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1.
Am J Prev Med ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38878985

RESUMO

INTRODUCTION: Sexual and gender minority (SGM) youth, who experience high mental and behavioral health needs, are overrepresented in the criminal legal system, which may exacerbate these needs. This study examined associations among arrest history and mental and behavioral health among SGM youth. METHODS: Using cross-sectional survey data from the 2022 LGBTQ+ National Teen Survey, this study created a case-control sample of 287 SGM youth with an arrest history and 1148 propensity-matched SGM youth without an arrest history. Associations between arrest history and SGM developmental milestones, minority stressors, and mental and behavioral health outcomes were examined. Statistical analyses were conducted between 2022 and 2024. RESULTS: Arrest history was significantly associated with several SGM developmental milestones (e.g., earlier age of identity realization and disclosure) and minority stressors (e.g., greater bullying and parental rejection). SGM youth with an arrest history had poorer mental and behavioral health, including greater sleep disturbance (adjusted odds ratio (aOR):1.46; 95% CI: 1.08-2.00) and positive screenings for depression (aOR:1.60; 95% CI: 1.20-2.14), anxiety (aOR:1.35; 95% CI: 1.01-1.82), and risk for substance use disorder development (aOR: 5.81; 95% CI: 4.26 - 7.94). CONCLUSIONS: Arrest history is associated with the mental and behavioral health of SGM youth, highlighting systemic inequities. Tailored public health interventions are needed to reduce criminal-legal contact in this population.

3.
MDM Policy Pract ; 9(1): 23814683231222469, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38293655

RESUMO

Introduction. The risk of infectious disease transmission, including COVID-19, is disproportionately high in correctional facilities due to close living conditions, relatively low levels of vaccination, and reduced access to testing and treatment. While much progress has been made on describing and mitigating COVID-19 and other infectious disease risk in jails and prisons, there are open questions about which data can best predict future outbreaks. Methods. We used facility data and demographic and health data collected from 24 prison facilities in the Pennsylvania Department of Corrections from March 2020 to May 2021 to determine which sources of data best predict a coming COVID-19 outbreak in a prison facility. We used machine learning methods to cluster the prisons into groups based on similar facility-level characteristics, including size, rurality, and demographics of incarcerated people. We developed logistic regression classification models to predict for each cluster, before and after vaccine availability, whether there would be no cases, an outbreak defined as 2 or more cases, or a large outbreak, defined as 10 or more cases in the next 1, 2, and 3 d. We compared these predictions to data on outbreaks that occurred. Results. Facilities were divided into 8 clusters of sizes varying from 1 to 7 facilities per cluster. We trained 60 logistic regressions; 20 had test sets with between 35% and 65% of days with outbreaks detected. Of these, 8 logistic regressions correctly predicted the occurrence of an outbreak more than 55% of the time. The most common predictive feature was incident cases among the incarcerated population from 2 to 32 d prior. Other predictive features included the number of tests administered from 1 to 33 d prior, total population, test positivity rate, and county deaths, hospitalizations, and incident cases. Cumulative cases, vaccination rates, and race, ethnicity, or age statistics for incarcerated populations were generally not predictive. Conclusions. County-level measures of COVID-19, facility population, and test positivity rate appear as potential promising predictors of COVID-19 outbreaks in correctional facilities, suggesting that correctional facilities should monitor community transmission in addition to facility transmission to inform future outbreak response decisions. These efforts should not be limited to COVID-19 but should include any large-scale infectious disease outbreak that may involve institution-community transmission. Highlights: The risk of infectious disease transmission, including COVID-19, is disproportionately high in correctional facilities.We used machine learning methods with data collected from 24 prison facilities in the Pennsylvania Department of Corrections to determine which sources of data best predict a coming COVID-19 outbreak in a prison facility.Key predictors included county-level measures of COVID-19, facility population, and the test positivity rate in a facility.Fortifying correctional facilities with the ability to monitor local community rates of infection (e.g., though improved interagency collaboration and data sharing) along with continued testing of incarcerated people and staff can help correctional facilities better predict-and respond to-future infectious disease outbreaks.

