Developing a clinical-pathological framework of long COVID-related fatigue applied to public safety workers.

In the wake of the COVID-19 pandemic, millions worldwide are still struggling with persistent or recurring symptoms known as long COVID. Fatigue is one of the most prevalent symptoms associated with long COVID, and for many it can be debilitating. Understanding the potential pathological processes that link fatigue to long COVID is critical to better guide treatment. Challenges with diagnosis and treatment are reviewed, recognizing that post-COVID fatigue does not always present with corroborating clinical evidence, a situation that is frustrating for both patients and healthcare providers. Firefighters are a group of public safety workers who are particularly impacted by long COVID-related fatigue. Firefighters must be able to engage in strenuous physical activity and deal with demanding psychological situations, both of which may be difficult for those suffering from fatigue. Disruption in public safety worker health can potentially impact community welfare. This review creates a framework to explain the clinical-pathological features of fatigue resulting from long COVID, addresses diagnosis and treatment challenges, and explores the unique impact fatigue may pose for public safety workers and their organizations.

Citations in Wikipedia for understanding research reach.

Objective: Wikipedia is the most frequently accessed online health information resource and is well positioned as a valuable tool for public health communication and knowledge translation. The authors aimed to explore their institution's health and medical research reach by analyzing its presence in Wikipedia articles. Methods: In October 2022, a comprehensive database search was constructed in PubMed to retrieve clinical evidence syntheses published by at least one author affiliated with McMaster University from 2017 to 2022, inclusive. Altmetric Explorer was queried using PubMed Identifiers and article titles to access metadata and Wikipedia citation data. 3,582 health evidence syntheses from at least one McMaster University affiliated author were analyzed. Results: Six percent (n=219) of health evidence syntheses from the authors' institution were cited 568 times in 524 unique Wikipedia articles across 28 different language editions. 45% of citations appeared in English Wikipedia, suggesting a broad global reach for the institutions' research outputs. When adjusted for open access publications, 8% of McMaster University's health evidence syntheses appear in Wikipedia. Conclusion: Altmetric Explorer is a valuable tool for exploring the reach of an institution's research outputs. Isolating Altmetric data to focus on Wikipedia citations has value for any institution wishing to gain more insight into the global, community-level reach of its contributions to the latest health and medical evidence.

Racial and Ethnic Disparities in Providing Guideline-Concordant Care After Hip Fracture Surgery.

Importance: Institutions have adopted protocol-driven standardized hip fracture programs (SHFPs). However, concerns persist regarding bias in adherence to guideline-concordant care leading to disparities in implementing high-quality care for patients recovering from surgery for hip fracture. Objective: To assess disparities in the implementation of guideline-concordant care for patients after hip fracture surgery in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Targeted Hip Fracture (THF) Database. Design, Setting, and Participants: This cross-sectional study was conducted using the ACS-NSQIP THF database from 2016 to 2021 for patients aged 65 years and older with hip fractures undergoing surgical fixation. Care outcomes of racial and ethnic minority patients (including American Indian or Alaska Native, Asian, Black or African American, Native Hawaiian or Pacific Islander, or multiple races and Hispanic ethnicity) were compared with non-Hispanic White patients via risk difference, stratified by care institution SHFP status. Modified Poisson regression was used to measure interactions. Statistical analysis was performed from November 2022 to June 2024. Main Outcomes and Measures: The primary outcomes of interest encompassed weight-bearing as tolerated (WBAT) on postoperative day 1 (POD1), venous thromboembolism (VTE) prophylaxis, bone-protective medication, and the presence of SHFP at the institution. Results: Among 62 194 patients (mean [SD] age, 82.4 [7.3] years; 43 356 [69.7%] female) who met inclusion criteria and after multiple imputation, 11.2% (95% CI, 10.8%-11.5%) were racial and ethnic minority patients, 3.3% (95% CI, 3.1%-3.4%) were Hispanic patients, and 92.0% (95% CI, 91.7%-92.2%) were White. Receiving care at an institution with an SHFP was associated with improved likelihood of receiving guideline-concordant care for all patients to varying degrees across care outcomes. SHFP was associated with higher probability of being WBAT-POD1 (risk difference for racial and ethnic minority patients, 0.030 [95% CI, 0.004-0.056]; risk difference for non-Hispanic White patients, 0.037 [95% CI, 0.029-0.45]) and being prescribed VTE prophylaxis (risk difference for racial and ethnic minority patients, 0.066 [95% CI, 0.040-0.093]; risk difference for non-Hispanic White patients, 0.080 [95% CI, 0.071-0.089]), but SHFP was associated with the largest improvements in receipt of bone-protective medications (risk difference for racial and ethnic minority patients, 0.149 [95% CI, 0.121-0.178]; risk difference for non-Hispanic White patients, 0.181 [95% CI, 0.173-0.190]). While receiving care at an SHFP was associated with improved probability of receiving guideline-concordant care in both race and ethnicity groups, greater improvements were seen among non-Hispanic White patients compared with racial and ethnic minority patients. Conclusions and Relevance: Older adults who received care at an institution with an SHFP were more likely to receive guideline-concordant care (bone-protective medication, WBAT-POD1, and VTE prophylaxis), regardless of race and ethnicity. However, the probability of receiving guideline-concordant care at an institution with an SHFP increased more for non-Hispanic White patients than racial and ethnic minority patients.

