared to White individuals. Additionally, Black individuals, especially men, were more likely than White individuals to be current non-daily smokers. Conclusions: Our findings show that Black individuals living in non-metropolitan areas do not, in aggregate, have more cigarette smoking exposure relative to White individuals. Additional research is needed to further understand smoking-related exposures and other factors that may contribute to lung cancer disparities, especially in non-metropolitan areas.

Determine injury incidence and severity and potential associated risk factors for injury, among janitors.Questionnaires were disseminated to 1200 full-time janitors in the Service Employees International Union (SEIU) Local 26 union; 390 responded and provided information on their injury experiences and exposures, based on personal characteristics and work-related activities. Multivariable analyses, including bias adjustment, were implemented using directed acyclic graphs to determine potential risk.Among the janitors, 34% reported experiencing at least one injury; 16% of cases resulted in hospital admittance. Significantly increased risks were identified for age, ethnicity, shift start time, and physician-diagnosed depression.Knowledge of specific risk and protective factors is valuable, and can serve as a basis for further in-depth studies and inform the development of targeted intervention strategies aimed to reduce occurrence of these injuries.

Background This study was designed to identify potential effects of workload and sleep on injury occurrence. Methods Questionnaires were disseminated to janitors in the SEIU Local 26 union; 390 responded and provided information on workload, sleep, and injury outcomes. Quantitative measurements of workload and sleep were collected via FitBit devices from a subset of 58 janitors. Regression techniques were implemented to determine risk. Results Thirty-seven percent reported increased workload over the study period Adjusted analyses indicated a significant effect of change in workload (RR: 1.94; 95%CI: 1.40-2.70) and sleep hours (RR: 2.21; 95%CI: 1.33-3.66) on occupational injury. Among those with sleep disturbances, injury risk was greater for those with less than five, versus more than five, days of moderate to vigorous physical activity; RR: 2.77; 95%CI: 1.16-6.59). Conclusions Increased workload and sleep disturbances increased the risk of injury, suggesting employers should address these factors to mitigate occupational injuries.

Lung cancer incidence is higher among African Americans (AAs) compared with European Americans (EAs) in the United States, especially among men. Although significant progress has been made profiling the genomic makeup of lung cancer in EAs, AAs continue to be underrepresented. Our objective was to chart the genome-wide landscape of somatic mutations in lung cancer tumors from AAs.In this study, we used the whole-exome sequencing of 82 tumor and noninvolved tissue pairs from AAs. Patients were selected from an ongoing case-control study conducted by the National Cancer Institute and the University of Maryland.Among all samples, we identified 178 significantly mutated genes (p0.05), five of which passed the threshold for false discovery rate (p0.1). In lung adenocarcinoma (LUAD) tumors, mutation rates in STK11 (p = 0.05) and RB1 (p = 0.008) were significantly higher in AA LUAD tumors (25% and 13%, respectively) compared with The Cancer Genome Atlas EA samples (14% and 4%, respectively). In squamous cell carcinomas, mutation rates in STK11 (p = 0.002) were significantly higher among AA (8%) than EA tumors from The Cancer Genome Atlas (1%). Integrated somatic mutation data with CIBERSORT (Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts) data analysis revealed LUAD tumors from AAs carrying STK11 mutations have decreased interferon signaling.Although a considerable degree of the somatic mutation landscape is shared between EAs and AAs, discrete differences in mutation frequency in potentially important oncogenes and tumor suppressors exist. A better understanding of the molecular basis of lung cancer in AA patients and leveraging this information to guide clinical interventions may help reduce disparities.

Reducing or eliminating persistent disparities in lung cancer incidence and survival has been challenging because our current understanding of lung cancer biology is derived primarily from populations of European descent. Here we show results from a targeted sequencing panel using NCI-MD Case Control Study patient samples and reveal a significantly higher prevalence of PTPRT and JAK2 mutations in lung adenocarcinomas among African Americans compared with European Americans. This increase in mutation frequency was validated with independent WES data from the NCI-MD Case Control Study and TCGA. We find that patients carrying these mutations have a concomitant increase in IL-6/STAT3 signaling and miR-21 expression. Together, these findings suggest the identification of these potentially actionable mutations could have clinical significance for targeted therapy and the enrollment of minority populations in clinical trials.

Approximately 2.4 million janitors work in the United States. High physical workload may explain a lost-work days rate 2.7 times that of other occupations. Information is limited about non-physical workload factors for janitors and their relations to injuries. For this retrospective cross-sectional study, specially designed, pre-tested questionnaires were distributed to full-time janitor members of a union for two six-month sequential intervals. Questions addressed mental workload (modified NASA Task Load Index), job satisfaction (Andrews and Withey Job Satisfaction Scale), stress (Perceived Stress Scale-4 [PSS-4], and the Single Item Stress Scale [SISS]), physical fitness, and occupational injury experiences. Descriptive and multivariable analyses, with bias adjustment, were conducted. A decreased risk of injury was associated with increased job satisfaction (expressed as a risk ratio (RR): 0.91 [95% confidence interval (CI): 0.83, 0.97]) and increased physical fitness (0.89, [0.83, 0.96]). A highly suggestive increased risk of injury was associated with increased mental workload (1.07, [1.00, 1.15]).

