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Sexual minoritized individuals engage in non-suicidal self-injury (NSSI) at higher rates than their heterosexual peers. Disclosing one's sexual minoritized identity can put one at risk for experiencing discrimination, which is linked to greater engagement in NSSI. However, discrimination has yet to be tested as a mechanism linking sexual identity disclosure to NSSI. Understanding how sexual identity disclosure impacts NSSI has the potential to inform interventions to reduce sexual orientation disparities in NSSI. To address this gap, the current study examined sexual orientation-based discrimination as a mediator of the longitudinal association between sexual identity disclosure and NSSI among 792 sexual minoritized young adults. Higher levels of disclosure at baseline were associated with greater likelihood of NSSI at two-month follow-up via greater discrimination at one-month follow-up, even after controlling for baseline levels of depression and demographic characteristics. The indirect effect became non-significant after controlling for previous levels of discrimination and NSSI. Findings provide partial support for the hypothesis that identity disclosure may precede exposure to discrimination and, in turn, engagement in NSSI. However, identity disclosure does not appear to predict acute increases in discrimination. Future research is encouraged to examine these prospective associations with longer intervals between assessments, as the indirect effect of identity disclosure on NSSI via discrimination may continue to accumulate over time. Findings highlight the need to reduce discrimination following sexual identity disclosure through the implementation of equitable and affirmative practices in school, healthcare, and other settings to improve the well-being of sexual minoritized young adults.
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Background: Volatile organic compounds (VOCs) are major components of air pollution and tobacco smoke, two known risk factors for cardiovascular diseases. VOCs are ubiquitous in the environment and originate from a wide range of sources, including the burning of biomass, fossil fuels, and consumer products. Direct evidence for associations between specific VOCs and ischemic heart disease (IHD) mortality in the general population is scarce. Methods: In a case-cohort study (stratified by age groups, sex, residence, and tobacco smoking), nested within the population-based Golestan cohort study (n = 50,045, 40-75 years, 58% women, enrollment: 2004-2008) in northeastern Iran, we measured urinary concentrations of 20 smoking-related VOC biomarkers using ultra high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. We calculated hazard ratio (HR) and 95% confidence interval (CI) for their associations with IHD mortality during follow-up to 2018, using Cox regression models adjusted for age, ethnicity, education, marital status, body mass index, physical activity, wealth, and urinary cotinine. Results: There were 575 non-cases from random subcohort and 601 participants who died from IHD, mean (standard deviation) age, 58.2 (9.3) years, with a median of 8.4 years follow-up. Significant associations [3rd vs. 1st tertile, HR (95% CI), P for trend] were observed between biomarkers of acrylamide [1.68(1.05,2.69), 0.025], acrylonitrile [2.06(1.14,3.72), 0.058], acrolein [1.98(1.30,3.01), 0.003 and 2.44(1.43,4.18), 0.002], styrene/ethylbenzene [1.83(1.19,2.84), 0.007 and 1.44(1.01,2.07), 0.046], dimethylformamide/methylisocyanate [2.15(1.33,3.50), 0.001], and 1,3butadiene [2.35(1.52,3.63),<0.001] and IHD mortality. These associations were independent of tobacco smoking, and they were only present in the non-smoking subgroup. Conclusion: Our findings provide direct evidence for associations between exposure to several VOCs with widespread household and commercial use and IHD mortality many years after these exposures. These results highlight the importance of VOC exposure in the general population as a risk factor for cardiovascular diseases and underline the importance of bio-monitoring non-tobacco VOC exposure.
