Proteomic Analysis of Unbounded Cellular Compartments: Synaptic Clefts.

Cellular compartments that cannot be biochemically isolated are challenging to characterize. Here we demonstrate the proteomic characterization of the synaptic clefts that exist at both excitatory and inhibitory synapses. Normal brain function relies on the careful balance of these opposing neural connections, and understanding how this balance is achieved relies on knowledge of their protein compositions. Using a spatially restricted enzymatic tagging strategy, we mapped the proteomes of two of the most common excitatory and inhibitory synaptic clefts in living neurons. These proteomes reveal dozens of synaptic candidates and assign numerous known synaptic proteins to a specific cleft type. The molecular differentiation of each cleft allowed us to identify Mdga2 as a potential specificity factor influencing Neuroligin-2's recruitment of presynaptic neurotransmitters at inhibitory synapses.

PIF4 enhances the expression of SAUR genes to promote growth in response to nitrate.

Nitrate supply is fundamental to support shoot growth and crop performance, but the associated increase in stem height exacerbates the risks of lodging and yield losses. Despite their significance for agriculture, the mechanisms involved in the promotion of stem growth by nitrate remain poorly understood. Here, we show that the elongation of the hypocotyl of Arabidopsis thaliana, used as a model, responds rapidly and persistently to upshifts in nitrate concentration, rather than to the nitrate level itself. The response occurred even in shoots dissected from their roots and required NITRATE TRANSPORTER 1.1 (NRT1.1) in the phosphorylated state (but not NRT1.1 nitrate transport capacity) and NIN-LIKE PROTEIN 7 (NLP7). Nitrate increased PHYTOCHROME INTERACTING FACTOR 4 (PIF4) nuclear abundance by posttranscriptional mechanisms that depended on NRT1.1 and phytochrome B. In response to nitrate, PIF4 enhanced the expression of numerous SMALL AUXIN-UP RNA (SAUR) genes in the hypocotyl. The growth response to nitrate required PIF4, positive and negative regulators of its activity, including AUXIN RESPONSE FACTORs, and SAURs. PIF4 integrates cues from the soil (nitrate) and aerial (shade) environments adjusting plant stature to facilitate access to light.

Transcriptome-wide mapping reveals a diverse dihydrouridine landscape including mRNA.

Dihydrouridine is a modified nucleotide universally present in tRNAs, but the complete dihydrouridine landscape is unknown in any organism. We introduce dihydrouridine sequencing (D-seq) for transcriptome-wide mapping of D with single-nucleotide resolution and use it to uncover novel classes of dihydrouridine-containing RNA in yeast which include mRNA and small nucleolar RNA (snoRNA). The novel D sites are concentrated in conserved stem-loop regions consistent with a role for D in folding many functional RNA structures. We demonstrate dihydrouridine synthase (DUS)-dependent changes in splicing of a D-containing pre-mRNA in cells and show that D-modified mRNAs can be efficiently translated by eukaryotic ribosomes in vitro. This work establishes D as a new functional component of the mRNA epitranscriptome and paves the way for identifying the RNA targets of multiple DUS enzymes that are dysregulated in human disease.

Disparities in cancer incidence by sexual orientation.

INTRODUCTION: Cancer risk factors are more common among sexual minority populations (e.g., lesbian, bisexual) than their heterosexual peers, yet little is known about cancer incidence across sexual orientation groups. METHODS: The 1989-2017 data from the Nurses' Health Study II, a longitudinal cohort of female nurses across the United States, were analyzed (N = 101,543). Sexual orientation-related cancer disparities were quantified by comparing any cancer incidence among four sexual minority groups based on self-disclosure-(1) heterosexual with past same-sex attractions/partners/identity; (2) mostly heterosexual; (3) bisexual; and (4) lesbian women-to completely heterosexual women using age-adjusted incidence rate ratios (aIRR) calculated by the Mantel-Haenszel method. Additionally, subanalyses at 21 cancer disease sites (e.g., breast, colon/rectum) were conducted. RESULTS: For all-cancer analyses, there were no statistically significant differences in cancer incidence at the 5% type I error cutoff among sexual minority groups when compared to completely heterosexual women; the aIRR was 1.17 (95% CI,0.99-1.38) among lesbian women and 0.80 (0.58-1.10) among bisexual women. For the site-specific analyses, incidences at multiple sites were significantly higher among lesbian women compared to completely heterosexual women: thyroid cancer (aIRR, 1.87 [1.03-3.41]), basal cell carcinoma (aIRR, 1.85 [1.09-3.14]), and non-Hodgkin lymphoma (aIRR, 2.13 [1.10-4.12]). CONCLUSION: Lesbian women may be disproportionately burdened by cancer relative to their heterosexual peers. Sexual minority populations must be explicitly included in cancer prevention efforts. Comprehensive and standardized sexual orientation data must be systematically collected so nuanced sexual orientation-related cancer disparities can be accurately assessed for both common and rare cancers.