Methylation-based biomarkers can provide molecular insight on the contribution of ancestry and histology to lung tumor biology. Loss of global methylation is a benchmark of aging and a signal of declining biological maintenance. In addition to aging, global loss of methylation occurs in response to some cancer-promoting exposures, including tobacco use. Reduced levels of global DNA methylation are associated with increased risk of several cancers, including lung. In lung tumors, global DNA hypomethylation is often associated with a more aggressive diseases and shorter survival time. Several studies have identified population-level differences in global methylation present at birth. Additionally, gender and ancestry influence DNA methylation age (DNAm) and may predispose some individuals to accelerated aging. We hypothesized that differences in global hypomethylation and accelerated aging may contribute to differences in lung tumor biology by genetic ancestry. Therefore, we investigated methylome differences between European Americans (EA) and African Americans (AA) from the NCI-Maryland Case Control Study, which is overrepresented with AA patients (~40%) from the Baltimore area. We assessed lung tumor and paired non-involved adjacent tissue (NAT) methylation (n = 77 EA, n = 39 AA) using the Illumina EPIC methylation array. We used the Repetitive Element Methylation Prediction (REMP) package in R to identify roughly 20,000 predicted LINE-1 CpG's. We observed significantly decreased LINE-1 methylation in tumor tissue compared with NAT in both AA and EA. Additionally, among tumor samples we observed significantly decreased LINE-1 methylation in AA LUSC samples compared to EA LUSC, with only modest differences between AA LUAD and EA LUAD. In addition to decreased levels, LINE-1 methylation in AA LUSC tumors also had the greatest heterogeneity within CpG's of the same sample and between other AA LUSC samples. We observed accelerated aging (increased DNAm relative to chronological age) in 57/67 EA NAT samples and 28/38 AA NAT samples with no significant differences in age acceleration between ancestry or histology. Our results show global hypomethylation of LINE-1 is a distinctive feature of LUSC in AA compared to EA, which is consistent with the enhanced genomic instability observed in AA LUSC relative to EA LUSC. We also observed accelerated aging in the vast majority of the NAT samples, which may implicate accelerated age with lung cancer risk. Future analysis will work towards completing a comprehensive analysis of the epigenetic landscape of lung cancer in AA and EA patients. We plan to study the relationship between global hypomethylation and genetic variants, smoking behaviors, and patient survival. Citation Format: Emily L. Rossi, Isaac Zhao, Rony F. Arauz, Adriana Zingone, Bríd M. Ryan. The effects of ancestry and histology on the lung tumor methylome [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1265.

Lung cancer incidence is higher among African Americans (AAs) compared with European Americans (EAs) and Asian Americans (AsA) in the United States. Although there has been a significant reduction in cigarette smoking, racial disparities in tobacco use and lung cancer risk persist in the US. While data exists suggesting that African Americans have a higher risk of lung cancer at lower cigs per day, data independently linking each measure of smoking exposures and lung cancer risk among AAs compared with EAs and AsA are limited. We conducted a pooled case-control study of 19,965 cases and 331,478 controls from 10 population-based case-control and cohort studies from the US within the International Lung Cancer Consortium (ILCCO). We used logistic regression models to examine associations between several smoking dimensions (status, age at initiation, duration, intensity, pack-years and cessation) and lung cancer risk. Overall, the magnitude of the relationship between each dimension of smoking exposure and lung cancer risk was higher among AAs. AAs who were light smokers had an increased odds of lung cancer compared with EAs and AsA (1-10 cigs/day: AA OR = 5.66, 95% CI: 4.73-6.76; EA OR = 2.86, 95% CI: 2.58-3.17; AsA OR = 2.82, 95% CI: 2.35-3.39) after adjustment for age, gender and study center. Similar trends were observed for age at smoking initiation (age at smoking initiation 25+ years: AA OR = 7.54, 95% CI: 6.35-8.96; EA OR = 5.49, 95% CI: 4.99-6.03; AsA OR = 4.00, 95% CI: 3.44-4.66). This study suggests that racial and ethnic differences between individual dimensions of smoking exposure and lung cancer exist. In general, at equal levels of exposure, AAs seem to be more susceptible than EAs and AsA. Future work will assess if these findings hold following adjustment for population specific smoking patterns. Citation Format: Rony F. Arauz, Neal D. Freedman, Maki Inoue-Choi, Ann G. Schwartz, Brid M. Ryan. Racial differences in the relationship between dimensions of smoking exposure and lung cancer risk: A pooled analysis from the International Lung Cancer Consortium Study [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A111.