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BACKGROUND: The adequacy of biomarkers of potential harm (BOPH) for assessing tobacco products was explored based on their ability to distinguish tobacco use from non-use, change with cessation, and to show biological gradient. METHODS: The sample included individuals with biomarker data in wave 1 of the Population Assessment of Tobacco Health study who never used tobacco, currently smoke cigarettes exclusively, used to smoke cigarettes exclusively (quit in past 12 months), currently use smokeless tobacco exclusively, and currently use e-cigarettes exclusively. We compared BOPH levels between groups and assessed the relationships between log-transformed biomarkers of exposure [BOE; total nicotine equivalents including seven nicotine metabolites (TNE-7), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanonol (NNAL), N-acetyl-S-(2-cyanoethyl)-L-cysteine, 1-hydroxypyrene, cadmium, and serum cotinine (SCOT)], and BOPH [high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), fibrinogen, soluble intercellular adhesion molecule-1 (sICAM-1), and 8-isoprostane]. RESULTS: Among people who smoke, both sICAM-1 and 8-isoprostane distinguished smoking from non-use and were associated with all six BOE. Among people who use smokeless tobacco, 8-isoprostane was associated with TNE-7 and NNAL whereas hs-CRP was associated with SCOT. Among people who use e-cigarettes, no associations between BOPH and BOE were observed. CONCLUSIONS: Both sICAM-1 and 8-isoprostane may be useful for assessing the use or changes in use of some tobacco products. Studies examining their predictive validity could further strengthen our understanding of these two biomarkers. IMPACT: We found that two biomarkers of potential harm, soluble intercellular adhesion molecule-1 and 8-isoprostane, may have utility in studies assessing the potential harm of tobacco use in absence of long-term epidemiological studies.
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Biomarcadores , Humanos , Femenino , Masculino , Biomarcadores/sangre , Persona de Mediana Edad , Adulto , Tabaco sin Humo/efectos adversos , Nicotina/sangre , Sistemas Electrónicos de Liberación de Nicotina , Adulto JovenRESUMEN
Purpose: This scoping review summarizes the literature on suicide-specific psychological interventions among lesbian, gay, bisexual, transgender, queer, and other sexual and gender minority (LGBTQ+) people to synthesize existing findings and support future intervention research and dissemination. Methods: Electronic databases PsycInfo and PubMed were searched for reports of psychological intervention studies with suicide-related outcome data among LGBTQ+ people. A total of 1269 articles were screened, and 19 studies met inclusion criteria (k = 3 examined suicide-specific interventions tailored to LGBTQ+ people, k = 4 examined nontailored suicide-specific interventions, k = 11 examined minority stress- or LGBTQ+ interventions that were not suicide-specific, and k = 1 examined other types of interventions). Results: Synthesis of this literature was made challenging by varied study designs, and features limit confidence in the degree of internal and external validity of the interventions evaluated. The only established suicide-specific intervention examined was Dialectical Behavior Therapy, and minority stress- and LGBTQ-specific interventions rarely targeted suicidal thoughts and behaviors (STBs). Nevertheless, most interventions reviewed demonstrated support for feasibility and/or acceptability. Only five studies tested suicide-related outcome differences between an LGBTQ+ group and a cisgender/heterosexual group. These studies did not find significant differences in STBs, but certain subgroups such as bisexual individuals may exhibit specific treatment disparities. Conclusion: Given the dearth of research, more research examining interventions that may reduce STBs among LGBTQ+ people is critically needed to address this public health issue.
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Caring Cards is a peer-adaptation of caring contacts for suicide prevention, in which people with lived experience of suicidal thoughts and behaviors create handmade cards for peers currently experiencing suicidal thoughts and/or behaviors. The present study used data from a feasibility/acceptability study of Caring Cards at a Veterans Affairs Medical Center to explore preferences for this type of recovery-oriented suicide prevention intervention. Participants were 55 Veterans with a past (card makers, n=21) or current (card recipients, n=34) high-risk indication for suicide. Card makers participated in a 3-month weekly 60-120-minute group therapy to create cards. Card recipients received these cards monthly for six months. Survey and interview data were collected post-intervention. Pragmatic analysis of interview responses revealed preferences related to participation length, card content and frequency, group formatting, and accessibility. Among both card makers (76.2%-85.7%) and card recipients (94.1%), a majority recommended offering this intervention for Veterans who have previously or are currently struggling with mental health concerns. Over 60% of card makers wanted receive cards and 52.9% of card recipients wanted to make cards. These data further support the importance of lived experience voices in intervention development. Caring Cards, an intervention specifically focusing on improving well-being, meaning-making, and fulfillment in one's life, regards Veteran preferences as salient in the future implementation of a recovery-oriented approach to suicide prevention.