Electrokinetic transport of CTAB induces multiphasic behavior during capillary adsorption and desorption.

Cationic surfactant coatings (e.g., CTAB) are commonly used in CE to control EOF and thereby improve separation efficiencies. However, our understanding of surfactant adsorption and desorption dynamics under EOF conditions is limited. Here, we apply automated zeta potential analysis to study the adsorption and desorption kinetics of CTAB in a capillary under different transport conditions: diameter, length, voltage alternation pattern and frequency, and applied pressure. In contrast to other studies, we observe slower kinetics at distinct capillary wall zeta potential ranges. Within these ranges, which we call "stagnant regimes," the EOF mobility significantly counteracts the electrophoretic (EP) mobility of CTA+ and hinders the net transport. By constructing a numerical model to compare with our experiments and recasting our experimental data in terms of the net CTA+ transport volume normalized by surface area, we reveal that the EP mobility of CTA+ and the capillary surface-area-to-volume ratio dictate the zeta potential range and the duration of the stagnant regime and thereby govern the overall reaction kinetics. Our results indicate that further transport-oriented studies can significantly aid in the understanding and design of electrokinetic systems utilizing CTAB and other charged surfactants.

Consuming Mushrooms When Adopting a Healthy Mediterranean-Style Dietary Pattern Does Not Influence Short-Term Changes of Most Cardiometabolic Disease Risk Factors in Healthy Middle-Aged and Older Adults.

BACKGROUND: Mushrooms are a nutritious food, though knowledge of the effects of mushroom consumption on cardiometabolic risk factors is limited and inconsistent. OBJECTIVE: We assessed the effects of consuming mushrooms as part of a healthy United States Mediterranean-style dietary pattern (MED) on traditional and emerging cardiometabolic disease (CMD) risk factors. We hypothesized that adopting a MED diet with mushrooms would lead to greater improvements in multiple CMD risk factors. METHODS: Using a randomized, parallel study design, 60 adults (36 females, 24 males; aged 46 ± 12 y; body mass index 28.3 ± 2.84 kg/m2, mean ± standard deviation) without diagnosed CMD morbidities consumed a MED diet (all foods provided) without (control with breadcrumbs) or with 84 g/d of Agaricus bisporus (White Button, 4 d/wk) and Pleurotus ostreatus (Oyster, 3 d/wk) mushrooms for 8 wk. Fasting baseline and postintervention outcome measurements were traditional CMD risk factors, including blood pressure and fasting serum lipids, lipoproteins, glucose, and insulin. Exploratory CMD-related outcomes included lipoprotein particle sizes and indexes of inflammation. RESULTS: Adopting the MED-mushroom diet compared with the MED-control diet without mushrooms improved fasting serum glucose (change from baseline -2.9 ± 1.18 compared with 0.6 ± 1.10 mg/dL; time × group P = 0.034). Adopting the MED diet, independent of mushroom consumption, reduced serum total cholesterol (-10.2 ± 3.77 mg/dL; time P = 0.0001). Concomitantly, there was a reduction in high-density lipoprotein (HDL) cholesterol, buoyant HDL2b, and apolipoprotein A1, and an increase in lipoprotein(a) concentrations (main effect of time P < 0.05 for all). There were no changes in other measured CMD risk factors. CONCLUSIONS: Consuming a Mediterranean-style healthy dietary pattern with 1 serving/d of whole Agaricus bisporus and Pleurotus ostreatus mushrooms improved fasting serum glucose but did not influence other established or emerging CMD risk factors among middle-aged and older adults classified as overweight or obese but with clinically normal cardiometabolic health. TRIAL REGISTRATION NUMBER: https://www. CLINICALTRIALS: gov/study/NCT04259229?term=NCT04259229&rank=1.

Trajectories of Mental Distress Among US Women by Sexual Orientation and Racialized Group During the First Year of the COVID-19 Pandemic.

