Causes of Childhood Cancer: A Review of the Recent Literature: Part I-Childhood Factors.

PURPOSE: To review the childhood risk factors for pediatric cancer (diagnosis before age 20). METHODS: We conducted literature searches using Ovid Medline and Scopus to find primary research studies, review articles, and meta-analyses published from 2014 to 3 March 2021. RESULTS: Strong evidence indicates that an array of genetic and epigenetic phenomena, structural birth defects, and chromosomal anomalies are associated with an increased risk of various childhood cancers. Increased risk is also associated with prior cancer, likely due to previous treatment agents and therapeutic ionizing radiation. Convincing evidence supports associations between several pediatric cancers and ionizing radiation, immunosuppression, and carcinogenic virus infection both in healthy children and in association with immune suppression following organ transplantation. Breastfeeding and a childhood diet rich in fruits and vegetables appears to reduce the risk of pediatric leukemia but the evidence is less strong. Childhood vaccination against carcinogenic viruses is associated with a lower risk of several cancers; there is less strong evidence that other childhood vaccinations more broadly may also lower risk. Ultraviolet (UV) radiation is associated with increased melanoma risk, although most melanomas following childhood UV exposure occur later, in adulthood. Evidence is weak or conflicting for the role of body mass index, other childhood infections, allergies, and certain treatments, including immunomodulator medications and human growth therapy.

Impact of heat on emergency hospital admission in Texas: geographic and racial/ethnic disparities.

BACKGROUND: Studies exploring the racial/ethnicity disparity of the impact of heat on hospital admission are notably limited, especially in Texas, a state with a diverse population and consistently ranking among the top ten U.S. states for heat-related deaths per capita from 2018 to 2020. OBJECTIVE: Our objective is to determine the correlation between elevated temperatures and emergency hospital admissions for various causes and age groups across 12 Metropolitan Statistical Areas(MSAs) in Texas. Additionally, we aim to investigate health inequalities in the five largest MSAs in Texas between 2004 and 2013. METHODS: We used MSA-level hospital admission and weather data to estimate the relationship between heat and emergency hospital admissions. We applied a Generalized Additive Model and random effects meta-analysis to calculate MSA-specific associations and overall correlation, repeating the analysis for age groups and specific causes of admission. We also investigated health disparities across racial and ethnic groups and performed a sensitivity analysis. RESULTS: The results showed that a 1 °C increase in temperature was associated with a 0.50% (95% CI [0.38%, 0.63%]) increase in all-cause emergency hospital admissions. Heat's impact on hospital admissions varied among age groups and causes, with children under 6 years showing the highest effect estimate (0.64% (95% CI [0.32%,0.96%])). Statistically significant associations were found for Cardiovascular Diseases (0.27% (95% CI [0.07%,0.47%])), Ischemic Heart Diseases (0.53% (95% CI [0.15%,0.92%])), Pneumonia (0.70% (95% CI [0.25%,1.16%])), and Respiratory Diseases (0.67% (95% CI [0.18%,1.17%])). Health disparities were found among racial and ethnic groups in the five largest MSAs. IMPACT STATEMENT: Studies exploring the impact of heat on hospital admission in Texas are notably limited. Our research provided a comprehensive examination of the connection between heat and emergency hospital admissions throughout Texas. Furthermore, we are the first to examine racial/ethnic disparities, identifying African American and Hispanic groups as disproportionately affected. These insights provide valuable insights for policymakers to allocate resources and implement strategies to mitigate the negative consequences of rising temperatures.

Obstetric Outcomes Among Women With a History of Intimate Partner Violence in the United States.