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INTRODUCTION: Disproportionate rates of cigar smoking across demographic groups can contribute to tobacco-related health disparities in the United States. We assessed overall and demographic-specific cigar cessation rates from 2010 to 2019. AIMS AND METHODS: To characterize cessation prevalence among selected demographic groups over time, we analyzed data from the 2010-2011, 2014-2015, and 2018-2019 Tobacco Use Supplement to the Current Population Survey (TUS-CPS). Individuals who reported either (1) current cigar smoking for at least 2 years or (2) quitting cigar smoking within the past 12 months were included in the study (nâ =â 5262 in 2010-2011; nâ =â 4741 in 2014-2015; nâ =â 3741 in 2018-2019). Among this group, individuals who reported not smoking a cigar within the past 6 months were considered cigar quitters. Chi-square tests were used to test differences in cessation prevalence between the two survey waves within demographic groups as well as between different groups within survey waves. RESULTS: The prevalence of cigar cessation decreased from 2010-2011 to 2018-2019 for non-Hispanic (NH) White individuals, Hispanic individuals, and both males and females. (pâ <â .05 for all groups). NH White individuals had significantly higher cessation prevalence than individuals who identified as NH Black (33.8% vs. 25.0%, respectively, in 2010-2011; 33.4% vs. 20.4% in 2014-2015; 31.1% vs. 22.3% in 2018-2019; pâ <â .05 for all differences). CONCLUSIONS: Overall cigar cessation prevalence significantly decreased from 2010-2011 to 2018-2019. Findings from the study could provide an opportunity to implement strategies that promote cessation strategies targeting certain subpopulations. IMPLICATIONS: Cigar cessation patterns are starkly different across different demographic groups, which leads to a disproportionate burden of health-related effects of continued use of these products. These results can inform policy actions around cigar cessation efforts. Future research to close this disparity should be focused on populations that have lower cessation prevalence.
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ABSTRACT: Musculoskeletal injuries occur frequently in sport during practice, training, and competition. Injury assessment and management are common responsibilities for the team physician. Initial Assessment and Management of Musculoskeletal Injury-A Team Physician Consensus Statement is title 23 in a series of annual consensus documents written for the practicing team physician. This statement was developed by the Team Physician Consensus Conference, an annual project-based alliance of six major professional associations. The goal of this document is to help the team physician improve the care and treatment of the athlete by understanding the initial assessment and management of selected musculoskeletal injuries.
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Médicos , Deportes , Humanos , Atletas , Consenso , Examen FísicoRESUMEN
Astronauts are known to exhibit a variety of immunological alterations during spaceflight including changes in leukocyte distribution and plasma cytokine concentrations, a reduction in T-cell function, and subclinical reactivation of latent herpesviruses. These alterations are most likely due to mission-associated stressors including circadian misalignment, microgravity, isolation, altered nutrition, and increased exposure to cosmic radiation. Some of these stressors may also occur in terrestrial situations. This study sought to determine if crewmembers performing winterover deployment at Palmer Station, Antarctica, displayed similar immune alterations. The larger goal was to validate a ground analog suitable for the evaluation of countermeasures designed to protect astronauts during future deep space missions. For this pilot study, plasma, saliva, hair, and health surveys were collected from Palmer Station, Antarctica, winterover participants at baseline, and at five winterover timepoints. Twenty-six subjects consented to participate over the course of two seasons. Initial sample processing was performed at Palmer, and eventually stabilized samples were returned to the Johnson Space Center for analysis. A white blood cell differential was performed (real time) using a fingerstick blood sample to determine alterations in basic leukocyte subsets throughout the winterover. Plasma and saliva samples were analyzed for 30 and 13 cytokines, respectively. Saliva was analyzed for cortisol concentration and three latent herpesviruses (DNA by qPCR), EBV, HSV1, and VZV. Voluntary surveys related to general health and adverse clinical events were distributed to participants. It is noteworthy that due to logistical constraints caused by COVID-19, the baseline samples for each season were collected in Punta Arenas, Chile, after long international travel and during isolation. Therefore, the Palmer pre-mission samples may not reflect a true normal 'baseline'. Minimal alterations were observed in leukocyte distribution during winterover. The mean percentage of monocyte concentration elevated at one timepoint. Plasma G-CSF, IL1RA, MCP-1, MIP-1ß, TNFα, and VEGF were decreased during at least one winterover timepoint, whereas RANTES was significantly increased. No statistically significant changes were observed in mean saliva cytokine concentrations. Salivary cortisol was substantially elevated throughout the entire winterover compared to baseline. Compared to shedding levels observed in healthy controls (23%), the percentage of participants who shed EBV was higher throughout all winterover timepoints (52-60%). Five subjects shed HSV1 during at least one timepoint throughout the season compared to no subjects shedding during pre-deployment. Finally, VZV reactivation, common in astronauts but exceptionally rare in ground-based stress analogs, was observed in one subject during pre-deployment and a different subject at WO2 and WO3. These pilot data, somewhat influenced by the COVID-19 pandemic, do suggest that participants at Palmer Station undergo immunological alterations similar to, but likely in reduced magnitude, as those observed in astronauts. We suggest that winterover at Palmer Station may be a suitable test analog for spaceflight biomedical countermeasures designed to mitigate clinical risks for deep space missions.