The Community As A Full Partner: A New Model For Public Health.

The COVID-19 pandemic demonstrated a need to strengthen the US public health system by shifting toward much greater community engagement and leadership. In November and December 2023, we conducted separate online surveys of community-based organizations and large metropolitan health departments to identify barriers and opportunities for building a public health system with strong community partnerships. Identified barriers included mistrust, siloed health departments with structural challenges in funding community-based organizations, and insufficient shared decision making. The surveys helped inform our six policy recommendations: establish state and local community councils to formalize the roles of community-based organizations in public health decision making; dedicate funding to these organizations; offer funding that is not limited to a specific disease or condition; simplify procurement and reporting processes directed to community-based organizations; create a training and technical assistance program for these organizations; and increase public health worker diversity, including sustainable funding for community health workers.

Biochemical, Biomarker, and Behavioral Characterization of the GrnR493X Mouse Model of Frontotemporal Dementia.

Heterozygous loss-of-function mutations in the progranulin gene (GRN) are a major cause of frontotemporal dementia due to progranulin haploinsufficiency; complete deficiency of progranulin causes neuronal ceroid lipofuscinosis. Several progranulin-deficient mouse models have been generated, including both knockout mice and knockin mice harboring a common patient mutation (R493X). However, the GrnR493X mouse model has not been characterized completely. Additionally, while homozygous GrnR493X and Grn knockout mice have been extensively studied, data from heterozygous mice is still limited. Here, we performed more in-depth characterization of heterozygous and homozygous GrnR493X knockin mice, which includes biochemical assessments, behavioral studies, and analysis of fluid biomarkers. In the brains of homozygous GrnR493X mice, we found increased phosphorylated TDP-43 along with increased expression of lysosomal genes, markers of microgliosis and astrogliosis, pro-inflammatory cytokines, and complement factors. Heterozygous GrnR493X mice did not have increased TDP-43 phosphorylation but did exhibit limited increases in lysosomal and inflammatory gene expression. Behavioral studies found social and emotional deficits in GrnR493X mice that mirror those observed in Grn knockout mouse models, as well as impairment in memory and executive function. Overall, the GrnR493X knockin mouse model closely phenocopies Grn knockout models. Lastly, in contrast to homozygous knockin mice, heterozygous GrnR493X mice do not have elevated levels of fluid biomarkers previously identified in humans, including neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in both plasma and CSF. These results may help to inform pre-clinical studies that use this Grn knockin mouse model and other Grn knockout models.

Challenges in IBD Research 2024: Environmental Triggers.

Environmental factors play an important role in inflammatory bowel diseases (IBD; Crohn's disease, [CD], ulcerative colitis [UC]). As part of the Crohn's & Colitis Challenges 2024 agenda, the Environmental Triggers workgroup summarized the progress made in the field of environmental impact on IBD since the last Challenges cycle in this document. The workgroup identified 4 unmet gaps in this content area pertaining to 4 broad categories: (1) Epidemiology; (2) Exposomics and environmental measurement; (3) Biologic mechanisms; and (4) Interventions and Implementation. Within epidemiology, the biggest unmet gaps were in the study of environmental factors in understudied populations including racial and ethnic minority groups and in populations witnessing rapid rise in disease incidence globally. The workgroup also identified a lack of robust knowledge of how environmental factors may impact difference stages of the disease and for different disease-related end points. Leveraging existing cohorts and targeted new prospective studies were felt to be an important need for the field. The workgroup identified the limitations of traditional questionnaire-based assessment of environmental exposure and placed high priority on the identification of measurable biomarkers that can quantify cross-sectional and longitudinal environmental exposure. This would, in turn, allow for identifying the biologic mechanisms of influence of environmental factors on IBD and understand the heterogeneity in effect of such influences. Finally, the working group emphasized the importance of generating high-quality data on effective environmental modification on an individual and societal level, and the importance of scalable and sustainable methods to deliver such changes.

