SnapShot: Mammalian Sirtuins.

The mammalian sirtuins have emerged as critical regulators of cellular stress resistance, energy metabolism, and tumorigenesis. In some contexts, they delay the onset of age-related diseases and promote a healthy lifespan. The seven mammalian sirtuins, SIRT1-7, share a highly conserved NAD+-binding catalytic core domain although they exhibit distinct expression patterns, catalytic activities, and biological functions. This SnapShot provides an overview of these properties, with an emphasis on their relevance to aging.

Thriving from work questionnaire: Spanish translation and validation.

BACKGROUND: Thriving from Work is a construct that has been highlighted as an important integrative positive worker well-being indicator that can be used in both research and practice. Recent public discourse emphasizes the important contributions that work should have on workers' lives in positive and meaningful ways and the importance of valid and reliable instruments to measure worker well-being. The Thriving from Work Questionnaire measures how workers' experiences of their work and conditions of work contributes in positive ways to their thriving both at and outside of work. METHODS: The purpose of this study was to translate the Thriving from Work Questionnaire from English to Spanish, and then validate the translated questionnaire in a sample of 8,795 finance workers in Peru and Mexico. We used item response theory models replicating methods that were used for the original validation studies. We conducted a differential item functioning analysis to evaluate any differences in the performance of models between Peru and Mexico. We evaluated criterion validity with organizational leadership, flourishing, vitality, community well-being, and worker's home location socio-economic position. RESULTS: The current study demonstrates that the Spanish (Peru/Mexico) questionnaire was found to be a reliable and valid measure of workers' thriving from work. One item was dropped from the long-form version of the original U.S. questionnaire. Both the long and short form versions of the questionnaire had similar psychometric properties. Empirical reliability was high. Criterion validity was established as hypothesized relationships between constructs was supported. There were no differences in the performance of the model between countries suggesting utility across Latin American countries. CONCLUSIONS: The current study demonstrated that the Spanish (Peru and Mexico) version of the questionnaire is both a reliable and valid measure of worker well-being in Latin America. Specific recommendations are made for the adaptation of the questionnaire and directions of future research.

Adding injury to insult: Unfair treatment at work and occupational injury among hospital patient-care workers.

BACKGROUND: Hospital patient-care workers have high occupational injury rates. While physical hazards within hospital work environments are established determinants of injury, social exposures may also contribute. This study examined how reports of unfair treatment at work, a dimension of work-related experiences of discrimination, were associated with injury among hospital-based patient-care workers. METHODS: We used data from the Boston Hospital Workers Health Study, a longitudinal cohort of nurses and nursing assistants at two Boston-area hospitals. In 2018, we conducted a worker survey asking about three types of unfair treatment at work and occupational injuries during the past year. We used mixed-effects logistic regression models to evaluate associations between specific types, total load, and high-frequency exposure of unfair treatment with injury, adjusting for age, gender, race and ethnicity, job title, and unit type. RESULTS: Among 1001 respondents, 21% reported being humiliated in front of others at work, 28% reported being watched more closely than other workers, and 47% reported having to work twice as hard as others for the same treatment. For each type of unfair treatment, we observed a monotonic relationship with occupational injury wherein increasing frequency of exposure was associated with increased odds of injury. We also observed monotonic relationships between total load and high-frequency exposure to unfair treatment and odds of injury. CONCLUSIONS: Work-related unfair treatment is associated with injury among hospital workers. Programs and policies that focus on preventing unfair treatment may lessen injury burden in hospital workers.

Epidemic management and control through risk-dependent individual contact interventions.