4.
Artigo em Inglês | MEDLINE | ID: mdl-37483654

RESUMO

Communities of color are disproportionately impacted by gun violence. Unlocking potential community-led solutions could be the key to quelling the gun violence epidemic and its impact on these communities. In this qualitative study, we explored community perspectives on local assets that may prevent and mitigate gun violence. We conducted semi-structured, in-depth interviews (n = 45) among individuals not directly involved in gun violence (i.e., shooting victim or perpetrator) despite having a high probability of being involved in gun violence in New Haven, CT. Participants were asked to describe social structures that may deter local gun violence. Here, we report emergent themes to preventing gun violence across multiple levels, including role models (interpersonal), social cohesion and home ownership (neighborhood), and community-based organizations (organizational). Our findings suggest that investments in stable housing, efforts to build social cohesion, access to community-based mental health services, and youth activities are needed to curb the drivers of community gun violence.

5.
J Psychopathol Clin Sci ; 132(5): 577-589, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37347909

RESUMO

Limited research has examined how multiple forms of oppression (e.g., racism, heterosexism, transphobia)-manifesting across multiple levels (e.g., interpersonal, structural)-can place Black and Latinx lesbian, gay, bisexual, transgender, queer, and other sexual/gender minority (LGBTQ+) adolescents at increased risk for internalizing psychopathology, including depression. Utilizing a national sample of 2,561 Black and Latinx LGBTQ+ adolescents (aged 13-17), we examined associations among depressive symptoms and several adolescent-focused manifestations of stigma, including: (a) interpersonal racial/ethnic bullying, (b) interpersonal sexual orientation bullying, (c) nine state-level forms of structural stigma or protection for LGBTQ+ adolescents, and (d) a new adolescent-focused composite index of state-level anti-LGBTQ+ structural stigma. Racial/ethnic bullying and sexual orientation bullying were found to be prevalent among the sample and were associated-both independently and jointly-with increased depressive symptoms. One harmful state-level anti-LGBTQ+ structural stigma indicator (i.e., anti-LGBTQ+ community attitudes) and seven protective state-level anti-LGBTQ+ structural stigma indicators (e.g., conversion therapy bans) were associated with odds of depressive symptoms, in the expected directions. Black and Latinx LGBTQ+ adolescents residing in states with greater overall anti-LGBTQ+ structural stigma reported increased depressive symptoms, even when adjusting for racial/ethnic and sexual orientation bullying. Additionally, Black and Latinx LGBTQ+ adolescents living in the most stigmatizing states demonstrated 32% increased odds of depressive symptoms, as compared to those living in the most LGBTQ+ affirming states. Multilevel, intersectional interventions could have optimal effects on the mental health and resilience of Black and Latinx LGBTQ+ adolescents. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assuntos
Negro ou Afro-Americano , Depressão , Hispânico ou Latino , Minorias Sexuais e de Gênero , Estigma Social , Adolescente , Feminino , Humanos , Masculino , Depressão/epidemiologia , Depressão/etnologia , Depressão/etiologia , Depressão/psicologia , Hispânico ou Latino/psicologia , Hispânico ou Latino/estatística & dados numéricos , Minorias Sexuais e de Gênero/psicologia , Minorias Sexuais e de Gênero/estatística & dados numéricos , Comportamento Sexual/etnologia , Comportamento Sexual/psicologia , Comportamento Sexual/estatística & dados numéricos , Estados Unidos/epidemiologia , Negro ou Afro-Americano/psicologia , Negro ou Afro-Americano/estatística & dados numéricos , Bullying/psicologia , Bullying/estatística & dados numéricos
6.
Discov Oncol ; 14(1): 34, 2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-36991198

RESUMO

PURPOSE: Triple-negative breast cancer continues to be one of the leading causes of death in women, making up 7% of all cancer deaths. Tumor-treating electric fields are low-energy, low-frequency oscillating electric fields that induce an anti-proliferative effect on mitotic cells in glioblastoma multiforme, non-small cell lung cancer, and ovarian cancer. Little is known about effects of tumor-treating fields on triple-negative breast cancer and known research for tumor-treating fields only utilizes low (< 3 V/cm) electric field intensities. METHODS: We have developed an in-house field delivery device capable of high levels of customization to explore a much wider variety of electric field and treatment parameters. Furthermore, we investigated the selectivity of tumor-treating field treatment between triple-negative breast cancer and human breast epithelial cells. RESULTS: Tumor-treating fields show greatest efficacy against triple-negative breast cancer cell lines between 1 and 3 V/cm electric field intensities while having little effect on epithelial cells. CONCLUSION: These results provide a clear therapeutic window for tumor-treating field delivery to triple-negative breast cancer.