Environmental factors are important in inflammatory bowel diseases. It is a high priority to identify environmental factors impacting different disease stages and in different populations, develop biomarkers for such exposures, and generate evidence for modifying them to improve outcomes.

A 7-Month Multidisciplinary Healthy Lifestyle Intervention Effectively Improved Cardiometabolic Risk Profile of Firefighters.

OBJECTIVE: We investigated the effect of a 7-month healthy lifestyle intervention on cardiometabolic risk factors (CMRF) among male career military firefighters (FFs). METHODS: Forty-nine FFs participated in a 7-month workplace multiddisciplinary healthy lifestyle intervention designed to reduce CMRF through exercise, diet, and improved sleep. Medical assessments, accelerometry, and surveys at the beginning and end determined program effectiveness. RESULTS: At the end of the intervention period, there was a significant improvement in measures of body composition and blood glucose. The prevalence of hypertension also decreased significantly ( P < 0.01). The 57% of participants who fully adhered to the program had significantly greater improvements across multiple CMRF. Participants increased their physical activity and improved their diet following the intervention. CONCLUSIONS: This healthy lifestyle intervention was effective in changing behavior and lowering cardiometabolic risk among FFs.

Evaluating workplace protection factors (WPFs) of different firefighter PPE interface control measures for select volatile organic compounds (VOCs).

Structural firefighters are exposed to a complex set of contaminants and combustion byproducts, including volatile organic compounds (VOCs). Additionally, recent studies have found structural firefighters' skin may be exposed to multiple chemical compounds via permeation or penetration of chemical byproducts through or around personal protective equipment (PPE). This mannequin-based study evaluated the effectiveness of four different PPE conditions with varying contamination control measures (incorporating PPE interface design features and particulate blocking materials) to protect against ingress of several VOCs in a smoke exposure chamber. We also investigated the effectiveness of long-sleeve base layer clothing to provide additional protection against skin contamination. Outside gear air concentrations were measured from within the smoke exposure chamber at the breathing zone, abdomen, and thigh heights. Personal air concentrations were collected from mannequins under PPE at the same general heights and under the base layer at abdomen and thigh heights. Sampled contaminants included benzene, toluene, styrene, and naphthalene. Results suggest that VOCs can readily penetrate the ensembles. Workplace protection factors (WPFs) were near one for benzene and toluene and increased with increasing molecular weight of the contaminants. WPFs were generally lower under hoods and jackets compared to under pants. For all PPE conditions, the pants appeared to provide the greatest overall protection against ingress of VOCs, but this may be due in part to the lower air concentrations toward the floor (and cuffs of pants) relative to the thigh-height outside gear concentrations used in calculating the WPFs. Providing added interface control measures and adding particulate-blocking materials appeared to provide a protective benefit against less-volatile chemicals, like naphthalene and styrene.

Association of Endogenous Testosterone with Physical Fitness Measures during Firefighter Occupational Health Evaluations.

Firefighting is a physically demanding profession associated with unacceptably high on-duty cardiovascular mortality. Low endogenous total testosterone (TT) is an emerging cardiometabolic (CM) risk factor in men, but limited data exists on its interactions with physical fitness (PF). Data from occupational health and fitness assessments of 301 male career firefighters (FFs) were analyzed. TT was categorized as low (<264 ng/dL), borderline (264-399 ng/dL), and reference (400-916 ng/dL). PF tests included cardiorespiratory fitness (submaximal treadmill), body fat percentage (BF%), push-ups, plank, and handgrip strength assessments. In the crude analyses, FFs in the low TT group had worse muscular and cardiorespiratory fitness measures compared to the referent group. However, after adjusting for age and BF%, none of the PF differences remained statistically significant. Similarly, the odds of less-fit FFs (PF performance below median values) having low TT were higher compared to the fitter ones only before adjusting for age and BF%. Therefore, in the final adjusted model, there was no significant association between TT and PF. Our data suggest that age and body fat confound the association between PF and TT. Low TT and poor PF are important components of FFs' CM risk profile, and there is potential benefit to considering TT screening as part of a comprehensive occupational health program that manages performing medical evaluations and provides education and preventative programming.