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Hidrocortisona , Vuelo Espacial , Humanos , Hidrocortisona/análisis , Regiones Antárticas , Pandemias , Proyectos Piloto , Astronautas , CitocinasRESUMEN
OBJECTIVE: Flavored non-cigarette tobacco product (NCTP) use is common among US adult tobacco users. To update the estimates of use patterns of flavored NCTPs, this study assessed current NCTP use among adults by flavor use and flavor categories from 2010 to 2019. METHODS: We analyzed data from the 2010-2019 Tobacco Use Supplement to the Current Population Survey to estimate the weighted proportion of adult NCTP users by flavor use across survey waves. Flavor use was defined as past 30-day use of any menthol/mint or fruit/other flavors. We used the 2018-2019 data to examine the differences in demographic characteristics and tobacco use patterns among users of menthol/mint or fruit/other flavors compared to exclusive users of tobacco flavor, by product type. RESULTS: Compared to 2014-2015, electronic nicotine delivery system (ENDS) users were more likely (79.0% vs. 66.6%, p < 0.001) to report flavor use in 2018-2019, whereas cigar (26.9% vs. 31.2%, p = 0.030) and pipe (56.3% vs. 65.5%, p = 0.015) smokers were less likely to report flavor use in 2018-2019. In 2018-2019, the most prevalent flavor categories were exclusive use of tobacco flavor among cigar (73.1%) and smokeless tobacco (48.3%) users, and use of fruit/other flavors among ENDS (64.9%) and pipe (48.4%) users. Flavored users were more likely to be young adults aged 18-24 years (cigars, ENDS, smokeless tobacco) and Non-Hispanic Black or Hispanic persons (cigars, ENDS, pipes) compared to tobacco-flavored users. CONCLUSIONS: Flavored product use increased among adult ENDS users but decreased among cigar and pipe smokers. These findings could inform tobacco regulatory efforts concerning flavored NCTPs.
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Sistemas Electrónicos de Liberación de Nicotina , Productos de Tabaco , Tabaquismo , Adulto Joven , Humanos , Mentol , Aromatizantes , Fumadores , Uso de TabacoRESUMEN
BACKGROUND: Biomarkers of exposure are tools for understanding the impact of tobacco use on health outcomes if confounders like demographics, use behavior, biological half-life, and other sources of exposure are accounted for in the analysis. METHODS: We performed multiple regression analysis of longitudinal measures of urinary biomarkers of alkaloids, tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons, volatile organic compounds (VOC), and metals to examine the sample-to-sample consistency in Waves 1 and 2 of the Population Assessment of Tobacco and Health (PATH) Study including demographic characteristics and use behavior variables of persons who smoked exclusively. Regression coefficients, within- and between-person variance, and intra-class correlation coefficients (ICC) were compared with biomarker smoking/nonsmoking population mean ratios and biological half-lives. RESULTS: Most biomarkers were similarly associated with sex, age, race/ethnicity, and product use behavior. The biomarkers with larger smoking/nonsmoking population mean ratios had greater regression coefficients related to recency of exposure. For VOC and alkaloid metabolites, longer biological half-life was associated with lower within-person variance. For each chemical class studied, there were biomarkers that demonstrated good ICCs. CONCLUSIONS: For most of the biomarkers of exposure reported in the PATH Study, for people who smoke cigarettes exclusively, associations are similar between urinary biomarkers of exposure and demographic and use behavior covariates. Biomarkers of exposure within-subject consistency is likely associated with nontobacco sources of exposure and biological half-life. IMPACT: Biomarkers measured in the PATH Study provide consistent sample-to-sample measures from which to investigate the association of adverse health outcomes with the characteristics of cigarettes and their use.
