RESUMO
The Paris Agreement calls for a cooperative response with the aim of limiting global warming to well below two degrees Celsius above pre-industrial levels while reaffirming the principles of equity and common, but differentiated responsibilities and capabilities1. Although the goal is clear, the approach required to achieve it is not. Cap-and-trade policies using uniform carbon prices could produce cost-effective reductions of global carbon emissions, but tend to impose relatively high mitigation costs on developing and emerging economies. Huge international financial transfers are required to complement cap-and-trade to achieve equal sharing of effort, defined as an equal distribution of mitigation costs as a share of income2,3, and therefore the cap-and-trade policy is often perceived as infringing on national sovereignty2-7. Here we show that a strategy of international financial transfers guided by moderate deviations from uniform carbon pricing could achieve the goal without straining either the economies or sovereignty of nations. We use the integrated assessment model REMIND-MAgPIE to analyse alternative policies: financial transfers in uniform carbon pricing systems, differentiated carbon pricing in the absence of financial transfers, or a hybrid combining financial transfers and differentiated carbon prices. Under uniform carbon prices, a present value of international financial transfers of 4.4 trillion US dollars over the next 80 years to 2100 would be required to equalize effort. By contrast, achieving equal effort without financial transfers requires carbon prices in advanced countries to exceed those in developing countries by a factor of more than 100, leading to efficiency losses of 2.6 trillion US dollars. Hybrid solutions reveal a strongly nonlinear trade-off between cost efficiency and sovereignty: moderate deviations from uniform carbon prices strongly reduce financial transfers at relatively small efficiency losses and moderate financial transfers substantially reduce inefficiencies by narrowing the carbon price spread. We also identify risks and adverse consequences of carbon price differentiation due to market distortions that can undermine environmental sustainability targets8,9. Quantifying the advantages and risks of carbon price differentiation provides insight into climate and sector-specific policy mixes.
Assuntos
Comércio/economia , Comércio/legislação & jurisprudência , Política Ambiental/economia , Política Ambiental/legislação & jurisprudência , Aquecimento Global/legislação & jurisprudência , Aquecimento Global/prevenção & controle , Cooperação Internacional/legislação & jurisprudência , Aquecimento Global/economia , Paris , Justiça Social , Fatores SocioeconômicosRESUMO
BACKGROUND: Beginning in July 2016, transgender service members in the US military were allowed to receive gender-affirming medical care, if so desired. OBJECTIVE: This study aimed to evaluate variation in time-to-hormone therapy initiation in active duty Service members after the receipt of a diagnosis indicative of gender dysphoria in the Military Health System. RESEARCH DESIGN: This retrospective cohort study included data from those enrolled in TRICARE Prime between July 2016 and December 2021 and extracted from the Military Health System Data Repository. PARTICIPANTS: A population-based sample of US Service members who had an encounter with a relevant International Classification of Diseases 9/10 diagnosis code. MEASURES: Time-to-gender-affirming hormone initiation after diagnosis receipt. RESULTS: A total of 2439 Service members were included (M age 24 y; 62% white, 16% Black; 12% Latine; 65% Junior Enlisted; 37% Army, 29% Navy, 25% Air Force, 7% Marine Corps; 46% first recorded administrative assigned gender marker female). Overall, 41% and 52% initiated gender-affirming hormone therapy within 1 and 3 years of diagnosis, respectively. In the generalized additive model, time-to-gender-affirming hormone initiation was longer for Service members with a first administrative assigned gender marker of male relative to female ( P <0.001), and Asian and Pacific Islander ( P =0.02) and Black ( P =0.047) relative to white Service members. In time-varying interactions, junior enlisted members had longer time-to-initiation, relative to senior enlisted members and junior officers, until about 2-years postinitial diagnosis. CONCLUSION: The significant variation and documented inequities indicate that institutional data-driven policy modifications are needed to ensure timely access for those desiring care.