Objectives. To describe longitudinal trends in the prevalence of mental distress across the first year of the COVID-19 pandemic (April 2020‒April 2021) among US women at the intersection of sexual orientation and racialized group. Methods. Participants included 49 805 cisgender women and female-identified people from the COVID-19 Sub-Study, a cohort of US adults embedded within the Nurses' Health Studies 2 and 3 and the Growing Up Today Study. We fit generalized estimating equation Poisson models to estimate trends in depressive and anxiety symptoms by sexual orientation (gay or lesbian, bisexual, mostly heterosexual, completely heterosexual); subsequent models explored further differences by racialized group (Asian, Black, Latine, White, other or unlisted). Results. Relative to completely heterosexual peers, gay or lesbian, bisexual, and mostly heterosexual women had a higher prevalence of depressive and anxiety symptoms at each study wave and experienced widening inequities over time. Inequities were largest for sexual minority women of color, although confidence intervals were wide. Conclusions. The COVID-19 pandemic may have exacerbated already-glaring mental health inequities affecting sexual minority women, especially those belonging to marginalized racialized groups. Future research should investigate structural drivers of these patterns to inform policy-oriented interventions. (Am J Public Health. 2024;114(5):511-522. https://doi.org/10.2105/AJPH.2024.307601).

Elastic/viscoelastic polymer bilayers: a model-based approach to stretch-responsive constructs.

The use of polymers in the fabrication of bilayers for stimuli-responsive systems is well-known, yet viscoelasticity and viscoelastic models representing bilayer behavior have received surprisingly little attention. Of particular recent interest to us are simple polymeric bilayers in which one material, such as styrene-ethylene-propylene-styrene (SEPS) or styrene-isobutylene-styrene (SIBS), shows typical rubbery elastic response upon extension and retraction, and the other, an unvulcanized, low-Tg polymer such as butyl rubber (butyl), exhibits a viscoelastic response. When such a bilayer strip is extended to a fixed strain and held for several seconds followed by sudden release of this strain, rapid curling is observed, achieving a maximum curvature within 1 second, with a gradual uncurling, typically taking 300-600 seconds to eventually return to a flat strip. Attention has been directed to modeling the observed bilayer behavior. We compare predicted curvature and relaxation time constants from finite element analysis (FEA) simulations using Maxwell, Zener, Generalized Maxwell, and Parallel Rheological Framework (PRF) viscoelastic models to the experimentally measured values. We find that the Generalized Maxwell model predicts curvature over time with the lowest overall mean absolute scaled error (MASE) of 0.519, corresponding to a 4.9% difference from the second lowest error model and a 76.8% difference from the highest error model. Building upon an understanding of the material mechanics in simple bilayer strips, more complex bilayer systems can be designed. Samples of cross and weave geometries were fabricated from bilayer films and initial testing demonstrates how these materials can be used in potential applications.

Sexual orientation disparities in gestational diabetes and hypertensive disorders of pregnancy.

BACKGROUND: Sexual minority (SM) individuals (e.g., those with same-sex attractions/partners or who identify as lesbian/gay/bisexual) experience a host of physical and mental health disparities. However, little is known about sexual orientation-related disparities in gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP; gestational hypertension [gHTN] and preeclampsia). OBJECTIVE: To estimate disparities in GDM, gHTN and preeclampsia by sexual orientation. METHODS: We used data from the Nurses' Health Study II-a cohort of nurses across the US enrolled in 1989 at 25-42 years of age-restricted to those with pregnancies ≥20 weeks gestation and non-missing sexual orientation data (63,518 participants; 146,079 pregnancies). Our primary outcomes were GDM, gHTN and preeclampsia, which participants reported for each of their pregnancies. Participants also reported their sexual orientation identity and same-sex attractions/partners. We compared the risk of each outcome in pregnancies among heterosexual participants with no same-sex experience (reference) to those among SM participants overall and within subgroups: (1) heterosexual with same-sex experience, (2) mostly heterosexual, (3) bisexual and (4) lesbian/gay participants. We used modified Poisson models to estimate risk ratios (RR) and 95% confidence intervals (CI), fit via weighted generalised estimating equations, to account for multiple pregnancies per person over time and informative cluster sizes. RESULTS: The overall prevalence of each outcome was ≤5%. Mostly heterosexual participants had a 31% higher risk of gHTN (RR 1.31, 95% CI 1.03, 1.66), and heterosexual participants with same-sex experience had a 31% higher risk of GDM (RR 1.31, 95% CI 1.13, 1.50), compared to heterosexual participants with no same-sex experience. The magnitudes of the risk ratios were high among bisexual participants for gHTN and preeclampsia and among lesbian/gay participants for gHTN. CONCLUSIONS: Some SM groups may be disparately burdened by GDM and HDP. Elucidating modifiable mechanisms (e.g., structural barriers, discrimination) for reducing adverse pregnancy outcomes among SM populations is critical.