7.
bioRxiv ; 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38168349

RESUMO

Skeletal muscles connect bones and tendons for locomotion and posture. Understanding the regenerative processes of muscle, bone and tendon is of importance to basic research and clinical applications. Despite their interconnections, distinct transcription factors have been reported to orchestrate each tissue's developmental and regenerative processes. Here we show that Scx expression is not detectable in adult muscle stem cells (also known as satellite cells, SCs) during quiescence. Scx expression begins in activated SCs and continues throughout regenerative myogenesis after injury. By SC-specific Scx gene inactivation (ScxcKO), we show that Scx function is required for SC expansion/renewal and robust new myofiber formation after injury. We combined single-cell RNA-sequencing and CUT&RUN to identify direct Scx target genes during muscle regeneration. These target genes help explain the muscle regeneration defects of ScxcKO, and are not overlapping with Scx -target genes identified in tendon development. Together with a recent finding of a subpopulation of Scx -expressing connective tissue fibroblasts with myogenic potential during early embryogenesis, we propose that regenerative and developmental myogenesis co-opt the Scx gene via different mechanisms.

8.
Pediatrics ; 150(6)2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36385576

RESUMO

OBJECTIVES: This study examined differences by sexual and gender minority (SGM) and incarceration statuses in mental health indicators among youth. METHODS: Population-based, cross-sectional data are from the 2019 Minnesota Student Survey (N = 72 324) and includes public school students (Mage = 15.49) and youth incarcerated in juvenile correctional facilities (Mage = 15.48). We categorized youth into 4 groups: (1) non-SGM youth in public schools, (2) non-SGM youth in correctional facilities, (3) SGM youth in public schools, and (4) SGM youth in correctional facilities. Multivariable regression models assessed associations among SGM and incarceration statuses and mental health indicators after controlling for sociodemographic characteristics and exposure to adverse childhood experiences. RESULTS: More youth in juvenile correctional facilities identified as SGM (28.8%) compared with youth in public schools (20.4%, P = .002). SGM youth in correctional facilities reported a higher prevalence of suicidal ideation (42.2%), suicide attempt (37.5%), and self-harm (57.8%) compared with all other groups. Depressive symptom severity was similarly elevated among SGM youth in correctional facilities and SGM youth in public schools. SGM youth in correctional facilities, compared with non-SGM youth in public schools, demonstrated elevated odds of suicide ideation (adjusted odds ratio [aOR] = 2.2, 95% confidence interval [95% CI] = 1.3-3.9), suicide attempt (aOR = 6.3, 95% CI = 3.6-10.9), and self-harm (aOR = 3.6, 95% CI = 2.1-6.3). CONCLUSIONS: Incarcerated SGM youth disproportionately experience negative mental health indicators. Findings suggest that tailored, intersectional, and responsive mental health interventions are needed to support incarcerated SGM youth.


Assuntos
Prisioneiros , Minorias Sexuais e de Gênero , Adolescente , Humanos , Saúde Mental , Estudos Transversais , Estabelecimentos Correcionais
9.
BMC Health Serv Res ; 22(1): 585, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35501855