Assuntos
Disforia de Gênero , Militares , Pessoas Transgênero , Humanos , Feminino , Masculino , Militares/estatística & dados numéricos , Estudos Retrospectivos , Estados Unidos , Adulto , Pessoas Transgênero/estatística & dados numéricos , Disforia de Gênero/tratamento farmacológico , Adulto Jovem , Tempo para o Tratamento/estatística & dados numéricos , Procedimentos de Readequação Sexual/estatística & dados numéricosRESUMO
RESEARCH QUESTION: What are the main arguments of reproductive healthcare providers in favour or against their involvement in offering expanded carrier screening (ECS) for recessive disorders at fertility clinics in the Netherlands? DESIGN: Semi-structured interview study with 20 reproductive healthcare providers between May 2020 and January 2021. Participants included 11 gynaecologists, seven fertility doctors, one nurse practitioner and one clinical embryologist, recruited from academic medical centres (nâ¯=â¯13), peripheral facilities associated with academic centres (nâ¯=â¯4), and independent fertility treatment centres (nâ¯=â¯3) in the Netherlands. An interview guide was developed, and thematic content analysis was performed using ATLAS.ti software. RESULTS: Arguments of reproductive healthcare providers in favour of their potential involvement in offering ECS included: (i) opportunities offered by the setting; (ii) motivation to assist in reproduction and prevent suffering; and (iii) to counter unwanted commercialization offers. Arguments against involvement included: (i) lack of knowledge and familiarity with offering ECS; (ii) insufficient staff and resources, and potential high costs for clinics and/or couples; (iii) the emotional impact it may have on couples; (iv) perceived complexity of counselling and expected elongation of waiting lists; and (v) expected low impact on reducing the burden of diseases. Participants felt that more evidence and research on the costs-benefits, implications and demand are needed prior to their involvement. CONCLUSION: While agreeing that the field of medically assisted reproduction provides a unique opportunity to offer ECS, reproductive healthcare workers feel a lack of capability and limited motivation to offer ECS to all or a selection of couples at their fertility clinics.
Assuntos
Atitude do Pessoal de Saúde , Clínicas de Fertilização , Triagem de Portadores Genéticos , Pesquisa Qualitativa , Humanos , Feminino , Triagem de Portadores Genéticos/métodos , Masculino , Pessoal de Saúde/psicologia , Países Baixos , Adulto , Aconselhamento Genético/psicologiaRESUMO
PURPOSE OF REVIEW: Oral contraceptive pills are among the most popular contraceptives worldwide, including among adolescents, and are available over the counter in over 100 countries. However, when a prescription is required, oral contraceptives may be difficult to obtain, particularly for adolescents. Recent approvals of over-the-counter progestin-only pills in the United Kingdom and United States have brought widespread attention to this topic. RECENT FINDINGS: Progestin-only pills, including the norgestrel pill recently approved for over-the-counter use in the United States, are highly effective and may be used safely without a prescription or medical monitoring, including by adolescents. These pills are associated with relatively high user satisfaction. Although over-the-counter availability may improve contraceptive access overall, issues related to insurance coverage and out-of-pocket cost may continue to pose practical barriers to access for many individuals. SUMMARY: Over-the-counter oral contraceptives are an appropriate and important contraceptive option for many adolescents. Over-the-counter availability has the potential to increase access to safe and effective contraception in the United States, United Kingdom, and other countries where a prescription is currently required. Future research on use patterns among adolescents is needed, as are advocacy efforts and policies to ensure access and affordability.
Assuntos
Acessibilidade aos Serviços de Saúde , Medicamentos sem Prescrição , Humanos , Medicamentos sem Prescrição/provisão & distribuição , Medicamentos sem Prescrição/economia , Adolescente , Feminino , Estados Unidos , Saúde Global , Reino Unido , Anticoncepcionais Orais Hormonais/provisão & distribuição , Contracepção HormonalRESUMO
Young adults experiencing homelessness (YAEH) are at elevated risk for HIV compared to their stably housed peers. Preexposure prophylaxis (PrEP) is highly effective at preventing HIV infection, yet YAEH have been largely overlooked in PrEP efforts to date despite YAEH reporting high overall interest in PrEP. We assessed individual, social, and structural variables associated with PrEP interest and use among a sample of 195 YAEH (ages 18-25) recruited from drop-in centers across Los Angeles County who met criteria for HIV risk. In the current sample, though most had heard of PrEP (81.0%), the majority were not interested in taking PrEP (68.2%) and only a minority had used/were using PrEP (11.8%). YAEH who identified as sexual and/or gender minority, reported knowing someone who had used PrEP, or recently accessed sexual health services were more likely to have used and/or reported interest in using PrEP. Those who reported more episodes of heavy drinking were less likely to report having used PrEP. Suggestions are provided for better integrating PrEP-related services into existing behavioral and health service programs for YAEH, as well as leveraging peers and fostering positive social norms to reduce PrEP-related stigma and increase interest and use of PrEP among YAEH.