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Alcaloides , Productos de Tabaco , Compuestos Orgánicos Volátiles , Humanos , Semivida , Biomarcadores , Fumar/epidemiologíaRESUMEN
BACKGROUND: Studying carcinogens in tobacco and nontobacco sources may be key to understanding the pathogenesis and geographic distribution of esophageal cancer. METHODS: The Golestan Cohort Study has been conducted since 2004 in a region with high rates of esophageal squamous cell carcinoma. For this nested study, the cases comprised of all incident cases by January 1, 2018; controls were matched to the case by age, sex, residence, time in cohort, and tobacco use. We measured urinary concentrations of 33 exposure biomarkers of nicotine, polycyclic aromatic hydrocarbons, volatile organic compounds, and tobacco-specific nitrosamines. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals for associations between the 90th vs the 10th percentiles of the biomarker concentrations and incident esophageal squamous cell carcinoma. RESULTS: Among individuals who did not currently use tobacco (148 cases and 163 controls), 2 acrolein metabolites, 2 acrylonitrile metabolites, 1 propylene oxide metabolite, and one 1,3-butadiene metabolite were significantly associated with incident esophageal squamous cell carcinoma (adjusted odds ratios between 1.8 and 4.3). Among tobacco users (57 cases and 63 controls), metabolites of 2 other volatile organic compounds (styrene and xylene) were associated with esophageal squamous cell carcinoma (OR = 6.2 and 9.0, respectively). In tobacco users, 2 tobacco-specific nitrosamines (NNN and N'-Nitrosoanatabine) were also associated with esophageal squamous cell carcinoma. Suggestive associations were seen with some polycyclic aromatic hydrocarbons (especially 2-hydroxynaphthalene) in nonusers of tobacco products and other tobacco-specific nitrosamines in tobacco users. CONCLUSION: These novel associations based on individual-level data and samples collected many years before cancer diagnosis, from a population without occupational exposure, have important public health implications.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Nitrosaminas , Hidrocarburos Policíclicos Aromáticos , Compuestos Orgánicos Volátiles , Humanos , Biomarcadores , Estudios de Cohortes , Neoplasias Esofágicas/epidemiología , Neoplasias Esofágicas/etiología , Carcinoma de Células Escamosas de Esófago/epidemiología , Carcinoma de Células Escamosas de Esófago/etiología , Incidencia , Hidrocarburos Policíclicos Aromáticos/efectos adversos , Compuestos Orgánicos Volátiles/efectos adversosRESUMEN
ABSTRACT: Musculoskeletal injuries occur frequently in sport during practice, training, and competition. Injury assessment and management are common responsibilities for the team physician. Initial Assessment and Management of Musculoskeletal Injury-A Team Physician Consensus Statement is title 23 in a series of annual consensus documents written for the practicing team physician. This statement was developed by the Team Physician Consensus Conference, an annual project-based alliance of six major professional associations. The goal of this document is to help the team physician improve the care and treatment of the athlete by understanding the initial assessment and management of selected musculoskeletal injuries.