RESUMO

BACKGROUND: Criminal justice system costs in the United States have exponentially increased over the last decades, and providing health care to individuals released from incarceration is costly. To better understand how to manage costs to state budgets for those who have been incarcerated, we aimed to assess state-level costs of an enhanced primary care program, Transitions Clinic Network (TCN), for chronically-ill and older individuals recently released from prison. METHODS: We linked administrative data from Connecticut Department of Correction, Medicaid, and Department of Mental Health and Addiction Services to identify a propensity matched comparison group and estimate costs of a primary care program serving chronically-ill and older individuals released from incarceration between 2013 and 2016. We matched 94 people released from incarceration who received care at a TCN program to 94 people released from incarceration who did not receive care at TCN program on numerous characteristics. People eligible for TCN program participation were released from incarceration within the prior 6 months and had a chronic health condition or were over the age of 50. We estimated 1) costs associated with the TCN program and 2) costs accrued by Medicaid and the criminal justice system. We evaluated associations between program participation and Medicaid and criminal justice system costs over a 12-month period using bivariate analyses with nonparametric bootstrapping method. RESULTS: The 12-month TCN program operating cost was estimated at $54,394 ($146 per participant per month). Average monthly Medicaid costs per participant were not statistically different between the TCN ($1737 ± $3449) and comparison ($1356 ± $2530) groups. Average monthly criminal justice system costs per participant were significantly lower among TCN group ($733 ± $1130) compared with the matched group ($1276 ± $1738, p < 0.05). We estimate every dollar invested in the TCN program yielded a 12-month return of $2.55 to the state. CONCLUSIONS: Medicaid investments in an enhanced primary care program for individuals returning from incarceration are cost neutral and positively impact state budgets by reducing criminal justice system costs.


Assuntos
Serviços de Saúde Mental , Prisões , Redução de Custos , Humanos , Medicaid , Atenção Primária à Saúde , Estados Unidos
10.
Artigo em Inglês | MEDLINE | ID: mdl-35409785

RESUMO

Limited research has focused on how substance use and sexual risk behaviors differ among individuals impacted by the criminal legal system based on social identities. Using the National Survey on Drug Use and Health, we estimated relative risk for reporting a sexually transmitted infection (STI) among intersectional social groups with criminal legal involvement using a modified Poisson regression. We then utilized multivariate logistic regression and marginal effects to measure associations between substance use behaviors and STIs and to estimate whether these varied among the intersectional social groups with elevated STI rates. Three groups had elevated risk of reporting an STI compared to white, heterosexual men: white, heterosexual women (1.53, 95% CI: 1.05-2.20); Black, heterosexual women (2.03, 95% CI: 1.18-3.49); and white, gay or bisexual men (5.65, 95% CI: 2.61-12.20). Considering the intersections of gender, race, and sexual orientation, elevated risks for STIs among white and Black heterosexual women were mitigated after adjusting for substance use alongside other confounders. Only those who identified as white, gay or bisexual, and male had increased STI risk after controlling for substance use. Interventions targeting Black and white heterosexual women's sexual health following incarceration should focus on substance use and interventions targeting white, gay or bisexual men should focus on healthy sexual behaviors, HIV/STI screening, and care continuum efforts.


Assuntos
Criminosos , Infecções por HIV , Infecções Sexualmente Transmissíveis , Transtornos Relacionados ao Uso de Substâncias , Adulto , Feminino , Infecções por HIV/diagnóstico , Humanos , Masculino , Comportamento Sexual , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia
11.
LGBT Health ; 9(2): 81-93, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35167353

RESUMO

Purpose: To facilitate identification of the impact of incarceration on the health of sexual and gender minority (SGM) populations, we sought to identify publicly accessible, representative health datasets that assessed SGM status and incarceration history from 2010 to 2020 and to examine SGM disparities in lifetime incarceration experiences. Methods: Datasets were identified and analyzed through a multistep process: (1) content search of 76 health datasets; (2) consultation with 14 subject matter experts; (3) a systematic review; and (4) a data analysis stage. Utilizing the identified health datasets, we produced representative estimates of sexual minority (SM) incarceration disparities. Results: Five publicly accessible databases were identified that assessed SM status and incarceration history; none assessed gender minority status and incarceration history. Across datasets, the weighted prevalence of lifetime incarceration among SM populations was substantially higher (range = 17.5%-26.3%) than among non-SM populations (range = 4.6%-21.2%). Conclusion: Few publicly accessible, representative health datasets collect standardized information regarding SM status and incarceration history, and none assess diverse gender identities and incarceration history. These data suggest that a disproportionate proportion of SM individuals may experience incarceration compared with non-SM individuals. Research assessing the health effects of incarceration on SGM populations remains limited; publicly accessible, representative health data are needed to address this gap.