Evaluation of the relationship between occupational-specific task performance and measures of physical fitness, cardiovascular and musculoskeletal health in firefighters.

INTRODUCTION: Firefighters are required to perform physically strenuous tasks such as hose drags, victim rescues, forcible entries and stair climbs to complete their public safety mission. Occupational-specific tasks are often used to evaluate the ability of firefighters to adequately/safely perform their duties. Depending on the regions, occupational-specific tasks include six to eight individual tasks, which emphasize distinct aspects of their physical fitness, while also requiring different levels of cardiovascular (CVH) and musculoskeletal health (MSH). Therefore, the aim of this study was to evaluate the relationship between specific occupational task performance and measures of physical fitness, cardiovascular and musculoskeletal health. METHODS: Using a cross-sectional design, 282 full-time male and female firefighters were recruited. A researcher-generated questionnaire and physical measures were used to collect data on sociodemographic characteristics, CVH, MSH and weekly physical activity habits. Physical measures were used to collect data on physical fitness and occupational-specific task performance. RESULTS: Absolute cardiorespiratory fitness (abV̇O2max), grip strength, leg strength, push-ups, sit-ups and lean body mass (all p < 0.001) had an inverse association with completion times on all occupational-specific tasks. Age was positively related to the performance of all tasks (all p < 0.05). Higher heart rate variability (HRV) was associated with better performance on all tasks (all p < 0.05). Bodyfat percentage (BF%) and diastolic blood pressure were positively associated with the step-up task (p < 0.05). Lower back musculoskeletal injury (LoBMSI), musculoskeletal discomfort (MSD), and lower limb MSD were associated with a decreased odds of passing the step-up. Upper body MSIs (UBMSI), LoBMSIs and Lower back MSD were associated with decreased odds of passing the rescue drag. CONCLUSION: Firefighters that were taller, leaner, stronger and fitter with a more favourable CVH profile, higher HRV and less musculoskeletal discomfort performed best on all occupational-specific tasks.

Perinatal Telehealth: Meeting Patients Where They Are.

INTRODUCTION: Prior to the coronavirus disease 2019 (COVID-19) pandemic, studies of innovative telehealth perinatal care models showed similar clinical outcomes and perceived quality of care between groups receiving a combination of virtual video and in-person visits. However, these studies included primarily White, English-speaking participants, excluding those who were economically disenfranchised or did not speak English. The purpose of this qualitative study was to describe perinatal patients' and providers' experiences with telehealth during and after the acute phase of the COVID-19 pandemic to inform future utilization of telehealth to drive the delivery of high-quality, accessible, and equitable perinatal care to diverse communities. METHODS: This descriptive qualitative study included a purposive sample of 14 patients and 17 providers who received or provided perinatal care via telehealth in either a certified nurse-midwifery practice or the nurse-family partnership care model between March 2020 and April 2022. Maximum variation sampling offered a diverse population based on race, ethnicity, and rurality. Researchers conducted 2 rounds of semistructured interviews with a focus on understanding social and geographic context. RESULTS: Six themes were identified through inductive analysis: (1) unexpected advantages of telehealth, (2) patient empowerment, (3) providers' fear of adverse outcomes, (4) concern for equitable care, (5) strategies to enhance the telehealth experience, and (6) strategies to address access to perinatal telehealth. Patients appreciated the increased ease and reduced cost of accessing visits, which led to fewer missed appointments. Health care providers saw great opportunity in telehealth but expressed concerns about accessibility for patients with language barriers or limited resources. DISCUSSION: This study provides insight into priorities for continued telehealth utilization focused on providing equitable access to perinatal care. Rather than returning to practices from before the COVID-19 pandemic formed from longstanding routines and perceived limitations, providers are encouraged to capitalize on the rapid innovations in telehealth to build a more effective, equitable, and patient-centered approach to perinatal care.

Inferior Outcomes for Patients Transferred Between Surgical Stages for Knee Periprosthetic Joint Infection.