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Traumatismos en Atletas , Médicos , Medicina Deportiva , Humanos , Traumatismos en Atletas/diagnóstico , Traumatismos en Atletas/terapiaRESUMEN
The gut microbiome and its metabolites are increasingly implicated in several cardiovascular diseases, but their role in human myocardial infarction (MI) injury responses have yet to be established. To address this, we examined stool samples from 77 ST-elevation MI (STEMI) patients using 16 S V3-V4 next-generation sequencing, metagenomics and machine learning. Our analysis identified an enriched population of butyrate-producing bacteria. These findings were then validated using a controlled ischemia/reperfusion model using eight nonhuman primates. To elucidate mechanisms, we inoculated gnotobiotic mice with these bacteria and found that they can produce beta-hydroxybutyrate, supporting cardiac function post-MI. This was further confirmed using HMGCS2-deficient mice which lack endogenous ketogenesis and have poor outcomes after MI. Inoculation increased plasma ketone levels and provided significant improvements in cardiac function post-MI. Together, this demonstrates a previously unknown role of gut butyrate-producers in the post-MI response.
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Infarto del Miocardio , Infarto del Miocardio con Elevación del ST , Humanos , Animales , Ratones , Butiratos/metabolismo , Corazón , Cuerpos CetónicosRESUMEN
Background. Benzene is a known human carcinogen. Human exposure to benzene can be assessed by measuring trans, trans-muconic acid (MUCA) in urine. Golestan Province in northeastern Iran has been reported to have high incidence of esophageal cancer linked to the use of tobacco products. This manuscript evaluates the urinary MUCA concentrations among the participants of the Golestan Cohort Study (GCS).Methods. We analyzed MUCA concentration in 177 GCS participants' urine samples and performed nonparametric pairwise multiple comparisons to determine statistically significant difference among six different product use groups. Mixed effects model was fitted on 22 participants who exclusively smoked cigarette and 51 participants who were classified as nonusers. The urinary MUCA data were collected at the baseline and approximately five years later, and intraclass correlation coefficient (ICC) was calculated from the model.Results. Compared with nonusers, tobacco smoking was associated with higher urinary MUCA concentrations. Based on the nonparametric test of pairwise multiple comparisons, MUCA concentrations among participants who smoked combusted tobacco products were statistically significantly higher compared to nonusers. Urinary MUCA collected five years apart from the same individuals showed moderate reliability (ICC = 0.41), which was expected given the relatively short half-life (â¼6 h) of MUCA.Conclusion. Our study revealed that tobacco smoke was positively associated with increased levels of urinary MUCA concentration, indicating that it is a significant source of benzene exposure among GCS participants.
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Benceno , Humo , Humanos , Benceno/análisis , Biomarcadores/orina , Estudios de Cohortes , Reproducibilidad de los ResultadosRESUMEN
People who smoke menthol cigarettes, particularly those who are non-Hispanic Black/African American, are less likely to achieve successful smoking cessation compared with people who smoke non-menthol cigarettes. This study examined the 2003-2019 Tobacco Use Supplement to the Current Population Survey (TUS-CPS) harmonized data to estimate cross-sectional trends in cigarette smoking cessation among U.S. adults, stratified by menthol cigarette use, race/ethnicity, sex, and age. The analytic sample included respondents who smoked for ≥ 2 years (current users and former users who reported quitting during the past year). We tested cessation trends using orthogonal polynomial contrasts for overall, menthol, and non-menthol smoking cessation prevalence and stratified by race/ethnicity, sex, and age in logistic regression models. We also analyzed the 2018-2019 non-harmonized TUS-CPS data among recent quitters to examine differences in characteristics (e.g., demographic characteristics, smoking frequency, use of smoking cessation aids, switching to other tobacco products) by menthol cigarette use. We observed significant linear changes in prevalence trends for overall cigarette smoking cessation, menthol smoking cessation, and non-menthol smoking cessation (p < 0.0001 for all linear trends), and changes in menthol cessation among non-Hispanic White and non-Hispanic Other race/ethnicity categories during 2003-2019. In the 2018-2019 wave, we observed differences in menthol status for sex, race/ethnicity, age, and educational attainment. We did not observe differences for other characteristics. We observed changes in overall cigarette smoking cessation, menthol, and non-menthol smoking cessation prevalence during the study period; however, gains in cigarette smoking cessation were not experienced among non-Hispanic Black/African American adults who smoke.