Economic costs associated with unhealthy weight control behaviors among Australian adolescents.

OBJECTIVE: This study explored the relationship between unhealthy weight control behaviors (UWCBs) and their associated economic costs among adolescents using the 2014-2018 Longitudinal Study of Australian Children (LSAC). METHODS: LSAC data in Wave 6 (n = 3538 adolescents aged 14-15 years), Wave 7 n = 3089 adolescents aged 16-17 years), and Wave 8 (n = 3037 adolescents aged 18-19 years) were derived from a representative sample of Australian adolescents. UWCBs were measured using the self-reported Branched Eating Disorder Test questionnaire. UWCBs were sub-classified into having fasting behaviors, using weight loss supplements or purging behaviors. Economic costs include healthcare and productivity costs to caregivers. Healthcare costs were measured using data from the Medicare and Pharmaceutical Benefits, which includes both medical and pharmaceutical costs. Productivity losses were measured using caregivers' lost leisure time due to UWCBs among adolescents. RESULTS: The mixed effect model identified statistically significant higher economic costs (mean difference = $453, 95% CIs $154, $752), higher health care costs (mean difference = $399, 95% CIs $102, $695), and higher productivity costs (mean difference = $59, 95% CIs $29, $90) for adolescents with UWCBs compared to their peers with no UWCBs. Subgroup analysis revealed that higher costs were associated with fasting and purging behaviors. DISCUSSION: UWCBs were associated with increased economic costs during adolescence. Our finding suggests there should be a policy focus on tackling UWCBs to reduce the economic burden on the healthcare system and society. PUBLIC SIGNIFICANCE: The study contributes to existing knowledge by investigating the direct healthcare costs and productivity losses associated with unhealthy weight control behaviors in Australian adolescents (14-18 years old) using a dataset that follows Australian adolescents over time. We found that engaging in unhealthy weight control behaviors such as fasting, using weight loss supplements, and purging was linked to higher costs among adolescents, suggesting policies should focus on addressing these behaviors.

Barriers to and opportunities for advancing racial equity in cervical cancer screening in the United States.

BACKGROUND: In the United States (U.S.), racially minoritized people have higher rates of cervical cancer morbidity and mortality compared to white individuals as a result of racialized structural, social, economic, and health care inequities. However, cervical cancer screening guidelines are based on studies of predominately white individuals and do not substantially discuss or address racialized cervical cancer inequities and their social determinants, including racism. METHODS: We conducted in-depth interviews with health care providers (N = 30) and key informants with expertise in health equity (N = 18). We utilized semi-structured interview guides that addressed providers' views and experiences delivering cervical cancer screening to racially minoritized individuals and key informants' recommendations for advancing racial equity in the development and implementation of cervical cancer screening guidelines. Interviews were analyzed using a template style thematic analysis approach involving deductive and inductive coding, memo writing, and matrix analysis for theme development. RESULTS: Most health care providers adopted a universal, one-size-fits-all approach to cervical cancer screening with the stated goal of ensuring racial equality. Despite frequently acknowledging the existence of racialized cervical cancer inequities, few providers recognized the role of social inequities in influencing them, and none discussed the impact of racism. In contrast, key informants overwhelmingly recommended that providers adopt an approach to cervical cancer screening and follow-up care that recognizes the role of racism in shaping racialized cervical cancer and related social inequities, is developed in partnership with racially minoritized communities, and involves person-centered, structurally-competent, and trauma-informed practices that address racially minoritized peoples' unique lived experiences in historical and social context. This racism-conscious approach is not to be confused with race-based medicine, which is an essentialist and racist approach to health care that treats race as a biological variable rather than as a social and political construct. CONCLUSIONS: Developers and implementers of cervical cancer screening guidelines should explicitly recognize and address the impact of racism on cervical cancer screening, follow-up care, and outcomes, meaningfully incorporate racially minoritized communities' perspectives and experiences, and facilitate provider- and institutional-level practices that foster racial equity in cervical cancer.

Unpacking differences in post-exercise affective experiences between physically underactive and active individuals.