BACKGROUND: Periprosthetic joint infection (PJI) in total knee arthroplasty may result in 2-stage revision surgery. There are limited data describing outcomes when the first stage is completed at an outside hospital and the patient is referred to a tertiary center. We hypothesized that patients have greater success when both surgeries occur at a single center. METHODS: There were 25 knee PJI patients who presented with an antibiotic spacer and had a minimum 2-year follow-up who were retrospectively identified at a single tertiary referral center from 2014 to 2021. A cohort matched for age, sex, body mass index, Elixhauser comorbidity measure, spacer type, infectious organism, and year of surgery was established with patients who had both stages completed at the investigating institution. Modified Delphi success criteria of no subsequent surgery or reinfection with any species were compared. RESULTS: The transferred group demonstrated a treatment success of 40% compared to 84% in the continuous group (P < .01). The transferred group was more likely to have an additional procedure between stages (44 versus 8%, P < .01), with a higher number of surgeries after primary total knee arthroplasty (4.8 versus 3.0, P < .01), between stages (1.4 versus 0.2, P < .01), and after second stage (0.8 versus 0.2, P = .03). The transferred group had longer durations between stages (20.1 versus 7.0 weeks, P < .01). CONCLUSION: Patients who have PJIs transferred between stages demonstrated higher treatment failure. Surgeons should consider transfer early with a goal of continuous management by a single institution.

Biochemical, biomarker, and behavioral characterization of the GrnR493X mouse model of frontotemporal dementia.

Heterozygous loss-of-function mutations in the progranulin gene (GRN) are a major cause of frontotemporal dementia due to progranulin haploinsufficiency; complete deficiency of progranulin causes neuronal ceroid lipofuscinosis. Several progranulin-deficient mouse models have been generated, including both knockout mice and knockin mice harboring a common patient mutation (R493X). However, the GrnR493X mouse model has not been characterized completely. Additionally, while homozygous GrnR493X and Grn knockout mice have been extensively studied, data from heterozygous mice is still limited. Here, we performed more in-depth characterization of heterozygous and homozygous GrnR493X knockin mice, which includes biochemical assessments, behavioral studies, and analysis of fluid biomarkers. In the brains of homozygous GrnR493X mice, we found increased phosphorylated TDP-43 along with increased expression of lysosomal genes, markers of microgliosis and astrogliosis, pro-inflammatory cytokines, and complement factors. Heterozygous GrnR493X mice did not have increased TDP-43 phosphorylation but did exhibit limited increases in lysosomal and inflammatory gene expression. Behavioral studies found social and emotional deficits in GrnR493X mice that mirror those observed in Grn knockout mouse models, as well as impairment in memory and executive function. Overall, the GrnR493X knockin mouse model closely phenocopies Grn knockout models. Lastly, in contrast to homozygous knockin mice, heterozygous GrnR493X mice do not have elevated levels of fluid biomarkers previously identified in humans, including neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in both plasma and CSF. These results may help to inform pre-clinical studies that use this Grn knockin mouse model and other Grn knockout models.

Sudden Shift to Telehealth in COVID-19: A Retrospective Cohort Study of Disparities in Use of Telehealth for Prenatal Care in a Large Midwifery Service.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic created disruption in health care delivery, including a sudden transition to telehealth use in mid-March 2020. The purpose of this study was to examine changes in the mode of prenatal care visits and predictors of telehealth use (provider-patient messaging, telephone visits, and video visits) during the COVID-19 pandemic among those receiving care in a large, academic nurse-midwifery service. METHODS: We conducted a retrospective cohort study of those enrolled for prenatal care in 2 nurse-midwifery clinics between 2019 and 2021 (n = 3172). Use outcomes included number and type of encounter: in-person and telehealth (primary outcome). Comparisons were made in frequency and types of encounters before and during COVID-19. A negative binomial regression was fit on the outcome of telehealth encounter count, with race/ethnicity, age, language, parity, hypertension, diabetes, and depression as predictors. RESULTS: When comparing pre-COVID-19 (before March 2020) with during COVID-19 (after March 2020), overall encounters increased from 15.9 to 19.5 mean number of encounters per person (P < .001). The increase was driven by telehealth encounters; there were no significant differences for in-person prenatal visit counts before and during the pandemic period. Direct patient-provider messaging was the most common type of telehealth encounter. Predictors of telehealth encounters included English as primary language and diagnoses of diabetes or depression. DISCUSSION: No differences in the frequency of in-person prenatal care visits suggests that telehealth encounters led to more contact with midwives and did not replace in-person encounters. Spanish-speaking patients were least likely to use telehealth-delivered prenatal care during the pandemic; a small, but significant, proportion of patients had no or few telehealth encounters, and a significant proportion had high use of telehealth. Integration of telehealth in future delivery of prenatal care should consider questions of equity, patient and provider satisfaction, access, redundancies, and provider workload.

