American Rhinologic Society Expert Practice Statement: Indications and Recommendations for Septoplasty in Children.

The goal of this American Rhinologic Society Expert Practice Statement (EPS) is to provide recommendations and guidance through evidence-based consensus statements regarding pediatric septoplasty. This EPS was developed following the previously published methodology and approval process. The topics of interest included appropriate indications, safety and efficacy, timing, relevant quality of life instruments, and surgical techniques. Following a modified Delphi approach, six statements were developed, five of which reached consensus and one that did not. These statements and accompanying evidence are summarized along with an assessment of future needs.

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.

Methods for structural sexism and population health research: Introducing a novel analytic framework to capture life-course and intersectional effects.

Accumulating evidence links structural sexism to gendered health inequities, yet methodological challenges have precluded comprehensive examinations into life-course and/or intersectional effects. To help address this gap, we introduce an analytic framework that uses sequential conditional mean models (SCMMs) to jointly account for longitudinal exposure trajectories and moderation by multiple dimensions of social identity/position, which we then apply to study how early life-course exposure to U.S. state-level structural sexism shapes mental health outcomes within and between gender groups. Data came from the Growing Up Today Study, a cohort of 16,875 children aged 9-14 years in 1996 who we followed through 2016. Using a composite index of relevant public policies and societal conditions (e.g., abortion bans, wage gaps), we assigned each U.S. state a year-specific structural sexism score and calculated participants' cumulative exposure by averaging the scores associated with states they had lived in during the study period, weighted according to duration of time spent in each. We then fit a series of SCMMs to estimate overall and group-specific associations between cumulative exposure from baseline through a given study wave and subsequent depressive symptomology; we also fit models using simplified (i.e., non-cumulative) exposure variables for comparison purposes. Analyses revealed that cumulative exposure to structural sexism: (1) was associated with significantly increased odds of experiencing depressive symptoms by the subsequent wave; (2) disproportionately impacted multiply marginalized groups (e.g., sexual minority girls/women); and (3) was more strongly associated with depressive symptomology compared to static or point-in-time exposure operationalizations (e.g., exposure in a single year). Substantively, these findings suggest that long-term exposure to structural sexism may contribute to the inequitable social patterning of mental distress among young people living in the U.S. More broadly, the proposed analytic framework represents a promising approach to examining the complex links between structural sexism and health across the life course and for diverse social groups.

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.

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.

Correction: Longitudinal effects of gender minority stressors on substance use and related risk and protective factors among gender minority adolescents.

[This corrects the article DOI: 10.1371/journal.pone.0250500.].

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).

Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.

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.

Quantitative profiling of human translation initiation reveals regulatory elements that potently affect endogenous and therapeutically modified mRNAs.

mRNA therapeutics offer a potentially universal strategy for the efficient development and delivery of therapeutic proteins. Current mRNA vaccines include chemically modified nucleotides to reduce cellular immunogenicity. Here, we develop an efficient, high-throughput method to measure human translation initiation on therapeutically modified as well as endogenous RNAs. Using systems-level biochemistry, we quantify ribosome recruitment to tens of thousands of human 5' untranslated regions and identify sequences that mediate 250-fold effects. We observe widespread effects of coding sequences on translation initiation and identify small regulatory elements of 3-6 nucleotides that are sufficient to potently affect translational output. Incorporation of N1-methylpseudouridine (m1Ψ) selectively enhances translation by specific 5' UTRs that we demonstrate surpass those of current mRNA vaccines. Our approach is broadly applicable to dissect mechanisms of human translation initiation and engineer more potent therapeutic mRNAs. Highlights: Measurement of >30,000 human 5' UTRs reveals a 250-fold range of translation outputSystematic mutagenesis demonstrates the causality of short (3-6nt) regulatory elementsN1-methylpseudouridine alters translation initiation in a sequence-specific mannerOptimal modified 5' UTRs outperform those in the current class of mRNA vaccines.

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.

Structural Racism-Related State Laws and Healthcare Access Among Black, Latine, and White U.S. Adults.