BACKGROUND: Affective response to exercise (i.e., how individuals feel during- and post-exercise) as well as post-behavioral evaluations of affective experiences with exercise (i.e., reflecting on the experience after engaging in exercise) may be important determinants of regular exercise. PURPOSE: We compared post-exercise affective response and post-behavioral evaluations of exercise between a physically active and underactive group. Physically active (n = 32) and underactive (n = 25) participants completed a 10-minute treadmill bout of vigorous exercise and reported affective valence, positive activated affect, negative activated affect, calmness, fatigue and relief at various points during and/or after the bout. RESULTS: As expected, both groups reported an improvement in affective valence immediately post-exercise (ps < 0.001). This improvement in affective valence was associated with a concurrent decrease in negative affect (ps < 0.05) for the physically underactive group and was only associated with a concurrent increase in positive affect (ps < 0.02) for the active group. There were significant differences between physically active and underactive groups in pre-post exercise changes in positive activated affect (ps < 0.005). The underactive group reported greater relief than the active group at all-post exercise time-points (ps < 0.05). CONCLUSIONS:  These findings have implications for understanding post-exercise affective response and post-behavioral evaluations of exercise and for interventions directed at influencing the post-exercise affective response and behavioral evaluations of exercise in physically underactive individuals.

Lower levels of social support are associated with risk for future suicide attempts in a clinical sample of transgender and gender diverse adults.

PURPOSE: Transgender and gender diverse (TGD) adults are disproportionately affected by suicide. Social support and connection to the broader TGD community may help lower TGD adults' odds of having a suicide attempt (SA). The current study examined whether baseline levels of social support and community connectedness were associated with TGD adult's prospective odds of having a SA over 12 months of follow-up. METHODS: Longitudinal data for the current study came from a patient cohort of TGD adults enrolled in the LEGACY Project. Descriptive statistics and an attrition analysis were used to examine characteristics of the cohort and missingness over time. Logistic generalized estimating equation models were used to examine factors associated with patients' odds of having a past 6-month SA at 6- or 12-month follow-up. RESULTS: During the 12-month follow-up period, a total of 26 patients (3.1%; N = 830) reported having a SA. The 6-month incidence of SAs was approximately 2% at both 6- and 12-months of follow-up (6 months: N = 830; 12 months: N = 495). Baseline factors associated with increased odds of a future SA included gender identity (transfeminine vs. transmasculine: adjusted odds ratio [aOR] = 3.73, 95% confidence interval [CI] = 1.26-11.08; nonbinary vs. transmasculine: aOR = 3.09, 95% CI = 1.03-9.21), having a prior SA (aOR = 6.44, 95% CI = 2.63-15.79), and having moderate vs. high perceived social support (aOR = 4.25, 95% CI = 1.65-10.90). CONCLUSION: Lower levels of social support are associated with risk for future suicide attempts among TGD adults. Findings may inform screening practices for future suicide risk and the development of interventions to improve mental health outcomes for TGD adults.

Nurses' use of 'wellness' supplements during the COVID-19 pandemic in the United States.

AIM: Quantify disparities and identify correlates and predictors of 'wellness' supplement use among nurses during the first year of the pandemic. DESIGN: Longitudinal secondary analysis of Nurses' Health Studies 2 and 3 and Growing Up Today Study data. METHODS: Sample included 36,518 total participants, 12,044 of which were nurses, who completed surveys during the first year of the COVID-19 pandemic (April 2020 to April 2021). Analyses were conducted in March 2023. Modified Poisson models were used to estimate disparities in 'wellness' supplement use between nurses and non-healthcare workers and, among nurses only, to quantify associations with workplace-related predictors (occupational discrimination, PPE access, workplace setting) and psychosocial predictors (depression/anxiety, county-level COVID-19 mortality). Models included race/ethnicity, gender identity, age and cohort as covariates. RESULTS: Nurses were significantly more likely to use all types of supplements than non-healthcare workers. Lacking personal protective equipment and experiencing occupational discrimination were significantly associated with new immune supplement use. Depression increased the risk of using weight loss, energy and immune supplements. CONCLUSION: Nurses' disproportionate use of 'wellness' supplements during the COVID-19 pandemic may be related to workplace and psychosocial stressors. Given well-documented risks of harm from the use of 'wellness' supplements, the use of these products by nurses is of concern. IMPACT: 'Wellness' supplements promoting weight loss, increased energy, boosted immunity and cleansing of organs are omnipresent in today's health-focused culture, though their use has been associated with harm. This is of added concern among nurses given their risk of COVID-19 infection at work. Our study highlighted the risk factors associated with use of these products (lacking PPE and experiencing occupational discrimination). Findings support prior research suggesting a need for greater public health policy and education around the use of 'wellness' supplements. REPORTING METHOD: STROBE guidelines were followed throughout manuscript. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution was involved.