OBJECTIVE: To evaluate the association between exposure to intimate partner violence (IPV) and delivery method in a U.S. obstetric cohort. METHODS: The study population included U.S. women with a history of recent live birth, drawn from the 2009-2018 PRAMS (Pregnancy Risk Assessment Monitoring System) cohort. The primary exposure was self-reported IPV. The primary outcome of interest was method of delivery (vaginal or cesarean). Secondary outcomes included preterm birth, small for gestational age (SGA), and admission to the neonatal intensive care unit (NICU). Bivariate associations between the primary exposure (ie, self-report of IPV vs no self-report of IPV) and each covariate of interest were assessed with weighted quasibinomial logistic regression. Weighted multivariable logistic regression was conducted to evaluate the association between IPV and delivery method controlling for confounders. RESULTS: A total of 130,000 women were included in this secondary analysis of a cross-sectional sample, representing 7,500,000 women nationwide based on PRAMS sampling design. Of these, 0.8% reported abuse in the 12 months before their current pregnancy and 1.3% reported abuse during pregnancy; 1.6% of the study population reported abuse both before and during pregnancy. After adjusting for maternal sociodemographic characteristics, IPV exposure at any time was not significantly associated with cesarean delivery, compared with no IPV exposure (odds ratio [OR] 0.98, 95% CI 0.86-1.11). Of secondary outcomes, 9.4% of women experienced preterm birth and 15.1% had neonates admitted to the NICU. Exposure to IPV was associated with a 21.0% increased risk of preterm birth, compared with women without exposure (OR 1.21, 95% CI 1.05-1.40), and a 33.3% increased risk of NICU admission (OR 1.33, 95% CI 1.17-1.52) after controlling for confounders. There was no difference in the risk of delivering a neonate who was SGA. CONCLUSION: Intimate partner violence was not associated with an increased risk of cesarean delivery. Intimate partner violence before or during pregnancy was associated with increased risk of adverse obstetric outcomes, such as preterm birth and NICU admission, corroborating previous research findings.

The New Hampshire Hospital Screening and Referral Algorithm (NHHSRA) for Substance Use in People With Serious Mental Illness.

Objective: Substance use is a common co-occurrence among psychiatrically hospitalized adults, yet it is especially difficult to identify in those with serious mental illness. Existing screening instruments are not feasible for individuals with serious mental illness, as they rely heavily on subjective self-report. This study aimed to develop and validate an objective substance use screening instrument for use in seriously mentally ill patient populations.Methods: Objective elements were extracted from existing substance use screening instruments and used to develop a new, data-driven referral tool, the New Hampshire Hospital screening and referral algorithm (NHHSRA). Descriptive statistics were employed to compare NHHSRA summed score and individual patient data elements in a convenience sample of patients who were referred to the Addiction Services by expert addiction psychiatrist evaluation to those who were not referred. Pearson correlation coefficients and logistic regression models assessed the association between patient referral and the overall NHHSRA score and individual items. The NHHSRA was then piloted in a smaller convenience sample of patients against the standard clinical-based identification for substance use treatment needs.Results: The instrument consists of 5 objective items. These were tested in a sample of 302 sequentially admitted adults with serious mental illness. Three of the items were significantly associated with likelihood of benefitting from referral for substance use interventions (maximum likelihood estimate and standard deviation [SD] for positive non-tetrahydrocannabinol [non-THC] toxicology screen or > 0% blood alcohol level = 3.61 [0.6]; diagnosis of a substance use disorder = 4.89 [0.73]; and medication-assisted treatment or relapse prevention = 2.78 [0.67]), and these were prioritized in building a decision tree algorithm. The area under the receiver operating characteristic (ROC) curve for the NHHSRA was 0.96, indicating that the NHHSRA has high overall sensitivity and the algorithm was capable of distinguishing between patients needing substance use intervention versus those who do not with 96% accuracy. In the pilot implementation study of another 20 patient admissions, the NHHSRA accurately identified 100% (n = 6) of patients deemed to benefit from substance use interventions by expert addiction psychiatric evaluation. The standard clinical-based referral process identified only 33% (n = 2) and erroneously identified another 4 for referral to substance use intervention that would not have been warranted.Conclusions: The NHHSRA holds promise in its ability to improve objective and timely identification of substance use in a seriously mentally ill inpatient population, helping to facilitate treatment.

Inclusion of Social and Structural Determinants of Health to Advance Understanding of their Influence on the Biology of Chronic Disease.

