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There is currently no gene expression assay that can assess if premalignant lesions will develop into invasive breast cancer. This study sought to identify biomarkers for selecting patients with a high potential for developing invasive carcinoma in the breast with normal histology, benign lesions, or premalignant lesions. A set of 26-gene mRNA expression profiles were used to identify invasive ductal carcinomas from histologically normal tissue and benign lesions and to select those with a higher potential for future cancer development (ADHC) in the breast associated with atypical ductal hyperplasia (ADH). The expression-defined model achieved an overall accuracy of 94.05% (AUC = 0.96) in classifying invasive ductal carcinomas from histologically normal tissue and benign lesions (n = 185). This gene signature classified cancer development in ADH tissues with an overall accuracy of 100% (n = 8). The mRNA expression patterns of these 26 genes were validated using RT-PCR analyses of independent tissue samples (n = 77) and blood samples (n = 48). The protein expression of PBX2 and RAD52 assessed with immunohistochemistry were prognostic of breast cancer survival outcomes. This signature provided significant prognostic stratification in The Cancer Genome Atlas breast cancer patients (n = 1100), as well as basal-like and luminal A subtypes, and was associated with distinct immune infiltration and activities. The mRNA and protein expression of the 26 genes was associated with sensitivity or resistance to 18 NCCN-recommended drugs for treating breast cancer. Eleven genes had significant proliferative potential in CRISPR-Cas9/RNAi screening. Based on this gene expression signature, the VEGFR inhibitor ZM-306416 was discovered as a new drug for treating breast cancer.

Appalachia’s health outcomes are inextricably linked to its political and environmental development. Many former lumber yards and coal towns are now ageing communities with diminished environments and few opportunities for employment. ARC Appalachia has faced deforestation, widescale fires, coal-related pollution and water contamination as a direct result of its courtship of powerful (yet environmentally destructive) industries. Further, its historic reliance on a single industry (first timber, and then coal) leaves communities vulnerable to labor market restructuring. What are communities to do in the face of rising pressure for economic diversification when they have little infrastracture with which to attract external investors? This chapter tackles this and other questions, arguing that by combining prudent environmental planning with long-term regional investment, Appalachia can achieve sustainable, economic security. However, doing so will require a fundamental paradigm shift away from short-term gains, toward future-oriented sustainable development.

Gender-age specific linear statistical models were fitted to analyze gender-based differences in serum concentrations of PFOA, PFNA, PFHxS, and PFOS for US adults and adolescents (N = 17,932) and children age12 years (N = 637) using nationally representative data for US for 2003-2018. Around the age of about 11-12 years for PFOS, PFNA, and PFNA, and around 15 years for PFOA, females begin to have reliably lower serum PFAS than males. This divergence is maximized around the ages of about 35 to 40 years for the alkylate compounds PFOA and PFNA, and from around 24-52 years for the sulfonate compounds PFOS and PFHxS. For example, for PFOS, gender divergence was 1.15 ng/mL at age 15, compared to 5.6 ng/mL at the age of 37 years. Uniquely, PFOS remained lower in females in most years after age 56, a contrast to the convergence in other PFAS studied. For males, increasing patterns were followed by somewhat decreasing patterns of concentration for most PFAS, the reverse was observed for females. The findings have implications for study design. Based on the results provided in detailed tables and figures for this study, we recommend separate analyses of male and female data. In addition, female serum concentration data should be considered for stratified analysis for pre- and post-menopausal time periods. From a mechanistic perspective, the data add support to existing questions about influences on gender differences in serum PFAS that may be attributed to causes other than menstruation, pregnancy, and lactation. These are amenable to further study.

Hospital work environment contains various biological and chemical exposures that can affect indoor air quality and have impact on respiratory health of the staff. The objective of this study was to investigate potential effects of occupational exposures on the risk of respiratory symptoms and lung function in hospital work, and to evaluate potential interaction between smoking and occupational exposures.We conducted a cross-sectional study of 228 staff members in a hospital and 228 employees of an office building as the reference group in Shiraz, Iran. All subjects completed a standardized ATS respiratory questionnaire and performed a spirometry test.In Poisson regression, the adjusted prevalence ratios (aPR) among the hospital staff were elevated for cough (aPR 1.90, 95% CI 1.15, 3.16), phlegm production (aPR 3.21, 95% CI 1.63, 6.32), productive cough (aPR 2.83, 95% CI 1.48, 5.43), wheezing (aPR 3.18, 95% CI 1.04, 9.66), shortness of breath (aPR 1.40, 95% CI 0.93, 2.12), and chest tightness (aPR 1.73, 95% CI 0.73, 4.12). Particularly laboratory personnel experienced increased risks of most symptoms. In linear regression adjusting for confounding, there were no significant differences in lung function between the hospital and office workers. There was an indication of synergism between hospital exposures and current smoking on FEV1/FVC% (interaction term β = - 5.37, 95% CI - 10.27, - 0.47).We present significant relations between hospital work, especially in laboratories, and increased risks of respiratory symptoms. Smoking appears to enhance these effects considerably. Our findings suggest that policymakers should implement evidence-based measures to prevent these occupational exposures.