Disparities in Mortality by Sexual Orientation in a Large, Prospective Cohort of Female Nurses.

Importance: Extensive evidence documents health disparities for lesbian, gay, and bisexual (LGB) women, including worse physical, mental, and behavioral health than heterosexual women. These factors have been linked to premature mortality, yet few studies have investigated premature mortality disparities among LGB women and whether they differ by lesbian or bisexual identity. Objective: To examine differences in mortality by sexual orientation. Design, Setting, and Participants: This prospective cohort study examined differences in time to mortality across sexual orientation, adjusting for birth cohort. Participants were female nurses born between 1945 and 1964, initially recruited in the US in 1989 for the Nurses' Health Study II, and followed up through April 2022. Exposures: Sexual orientation (lesbian, bisexual, or heterosexual) assessed in 1995. Main Outcome and Measure: Time to all-cause mortality from assessment of exposure analyzed using accelerated failure time models. Results: Among 116 149 eligible participants, 90 833 (78%) had valid sexual orientation data. Of these 90 833 participants, 89 821 (98.9%) identified as heterosexual, 694 (0.8%) identified as lesbian, and 318 (0.4%) identified as bisexual. Of the 4227 deaths reported, the majority were among heterosexual participants (n = 4146; cumulative mortality of 4.6%), followed by lesbian participants (n = 49; cumulative mortality of 7.0%) and bisexual participants (n = 32; cumulative mortality of 10.1%). Compared with heterosexual participants, LGB participants had earlier mortality (adjusted acceleration factor, 0.74 [95% CI, 0.64-0.84]). These differences were greatest among bisexual participants (adjusted acceleration factor, 0.63 [95% CI, 0.51-0.78]) followed by lesbian participants (adjusted acceleration factor, 0.80 [95% CI, 0.68-0.95]). Conclusions and Relevance: In an otherwise largely homogeneous sample of female nurses, participants identifying as lesbian or bisexual had markedly earlier mortality during the study period compared with heterosexual women. These differences in mortality timing highlight the urgency of addressing modifiable risks and upstream social forces that propagate and perpetuate disparities.

The economic and social costs of body dissatisfaction and appearance-based discrimination in the United States.

This study estimated the social and economic costs of body dissatisfaction and appearance-based discrimination (specifically, weight and skin-shade discrimination) in the United States (USA) in the 2019 calendar year. We used a prevalence-based approach and a cost-of-illness method to estimate the annual cost of harmful appearance ideals for cases of body dissatisfaction and discrimination based on weight and skin shade. Impacts on conditions/illnesses such as eating disorders that are attributable to body dissatisfaction, weight discrimination and skin-shade discrimination were identified through a quasi-systematic literature review, which captured financial, economic, and non-financial costs. For each impact attributable to body dissatisfaction or appearance-based discrimination, annual health system and productivity costs (or labor market costs) were primarily estimated by using a population attributable fraction methodology. Only direct costs that resulted from body dissatisfaction and appearance-based discrimination were included (for example, costs associated with conditions such as depression attributable to body dissatisfaction or appearance-based discrimination). In contrast, indirect costs (e.g. costs associated with a health condition developed following skin bleaching, which was undertaken as a result of body dissatisfaction) were not included. In 2019 body dissatisfaction incurred $84 billion in financial and economic costs and $221 billion through reduced well-being. Financial costs of weight discrimination and skin-shade discrimination were estimated to be $200 billion and $63 billion, respectively, and reduced well-being was estimated to be $206.7 billion due to weight discrimination and $8.4 billion due to skin-shade discrimination. Sensitivity testing revealed the costs likely range between $226 billion and $507 billion for body dissatisfaction, between $175 billion and $537 billion for skin-shade discrimination, and between $126 billion and $265 billion for weight discrimination. This study demonstrates that the prevalence and economic costs of body dissatisfaction and weight and skin-shade discrimination are substantial, which underscores the urgency of identifying policy actions designed to promote prevention.