Social Determinants of Health (SDOH) consider social, political, and economic factors that contribute to health disparities in patients and populations. The most common health-related SDOH exposures are food and housing insecurity, financial instability, transportation needs, low levels of education, and psychosocial stress. These domains describe risks that can impact health outcomes more than health care. Epidemiologic and translational research demonstrates that SDOH factors represent exposures that predict harm and impact the health of individuals. International and national guidelines urge health professionals to address SDOH in clinical practice and public health. The further implementation of these recommendations into basic and translational research, however, is lagging. Herein, we consider a precision health framework to describe how SDOH contributes to the exposome and exacerbates physiologic pathways that lead to chronic disease. SDOH factors are associated with various forms of stressors that impact physiological processes through epigenetic, inflammatory, and redox regulation. Many SDOH exposures may add to or potentiate the pathologic effects of additional environmental exposures. This overview aims to inform basic life science and translational researchers about SDOH exposures that can confound associations between classic biomedical determinants of disease and health outcomes. To advance the study of toxicology through either qualitative or quantitative assessment of exposures to chemical and biological substances, a more complete environmental evaluation should include SDOH exposures. We discuss common approaches to measure SDOH factors at individual and population levels and review the associations between SDOH risk factors and physiologic mechanisms that influence chronic disease. We provide clinical and policy-based motivation to encourage researchers to consider the impact of SDOH exposures on study results and data interpretation. With valid measures of SDOH factors incorporated into study design and analyses, future toxicological research may contribute to an evidence base that can better inform prevention and treatment options, to improve equitable clinical care and population health. © 2022 Wiley Periodicals LLC.

Machine Learning Approaches for Hospital Acquired Pressure Injuries: A Retrospective Study of Electronic Medical Records.

Background: Many machine learning heuristics integrate well with Electronic Medical Record (EMR) systems yet often fail to surpass traditional statistical models for biomedical applications. Objective: We sought to compare predictive performances of 12 machine learning and traditional statistical techniques to predict the occurrence of Hospital Acquired Pressure Injuries (HAPI). Methods: EMR information was collected from 57,227 hospitalizations acquired from Dartmouth Hitchcock Medical Center (April 2011 to December 2016). Twelve classification algorithms, chosen based upon classic regression and recent machine learning techniques, were trained to predict HAPI incidence and performance was assessed using the Area Under the Receiver Operating Characteristic Curve (AUC). Results: Logistic regression achieved a performance (AUC = 0.91 ± 0.034) comparable to the other machine learning approaches. We report discordance between machine learning derived predictors compared to the traditional statistical model. We visually assessed important patient-specific factors through Shapley Additive Explanations. Conclusions: Machine learning models will continue to inform clinical decision-making processes but should be compared to traditional modeling approaches to ensure proper utilization. Disagreements between important predictors found by traditional and machine learning modeling approaches can potentially confuse clinicians and need to be reconciled. These developments represent important steps forward in developing real-time predictive models that can be integrated into EMR systems to reduce unnecessary harm.

Health disparities: Intracellular consequences of social determinants of health.

Health disparities exist dependent on socioeconomic status, living conditions, race/ethnicity, diet, and exposures to environmental pollutants. Herein, the various exposures contributing to a person's exposome are collectively considered social determinants of health (SDOH), and the SDOH-exposome impacts health more than health care. This review discusses the extent of evidence of the physiologic consequences of these exposures at the intracellular level. We consider how the SDOH-exposome, which captures how individuals live, work and age, induces cell processes that modulate a conceptual "redox rheostat." Like an electrical resistor, the SDOH-exposome, along with genetic predisposition and age, regulate reductive and oxidative (redox) stress circuits and thereby stimulate inflammation. Regardless of the source of the SDOH-exposome that induces chronic inflammation and immunosenescence, the outcome influences cardiometabolic diseases, cancers, infections, sepsis, neurodegeneration and autoimmune diseases. The endogenous redox rheostat is connected with regulatory molecules such as NAD+/NADH and SIRT1 that drive redox pathways. In addition to these intracellular and mitochondrial processes, we discuss how the SDOH-exposome can influence the balance between metabolism and regulation of immune responsiveness involving the two main molecular drivers of inflammation, the NLRP3 inflammasome and NF-κB induction. Mitochondrial and inflammasome activities play key roles in mediating defenses against pathogens and controlling inflammation before diverse cell death pathways are induced. Specifically, pyroptosis, cell death by inflammation, is intimately associated with common disease outcomes that are influenced by the SDOH-exposome. Redox influences on immunometabolism including protein cysteines and ion fluxes are discussed regarding health outcomes. In summary, this review presents a translational research perspective, with evidence from in vitro and in vivo models as well as clinical and epidemiological studies, to outline the intracellular consequences of the SDOH-exposome that drive health disparities in patients and populations. The relevance of this conceptual and theoretical model considering the SARS-CoV-2 pandemic are highlighted. Finally, the case of asthma is presented as a chronic condition that is modified by adverse SDOH exposures and is manifested through the dysregulation of immune cell redox regulatory processes we highlight in this review.