The effect of mild to moderate COVID-19 infection on the cardiorespiratory fitness of firefighters.

Introduction: An adequate level of cardiorespiratory fitness (CRF) is critical for firefighters to perform the strenuous and physiologically demanding work of firefighting safely and effectively. The coronavirus disease 2019 (COVID-19) has been shown to negatively impact CRF in both the acute phase and longer-term following infection. This study aimed to determine changes to the CRF of firefighters pre- to post-mild to moderate COVID-19 infection and to investigate the impact of days past COVID-19 infection on change in CRF. Methods: CRF measures from cardiopulmonary exercise testing (CPET) at annual occupational health exams that occurred pre-COVID-19 infection in 2019 were obtained for firefighters from seven Arizona fire departments. Measures were compared to CPET evaluations from annual health exams the following year in a cohort of firefighters who self-reported mild to moderate illness following COVID-19 infection between exams. Results: Among a cohort of 103 firefighters, mean age 40 ± 9 years, CRF [as measured by peak oxygen consumption (VO2)] declined by an average of 2.55 ml·kg-1·min-1 or 7.3% (d = -0.38, p < 0.001) following COVID-19 infection (mean time from COVID-19 infection to CPET was 110 ± 78 days). The number of days past COVID-19 infection showed a small, yet significant, relationship to peak VO2 (r = 0.250, p = 0.011). Estimated marginal effects indicated that when biological sex, age, and BMI are controlled for, predicted peak VO2 returned to pre-COVID-19 values ~300 days after COVID-19 infection. Conclusion: Peak VO2 (ml·kg-1·min-1) declined 7.3% among firefighters an average of 110 days past reporting mild to moderate COVID-19 infection. This decrease has implications for the operational readiness and safety of firefighters.

Antisense oligonucleotides targeting the miR-29b binding site in the GRN mRNA increase progranulin translation.

Heterozygous GRN (progranulin) mutations cause frontotemporal dementia (FTD) due to haploinsufficiency, and increasing progranulin levels is a major therapeutic goal. Several microRNAs, including miR-29b, negatively regulate progranulin protein levels. Antisense oligonucleotides (ASOs) are emerging as a promising therapeutic modality for neurological diseases, but strategies for increasing target protein levels are limited. Here, we tested the efficacy of ASOs as enhancers of progranulin expression by sterically blocking the miR-29b binding site in the 3' UTR of the human GRN mRNA. We found 16 ASOs that increase progranulin protein in a dose-dependent manner in neuroglioma cells. A subset of these ASOs also increased progranulin protein in iPSC-derived neurons and in a humanized GRN mouse model. In FRET-based assays, the ASOs effectively competed for miR-29b from binding to the GRN 3' UTR RNA. The ASOs increased levels of newly synthesized progranulin protein by increasing its translation, as revealed by polysome profiling. Together, our results demonstrate that ASOs can be used to effectively increase target protein levels by partially blocking miR binding sites. This ASO strategy may be therapeutically feasible for progranulin-deficient FTD as well as other conditions of haploinsufficiency.

Contribution of Spontaneous Mutations to Quantitative and Molecular Variation at the Highly Repetitive rDNA Locus in Yeast.