Assuntos
Infecções por HIV , Pessoas Mal Alojadas , Profilaxia Pré-Exposição , Masculino , Humanos , Adulto Jovem , Adolescente , Adulto , Homossexualidade Masculina , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Los Angeles/epidemiologia , Comportamento SexualRESUMO
Exposure to discrimination has been linked to lower HIV antiretroviral therapy (ART) adherence and poor HIV care outcomes among Black Americans. Coping has been shown to mitigate the harmful effects of discrimination on health behaviors, but the use of cultural relevant Africultural coping strategies is understudied as a moderator of the association between intersectional discrimination and ART adherence among Black Americans. We used adjusted logistic regression to test whether Africultural coping strategies (cognitive/emotional debriefing; collective; spiritual-centered; ritual-centered) moderated associations between multiple forms of discrimination (HIV, sexual orientation, race) and good ART adherence (minimum of 75% or 85% of prescribed doses taken, as measured by electronic monitoring in separate analyses) among 92 sexual minority Black Americans living with HIV. Mean adherence was 66.5% in month 8 after baseline (36% ≥ 85% adherence; 49% ≥ 75% adherence). Ritual-centered coping moderated the relationship between each of the three types of discrimination at baseline and good ART adherence in month 8 (regardless of the minimum threshold for good adherence); when use of ritual coping was low, the association between discrimination and adherence was statistically significant. The other three coping scales each moderated the association between racial discrimination and good ART adherence (defined by the 75% threshold); cognitive/emotional debriefing was also a moderator for both HIV- and race-related discrimination at the 85% adherence threshold. These findings support the benefits of Africultural coping, particularly ritual-centered coping, to help sexual minority Black Americans manage stressors associated with discrimination and to adhere well to ART.
Assuntos
Antirretrovirais , Negro ou Afro-Americano , Assistência à Saúde Culturalmente Competente , Infecções por HIV , Adesão à Medicação , Minorias Sexuais e de Gênero , Feminino , Humanos , Masculino , Antirretrovirais/uso terapêutico , Negro ou Afro-Americano/psicologia , Capacidades de Enfrentamento , Assistência à Saúde Culturalmente Competente/etnologia , Infecções por HIV/psicologia , Homofobia/etnologia , Adesão à Medicação/psicologia , Preconceito/etnologia , Racismo/etnologia , Minorias Sexuais e de Gênero/psicologiaRESUMO
Peer advocacy can promote HIV protective behaviors, but little is known about the concordance on prevention advocacy(PA) reports between people living with HIV(PLWH) and their social network members. We examined prevalence and correlates of such concordance, and its association with the targeted HIV protective behavior of the social network member. Data were analyzed from 193 PLWH(index participants) and their 599 social network members(alters). Kappa statistics measured concordance between index and alter reports of PA in the past 3 months. Logistic and multinomial regressions evaluated the relationship between advocacy concordance and alter condom use and HIV testing behavior and correlates of PA concordance. Advocacy concordance was observed in 0.3% of index-alter dyads for PrEP discussion, 9% for condom use, 18% for HIV testing, 26% for care engagement, and 49% for antiretroviral use discussions. Fewer indexes reported condom use(23.5% vs. 28.1%;[Formula: see text]=3.7, p=0.05) and HIV testing(30.5% vs. 50.5%; [Formula: see text]=25.3, p<0.001) PA occurring. Condom advocacy concordance was higher if the index and alter were romantic partners(OR=3.50; p=0.02), and lower if the index was 10 years younger than the alter(OR=0.23; p = 0.02). Alters had higher odds of using condoms with their main partner when both reported condom advocacy compared to dyads where neither reported advocacy(OR=3.90; p<0.001) and compared to dyads where only the index reported such advocacy(OR = 3.71; p=0.01). Age difference and relationship status impact advocacy agreement, and concordant perceptions of advocacy are linked to increased HIV protective behaviors. Alters' perceptions may be crucial for behavior change, informing strategies for improving advocacy.