Development of a Nursing Assignment Tool Using Workload Acuity Scores.

OBJECTIVE: To determine a just and consistent practice for creating nursing assignments. BACKGROUND: Traditional methods of assigning patients to nurses may lead to unbalanced nursing workload. This article describes the ongoing, hospital-wide effort to evaluate and implement a nursing assignment tool based on electronic health record (EHR) functionality and auto-calculated nursing workload scores. METHODS: EHR records of individual patient workload scores from all hospital units were collected from August 2017 to June 2018. A nurse-specific total workload score was summed for each staff. Then, each hospital unit's mean nurse workload score and standard deviation, along with the unit's nurse-to-patient ratio, were used to calculate levels of high, medium, and low nursing workload measurement (NWM). RESULTS: Mean patient-specific workload scores varied greatly across hospital units. Unit-specific nurse-to-patient ratios were factored into NWM scores to create ranges for assignments that were relatively consistent across the institution. CONCLUSION: The use of objective, electronically generated nursing workload scores, combined with traditional nurse-to-patient ratios, provides accurate real-time nurse staffing needs that can inform best practice in staffing. The confirmation of individual patient workload scores and an appreciation for the complexity of EHR vendor rules are necessary for successful implementation. Automation ensures patient safety, staff satisfaction, and optimal resource allocation.

Patient-specific factors associated with pressure injuries revealed by electronic health record analyses.

Hospital-acquired pressure injuries (HAPIs) are a major source of unintended patient harm and unnecessary costs. The Braden Scale is widely used for risk assessment, yet it lacks specificity and clinical applications. This study used the electronic health record to examine associations between patient-specific factors and pressure injury. Adult patients (age >18) with 3-day length of stay from April 2011 to December 2016 were included. Pressure injuries were identified by ICD-9/ICD-10 codes. Longitudinal multivariate logistic regression was used to evaluate the association between patient-specific factors and HAPIs. This included 57,227 hospital encounters and 241 HAPIs. We observed 2-3 times increased likelihood of acquiring a pressure injury among patients who were malnourished or who had increased intraoperative time. The Braden subscales of nutrition, mobility, and friction showed significant predictive value. Future work is needed to assess the clinical applicability of this work.

Association of Receiving Multiple, Concurrent Fracture-Associated Drugs With Hip Fracture Risk.