Objectives: To evaluate if serum perfluoroalkylated substances (PFAS) were associated with abdominal aortic calcification (AAC). Methods: We used weighted logistic regression to investigate the gender-specific association between PFAS serum levels and AAC more than or equal to 6 from dual-energy X-ray absorptiometry (DXA) scans of the thoraco-lumbar spine from National Health and Nutrition Examination Survey 2013–2014 survey participants aged more than or equal to 40 years. Results: After adjusting for confounding, none of log-transformed perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonic acid (PFHxS), or perfluorononanoic acid (PFNA) were significantly associated with AAC for either men or women (adjusted odds ratios [ORs] ranged from 0.80 to 1.33, P> 0.05 each). For PFOA and PFOS, the association was positive only in women (although the difference was not statistically significant in either case). Conclusions: These findings do not provide general support for a relationship of PFAS exposure to AAC, although the results show a need for gender-specific consideration in a larger dataset.

Background: The hospital work environment contains various biological and chemical exposures that can affect indoor air quality and have impact on respiratory health of the staff. The objective of this study was to investigate potential effects of occupational exposures on the risk of respiratory symptoms and lung function in hospital work, and to evaluate potential interaction between smoking and occupational exposures.Methods: We conducted a cross-sectional study of 228 staff members in a hospital and 228 employees of an office building as the reference group in Shiraz, Iran. All subjects completed a standardized respiratory ATS questionnaire and performed a spirometry test. Results: In Poisson regression, the adjusted prevalence ratios (aPR) among the hospital staff were elevated for cough (aPR 1.90, 95% CI: 1.15, 3.16), phlegm production (aPR 3.21, 95% CI: 1.63, 6.32), productive cough (aPR 2.83, 95% CI: 1.48, 5.43), wheezing (aPR 3.18, 95% CI: 1.04, 9.66), shortness of breath (aPR 1.40, 95% CI: 0.93, 2.12), and chest tightness (aPR 1.73, 95% CI: 0.73, 4.12). Particularly laboratory personnel experienced increased risk of most symptoms. In linear regression adjusting for confounding, there were no significant differences in lung function between the hospital and office workers. There was an indication of synergism between hospital exposures and current smoking on FEV1/FVC% (β = -5.37, 95%CI: -10.27, -0.47).Conclusions: This study provides evidence that hospital work, especially in laboratories, increases the risk of respiratory symptoms. Smoking appears to enhance these effects considerably. Our findings suggest that policymakers should implement evidence-based measures to prevent these occupational exposures.

Additional file1. Table S1: Unadjusted and adjusted effects of occupational exposure on lung function parameters.

Background: Hospital work environment contains various biological and chemical exposures that can affect indoor air quality and have impact on respiratory health of the staff. The objective of this study was to investigate potential effects of occupational exposures on the risk of respiratory symptoms and lung function in hospital work, and to evaluate potential interaction between smoking and occupational exposures. Methods: We conducted a cross-sectional study of 228 staff members in a hospital and 228 employees of an office building as the reference group in Shiraz, Iran. All subjects completed a standardized ATS respiratory questionnaire and performed a spirometry test. Results: In Poisson regression, the adjusted prevalence ratios (aPR) among the hospital staff were elevated for cough (aPR 1.90, 95% CI 1.15, 3.16), phlegm production (aPR 3.21, 95% CI 1.63, 6.32), productive cough (aPR 2.83, 95% CI 1.48, 5.43), wheezing (aPR 3.18, 95% CI 1.04, 9.66), shortness of breath (aPR 1.40, 95% CI 0.93, 2.12), and chest tightness (aPR 1.73, 95% CI 0.73, 4.12). Particularly laboratory personnel experienced increased risks of most symptoms. In linear regression adjusting for confounding, there were no significant differences in lung function between the hospital and office workers. There was an indication of synergism between hospital exposures and current smoking on FEV1/FVC% (interaction term β = − 5.37, 95% CI − 10.27, − 0.47). Conclusions: We present significant relations between hospital work, especially in laboratories, and increased risks of respiratory symptoms. Smoking appears to enhance these effects considerably. Our findings suggest that policymakers should implement evidence-based measures to prevent these occupational exposures.

Background Environmental health agencies are critical sources of information for communities affected by chemical contamination. Impacted residents and their healthcare providers often turn to federal and state agency webpages, fact sheets, and other documents to weigh exposure risks and interventions. Main body This commentary briefly reviews scientific evidence concerning per- and polyfluoroalkyl substances (PFAS) for health outcomes that concern members of affected communities and that have compelling or substantial yet differing degree of scientific evidence. It then features official documents in their own language to illustrate communication gaps, as well as divergence from scientific evidence and from best health communication practice. We found official health communications mostly do not distinguish between the needs of heavily contaminated communities characterized by high body burdens and the larger population with ubiquitous but substantially smaller exposures. Most health communications do not distinguish levels of evidence for health outcomes and overemphasize uncertainty, dismissing legitimate reasons for concern in affected communities. Critically, few emphasize helpful approaches to interventions. We also provide examples that can be templates for improvement. Conclusions Immediate action should be undertaken to review and improve official health communications intended to inform the public and health providers about the risks of PFAS exposure and guide community and medical decisions.

Exposures to per- and polyfluoroalkyl substances (PFAS) cause oxidative stress, a risk factor for tissue damage leading to kidney and cardiovascular diseases. The antiaging protein klotho is known to act as an anti-oxidative agent, and how klotho homeostasis interacts with PFAS has not been reported. This study among 3981 US adults aged 40-79 years old evaluated relationships of internal PFAS contamination to α-klotho across stages of estimated glomerular filtration rate or eGFR-based kidney function and albuminuria defined as urinary albumin creatinine ratio of30 mg/g creatinine. In the absence of albuminuria and when eGFR based kidney function was in stage GF-1 (eGFR ≥ 90 mL/min/1.73 m