RESUMO
Receiving peer advocacy has been shown to result in increased HIV protective behaviors, but little research has gone beyond assessment of the mere presence of advocacy to examine aspects of advocacy driving these effects. With baseline data from a controlled trial of an advocacy training intervention, we studied characteristics of HIV prevention advocacy received among 599 social network members of persons living with HIV in Uganda and the association of these characteristics with the social network members' recent HIV testing (past six months) and consistent condom use, as well as perceived influence of advocacy on these behaviors. Participants reported on receipt of advocacy specific to HIV testing and condom use, as well as on measures of advocacy content, tone of delivery, support for autonomous regulation, and perceived influence on behavior. Receiving HIV testing advocacy and condom use advocacy were associated with recent HIV testing [65.2% vs. 51.4%; OR (95% CI) = 1.77 (1.11-2.84)], and consistent condom use with main sex partner [19.3% vs. 10.0%; OR (95% CI) = 2.16 (1.12-4.13)], respectively, compared to not receiving advocacy. Among those who received condom advocacy, perceived influence of the advocacy was positively correlated with consistent condom use, regardless of type of sex partner; support of autonomous regulation was a correlate of consistent condom use with casual sex partners, while judgmental advocacy was a correlate of consistent condom use with serodiscordant main partners. Among those who received testing advocacy, HIV testing in the past 6 months was positively correlated with receipt of direct support for getting tested. In multiple regression analysis, perceived influence of both HIV testing and condom use advocacy were positively correlated with advocacy that included access information and support of autonomous regulation; confrontational advocacy and judgmental advocacy were independent positive correlates of perceived influence of testing and condom use advocacy, respectively. These findings support associations that suggest potential benefits of peer advocacy from PLWH on HIV testing and condom use among their social network members, and indicate that advocacy content, tone of delivery, and support of autonomous regulation advocacy may play an important role in the success of advocacy.
Assuntos
Preservativos , Infecções por HIV , Teste de HIV , Grupo Associado , Parceiros Sexuais , Apoio Social , Humanos , Uganda , Preservativos/estatística & dados numéricos , Masculino , Feminino , Infecções por HIV/prevenção & controle , Infecções por HIV/psicologia , Adulto , Teste de HIV/estatística & dados numéricos , Parceiros Sexuais/psicologia , Defesa do Paciente , Pessoa de Meia-Idade , Conhecimentos, Atitudes e Prática em Saúde , Adulto Jovem , Comportamento Sexual , Sexo SeguroRESUMO
Mobile populations such as fisherfolk show high HIV incidence and prevalence. We pilot-tested implementation strategies to enhance pre-exposure prophylaxis (PrEP) uptake and adherence in the context of healthcare outreach events in two mainland fisherfolk communities on Lake Victoria, Uganda from September 2021 to February 2022. The implementation strategies included PrEP adherence supporters (selected from PrEP users' social networks), community workshops (to address misconceptions and stigma, and empower PrEP advocacy), and check-in calls (including refill reminders). PrEP medical records data were collected from 6-months pre-intervention to 6-months post-intervention. Qualitative interviews with 20 PrEP users (10 who continued, 10 who discontinued), 9 adherence supporters, and 7 key partners (providers, community leaders) explored acceptability. Percentages of PrEP initiators (of those eligible) were significantly higher during the intervention (96.5%) than 6-months before the intervention (84.5%), p < 0.0001; percentages of PrEP users who persisted (i.e., possessed a refill) 6-months post-initiation (47.9% vs. 6.7%) and had at least 80% PrEP coverage (based on their medication possession ratio) from the initiation date to 6-months later (35.9% vs. 0%) were higher during versus pre-intervention, p < 0.0001. A comparison fisherfolk community with better healthcare access had lower uptake (78.3%; p < 0.0001) and persistence at 6-months (34.0%; p < 0.001), but higher coverage during the intervention period (70.4%; p < 0.0001). Qualitative data suggested the strategies promoted PrEP use through reduced stigma and misconceptions. The intervention bundle cost was $223.95, $172.98, and $94.66 for each additional person for PrEP initiation, persistence, and coverage, respectively. Enhanced community-based PrEP implementation that fosters a supportive community environment can improve PrEP use in mobile populations without easy access to healthcare. (NCT05084716).