Importance: Many prescription drugs increase fracture risk, which raises concern for patients receiving 2 or more such drugs concurrently. Logic suggests that risk will increase with each additional drug, but the risk of taking multiple fracture-associated drugs (FADs) is unknown. Objective: To estimate hip fracture risk associated with concurrent exposure to multiple FADs. Design, Setting, and Participants: This cohort study used a 20% random sample of Medicare fee-for-service administrative data for age-eligible Medicare beneficiaries from 2004 to 2014. Sex-stratified Cox regression models estimated hip fracture risk associated with current receipt of 1, 2, or 3 or more of 21 FADs and, separately, risk associated with each FAD and 2-way FAD combination vs no FADs. Models included sociodemographic characteristics, comorbidities, and use of non-FAD medications. Analyses began in November 2018 and were completed April 2019. Exposure: Receipt of prescription FADs. Main Outcomes and Measures: Hip fracture hospitalization. Results: A total of 11.3 million person-years were observed, reflecting 2 646 255 individuals (mean [SD] age, 77.2 [7.3] years, 1 615 613 [61.1%] women, 2 136 585 [80.7%] white, and 219 579 [8.3%] black). Overall, 2 827 284 person-years (25.1%) involved receipt of 1 FAD; 1 322 296 (11.7%), 2 FADs; and 954 506 (8.5%), 3 or more FADs. In fully adjusted, sex-stratified models, an increase in hip fracture risk among women was associated with the receipt of 1, 2, or 3 or more FADs (1 FAD: hazard ratio [HR], 2.04; 95% CI, 1.99-2.11; P < .001; 2 FADs: HR, 2.86; 95% CI, 2.77-2.95; P < .001; ≥3 FADs: HR, 4.50; 95% CI, 4.36-4.65; P < .001). Relative risks for men were slightly higher (1 FAD: HR, 2.23; 95% CI, 2.11-2.36; P < .001; 2 FADs: HR, 3.40; 95% CI, 3.20-3.61; P < .001; ≥3 FADs: HR, 5.18; 95% CI, 4.87-5.52; P < .001). Among women, 2 individual FADs were associated with HRs greater than 3.00; 80 pairs of FADs exceeded this threshold. Common, risky pairs among women included sedative hypnotics plus opioids (HR, 4.90; 95% CI, 3.98-6.02; P < .001), serotonin reuptake inhibitors plus benzodiazepines (HR, 4.50; 95% CI, 3.76-5.38; P < .001), and proton pump inhibitors plus opioids (HR, 4.00; 95% CI, 3.56-4.49; P < .001). Receipt of 1, 2, or 3 or more non-FADs was associated with a small, significant reduction in fracture risk compared with receipt of no non-FADs among women (1 non-FAD: HR, 0.93; 95% CI, 0.90-0.96; P < .001; 2 non-FADs: HR, 0.84; 95% CI, 0.81-0.87; P < .001; ≥3 non-FADs: HR, 0.74; 95% CI, 0.72-0.77; P < .001). Conclusions and Relevance: Among older adults, FADs are commonly used and commonly combined. In this cohort study, the addition of a second and third FAD was associated with a steep increase in fracture risk. Many risky pairs of FADs included potentially avoidable drugs (eg, sedatives and opioids). If confirmed, these findings suggest that fracture risk could be reduced through tighter adherence to long-established prescribing guidelines and recommendations.

Epigenetic upregulation of FKBP5 by aging and stress contributes to NF-κB-driven inflammation and cardiovascular risk.

Aging and psychosocial stress are associated with increased inflammation and disease risk, but the underlying molecular mechanisms are unclear. Because both aging and stress are also associated with lasting epigenetic changes, a plausible hypothesis is that stress along the lifespan could confer disease risk through epigenetic effects on molecules involved in inflammatory processes. Here, by combining large-scale analyses in human cohorts with experiments in cells, we report that FKBP5, a protein implicated in stress physiology, contributes to these relations. Across independent human cohorts (total n > 3,000), aging synergized with stress-related phenotypes, measured with childhood trauma and major depression questionnaires, to epigenetically up-regulate FKBP5 expression. These age/stress-related epigenetic effects were recapitulated in a cellular model of replicative senescence, whereby we exposed replicating human fibroblasts to stress (glucocorticoid) hormones. Unbiased genome-wide analyses in human blood linked higher FKBP5 mRNA with a proinflammatory profile and altered NF-κB-related gene networks. Accordingly, experiments in immune cells showed that higher FKBP5 promotes inflammation by strengthening the interactions of NF-κB regulatory kinases, whereas opposing FKBP5 either by genetic deletion (CRISPR/Cas9-mediated) or selective pharmacological inhibition prevented the effects on NF-κB. Further, the age/stress-related epigenetic signature enhanced FKBP5 response to NF-κB through a positive feedback loop and was present in individuals with a history of acute myocardial infarction, a disease state linked to peripheral inflammation. These findings suggest that aging/stress-driven FKBP5-NF-κB signaling mediates inflammation, potentially contributing to cardiovascular risk, and may thus point to novel biomarker and treatment possibilities.