The ribosomal DNA array in Saccharomyces cerevisiae consists of many tandem repeats whose copy number is believed to be functionally important but highly labile. Regulatory mechanisms have evolved to maintain copy number by directed mutation, but how spontaneous variation at this locus is generated and selected has not been well characterized. We applied a mutation accumulation approach to quantify the impacts of mutation and selection on this unique genomic feature across hundreds of mutant strains. We find that mutational variance for this trait is relatively high, and that unselected mutations elsewhere in the genome can disrupt copy number maintenance. In consequence, copy number generally declines gradually, consistent with a previously proposed model of rDNA maintenance where a downward mutational bias is normally compensated by mechanisms that increase copy number when it is low. This pattern holds across ploidy levels and strains in the standard lab environment but differs under some stressful conditions. We identify several alleles, gene categories, and genomic features that likely affect copy number, including aneuploidy for chromosome XII. Copy number change is associated with reduced growth in diploids, consistent with stabilizing selection. Levels of standing variation in copy number are well predicted by a balance between mutation and stabilizing selection, suggesting this trait is not subject to strong diversifying selection in the wild. The rate and spectrum of point mutations within the rDNA locus itself are distinct from the rest of the genome and predictive of polymorphism locations. Our findings help differentiate the roles of mutation and selection and indicate that spontaneous mutation patterns shape several aspects of ribosomal DNA evolution.

Measuring midwives' perceptions of their practice climate across racial-ethnic identities: An invariance analysis of the Midwifery Practice Climate Scale.

Diversification of the midwifery workforce is key to addressing disparities in maternal health in the United States. Midwives who feel supported in their practice environments report less burnout and turnover; therefore, creating positive practice environments for midwives of color is an essential component of growing and retaining midwives of color in the workforce. The Midwifery Practice Climate Scale (MPCS) is a 10-item instrument developed through multiphase empirical analysis to measure midwives' practice environments, yet the MPCS had not been independently tested with midwives of color. We conducted invariance analyses to test whether latent means can be compared between midwives of color and non-Hispanic White samples. A step-up approach applied a series of increasingly stringent constraints to model estimations with multiple group confirmatory factor analyses with two pooled samples. A configural model was estimated as the basis of multiple group comparisons where all parameters were allowed to freely vary. Metric invariance was estimated by constraining item factor loadings to be equal. Scalar invariance was estimated by constraining intercepts of indicators to be equal. Each model was compared to the baseline model. The findings supported scalar invariance of MPCS across midwives of color and non-Hispanic White midwives, indicating that the MPCS is measuring the same intended construct across groups, and that differences in scores between these two groups reflect true group differences and are not related to measurement error. Additionally, in this sample, there was no statistically significant difference in perceptions of the practice environments across midwives of color and non-Hispanic White midwives (p > 0.05).

Physical fitness, cardiovascular and musculoskeletal health, and occupational performance in firefighters.

Introduction: To perform their work efficiently and safely, firefighters should maintain all aspects of physical fitness. Cardiac-related incidents are the leading cause of duty-related deaths in firefighters, and many firefighters have poor musculoskeletal health (MSH) that hinder their occupational performance (OP). Establishing the relationship between physical fitness, cardiovascular health (CVH), MSH and OP may add new insight on the most significant factors influencing OP in firefighters, specifically in the City of Cape Town Fire and Rescue Service (CoCTFS), which had not been studied before. Therefore, the purpose of this study was to investigate whether physical fitness, CVH and MSH were associated with OP in firefighters, in the COCTFRS. Methods: This cross-sectional study included 283 full-time firefighters aged 20-65 years from Cape Town, South Africa. A researcher-generated questionnaire was used to collect data on sociodemographic characteristics, lifestyle factors and MSH. Physical measures were used to collect information on physical fitness, CVH, and OP [using a physical ability test (PAT)]. Linear and binary logistic regressions, adjusted for age, sex, height and weekly metabolic equivalent minutes (WMETM), multivariate analysis of covariance (MANCOVA), adjusted for age, sex, height and body mass index (BMI) and backward stepwise regressions were used to investigate the associations between the various constructs. Results: From multivariable analyses, age, lean body mass, body fat percentage (BF%), estimated absolute oxygen consumption (abV̇O2max), grip strength, leg strength, push-ups, sit-ups, WMETM and heart rate variability were associated with PAT completion times (all p < 0.01). The MANCOVA showed a significant difference between performance categories of the PAT based on physical fitness and CVH (both p < 0.001). WMETM, BF%, abV̇O2max, grip strength, leg strength and sit-ups explained the highest proportion (50.5%) of the variation in PAT completion times. Conclusion: Younger, non-obese, fitter and stronger firefighters, with a better CVH status, performed significantly better and were most likely to pass the PAT in firefighters, in Cape Town, South Africa. Firefighters should maintain high levels of physical fitness and a good level of CVH to ensure a satisfactory level of OP.