RESUMO
OBJECTIVE: Despite unique experiences that may increase eating disorder risk, U.S. military service members are an understudied population. The current study examined incidence and prevalence of eating disorder diagnoses in U.S. military personnel. METHOD: This retrospective cohort study utilized Military Health System Data Repository (MDR) data on eating disorder diagnoses (2016-2021). Active duty, Reserve, and National Guard U.S. military service members who received care via TRICARE Prime insurance were identified by ICD-10 eating disorder diagnostic codes. RESULTS: During the 6-year surveillance period, 5189 Service members received incident eating disorders diagnoses, with a crude overall incidence rate of 6.2 cases per 10,000 person-years. The most common diagnosis was other/unspecified specified eating disorders, followed by binge-eating disorder, bulimia nervosa, and anorexia nervosa. There was an 18.5% overall rise in total incident cases across the surveillance period, but this trend was not statistically significant (p = 0.09). Point prevalence significantly increased across the 6-year timeframe for total eating disorders (p < 0.001). Period prevalence for 6-year surveillance period was 0.244% for total eating disorders, 0.149% for other/unspecified eating disorder, 0.043% for bulimia nervosa, 0.038% for binge-eating disorder, and 0.013% for anorexia nervosa. DISCUSSION: Overall crude incidence estimates for total eating disorders were higher than reported in prior research that included only active duty Service members and required an eating disorder diagnosis code in the first or second diagnostic position of the medical record. Comprehensive and confidential studies are needed to more thoroughly characterize the nature and scope of eating disorder symptomatology within U.S. military personnel. PUBLIC SIGNIFICANCE: U.S. military service members are a vulnerable population with regard to eating disorder symptoms. Previously reported incidence and prevalence estimates using data from the Military Health System may have been underestimated due to overly stringent case definitions. Given personal and occupational barriers (e.g., career consequences), confidential studies of military personnel may provide more complete data on the scope of eating disorders to inform screening and clinical practice guidelines for military populations.
RESUMO
OBJECTIVE: Adolescent children of US service members (i.e., military-dependent youth) face unique stressors that increase risk for various forms of disinhibited eating, including emotional eating. Difficulties with adaptively responding to stress and aversive emotions may play an important role in emotional eating. This study examined emotion dysregulation as a potential moderator of the association between perceived stress and emotional eating in adolescent military dependents. METHOD: Participants were military-dependent youth (N = 163, 57.7% female, Mage = 14.5 ± 1.6, MBMI-z = 1.9 ± 0.4) at risk for adult binge-eating disorder and high weight enrolled in a randomized controlled prevention trial. Prior to intervention, participants completed questionnaires assessing perceived stress and emotional eating. Parents completed a questionnaire assessing their adolescent's emotion dysregulation. Moderation analyses were conducted using the PROCESS macro in SPSS and adjusted for theoretically relevant sociodemographic covariates. RESULTS: The interaction between adolescent perceived stress and emotion dysregulation (parent-reported about the adolescent) in relation to adolescent emotional eating was found to be significant, such that higher emotion dysregulation magnified the association between perceived stress and emotional eating (p = .010). Examination of simple slopes indicated that associations between perceived stress and emotional eating were strongest for youth with above-average emotion dysregulation, and non-significant for youth with average or below-average emotion dysregulation. DISCUSSION: Findings suggest that greater emotion dysregulation may increase risk for emotional eating in response to stress among military-dependent youth at risk for binge-eating disorder or high weight. Improving emotion regulation skills may be a useful target for eating disorder prevention among youth who are at risk for emotional eating. PUBLIC SIGNIFICANCE: Prior research has shown that adolescent military dependents are at increased risk for eating disorders and high weight. The current study found that emotion dysregulation moderated the relationship between perceived stress and emotional eating among military-dependent youth. There may be clinical utility in intervening on emotion regulation for adolescent dependents at particular risk for emotional eating and subsequent eating disorders.