Reduction of Hospital-acquired Pressure Injuries Using a Multidisciplinary Team Approach: A Descriptive Study.

INTRODUCTION: Hospital-acquired pressure injuries (HAPIs) increase patient mortality and length of stay (LOS). Twenty-eight full-thickness HAPIs occurred in fiscal year 2015 (FY15), and that trend continued into FY16 with 14 injuries on multiple units throughout a tertiary acute care center with 400 beds. To address this trend, a multidisciplinary Pressure Injury Prevention (PIP) team was created. OBJECTIVE: This report is a description of ongoing, hospital-wide efforts to understand the common factors of HAPI causality and to establish corrective action plans institutionally to prevent similar events in the future. METHODS: The team goals were to document the occurrence of HAPIs across all hospital units, reduce preventable full-thickness PIs to zero, and recommend institution-wide changes as those opportunities were recognized. RESULTS: Since the committee's inception in July 2015, an 89% reduction of full-thickness HAPIs, with only 2 full-thickness HAPIs in FY17 and 3 in FY18, has been seen. This effort has been hospital wide with involvement of all inpatient units and perioperative areas (including the operating rooms). Opportunities remain for improvement around the prevention of deep tissue and partial-thickness HAPIs. CONCLUSIONS: The data demonstrate that the formation of a multidisciplinary PIP team of engaged clinicians can reduce the number of preventable full-thickness HAPIs.

Prenatal exposure to mercury in relation to infant infections and respiratory symptoms in the New Hampshire Birth Cohort Study.

BACKGROUND: Mechanistic studies support the potential for mercury (Hg) to alter immunity, including via in utero exposure. As yet, there are few prospective studies of in utero Hg exposure and subsequent immune-related outcomes, especially in infancy. OBJECTIVES: We investigated the association of biomarkers of prenatal Hg exposure and maternal silver-mercury dental amalgams with the occurrence of infant allergy, respiratory infection, and respiratory symptoms in the first year of life. METHODS: The New Hampshire Birth Cohort Study (NHBCS) ascertained information on infant allergies, infections and symptoms through telephone interviews at 4, 8 and 12 months postpartum and measured total Hg in maternal toenails collected at ~28-30 weeks gestation. Information on maternal fish consumption and presence of dental amalgams was obtained from a questionnaire administered at study enrollment at 24-28 weeks. A total of 1321 NHBCS mother-infant pairs had at least one Hg exposure measure (toenail Hg or information on dental amalgams) and information on dietary fish intake. Generalized linear models and generalized estimating equation models with Poisson regression adjusted for potential confounders (maternal age, level of education, parity, smoking, alternative Healthy Eating Index-2010, infant sex, gestational age, feeding mode, and day care attendance) were used to assess the association between infant outcomes and prenatal toenail Hg levels. We subsetted this analysis on mothers who consumed fish (n = 706) as a measure of in utero methylmercury (MeHg) exposure. Associations between infant outcomes and dental amalgams as a measure of in utero inorganic Hg exposure were assessed among mothers who did not consume fish (n = 218). RESULTS: Among women who ate fish during pregnancy, higher maternal toenail Hg concentrations were associated with an increased risk of lower respiratory infections and respiratory symptoms requiring a doctor visit among infants age 9-12 months (relative risk (RR) 1.4 (95% CI: 1.1, 1.9) and 1.2 (95% CI: 1.0, 1.4) respectively), whereas a reduced risk of lower respiratory infections was observed among infants 0-4 months of age (RR = 0.7 (95% CI: 0.5, 1.0). We found little to no evidence of associations of toenail Hg with upper respiratory infections, allergy or eczema at any age to one year. Among infants of mothers who did not consume fish, we found an elevated risk of upper respiratory infections requiring a doctor visit in relation to having dental amalgams during pregnancy (RR = 1.5 (95% CI: 1.1, 2.1)). Overall, weaker associations were observed with lower respiratory infections, respiratory symptoms, and medically confirmed allergies, and there was no association with eczema. CONCLUSIONS: Our analyses of a US birth cohort, along with prior mechanistic work, raise the possibility that gestational Hg exposure through fish/seafood consumption and dental amalgams may alter respiratory infections and respiratory symptoms in infants.