Testing, contact tracing, and isolation (TTI) is an epidemic management and control approach that is difficult to implement at scale because it relies on manual tracing of contacts. Exposure notification apps have been developed to digitally scale up TTI by harnessing contact data obtained from mobile devices; however, exposure notification apps provide users only with limited binary information when they have been directly exposed to a known infection source. Here we demonstrate a scalable improvement to TTI and exposure notification apps that uses data assimilation (DA) on a contact network. Network DA exploits diverse sources of health data together with the proximity data from mobile devices that exposure notification apps rely upon. It provides users with continuously assessed individual risks of exposure and infection, which can form the basis for targeting individual contact interventions. Simulations of the early COVID-19 epidemic in New York City are used to establish proof-of-concept. In the simulations, network DA identifies up to a factor 2 more infections than contact tracing when both harness the same contact data and diagnostic test data. This remains true even when only a relatively small fraction of the population uses network DA. When a sufficiently large fraction of the population (≳ 75%) uses network DA and complies with individual contact interventions, targeting contact interventions with network DA reduces deaths by up to a factor 4 relative to TTI. Network DA can be implemented by expanding the computational backend of existing exposure notification apps, thus greatly enhancing their capabilities. Implemented at scale, it has the potential to precisely and effectively control future epidemics while minimizing economic disruption.

Thriving from Work Questionnaire: Dimensionality, reliability, and validity of the long and short form questionnaires.

INTRODUCTION: Thriving from Work is defined as the state of positive mental, physical, and social functioning in which workers' experiences of their work and working conditions enable them to thrive in their overall lives, contributing to their ability to achieve their full potential at work, at home, and in the community. The purpose of this study was to develop a psychometrically-sound questionnaire measuring the positive contribution that work can have on one's well-being both at, and outside of, their work. METHODS: We used both a qualitative and quantitative approach of item reduction, domain mapping dimensionality testing, development of "long-" and "short-" versions of the questionnaire, reliability, and construct and criterion validity testing. This was established in two independent online samples of US based workers (n = 1550, n = 500). RESULTS: We developed a bi-factor model 30-item long-form and a uni-factorial 8-item short-version. The long-form measures both the latent construct of Thriving from Work and six domains (psychological/emotional; work-life integration; social; experience of work; basic needs; health). Both long- and short- forms were found to have high empirical reliability (0.93  and 0.87 respectively). The short-form captures 94% of variance of the long-form. Construct and criterion validity were supported. Test-retest reliability was high. CONCLUSIONS: The Thriving from Work Questionnaire appears to be a valid and reliable measure of work-related well-being in United States workers. Further testing is needed to refine and test the instrument in specific industries, unique worker populations, and across geographic regions.

Mesoscopic and multiscale modelling in materials.

The concept of multiscale modelling has emerged over the last few decades to describe procedures that seek to simulate continuum-scale behaviour using information gleaned from computational models of finer scales in the system, rather than resorting to empirical constitutive models. A large number of such methods have been developed, taking a range of approaches to bridging across multiple length and time scales. Here we introduce some of the key concepts of multiscale modelling and present a sampling of methods from across several categories of models, including techniques developed in recent years that integrate new fields such as machine learning and material design.

Rapid Antigen Screening of Students and Staff for SARS-CoV-2 in Rural School Districts, Pierce County, WA, 2020.

During fall 2020 in rural Pierce County, Washington, school districts and the county health department offered weekly rapid antigen screening to students and staff. Asymptomatic screening identified 42.5% of confirmed cases from the population. Parents reported it was a positive experience for their children. The program supported decisions to return to in-person learning, but screening ended because of resource and technical limitations. When planning in-school screening, stakeholder engagement and resource sustainability are important factors to consider. (Am J Public Health. 2022;112(8):1134-1137. https://doi.org/10.2105/AJPH.2022.306875).

Nonenzymatic protein acylation as a carbon stress regulated by sirtuin deacylases.