Assuntos
Regulação Emocional , Militares , Estresse Psicológico , Humanos , Adolescente , Feminino , Masculino , Estresse Psicológico/psicologia , Militares/psicologia , Emoções , Inquéritos e Questionários , Comportamento Alimentar/psicologiaRESUMO
BACKGROUND AND OBJECTIVES: Limited research has examined how discrimination in young adulthood relates to substance use. We examined how multiple and specific types (e.g., race-based) of experiences of unfair treatment are related to problematic alcohol and cannabis use. METHODS: We analyzed cross-sectional data from a diverse cohort of young adults (mean age 24.7) predominantly residing in southern California (n = 2303) to examine associations of multiple (count) and specific experiences (race-, sexual orientation-, gender-based) of perceived everyday discrimination with self-reported alcohol and cannabis use outcomes (consequences, use disorders, and solitary use). We also tested interactions between the three specific discrimination experiences and sociodemographic characteristics (e.g., race-based discrimination × race/ethnicity). RESULTS: In this diverse sample (e.g., 47% Latinx/o and 22% Asian; 22% sexual/gender diverse; 56% female) of young adults, about 46% reported up to four different discrimination experiences and 27% reported race-, 26% gender-, and 5% sexual orientation-based discrimination. Race- and gender-based discrimination and experiencing more types of discrimination were associated with worse cannabis use outcomes. Race-based discrimination was associated with fewer alcohol consequences and lower Alcohol Use Disorders Identification Test (AUDIT) scores. Associations with sexual orientation-based discrimination and the interactions were not significant. DISCUSSION AND CONCLUSIONS: Findings build on limited research on associations of discrimination with cannabis use in young adults. More work is needed to understand the mechanisms by which discrimination influences drinking behaviors. SCIENTIFIC SIGNIFICANCE: This study advances the field by examining the unique contributions of specific and multiple types of discrimination experiences in young adulthood, a critical developmental period in which substance use peaks.
RESUMO
Improvements in whole genome amplification (WGA) would enable new types of basic and applied biomedical research, including studies of intratissue genetic diversity that require more accurate single-cell genotyping. Here, we present primary template-directed amplification (PTA), an isothermal WGA method that reproducibly captures >95% of the genomes of single cells in a more uniform and accurate manner than existing approaches, resulting in significantly improved variant calling sensitivity and precision. To illustrate the types of studies that are enabled by PTA, we developed direct measurement of environmental mutagenicity (DMEM), a tool for mapping genome-wide interactions of mutagens with single living human cells at base-pair resolution. In addition, we utilized PTA for genome-wide off-target indel and structural variant detection in cells that had undergone CRISPR-mediated genome editing, establishing the feasibility for performing single-cell evaluations of biopsies from edited tissues. The improved precision and accuracy of variant detection with PTA overcomes the current limitations of accurate WGA, which is the major obstacle to studying genetic diversity and evolution at cellular resolution.
Assuntos
Variação Genética , Genoma Humano , Técnicas de Amplificação de Ácido Nucleico , Análise de Célula Única , Moldes Genéticos , Pareamento de Bases/genética , Sistemas CRISPR-Cas/genética , Linhagem Celular Tumoral , Humanos , Mutagênicos/metabolismo , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
BACKGROUND: Urban American Indian/Alaska Native (AI/AN) adolescents are vulnerable to sleep and other health-related disparities due to numerous social drivers, including historical trauma and relocation to urban areas. This study aims to identify strategies to increase protective factors and culturally tailor sleep health interventions for this population. METHODS: Using community-based participatory research, the NAYSHAW study conducted in-depth interviews with urban AI/AN adolescents aged 12-19 years to understand critical components needed for developing a culturally sensitive sleep health intervention. Data from two qualitative subsamples (N = 46) and parent surveys (N = 110) were analyzed, focusing on factors that affect sleep health behaviors, including parental involvement, technology, and traditional practices. RESULTS: Key findings include the detrimental impact of electronics use at night and protective effects of traditional practices on sleep. Parental involvement in sleep routines varied by adolescent's age. Adolescents desired sleep health education in interactive formats, whereas parents preferred workshops and digital applications for sleep health strategies. Findings suggest that interventions need to address electronics use and should also be culturally tailored to address the unique experiences of urban AI/AN adolescents. CONCLUSIONS: Results underscore the importance of utilizing community-based strategies to develop culturally tailored sleep interventions for underserved populations, specifically urban AI/AN adolescents. Integrating traditional practices with evidence-based sleep health strategies can provide a holistic approach to improving sleep and overall well-being. Parental education and involvement will be critical to the success of such interventions.