Lack of supportive leadership behavior predicts suboptimal self-rated health independent of job strain after 10 years of follow-up: findings from the population-based MONICA/KORA study.

OBJECTIVES: Emerging cross-sectional research has identified lack of supportive leadership behavior (SLB) as a risk factor for workforce health. However, prospective evidence is hitherto lacking. SLB denotes support in difficult situations, recognition and feedback on work tasks. This study aims to determine the effect of SLB on suboptimal self-rated health (SRH) after 10 years considering potential moderators such as ages, sex, occupation and job strain. METHODS: The sample included 884 employed participants drawn from the population-based prospective MONICA/KORA Study. SLB, SRH, as well as job strain were assessed by questionnaire. Logistic regressions estimated odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the effect of SLB at baseline on suboptimal SRH at follow-up. Analyses were adjusted for age, gender, lifestyle (alcohol, smoking, physical activity), socioeconomic status as well as for SRH and job strain at baseline. RESULTS: Lack of SLB was associated with suboptimal SRH at baseline [OR 2.00, (95% CI 1.19-3.46)] and at follow-up [OR 2.33, (95% CI 1.40-3.89)]. Additional adjustment for job strain did not substantially alter this association [OR 2.06, (95% CI 1.20-3.52)]. However, interactions between SLB and job strain as well as gender became evident, indicating moderating influences on the association between SLB and SRH. CONCLUSION: Lack of supportive leadership was associated with suboptimal SRH at 10 years' follow-up in men, even if SRH at baseline and other risk factors were taken into account. This effect is likely to be moderated by job strain.

The association of sarcopenia, telomere length, and mortality: data from the NHANES 1999-2002.

BACKGROUND/OBJECTIVES: Sarcopenia is defined as the loss of muscle mass or function with aging and is associated with adverse outcomes. Telomere shortening is associated with mortality, yet its relationship with sarcopenia is unknown. SUBJECTS/METHODS: Adults ≥60 years from the 1999-2002 NHANES with body composition measures were identified. Sarcopenia was defined using the two Foundation for the National Institute of Health definitions: appendicular lean mass (ALM) (men <19.75; women <15.02 kg); or ALM divided by body mass index (BMI) (ALM:BMI, men <0.789; women <0.512). Telomere length was assessed using quantitative PCR. Regression models predicted telomere length with sarcopenia (referent = no sarcopenia). RESULTS: We identified 2672 subjects. Mean age was 70.9 years (55.5% female). Prevalence of ALM and ALM:BMI sarcopenia was 29.2 and 22.1%. Deaths were higher in persons with sarcopenia as compared to those without sarcopenia (ALM: 46.4 vs. 33.4%, p < 0.001; ALM:BMI: 46.7 vs. 33.2%, p < 0.001). No adjusted differences were observed in telomere length in those with/without sarcopenia (ALM: 0.90 vs. 0.92, p = 0.74, ALM:BMI 0.89 vs. 0.92, p = 0.24). In men with ALM:BMI-defined sarcopenia, adjusted telomere length was significantly lower compared to men without sarcopenia (0.85 vs. 0.91, p = 0.013). With sarcopenia, we did not observe a significant association between telomere length and mortality (ALM: HR 1.11 [0.64,1.82], p = 0.68; ALM:BMI: HR 0.97 [0.53,1.77], p = 0.91), but noted significance in those without sarcopenia with mortality (ALM: HR 0.59 [0.40,0.86], p = 0.007; ALM:BMI: HR 0.62 [0.42,0.91]; p = 0.01). CONCLUSIONS: We observed a potentially inverse relationship between telomere length and mortality in those without sarcopenia but did not observe a significant relationship between telomere length and mortality in the presence of sarcopenia.