Cellular proteins are decorated with a wide range of acetyl and other acyl modifications. Many studies have demonstrated regulation of site-specific acetylation by acetyltransferases and deacetylases. Acylation is emerging as a new type of lysine modification, but less is known about its overall regulatory role. Furthermore, the mechanisms of lysine acylation, its overlap with protein acetylation, and how it influences cellular function are major unanswered questions in the field. In this review, we discuss the known roles of acetyltransferases and deacetylases and the sirtuins as a conserved family of a nicotinamide adenine dinucleotide (NAD⁺)-dependent protein deacylases that are important for response to cellular stress and homeostasis. We also consider the evidence for an emerging idea of nonenzymatic protein acylation. Finally, we put forward the hypothesis that protein acylation is a form of protein "carbon stress" that the deacylases evolved to remove as a part of a global protein quality-control network.

Implementation of an organizational intervention to improve low-wage food service workers' safety, health and wellbeing: findings from the Workplace Organizational Health Study.

BACKGROUND: Many organizational interventions aim to improve working conditions to promote and protect worker safety, health, and well-being. The Workplace Organizational Health Study used process evaluation to examine factors influencing implementation of an organizational intervention. This paper examines the extent to which the intervention was implemented as planned, the dose of intervention implemented, and ways the organizational context hindered or facilitated the implementation of the intervention. METHODS: This proof-of-concept trial was conducted with a large, multinational company that provides food service through contractual arrangements with corporate clients. The 13-month intervention was launched in five intervention sites in October 2018. We report findings on intervention implementation based on process tracking and qualitative data. Qualitative data from 25 post-intervention interviews and 89 process tracking documents were coded and thematically analyzed. RESULTS: Over the 13-month intervention, research team representatives met with site managers monthly to provide consultation and technical assistance on safety and ergonomics, work intensity, and job enrichment. Approximately two-thirds of the planned in-person or phone contacts occurred. We tailored the intervention to each site as we learned more about context, work demands, and relationships. The research team additionally met regularly with senior leadership and district managers, who provided corporate resources and guidance. By assessing the context of the food service setting in which the intervention was situated, we explored factors hindering and facilitating the implementation of the intervention. The financial pressures, competing priorities and the fast-paced work environment placed constraints on site managers' availability and limited the full implementation of the intervention. CONCLUSIONS: Despite strong support from corporate senior leadership, we encountered barriers in the implementation of the planned intervention at the worksite and district levels. These included financial demands that drove work intensity; turnover of site and district managers disrupting continuity in the implementation of the intervention; and staffing constraints that further increased the work load and pace. Findings underscore the need for ongoing commitment and support from both the parent employer and the host client. TRIAL REGISTRATION: This study was retrospectively registered with the Clinical Trials. Gov Protocol and Results System on June 2, 2021 with assigned registration number NCT04913168 .

Deletion of the Mitochondrial Protein VWA8 Induces Oxidative Stress and an HNF4α Compensatory Response in Hepatocytes.

von Willebrand A domain-containing protein 8 (VWA8) is a poorly characterized, mitochondrial matrix-targeted protein with an AAA ATPase domain and ATPase activity that increases in livers of mice fed a high-fat diet. This study was undertaken to use CRISPR/Cas9 to delete VWA8 in cultured mouse hepatocytes and gain insight into its function. Unbiased omics techniques and bioinformatics were used to guide subsequent assays, including the assessment of oxidative stress and the determination of bioenergetic capacity. Metabolomics analysis showed VWA8 null cells had higher levels of oxidative stress and protein degradation; assays of hydrogen peroxide production revealed higher levels of production of reactive oxygen species (ROS). Proteomics and transcriptomics analyses showed VWA8 null cells had higher levels of expression of mitochondrial proteins (electron transport-chain Complex I, ATP synthase), peroxisomal proteins, and lipid transport proteins. The pattern of higher protein abundance in the VWA8 null cells could be explained by a higher level of hepatocyte nuclear factor 4 α (HNF4α) expression. Bioenergetic assays showed higher rates of carbohydrate oxidation and mitochondrial and nonmitochondrial lipid oxidation in intact and permeabilized cells. Inhibitor assays localized sites of ROS production to peroxisomes and NOX1/4. The rescue of VWA8 protein restored the wild-type phenotype, and treatment with antioxidants decreased the level of HNF4α expression. Thus, loss of VWA8 produces a mitochondrial defect that may be sensed by NOX4, leading to an increase in the level of ROS that results in a higher level of HNF4α. The compensatory HNF4α response results in a higher oxidative capacity and an even higher level of ROS production. We hypothesize that VWA8 is an AAA ATPase protein that plays a role in mitochondrial protein quality.