Assuntos
Nativos do Alasca , Indígenas Norte-Americanos , População Urbana , Humanos , Adolescente , Feminino , Masculino , Nativos do Alasca/psicologia , Criança , Adulto Jovem , Indígenas Norte-Americanos/psicologia , Pesquisa Participativa Baseada na Comunidade , SonoRESUMO
BACKGROUND: The FACT complex is a conserved histone chaperone with critical roles in transcription and histone deposition. FACT is essential in pluripotent and cancer cells, but otherwise dispensable for most mammalian cell types. FACT deletion or inhibition can block induction of pluripotent stem cells, yet the mechanism through which FACT regulates cell fate decisions remains unclear. RESULTS: To explore the mechanism for FACT function, we generated AID-tagged murine embryonic cell lines for FACT subunit SPT16 and paired depletion with nascent transcription and chromatin accessibility analyses. We also analyzed SPT16 occupancy using CUT&RUN and found that SPT16 localizes to both promoter and enhancer elements, with a strong overlap in binding with OCT4, SOX2, and NANOG. Over a timecourse of SPT16 depletion, nucleosomes invade new loci, including promoters, regions bound by SPT16, OCT4, SOX2, and NANOG, and TSS-distal DNaseI hypersensitive sites. Simultaneously, transcription of Pou5f1 (encoding OCT4), Sox2, Nanog, and enhancer RNAs produced from these genes' associated enhancers are downregulated. CONCLUSIONS: We propose that FACT maintains cellular pluripotency through a precise nucleosome-based regulatory mechanism for appropriate expression of both coding and non-coding transcripts associated with pluripotency.
Assuntos
Células-Tronco Embrionárias , Histonas , Animais , Camundongos , Histonas/genética , Células-Tronco Embrionárias/metabolismo , Cromatina/metabolismo , Nucleossomos , Regulação da Expressão Gênica , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/metabolismo , Mamíferos/genéticaRESUMO
The Women in Wilderness Medicine Research Committee of the Wilderness Medical Society conducted a narrative review to address considerations for pregnant individuals in wilderness environments. There is limited evidence behind many opinion-based recommendations on the safety of various environmental exposures in pregnancy. The authors reviewed the literature for the best available evidence, including observational studies, case series, limited controlled trials, and extrapolation from physiological data, as well as evaluating expert consensus statements. The benefits of exposure to natural environments include better pregnancy outcomes and improved maternal mental and physical health. Risks are similar to nonpregnant individuals with the added risks associated with maternal-fetal physiology in wilderness environments and difficulties of evacuation. This narrative review discusses pregnancy-specific concerns in extreme environments, including high altitude, hypothermia, hyperthermia, lightning strikes, envenomations, and common outdoor exposures.
RESUMO
BACKGROUND: Nucleosome remodeling factors regulate the occupancy and positioning of nucleosomes genome-wide through ATP-driven DNA translocation. While many nucleosomes are consistently well-positioned, some nucleosomes and alternative nucleosome structures are more sensitive to nuclease digestion or are transitory. Fragile nucleosomes are nucleosome structures that are sensitive to nuclease digestion and may be composed of either six or eight histone proteins, making these either hexasomes or octasomes. Overlapping dinucleosomes are composed of two merged nucleosomes, lacking one H2A:H2B dimer, creating a 14-mer wrapped by ~ 250 bp of DNA. In vitro studies of nucleosome remodeling suggest that the collision of adjacent nucleosomes by sliding stimulates formation of overlapping dinucleosomes. RESULTS: To better understand how nucleosome remodeling factors regulate alternative nucleosome structures, we depleted murine embryonic stem cells of the transcripts encoding remodeler ATPases BRG1 or SNF2H, then performed MNase-seq. We used high- and low-MNase digestion to assess the effects of nucleosome remodeling factors on nuclease-sensitive or "fragile" nucleosome occupancy. In parallel we gel-extracted MNase-digested fragments to enrich for overlapping dinucleosomes. We recapitulate prior identification of fragile nucleosomes and overlapping dinucleosomes near transcription start sites, and identify enrichment of these features around gene-distal DNaseI hypersensitive sites, CTCF binding sites, and pluripotency factor binding sites. We find that BRG1 stimulates occupancy of fragile nucleosomes but restricts occupancy of overlapping dinucleosomes. CONCLUSIONS: Overlapping dinucleosomes and fragile nucleosomes are prevalent within the ES cell genome, occurring at hotspots of gene regulation beyond their characterized existence at promoters. Although neither structure is fully dependent on either nucleosome remodeling factor, both fragile nucleosomes and overlapping dinucleosomes are affected by knockdown of BRG1, suggesting a role for the complex in creating or removing these structures.