Anxiety Associated Increased CpG Methylation in the Promoter of Asb1: A Translational Approach Evidenced by Epidemiological and Clinical Studies and a Murine Model.

Epigenetic regulation in anxiety is suggested, but evidence from large studies is needed. We conducted an epigenome-wide association study (EWAS) on anxiety in a population-based cohort and validated our finding in a clinical cohort as well as a murine model. In the KORA cohort, participants (n=1522, age 32-72 years) were administered the Generalized Anxiety Disorder (GAD-7) instrument, whole blood DNA methylation was measured (Illumina 450K BeadChip), and circulating levels of hs-CRP and IL-18 were assessed in the association between anxiety and methylation. DNA methylation was measured using the same instrument in a study of patients with anxiety disorders recruited at the Max Planck Institute of Psychiatry (MPIP, 131 non-medicated cases and 169 controls). To expand our mechanistic understanding, these findings were reverse translated in a mouse model of acute social defeat stress. In the KORA study, participants were classified according to mild, moderate, or severe levels of anxiety (29.4%/6.0%/1.5%, respectively). Severe anxiety was associated with 48.5% increased methylation at a single CpG site (cg12701571) located in the promoter of the gene encoding Asb1 (ß-coefficient=0.56 standard error (SE)=0.10, p (Bonferroni)=0.005), a protein hypothetically involved in regulation of cytokine signaling. An interaction between IL-18 and severe anxiety with methylation of this CpG cite showed a tendency towards significance in the total population (p=0.083) and a significant interaction among women (p=0.014). Methylation of the same CpG was positively associated with Panic and Agoraphobia scale (PAS) scores (ß=0.005, SE=0.002, p=0.021, n=131) among cases in the MPIP study. In a murine model of acute social defeat stress, Asb1 gene expression was significantly upregulated in a tissue-specific manner (p=0.006), which correlated with upregulation of the neuroimmunomodulating cytokine interleukin 1 beta. Our findings suggest epigenetic regulation of the stress-responsive Asb1 gene in anxiety-related phenotypes. Further studies are necessary to elucidate the causal direction of this association and the potential role of Asb1-mediated immune dysregulation in anxiety disorders.

Low Lean Mass With and Without Obesity, and Mortality: Results From the 1999-2004 National Health and Nutrition Examination Survey.

BACKGROUND: The Foundation for the NIH Sarcopenia Project validated cutpoints for appendicular lean mass. We ascertained the relationship between low lean mass (LLM), obesity, and mortality and identified predictors in this subgroup. METHODS: A total of 4,984 subjects aged 60 years and older were identified from the National Health and Nutrition Examination Survey 1999-2004 linked to the National Death Index. LLM was defined using reduced appendicular lean mass (men < 19.75 kg; females < 15.02 kg). Obesity was defined using dual-energy x-ray absorptiometry body fat (males ≥ 25%; females ≥ 35%). LLM with obesity was defined using criteria for both LLM and obesity. Proportional hazard models determined mortality risk for LLM and LLM with obesity, separately (referent = no LLM and no LLM with obesity, respectively). RESULTS: Mean age was 71.1 ± 0.19 years (56.5% female). Median follow-up was 102 months (interquartile range: 78, 124) with 1,901 deaths (35.0%). Prevalence of LLM with obesity was 33.5% in females and 12.6% in males. In those with LLM, overall mortality risk was 1.49 (1.27, 1.73) in males and 1.19 (1.02, 1.40) in females. Mortality risk in LLM with obesity was 1.31 (1.11, 1.55) and 0.99 (0.85, 1.16) in males and females, respectively. Age, diabetes, history of stroke, congestive heart failure, cancer, and kidney disease were predictive of death. CONCLUSIONS: Risk of death is higher in subjects with LLM than with LLM and obesity. Having advanced age, diabetes, stroke, heart failure, cancer, and renal disease predict a worse prognosis in both classifications.