Introduction : The goal of this study was to evaluate and improve janitors' knowledge of workers' rights and responsibilities for assessing and reporting work-related injuries, and to determine the barriers for reporting occupational injuries. Methods : Questionnaires, designed to collect data retrospectively for two, sequential six-month periods, were disseminated to 1200 full-time unionized janitors in the Twin Cities. Immediately following the baseline questionnaire administration, a randomly selected sub-group of janitors (~ 600) received information on workers' rights and responsibilities for reporting injuries; six-months later a questionnaire comparable to the baseline questionnaire was disseminated to the 1200 janitors. Analyses included basic descriptive analyses and identification of potential differences in proportions of job-specific reporting barriers pre-post-intervention. Results : Among the participating janitors (n = 390), approximately half (53%) were initially unsure of what an OSHA 300 Log was; 56% reported not knowing what workers' compensation was. At baseline, in both intervention and non-intervention groups, approximately 25% reported having a perceived barrier to reporting an injury to their employer. Reported barriers included “fear,” “reporting takes too long,” “being unsure of the reporting process,” and an “understanding that injuries are a part of the job.” At follow-up, among the intervention group, there was an important reduction (24%–12%) in having a perceived barrier for reporting a work-related injury. Conclusions : A majority of janitors lacked knowledge and awareness of OSHA injury reporting and Workers' Compensation. In order to improve reporting, it is essential to educate employees on OSHA and Workers' Compensation and inform janitors of the injury reporting process through training. Practical applications : Future intervention efforts must focus on the specific barriers for reporting occupational injuries and be tailored specifically to the janitor population. To reduce underreporting of injuries, they must be encouraged to report their occupational injuries. Barriers to reporting these injuries must be eliminated.

There is convincing evidence that heat-shock proteins (HSP) are upregulated by stress conditions in insects; however, the relative contribution of each HSP gene to the heat-shock response remains unclear. Here we considered the whitefly Bemisia tabaci (MEAM 1), a phloem feeder and invasive species whose molecular stress response is an important mechanism for overcoming heat stress. We assessed the expression of the hsp23, 40, 70 and 90 genes at the mRNA level when submitted to heat shocks of 40 and 44°C/1h (control at 25°C). For this, we evaluated a set of available and suitable reference genes in order to perform data normalization using the real-time polymerase chain reaction (qRT-PCR) technique, and then confirmed the production of HSP70 protein based on Western blot. Results were compared with the hardening capacity of B. tabaci, measured by fitness components as a response to heat shocks, using 40°C as the induction temperature. Three of the four genes (hsp23, 70 and 90) were upregulated by heat stress at mRNA, showing differential expression patterns. Hsp70 expression was confirmed at the protein level. Hardening significantly increased fitness following heat stress, suggesting that HSPs may contribute to hardening capacity in B. tabaci. Potential role of each gene in the heat-shock response for whiteflies is discussed.

Background Occupational exposure to airborne silica, dust containing silica (total dust), and dust without silica (mostly iron oxide) have been known to cause cardio-respiratory disease. However, with dust exposure in general, disease detection usually occurs in advanced stages of the disease process, in part due to the lack of sensitivity of current diagnostic tools that would allow for earlier detection of the disease. Methods Using a multiplexed bead-based assay, we measured plasma levels of 11 immune/inflammation markers in a cross-sectional study of 134 current workers employed in various operations in mining and processing of taconite (a low grade iron ore). These are markers previously demonstrated to be related to silica exposure and/or restrictive/obstructive lung disease in other settings. We used linear regression models to examine the associations between quartiles of silica, total dust, and dust without silica with levels of markers adjusting for age, BMI, gender, and smoking. Results In adjusted models, of the 11 markers selected, C-reactive protein (CRP) had the strongest association and showed a graded response across quartiles of silica. Total dust and dust without silica had little association with these markers. Conclusions This study suggests that exposure to silica, total dust, and dust without silica may be associated with alterations in CRP. Total dust and dust containing iron oxide, in general, do not demonstrate associations with other markers in our study. Further research is needed to understand the potential utility of CRP as a marker linking occupational exposures and health outcomes in taconite workers.