Assuntos
Proteínas de Ligação a DNA , Nucleossomos , Animais , Camundongos , Nucleossomos/genética , Proteínas de Ligação a DNA/genética , Histonas/metabolismo , Células-Tronco Embrionárias/metabolismo , Sítios de LigaçãoRESUMO
Research among adults reveals robust associations between discrimination and suicidality. However, the relationship between discrimination and suicidality is understudied in youth. Participants in the Adolescent Brain Cognitive Development study (n = 10â 312) completed a measure of discrimination based on multiple attributes. The Kiddie Schedule for Affective Disorders and Schizophrenia was administered 1 year later to assess depressive disorders and suicidality (ideation and behavior). Logistic regressions, adjusting for age, sex, race/ethnicity, family income, lifetime depressive disorders, and body composition were conducted. Adjusting for covariates, discrimination based on weight (OR: 2.19), race/ethnicity/color (OR: 3.21), and sexual orientation (OR: 3.83) were associated with greater odds of reporting suicidality 1 year later (ps < 0.025). Nationality-based discrimination was not significantly associated with suicidality. Compared with those reporting no discrimination, youths reporting discrimination based on 2 or more attributes had nearly 5 times greater odds of recent suicidality (OR: 4.72; P < .001). The current study highlights the deleterious impacts of discrimination on mental health among youths reporting multiple forms of discrimination.
Assuntos
Suicídio , Adulto , Humanos , Adolescente , Masculino , Feminino , Suicídio/psicologia , Tentativa de Suicídio/psicologia , Discriminação Percebida , Ideação Suicida , Comportamento Sexual , Fatores de RiscoRESUMO
BACKGROUND: Transgender and/or gender-diverse (TGD) persons are vulnerable to stigma and health care inequities; however, data are particularly limited among TGD active duty military service members despite ongoing changes to service policies. TGD-related stressors may impede access to and utilization of health care due to fear of potential discrimination and distress, thereby adversely impacting military readiness. METHODS: We examined stigma and barriers in health care and associations with physical and mental health in an online sample of 177 active duty service members who self-identified as TGD. To assess associations between stigma and barriers in health care with mental and physical health, linear regressions were conducted adjusting for age, gender identity, race, and rank. RESULTS: Over half (65%) of the participants reported at least 1 instance of stigma and/or barrier in health care. Stigma and barriers to health care were significantly associated with greater self-reported depressive symptoms (ß=0.20, P =0.03), anxiety (ß=0.21, P =0.03), stress (ß=0.30, P =0.001), and poorer overall mental health (ß=-0.23, P =0.007), after adjusting for covariates. Nearly one-quarter of participants had not disclosed their gender identity to their primary care clinician. CONCLUSIONS: Findings suggested that stigma and barriers to affirming health care were prevalent among active duty service members identifying as TGD, specifically, difficulty accessing gender-affirming care and negative assumptions from clinicians. These experiences may adversely affect mental health and impede the quality of health care received by a population already vulnerable to health inequities. Given recent changes to military policy, efforts may be warranted to improve access to timely, affirming care and clinician training.
Assuntos
Militares , Pessoas Transgênero , Humanos , Masculino , Feminino , Pessoas Transgênero/psicologia , Identidade de Gênero , Estigma Social , Acessibilidade aos Serviços de Saúde , Militares/psicologiaRESUMO
The current study examined the prevalence and typology of unmet needs and the association between unmet needs and HIV antiretroviral therapy (ART) medication adherence among a sample of Black people living with HIV(PLHIV) (N = 304) in Los Angeles, CA. We found a high prevalence of unmet needs, with 32% of participants reporting having two or more unmet needs. The most common unmet needs category was basic benefits needs (35%), followed by subsistence needs (33%), and health needs (27%). Significant correlates of unmet needs included food insecurity, history of homelessness, and history of incarceration. A greater number of unmet needs and any unmet basic benefits needs were each significantly associated with lower odds of HIV ART medication adherence. These findings provide further evidence linking the social determinants of health and social disenfranchisement to ART medication adherence among Black PLHIV.