Psychological well-being as part of the public health debate? Insight into dimensions, interventions, and policy.

BACKGROUND: Increasing evidence suggests that psychological well-being (PWB) is associated with lower disease and mortality risk, and may be enhanced with relatively low-cost interventions. Yet, dissemination of these interventions remains limited, in part because insufficient attention has been paid to distinct PWB dimensions, which may impact physical health outcomes differently. METHODS: This essay first reviews the empirical evidence regarding differential relationships between all-cause mortality and multiple dimensions of PWB (e.g., life purpose, mastery, positive affect, life satisfaction, optimism). Then, individual-level positive psychology interventions aimed at increasing PWB and tested in randomized-controlled trials are reviewed as these allow for easy implementation and potentially broad outreach to improve population well-being, in concert with efforts targeting other established social determinants of health. RESULTS: Several PWB dimensions relate to mortality, with varying strength of evidence. Many of positive psychology trials indicate small-to-moderate improvements in PWB; rigorous institution-level interventions are comparatively few, but preliminary results suggest benefits as well. Examples of existing health policies geared towards the improvement of population well-being are also presented. Future avenues of well-being epidemiological and intervention research, as well as policy implications, are discussed. CONCLUSIONS: Although research in the fields of behavioral and psychosomatic medicine, as well as health psychology have substantially contributed to the science of PWB, this body of work has been somewhat overlooked by the public health community. Yet, the growing interest in documenting well-being, in addition to examining its determinants and consequences at a population level may provoke a shift in perspective. To cultivate optimal well-being-mental, physical, social, and spiritual-consideration of a broader set of well-being measures, rigorous studies, and interventions that can be disseminated is critically needed.

Preventive care utilization: Association with individual- and workgroup-level policy and practice perceptions.

Preventive medical care may reduce downstream medical costs and reduce population burden of disease. However, although social, demographic, and geographic determinants of preventive care have been studied, there is little information about how the workplace affects preventive care utilization. This study examines how four types of organizational policies and practices (OPPs) are associated with individual workers' preventive care utilization. We used data collected in 2012 from 838 hospital patient care workers, grouped in 84 patient care units at two hospitals in Boston. Via survey, we assessed individuals' perceptions of four types of OPPs on their work units. We linked the survey data to a database containing detailed information on medical expenditures. Using multilevel models, we tested whether individual-level perceptions, workgroup-average perceptions, and their combination were associated with individual workers' preventive care utilization (measured by number of preventive care encounters over a two-year period). Adjusting for worker characteristics, higher individual-level perceptions of workplace flexibility were associated with greater preventive care utilization. Higher average unit-level perceptions of people-oriented culture, ergonomic practices, and flexibility were associated with greater preventive care utilization. Overall, we find that workplace policies and practices supporting flexibility, ergonomics, and people-oriented culture are associated with positive preventive care-seeking behavior among workers, with some policies and practices operating at the individual level and some at the group level. Improving the work environment could impact employers' health-related expenditures and improve workers' health-related quality of life.

The relationship between organizational policies and practices and work limitations among hospital patient care workers.