Assuntos
Minorias Sexuais e de Gênero , Identidade de Gênero , Humanos , Grupos Minoritários , Comportamento Sexual , Estados Unidos/epidemiologia
12.
Psychotherapy (Chic) ; 59(1): 96-112, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35025569

RESUMO

We tested the feasibility and acceptability of a group therapy treatment that addresses the intersecting stigma-related stressors theorized to drive elevated mental health risk, sexual health risk, and their co-occurrence among Black and Latino gay, bisexual, and other men who have sex with men (GBM). First, we modified an existing 10-week, one-on-one, cognitive-behavioral treatment addressing co-occurring health risks among GBM to develop a group-based, intersectionally informed treatment for GBM of color. Then, an open pilot was conducted (n = 21, across two cohorts) with young Black and Latino GBM. An evaluation of feasibility metrics (e.g., eligibility-enrollment ratio, session attendance, rate of retention) supported overall treatment feasibility. Qualitative data suggest high acceptability of the treatment length, format, and content-and revealed a powerful theme: The treatment and group composition led participants to feel less alone as GBM of color. To further evaluate acceptability, baseline and 3-month posttreatment assessments and exit interviews were used to examine the treatment's impact on stigma coping, mental health, and sexual health. Expected changes were found for: (a) stigma coping, as demonstrated by decreases in perceived sexual minority stress, racial minority stress, and intersectional stress; (b) mental health, including depression, anxiety, stress, and suicidality, but not alcohol use; and (c) sexual health, including condom use efficacy, sexual compulsivity, and preexposure prophylaxis uptake; with partial support for decreased in human immunodeficiency virus; HIV-transmission risk acts. This study lays the groundwork for a group treatment to address intersectional stigma, mental health, and HIV risk among young Black and Latino GBM in the U.S. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , Infecções por HIV/prevenção & controle , Homossexualidade Masculina/psicologia , Humanos , Masculino , Saúde Mental , Pigmentação da Pele , Estigma Social
13.
Matrix Biol Plus ; 13: 100099, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35036900

RESUMO

Tendon is a vital musculoskeletal tissue that is prone to degeneration. Proper tendon maintenance requires complex interactions between extracellular matrix components that remain poorly understood. Collagen VI and biglycan are two matrix molecules that localize pericellularly within tendon and are critical regulators of tissue properties. While evidence suggests that collagen VI and biglycan interact within the tendon matrix, the relationship between the two molecules and its impact on tendon function remains unknown. We sought to elucidate potential coordinate roles of collagen VI and biglycan within tendon by defining tendon properties in knockout models of collagen VI, biglycan, or both molecules. We first demonstrated co-expression and co-localization of collagen VI and biglycan within the healing tendon, providing further evidence of cooperation between the two molecules during nascent tendon matrix formation. Deficiency in collagen VI and/or biglycan led to significant reductions in collagen fibril size and tendon mechanical properties. However, collagen VI-null tendons displayed larger reductions in fibril size and mechanics than seen in biglycan-null tendons. Interestingly, knockout of both molecules resulted in similar properties to collagen VI knockout alone. These results indicate distinct and non-additive roles for collagen VI and biglycan within tendon. This work provides better understanding of regulatory interactions between two critical tendon matrix molecules.

14.
Front Public Health ; 9: 681128, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34422744

RESUMO

Over half a million individuals return from United States prisons and millions more from jails every year, many of whom with complex health and social needs. Community health workers (CHWs) perform diverse roles to improve health outcomes in disadvantaged communities, but no studies have assessed their role as integrated members of a primary care team serving individuals returning from incarceration. Using data from participants who received primary care through the Transitions Clinic Network, a model of care that integrates CHWs with a lived experienced of incarceration into primary care teams, we characterized how CHWs address participant health and social needs during interactions outside of clinic visits for 6 months after participants established primary care. Among the 751 participants, 79% had one or more CHW interactions outside of the clinic documented. Participants with more comorbid conditions, longer stays during their most recent incarceration, and released with a prescription had more interactions with CHWs compared to those with fewer comorbidities, shorter stays, and no prescription at release. Median number of interactions was 4 (interquartile range, IQR 2-8) and 56% were in person. The most common issues addressed (34%) were social determinants of health, with the most common being housing (35%). CHWs working in interdisciplinary primary care teams caring for people with histories of incarceration perform a variety of functions for clients outside of scheduled primary care visits. To improve health outcomes among disadvantaged populations, CHWs should be able to work across multiple systems, with supervision and support for CHW activities both in the primary care clinic and within the community.