A Minnesota union identified to researchers at the University of Minnesota a concern relevant to a possible relation between their daily workload and outcome of occupational injuries among a population of janitors.To assess if the ergonomic workload is related to injuries among janitors.Following an initial group discussion among janitors, which identified common and hazardous tasks potentially leading to occupational injuries, a questionnaire was developed, pre-tested, and distributed to the janitors. Questions addressed various exposures, including workload, and comprehensive information regarding injury occurrence over two six-month sequential periods (May 2016-October 2016, November 2016-April 2017). Quantitative ergonomic analyses were performed on a sub-group of janitors (n = 30); these included data collection to identify Borg Perceived Exertion (Borg) and Rapid Entire Body Assessment (REBA) scores. Descriptive, multivariable with bias adjustment analyses were conducted on the resulting data.Eight tasks were found to be common for janitors. All average REBA scores for the tasks were identified in the high-risk category. The task of repeatedly emptying small trash cans (25lb) was significantly related to injuries. Average Borg scores fell between the very light perceived exertion and somewhat difficult perceived exertion categories. Multivariable regression analyses indicated that age-sex-standardized ergonomic workload, measured by task frequencies and REBA or Borg scores, was positively related to injury occurrence.Standardized ergonomic workload was positively related to injury occurrence. This information serves as a basis for further research and potential intervention efforts.

Objective To examine the association between exposure to airborne iron and pleural disease among Minnesota taconite mining workers. Methods The goal of this study is to assess the association between exposure to airborne iron concentrations and pleural abnormalities in 1176 current and former workers employed in various operations in mining and processing of taconite (a low grade iron ore). Pleural abnormality, consistent with pneumoconiosis, was identified by consensus of two certified B-readers based on a single radiograph of the taconite workers. The workers’ cumulative exposure to airborne iron was estimated using 679 present-day and 17,083 historical exposure measurements along with area measurements that were combined with the workers’ employment histories. Cumulative exposures to respirable silica (RS) and elongated mineral particles (EMP) were also estimated using present-day and historical measurements. Logistic regression was used to estimate associations between iron exposure and pleural abnormalities adjusting for possible confounders (EMP exposure, smoking status). Results Of the 1,176 participants 197 had pleural abnormalities. The averaged cumulative exposures to iron, RS, and EMP in the pleural abnormalities group were significantly higher than those in pleural normal group (Iron: 2.02 (mg/m³) × year vs 1.71 (mg/m³) × year; RS: 1.21 (mg/m³) × year vs 1.08 (mg/m³) × year; EMP: 3.9 (EMP/cc) × year vs 2.8 (EMP/cc) × year). The crude OR for Iron exposure was 1.21 (95% CI: 1.07 to 1.36) and 1.12 (95% CI: 0.98 to 1.27) after adjusting for EMP exposure, age and BMI. Conclusions This study provides modest evidence that Iron exposure may play a role in the development of the pleural disease among taconite workers. Given the correlated multiple exposures in the taconite mine, the joint effect of Iron and EMP exposure warrants future investigation.

Holoprosencephaly (HPE), the most common malformation of the human forebrain, may arise due to interacting genetic and environmental factors. To date, at least 12 contributory genes have been identified. Fibroblast growth factor 8 (Fgf8) belongs to the FGF family of genes expressed in several developmental signaling centers, including the anterior neural ridge, which is implicated in midline anomalies in mice. In humans, FGF8 mutations have been previously reported in facial clefting and in hypogonadotropic hypogonadism, but have not been reported in patients with HPE. We screened 360 probands with HPE for sequence variations in FGF8 using High Resolution DNA Melting (HRM) and sequenced all identified variations. Here we describe a total of 8 sequence variations in HPE patients, including a putative loss-of-function mutation in 3 members of a family with variable forms of classic HPE, and relate these findings to the phenotypes seen in other conditions.

Background Although migrant and seasonal farmworkers are highly vulnerable to ambient heat because of their working conditions, heat effects in this population have been rarely studied. Objectives We estimated effects of heat on mean daily counts of clinic visits among migrant and seasonal farmworkers by taking advantage of a unique longitudinal medical records database in the USA. Methods We compiled a daily weather and clinic visit data set based on data from a health centre in Colorado for the summer of 2013. A total of 14 481 patients were included in our analysis, including 150 migrant farmworkers and 231 seasonal farmworkers with an average of 3 and 4 visits per day. We used Poisson regression to estimate the associations between heat and daily all-cause or cardiovascular-specific clinic visits among migrant or seasonal farmworkers or other stratified patients. We defined heat effects as the percentage difference in average daily counts of clinic visits, comparing 90–50th centiles of daily mean apparent temperature, a composite index accounting for both temperature and humidity. We conducted a sensitivity analysis to evaluate the impact of adjustment for ozone levels and different heat definitions. Results Estimates of heat effects on average daily clinic visits among migrant farmworkers were positive (88.0%, 95% CI: 26.2% to 180.0%). We did not observe statistically significant associations between heat and clinic visits among other stratified groups. Conclusions Our study appears to be the first to link heat effects with clinic data among migrant and seasonal farmworkers. This research suggests possible significant impact of heat on migrant farmworkers and provides justifications for further studies.