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Dolor Abdominal , Fiebre , Femenino , Humanos , Fiebre/etiología , Dolor Abdominal/etiologíaRESUMEN
BACKGROUND: Remuscularization of the mammalian heart can be achieved after cell transplantation of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs). However, several hurdles remain before implementation into clinical practice. Poor survival of the implanted cells is related to insufficient vascularization, and the potential for fatal arrhythmogenesis is associated with the fetal cell-like nature of immature CMs. METHODS: We generated 3 lines of hiPSC-derived endothelial cells (ECs) and hiPSC-CMs from 3 independent donors and tested hiPSC-CM sarcomeric length, gap junction protein, and calcium-handling ability in coculture with ECs. Next, we examined the therapeutic effect of the cotransplantation of hiPSC-ECs and hiPSC-CMs in nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice undergoing myocardial infarction (n≥4). Cardiac function was assessed by echocardiography, whereas arrhythmic events were recorded using 3-lead ECGs. We further used healthy non-human primates (n=4) with cell injection to study the cell engraftment, maturation, and integration of transplanted hiPSC-CMs, alone or along with hiPSC-ECs, by histological analysis. Last, we tested the cell therapy in ischemic reperfusion injury in non-human primates (n=4, 3, and 4 for EC+CM, CM, and control, respectively). Cardiac function was evaluated by echocardiography and cardiac MRI, whereas arrhythmic events were monitored by telemetric ECG recorders. Cell engraftment, angiogenesis, and host-graft integration of human grafts were also investigated. RESULTS: We demonstrated that human iPSC-ECs promote the maturity and function of hiPSC-CMs in vitro and in vivo. When cocultured with ECs, CMs showed more mature phenotypes in cellular structure and function. In the mouse model, cotransplantation augmented the EC-accompanied vascularization in the grafts, promoted the maturity of CMs at the infarct area, and improved cardiac function after myocardial infarction. Furthermore, in non-human primates, transplantation of ECs and CMs significantly enhanced graft size and vasculature and improved cardiac function after ischemic reperfusion. CONCLUSIONS: These results demonstrate the synergistic effect of combining iPSC-derived ECs and CMs for therapy in the postmyocardial infarction heart, enabling a promising strategy toward clinical translation.
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Células Madre Pluripotentes Inducidas , Infarto del Miocardio , Humanos , Ratones , Animales , Miocitos Cardíacos/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Células Endoteliales/metabolismo , Ratones SCID , Ratones Endogámicos NOD , Infarto del Miocardio/patología , Primates , Diferenciación Celular , MamíferosRESUMEN
Mental and behavioral health (MBH) emergencies in children and youth continue to increasingly affect not only the emergency department (ED), but the entire spectrum of emergency medical services for children, from prehospital services to the community. Inadequate community and institutional infrastructure to care for children and youth with MBH conditions makes the ED an essential part of the health care safety net for these patients. As a result, an increasing number of children and youth are referred to the ED for evaluation of a broad spectrum of MBH emergencies, from depression and suicidality to disruptive and aggressive behavior. However, challenges in providing optimal care to these patients include lack of personnel, capacity, and infrastructure, challenges with timely access to a mental health professional, the nature of a busy ED environment, and paucity of outpatient post-ED discharge resources. These factors contribute to prolonged ED stays and boarding, which negatively affects patient care and ED operations. Strategies to improve care for MBH emergencies, including systems level coordination of care, is therefore essential. The goal of this policy statement and its companion technical report is to highlight strategies, resources, and recommendations for improving emergency care delivery for pediatric MBH.
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Trastornos de la Conducta Infantil , Urgencias Médicas , Trastornos Mentales , Humanos , Masculino , Femenino , Niño , Adolescente , Trastornos Mentales/terapia , Servicios Médicos de Urgencia , Trastornos de la Conducta Infantil/terapia , Personal de Salud , Servicios de Salud MentalRESUMEN
ABSTRACT: Cycling is a growing sport worldwide since the COVID-19 pandemic. With the growing availability and interest in long distance events, professional and amateur cyclists are pushing themselves further and harder than ever before. Training and nutrition should be understood by the sports medicine professional in order to guide counseling toward proper fueling to avoid health consequences. This article reviews macronutrients and micronutrients, periodized training and nutrition, and the relevance of the ketogenic diet for endurance cyclists riding greater than 90 min.