Assuntos
Agentes Comunitários de Saúde , Prisioneiros , Instituições de Assistência Ambulatorial , Humanos , Atenção Primária à Saúde , Estados Unidos
15.
JAMA Netw Open ; 4(5): e2111821, 2021 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-34047791

RESUMO

Importance: More than half of the adult population in the United States has ever had a family member incarcerated, an experience more common among Black individuals. The impacts of family incarceration on well-being are not fully understood. Objective: To assess the associations of incarceration of a family member with perceived well-being and differences in projected life expectancy. Design, Setting, and Participants: This nationally representative cross-sectional study used data from the 2018 Family History of Incarceration Survey to examine how experiences of family member incarceration were associated with a holistic measure of well-being, including physical, mental, social, financial, and spiritual domains. Well-being was used to estimate change in life expectancy and was compared across varying levels of exposure to immediate and extended family member incarceration using logistic regression models to adjust for individual and household characteristics. Data were analyzed from October 2019 to April 2020. Exposures: Respondents' history of family member incarceration, including immediate and extended family members. Main Outcomes and Measures: The main outcome was self-reported life-evaluation, a measure of overall well-being from the 100 Million Healthier Lives Adult Well-being Assessment. Respondents were considered thriving with a current life satisfaction score of 7 or greater and a future life optimism score of 8 or greater, each on a scale of 0 to 10. Other outcomes included physical health, mental health, social support, financial well-being, and spiritual well-being, each measured with separate scales. Additionally, life expectancy projections were estimated using population-level correlations with the Life Evaluation Index. All percentages were weighted to more closely represent the US population. Results: Of 2815 individuals included in analysis, 1472 (51.7%) were women, 1765 (62.8%) were non-Hispanic White, and 868 (31.5%) were aged 35 to 54 years. A total of 1806 respondents (45.0%) reported having an immediate family member who was incarcerated. Compared with respondents with no family incarceration, any family member incarceration was associated with lower well-being overall (thriving: 69.5% [95% CI, 65.0%-75.0%] vs 56.9% [95% CI, 53.9%-59.9%]) and in every individual domain (eg, physical thriving: 51.1% [95% CI, 46.2-56.0] vs 35.5% [95% CI, 32.6%-38.3%]) and with a mean (SE) estimated 2.6 (0.03) years shorter life expectancy. Among those with any family incarceration, Black respondents had a mean (SE) estimated 0.46 (0.04) fewer years of life expectancy compared with White respondents. Conclusions and Relevance: These findings suggest that family member health and well-being may be an important avenue through which incarceration is associated with racial disparities in health and mortality. Decarceration efforts may improve population-level well-being and life expectancy by minimizing detrimental outcomes associated with incarceration among nonincarcerated family members.


Assuntos
Relações Familiares/psicologia , Família/psicologia , Expectativa de Vida , Prisioneiros/psicologia , Prisioneiros/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos , Adulto Jovem
16.
Nature ; 595(7865): 107-113, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33915569

RESUMO

COVID-19, which is caused by SARS-CoV-2, can result in acute respiratory distress syndrome and multiple organ failure1-4, but little is known about its pathophysiology. Here we generated single-cell atlases of 24 lung, 16 kidney, 16 liver and 19 heart autopsy tissue samples and spatial atlases of 14 lung samples from donors who died of COVID-19. Integrated computational analysis uncovered substantial remodelling in the lung epithelial, immune and stromal compartments, with evidence of multiple paths of failed tissue regeneration, including defective alveolar type 2 differentiation and expansion of fibroblasts and putative TP63+ intrapulmonary basal-like progenitor cells. Viral RNAs were enriched in mononuclear phagocytic and endothelial lung cells, which induced specific host programs. Spatial analysis in lung distinguished inflammatory host responses in lung regions with and without viral RNA. Analysis of the other tissue atlases showed transcriptional alterations in multiple cell types in heart tissue from donors with COVID-19, and mapped cell types and genes implicated with disease severity based on COVID-19 genome-wide association studies. Our foundational dataset elucidates the biological effect of severe SARS-CoV-2 infection across the body, a key step towards new treatments.