Appearance ideals in the USA have been widely critiqued for placing unfair burden on people of color and women of all race/ethnicity groups, but little is known about the economic consequences of biased appearance standards. To attain a comprehensive understanding of the economic impact of these harmful appearance ideals on the US economy, we estimated the one-year financial, economic and non-financial costs to the economy caused by body dissatisfaction, weight discrimination, and skin-shade discrimination. We considered a wide range of costs, including costs to the healthcare system, workplace, and other costs for individuals, households, employers, and government. We found that the impact of harmful appearance ideals on the USA economy is substantial. In 2019 body dissatisfaction incurred $84 billion in financial and economic costs and $221 billion through reduced well-being. Financial costs of weight discrimination and skin-shade discrimination were estimated to be $200 billion and $63 billion, respectively, and reduced well-being was estimated to be $207 billion due to weight discrimination and $8 billion due to skin-shade discrimination. Women of all race/ethnicity groups bore the bulk of the burden, shouldering 58% of the costs for body dissatisfaction and 66% for weight discrimination. Women bore 50% of the costs for skin-shade discrimination. These costs are substantial and underscore the urgency of identifying effective policy actions to reduce the damaging effects of harmful appearance ideals.

DNA-Intercalating Supramolecular Hydrogels for Tunable Thermal and Viscoelastic Properties.

Polymeric supramolecular hydrogels (PSHs) leverage the thermodynamic and kinetic properties of non-covalent interactions between polymer chains to govern their structural characteristics. As these materials are formed via endothermic or exothermic equilibria, their thermal response is challenging to control without drastically changing the nature of the chemistry used to join them. In this study, we introduce a novel class of PSHs utilizing the intercalation of double-stranded DNA (dsDNA) as the primary dynamic non-covalent interaction. The resulting dsDNA intercalating supramolecular hydrogels (DISHs) can be tuned to exhibit both endothermically or exothermically driven binding through strategic selection of intercalators. Bifunctional polyethylene glycol (MW ~ 2000 Da) capped with intercalators of varying hydrophobicity, charge, and size (acridine, psoralen, thiazole orange, and phenanthridine) produced DISHs with comparable moduli (500 - 1000 Pa) but unique thermal viscoelastic response. Notably, acridine-based cross-linkers displayed invariant and even increasing elasticity with temperature, suggesting an endothermic binding mechanism. This methodology expands the set of structure-properties available to biomass-derived DNA biomaterials and promises a new material system where a broad set of thermal and viscoelastic responses can be obtained due to the sheer number and variety of intercalating molecules.

Genetic Variation in Sexual Size Dimorphism Is Associated with Variation in Sex-Specific Plasticity in Drosophila.

AbstractThe difference in body size between females and males, or sexual size dimorphism (SSD), is ubiquitous, yet we have a poor understanding of the developmental genetic mechanisms that generate it and how these mechanisms may vary within and among species. Such an understanding of the genetic architecture of SSD is important if we are to evaluate alternative models of SSD evolution, but the genetic architecture is difficult to describe because SSD is a characteristic of populations, not individuals. Here, we overcome this challenge by using isogenic lineages of Drosophila to measure SSD for 196 genotypes. We demonstrate extensive genetic variation for SSD, primarily driven by higher levels of genetic variation for body size among females than among males. While we observe a general increase in SSD with sex-averaged body size (pooling for sex) among lineages, most of the variation in SSD is independent of sex-averaged body size and shows a strong genetic correlation with sex-specific plasticity, such that increased female-biased SSD is associated with increased body size plasticity in females. Our data are consistent with the condition dependence hypothesis of sexual dimorphism and suggest that SSD in Drosophila is a consequence of selection on the developmental genetic mechanisms that regulate the plasticity of body size.

The Difference Between Cystatin C- and Creatinine-Based Estimated GFR in Heart Failure With Reduced Ejection Fraction: Insights From PARADIGM-HF.