Racialized healthcare inequities in the USA remain glaring, yet root causes are understudied. To address this gap, we created a state-level structural racism legal index (SRLI) using the Structural Racism-Related State Law Database and analyzed its association with racialized inequities in four outcomes (lacking health insurance coverage, lacking a personal doctor, avoiding care due to cost, lacking a routine check-up) from the 2013 Behavioral Risk Factor Surveillance System (N = 454,834). To obtain predicted probabilities by SRLI quartiles (Q1 = less structural racism, Q4 = more structural racism) and racialized group, we fit survey-weighted multilevel logistic models adjusted for individual- and state-level covariates. We found substantial healthcare access inequities across racialized groups within SRLI quartiles and less pronounced, but still meaningful, inequities within racialized groups across SRLI quartiles. For example, the predicted probabilities of lacking health insurance coverage across SRLI quartiles ranged from 13 to 20% among Black adults, 31 to 41% among Latine adults, and 8 to 11% among White adults. Across racialized groups in Q4 states, predicted probabilities ranged from 11% among White adults to 41% among Latine adults. Similar patterns were observed for lacking a personal doctor and avoiding care due to cost. Findings underscore the need to address structural racism in laws and policies to mitigate these inequities.

The transcriptional response of cortical neurons to concussion reveals divergent fates after injury.

Traumatic brain injury (TBI) is a risk factor for neurodegeneration, however little is known about how different neuron types respond to this kind of injury. In this study, we follow neuronal populations over several months after a single mild TBI (mTBI) to assess long ranging consequences of injury at the level of single, transcriptionally defined neuronal classes. We find that the stress responsive Activating Transcription Factor 3 (ATF3) defines a population of cortical neurons after mTBI. We show that neurons that activate ATF3 upregulate stress-related genes while repressing many genes, including commonly used markers for these cell types. Using an inducible reporter linked to ATF3, we genetically mark damaged cells to track them over time. Notably, we find that a population in layer V undergoes cell death acutely after injury, while another in layer II/III survives long term and retains the ability to fire action potentials. To investigate the mechanism controlling layer V neuron death, we genetically silenced candidate stress response pathways. We found that the axon injury responsive kinase MAP3K12, also known as dual leucine zipper kinase (DLK), is required for the layer V neuron death. This work provides a rationale for targeting the DLK signaling pathway as a therapeutic intervention for traumatic brain injury. Beyond this, our novel approach to track neurons after a mild, subclinical injury can inform our understanding of neuronal susceptibility to repeated impacts.

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.

Promoting equitable sexual health communication among patients with minoritized racial/ethnic, sexual orientation, and gender identities: Strategies, challenges, and opportunities.

People assigned female at birth (AFAB) with minoritized racial/ethnic, sexual orientation, and gender identities experience notable barriers to high-quality sexual healthcare. In confronting these barriers, patient-provider communication can be a crucial factor, influencing patients' experiences and access to relevant sexual health information and services by determining the quality of care. However, research that investigates this communication among AFAB patients with minoritized social positions is scarce, indicating a research gap regarding the perspectives and roles of healthcare providers in addressing such barriers to care for minoritized patients. Thus, we conducted a qualitative research study, using individual in-depth interviews, to explore the multi-level factors that influence providers' attitudes, knowledge, and skills regarding sexual health communication with AFAB patients with minoritized racial/ethnic, sexual orientation, and gender identities. Interpreting study findings within frameworks of person-centered care, intersectionality, and structural competency, we identified three cross-cutting themes. We found that providers frequently drew on their prior professional training, personal lived experiences, and population-level health disparities data when engaging in sexual health communication with minoritized AFAB patients. Participants reported minimal explicit training in anti-racist and lesbian, gay, bisexual, transgender, and queer (LGBTQ+)-competent care as a significant barrier to engaging in equitable sexual health communication with minoritized AFAB patients, which was exacerbated by many providers' lack of shared social positions and lived experiences with these patients. Providers also frequently applied population-level data to individual patients when formulating counseling and recommendations, which may undermine person-centered sexual health communication. Our findings suggest that critical anti-racist and LGBTQ+-competent provider training is urgently needed, and that health professional education and institutions must be transformed to better reflect and consider the experiences of patients with minoritized racial/ethnic, sexual orientation, and gender identities.