OBJECTIVE: We examined relationships between organizational policies and practices (OPPs) (safety practices, ergonomic practices, and people-oriented culture) and work limitations in a sample of hospital workers. METHODS: We used the 6-item Work Limitations Questionnaire (WLQ) to assess workers' perceptions of health-related work limitations. Self-reported OPPs and the WLQ were collected from workers in Boston, Massachusetts (n = 1277). We conducted random-intercept multi-level logistic regression models for each OPP using stepwise selection of covariates. RESULTS: As the unit-average ergonomic practice score increased by one, the odds of a worker reporting work limitations decreased by approximately 39% (P-value = 0.018), adjusted for job title, age, and body mass index. A similar relationship existed for people-oriented culture (P-value = 0.038). The association between safety practices and work limitations was similar, but not statistically significant. CONCLUSIONS: This study demonstrated the importance of workplace OPPs. OPPs that promote positive and supportive environments and that foster improvements in ergonomics may help reduce work limitations.

Lessons From COVID-19 for Protecting Workers in the Next Pandemic.

This Viewpoint examines some of the missteps during the COVID-19 pandemic to protect health care workers and how to use lessons from those mistakes for future pandemics.

RVX-297, a BET Bromodomain Inhibitor, Has Therapeutic Effects in Preclinical Models of Acute Inflammation and Autoimmune Disease.

Bromodomain (BD) and extra-terminal domain containing proteins (BET) are chromatin adapters that bind acetylated histone marks via two tandem BDs, BD1 and BD2, to regulate gene transcription. BET proteins are involved in transcriptional reprogramming in response to inflammatory stimuli. BET BD inhibitors (BETis) that are nonselective for BD1 or BD2 have recognized anti-inflammatory properties in vitro and counter pathology in models of inflammation or autoimmune disease. Although both BD1 and BD2 bind acetylated histone residues, they may independently regulate the expression of BET-sensitive genes. Here we characterized the ability of RVX-297, a novel orally active BETi with selectivity for BD2, to modulate inflammatory processes in vitro, in vivo, and ex vivo. RVX-297 suppressed inflammatory gene expression in multiple immune cell types in culture. Mechanistically, RVX-297 displaced BET proteins from the promoters of sensitive genes and disrupted recruitment of active RNA polymerase II, a property shared with pan-BETis that nonselectively bind BET BDs. In the lipopolysaccharide model of inflammation, RVX-297 reduced proinflammatory mediators assessed in splenic gene expression and serum proteins. RVX-297 also countered pathology in three rodent models of polyarthritis: rat and mouse collagen-induced arthritis, and mouse collagen antibody-induced arthritis. Further, RVX-297 prevented murine experimental autoimmune encephalomyelitis (a model of human multiple sclerosis) disease development when administered prophylactically and reduced hallmarks of pathology when administered therapeutically. We show for the first time that a BD2-selective BETi maintains anti-inflammatory properties and is effective in preclinical models of acute inflammation and autoimmunity.

An Approach to Assess the Burden of Work-Related Injury, Disease, and Distress.

The true burden (morbidity, mortality, disability, cost, pain, distress) of occupational and work-related diseases and injuries is unknown, and what is reported as burden is significantly underestimated. This underestimation affects the way decision-makers view investments in research and worker protection, which in turn has a substantial impact on national welfare and public health. To better describe the societal and individual burdens of occupational and work-related diseases and injuries, we propose an approach to gauge what is known about burden and where new assessments may be made. This approach consists of 4 elements to consider in burden assessments: (1) utilizing multiple domains, including the individual worker, the worker's family, the community in which the workplace is located, the employer, and society as a whole; (2) taking a broader view of the work-relatedness of disease and injury; (3) assessing the impact of the entire working-life continuum; and (4) applying the comprehensive concept of "well-being" as an indicator in addressing contemporary changes in the nature of work, the workplace, and the workforce. Further research on burden and enhanced surveillance is needed to develop these elements.

High-Resolution Metabolomics with Acyl-CoA Profiling Reveals Widespread Remodeling in Response to Diet.