Assuntos
COVID-19/patologia , COVID-19/virologia , Rim/patologia , Fígado/patologia , Pulmão/patologia , Miocárdio/patologia , SARS-CoV-2/patogenicidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Atlas como Assunto , Autopsia , Bancos de Espécimes Biológicos , COVID-19/genética , COVID-19/imunologia , Células Endoteliais , Células Epiteliais/patologia , Células Epiteliais/virologia , Feminino , Fibroblastos , Estudo de Associação Genômica Ampla , Coração/virologia , Humanos , Inflamação/patologia , Inflamação/virologia , Rim/virologia , Fígado/virologia , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Especificidade de Órgãos , Fagócitos , Alvéolos Pulmonares/patologia , Alvéolos Pulmonares/virologia , RNA Viral/análise , Regeneração , SARS-CoV-2/imunologia , Análise de Célula Única , Carga Viral
17.
bioRxiv ; 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33655247

RESUMO

The SARS-CoV-2 pandemic has caused over 1 million deaths globally, mostly due to acute lung injury and acute respiratory distress syndrome, or direct complications resulting in multiple-organ failures. Little is known about the host tissue immune and cellular responses associated with COVID-19 infection, symptoms, and lethality. To address this, we collected tissues from 11 organs during the clinical autopsy of 17 individuals who succumbed to COVID-19, resulting in a tissue bank of approximately 420 specimens. We generated comprehensive cellular maps capturing COVID-19 biology related to patients' demise through single-cell and single-nucleus RNA-Seq of lung, kidney, liver and heart tissues, and further contextualized our findings through spatial RNA profiling of distinct lung regions. We developed a computational framework that incorporates removal of ambient RNA and automated cell type annotation to facilitate comparison with other healthy and diseased tissue atlases. In the lung, we uncovered significantly altered transcriptional programs within the epithelial, immune, and stromal compartments and cell intrinsic changes in multiple cell types relative to lung tissue from healthy controls. We observed evidence of: alveolar type 2 (AT2) differentiation replacing depleted alveolar type 1 (AT1) lung epithelial cells, as previously seen in fibrosis; a concomitant increase in myofibroblasts reflective of defective tissue repair; and, putative TP63+ intrapulmonary basal-like progenitor (IPBLP) cells, similar to cells identified in H1N1 influenza, that may serve as an emergency cellular reserve for severely damaged alveoli. Together, these findings suggest the activation and failure of multiple avenues for regeneration of the epithelium in these terminal lungs. SARS-CoV-2 RNA reads were enriched in lung mononuclear phagocytic cells and endothelial cells, and these cells expressed distinct host response transcriptional programs. We corroborated the compositional and transcriptional changes in lung tissue through spatial analysis of RNA profiles in situ and distinguished unique tissue host responses between regions with and without viral RNA, and in COVID-19 donor tissues relative to healthy lung. Finally, we analyzed genetic regions implicated in COVID-19 GWAS with transcriptomic data to implicate specific cell types and genes associated with disease severity. Overall, our COVID-19 cell atlas is a foundational dataset to better understand the biological impact of SARS-CoV-2 infection across the human body and empowers the identification of new therapeutic interventions and prevention strategies.