RATIONALE & OBJECTIVE: The clinical implications of the discrepancy between cystatin C (cysC)- and serum creatinine (Scr)-estimated glomerular filtration rate (eGFR) in patients with heart failure (HF) and reduced ejection fraction (HFrEF) are unknown. STUDY DESIGN: Post-hoc analysis of randomized trial data. SETTING & PARTICIPANTS: 1,970 patients with HFrEF enrolled in PARADIGM-HF with available baseline cysC and Scr measurements. EXPOSURE: Intraindividual differences between eGFR based on cysC (eGFRcysC) and Scr (eGFRScr; eGFRdiffcysC-Scr). OUTCOMES: Clinical outcomes included the PARADIGM-HF primary end point (composite of cardiovascular [CV] mortality or HF hospitalization), CV mortality, all-cause mortality, and worsening kidney function. We also examined poor health-related quality of life (HRQoL), frailty, and worsening HF (WHF), defined as HF hospitalization, emergency department visit, or outpatient intensification of therapy between baseline and 8-month follow-up. ANALYTICAL APPROACH: Fine-Gray subdistribution hazard models and Cox proportional hazards models were used to regress clinical outcomes on baseline eGFRdiffcysC-Scr. Logistic regression was used to investigate the association of baseline eGFRdiffcysC-Scr with poor HRQoL and frailty. Linear regression models were used to assess the association of WHF with eGFRcysC, eGFRScr, and eGFRdiffcysC-Scr at 8-month follow-up. RESULTS: Baseline eGFRdiffcysC-Scr was higher than +10 and lower than-10mL/min/1.73m2 in 13.0% and 35.7% of patients, respectively. More negative values of eGFRdiffcysC-Scr were associated with worse outcomes ([sub]hazard ratio per standard deviation: PARADIGM-HF primary end point, 1.18; P=0.008; CV mortality, 1.34; P=0.001; all-cause mortality, 1.39; P<0.001; worsening kidney function, 1.31; P=0.05). For a 1-standard-deviation decrease in eGFRdiffcysC-Scr, the prevalences of poor HRQoL and frailty increased by 29% and 17%, respectively (P≤0.008). WHF was associated with a more pronounced decrease in eGFRcysC than in eGFRScr, resulting in a change in 8-month eGFRdiffcysC-Scr of-4.67mL/min/1.73m2 (P<0.001). LIMITATIONS: Lack of gold-standard assessment of kidney function. CONCLUSIONS: In patients with HFrEF, discrepancies between eGFRcysC and eGFRScr are common and are associated with clinical outcomes, HRQoL, and frailty. The decline in kidney function associated with WHF is more marked when assessed with eGFRcysC than with eGFRScr. PLAIN-LANGUAGE SUMMARY: Kidney function assessment traditionally relies on serum creatinine (Scr) to establish an estimated glomerular filtration rate (eGFR). However, this has been challenged with the introduction of an alternative marker, cystatin C (cysC). Muscle mass and nutritional status have differential effects on eGFR based on cysC (eGFRcysC) and Scr (eGFRScr). Among ambulatory patients with heart failure enrolled in PARADIGM-HF, we investigated the clinical significance of the difference between eGFRcysC and eGFRScr. More negative values (ie, eGFRScr>eGFRcysC) were associated with worse clinical outcomes (including mortality), poor quality of life, and frailty. In patients with progressive heart failure, which is characterized by muscle loss and poor nutritional status, the decline in kidney function was more pronounced when eGFR was estimated using cysC rather than Scr.

Measurement of Perceived Risk of Developing Diabetes Mellitus: A Systematic Literature Review.

BACKGROUND: This systematic review describes approaches to measuring perceived risk of developing type 2 diabetes among individuals without diagnoses and describes the use of theories, models, and frameworks in studies assessing perceived risk. While a systematic review has synthesized perceived risk of complications among individuals with diabetes, no reviews have systematically assessed how perceived risk is measured among those without a diagnosis. METHODS: Medline, PubMed, PsycINFO, and CINAHAL databases were searched for studies conducted through October 2022 with measures of perceived risk among adults ≥ 18 years without a diabetes diagnosis. Extracted data included study characteristics, measures, and health behavior theories, models, or frameworks used. RESULTS: Eighty-six studies met inclusion criteria. Six examined perceived risk scales' psychometric properties. Eighty measured perceived risk using (1) a single item; (2) a composite score from multiple items or subconstructs; and (3) multiple subconstructs but no composite score. Studies used items measuring "comparative risk," "absolute or lifetime risk," and "perceived risk" without defining how each differed. Sixty-four studies used cross-sectional designs. Twenty-eight studies mentioned use of health behavior theories in study design or selection of measures. DISCUSSION: There was heterogeneity in how studies operationalized perceived risk; only one third of studies referenced a theory, model, or framework as guiding design or scale and item selection. Use of perceived lifetime risk, absolute risk, or comparative risk limits comparisons across studies. Consideration of context, target population, and how data are utilized is important when selecting measures; we present a series of questions to ask when selecting measures for use in research and clinical settings. This review is the first to categorize how perceived risk is measured in the diabetes prevention domain; most literature focuses on perceived risk among those with diabetes diagnoses. Limitations include exclusion of non-English and gray literature and single reviewer screening and data extraction.