The availability of acyl-Coenzyme A (acyl-CoA) thioester compounds affects numerous cellular functions including autophagy, lipid oxidation and synthesis, and post-translational modifications. Consequently, the acyl-CoA level changes tend to be associated with other metabolic alterations that regulate these critical cellular functions. Despite their biological importance, this class of metabolites remains difficult to detect and quantify using current analytical methods. Here we show a universal method for metabolomics that allows for the detection of an expansive set of acyl-CoA compounds and hundreds of other cellular metabolites. We apply this method to profile the dynamics of acyl-CoA compounds and corresponding alterations in metabolism across the metabolic network in response to high fat feeding in mice. We identified targeted metabolites (>50) and untargeted features (>1000) with significant changes (FDR < 0.05) in response to diet. A substantial extent of this metabolic remodeling exhibited correlated changes in acyl-CoA metabolism with acyl-carnitine metabolism and other features of the metabolic network that together can lead to the discovery of biomarkers of acyl-CoA metabolism. These findings show a robust acyl-CoA profiling method and identify coordinated changes of acyl-CoA metabolism in response to nutritional stress.

Integrating worksite health protection and health promotion: A conceptual model for intervention and research.

There is increasing recognition of the value added by integrating traditionally separate efforts to protect and promote worker safety and health. This paper presents an innovative conceptual model to guide research on determinants of worker safety and health and to inform the design, implementation and evaluation of integrated approaches to promoting and protecting worker health. This model is rooted in multiple theories and the premise that the conditions of work are important determinants of individual safety and health outcomes and behaviors, and outcomes important to enterprises such as absence and turnover. Integrated policies, programs and practices simultaneously address multiple conditions of work, including the physical work environment and the organization of work (e.g., psychosocial factors, job tasks and demands). Findings from two recent studies conducted in Boston and Minnesota (2009-2015) illustrate the application of this model to guide social epidemiological research. This paper focuses particular attention on the relationships of the conditions of work to worker health-related behaviors, musculoskeletal symptoms, and occupational injury; and to the design of integrated interventions in response to specific settings and conditions of work of small and medium size manufacturing businesses, based on a systematic assessment of priorities, needs, and resources within an organization. This model provides an organizing framework for both research and practice by specifying the causal pathways through which work may influence health outcomes, and for designing and testing interventions to improve worker safety and health that are meaningful for workers and employers, and responsive to that setting's conditions of work.

Investigation of the electronic ground states for a reduced pyridine(diimine) uranium series: evidence for a ligand tetraanion stabilized by a uranium dimer.

The electronic structures of a series of highly reduced uranium complexes bearing the redox-active pyridine(diimine) ligand, (Mes)PDI(Me) ((Mes)PDI(Me) = 2,6-(2,4,6-Me3-C6H2-N═CMe)2C5H3N) have been investigated. The complexes, ((Mes)PDI(Me))UI3(THF) (1), ((Mes)PDI(Me))UI2(THF)2 (2), [((Mes)PDI(Me))UI]2 (3), and [((Mes)PDI(Me))U(THF)]2 (4), were examined using electronic and X-ray absorption spectroscopies, magnetometry, and computational analyses. Taken together, these studies suggest that all members of the series contain uranium(IV) centers with 5f (2) configurations and reduced ligand frameworks, specifically [(Mes)PDI(Me)](•/-), [(Mes)PDI(Me)](2-), [(Mes)PDI(Me)](3-) and [(Mes)PDI(Me)](4-), respectively. In the cases of 2, 3, and 4 no unpaired spin density was found on the ligands, indicating a singlet diradical ligand in monomeric 2 and ligand electron spin-pairing through dimerization in 3 and 4. Interaction energies, representing enthalpies of dimerization, of -116.0 and -144.4 kcal mol(-1) were calculated using DFT for the monomers of 3 and 4, respectively, showing there is a large stabilization gained by dimerization through uranium-arene bonds. Highlighted in these studies is compound 4, bearing a previously unobserved pyridine(diimine) tetraanion, that was uniquely stabilized by backbonding between uranium cations and the η(5)-pyridyl ring.