18.
Soc Sci Med ; 272: 113735, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33561571

RESUMO

Gay and bisexual men (GBM) are incarcerated at nearly twice the rate as the general United States male population. Minority stress, namely the unique social stressors related to anti-GBM stigma and discrimination, is central to GBM's experiences in ways that might put them at risk of incarceration and psychosocial risks during and after incarceration. In this qualitative study, we examined how GBM navigate minority stress and how this navigation influences their psychosocial health before, during, and after incarceration. We conducted semi-structured, in-depth interviews with 20 formerly incarcerated GBM in New York City, diverse in terms of race and time since last release. Our findings document the many ways in which GBM manage their identities in the context of minority stress and how such management exposes them to, or helps them avoid, minority stress and associated psychosocial health risks surrounding their incarcerations. Here, we report dominant themes before, during, and after incarceration for GBM, including minority stress: 1) as catalyzing incarceration-related experiences, 2) as motiving identity management techniques to survive the hegemonic masculinity and normative anti-GBM stigma of incarceration, and 3) as a determinant to reentry support and sexual expression after incarceration. These findings suggest potential changes to public health policy and practice to better serve the needs of currently and formerly incarcerated GBM and to prevent such incarceration in the first place.


Assuntos
Homossexualidade Masculina , Minorias Sexuais e de Gênero , Bissexualidade , Humanos , Masculino , Cidade de Nova Iorque , Comportamento Sexual , Estados Unidos
19.
BMJ Open ; 11(2): e042898, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33597139

RESUMO

OBJECTIVES: We aim to estimate the impact of various mitigation strategies on COVID-19 transmission in a US jail beyond those offered in national guidelines. DESIGN: We developed a stochastic dynamic transmission model of COVID-19. SETTING: One anonymous large urban US jail. PARTICIPANTS: Several thousand staff and incarcerated individuals. INTERVENTIONS: There were four intervention phases during the outbreak: the start of the outbreak, depopulation of the jail, increased proportion of people in single cells and asymptomatic testing. These interventions were implemented incrementally and in concert with one another. PRIMARY AND SECONDARY OUTCOME MEASURES: The basic reproduction ratio, R0 , in each phase, as estimated using the next generation method. The fraction of new cases, hospitalisations and deaths averted by these interventions (along with the standard measures of sanitisation, masking and social distancing interventions). RESULTS: For the first outbreak phase, the estimated R0 was 8.44 (95% credible interval (CrI): 5.00 to 13.10), and for the subsequent phases, R0,phase 2 =3.64 (95% CrI: 2.43 to 5.11), R0,phase 3 =1.72 (95% CrI: 1.40 to 2.12) and R0,phase 4 =0.58 (95% CrI: 0.43 to 0.75). In total, the jail's interventions prevented approximately 83% of projected cases, hospitalisations and deaths over 83 days. CONCLUSIONS: Depopulation, single celling and asymptomatic testing within jails can be effective strategies to mitigate COVID-19 transmission in addition to standard public health measures. Decision makers should prioritise reductions in the jail population, single celling and testing asymptomatic populations as additional measures to manage COVID-19 within correctional settings.


Assuntos
COVID-19/prevenção & controle , COVID-19/transmissão , Surtos de Doenças/prevenção & controle , Prisões Locais , Humanos , Saúde Pública , Estados Unidos
20.
Ann Epidemiol ; 53: 103-105, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32919033

RESUMO

PURPOSE: To estimate the basic reproduction ratio () of SARS-CoV-2 inside a correctional facility early in the COVID-19 pandemic. METHODS: We developed a dynamic transmission model for a large, urban jail in the United States. We used the next generation method to determine the basic reproduction ratio We included anonymized data of incarcerated individuals and correctional staff with confirmed COVID-19 infections in our estimation of the basic reproduction ratio () of SARS-CoV-2. RESULTS: The estimated is 8.44 (95% Credible Interval (CrI): 5.00-13.13) for the entire jail. CONCLUSIONS: The high of SARS-CoV-2 in a large urban jail highlights the importance of including correctional facilities in public health strategies for COVID-19. In the absence of more aggressive mitigation strategies, correctional facilities will continue to contribute to community infections.


Assuntos
Número Básico de Reprodução/estatística & dados numéricos , COVID-19/epidemiologia , COVID-19/transmissão , Surtos de Doenças/prevenção & controle , Prisões Locais , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Saúde Pública , SARS-CoV-2 , Estados Unidos/epidemiologia
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