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BACKGROUND AND OBJECTIVES: Hispanic young adults in the United States have consistently high rates of risky drinking, adverse childhood experiences (ACEs), depression, and anxiety. There is a positive association between ACEs and alcohol use among Hispanic populations; it is unknown if mental health symptomatology mediates this relationship. The purpose of this study was to test whether depression and anxiety mediated the relationship between ACEs and risky drinking among Hispanic young adults who engage in risky drinking. METHODS: Data from 264 Hispanic young adults, ages 19 to 30, were collected via an online questionnaire. Participants were recruited via social media, emails/listservs across colleges, the community, and web-panels. The questionnaire assessed ACEs, risky drinking, depression, and anxiety. We conducted a mediational analysis to test whether depression and anxiety mediated the relationship between ACEs and risky drinking. RESULTS: Of the sample, 59.8% identified as female and 40.2% as male. The average age was 24.37 (SD = 3.069). Participants (61%) identified as Mexican, Mexican American, or Chicano, and 84.1% identified as second-generation. ACEs were positively associated with risky drinking, depression, and anxiety. Depression mediated the relationship between ACEs and risky drinking. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Depression explained the association between ACEs and risky drinking among Hispanic young adults, adding to our understanding of how mediators can illustrate pathways that lead from ACEs to risky drinking. Practitioners and interventionists should continue supporting Hispanic youth by integrating them into early prevention programs to mitigate the mental health consequences of ACEs that could lead to risky drinking.
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Experiências Adversas da Infância , Ansiedade , Depressão , Hispânico ou Latino , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Experiências Adversas da Infância/estatística & dados numéricos , Experiências Adversas da Infância/psicologia , Hispânico ou Latino/psicologia , Hispânico ou Latino/estatística & dados numéricos , Depressão/epidemiologia , Depressão/psicologia , Depressão/etnologia , Ansiedade/psicologia , Ansiedade/epidemiologia , Ansiedade/etnologia , Assunção de Riscos , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/psicologia , Consumo de Bebidas Alcoólicas/etnologia , Estados Unidos/epidemiologia , Inquéritos e QuestionáriosRESUMO
Differences in the access and use of digital health interventions are driven by culture, in addition to economic and physical factors. To avoid the systematic exclusion of traditionally underserved cultural groups, creating inclusive digital health interventions is essential. One way to achieve this is through cultural adaptations, defined as the systematic modification of an existing intervention that aligns with a target audience's cultural norms, beliefs, and values. In theory, cultural adaptations can potentially increase the reach and engagement of digital health interventions. However, the evidence of whether and how that is achieved is limited. Justifying, planning, and implementing an adaptation comes with various challenges and takes time and money. This perspective provides a critical overview of the field's current state and emphasizes the need for technology-specific frameworks that address when and how to culturally adapt digital health interventions.
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Objective: An association exists between perceived belonging and depression among college students. Because a student's sense of belongingness may vary as a function of their social identity, three identities - ethnicity, first-generation college student status, and sex - were investigated as potential moderators of this relationship. Participants: One hundred eighty-seven heavy-drinking college students (63% female; 52% non-Latinx White; M = 20 years of age) were assessed. Methods: Three hierarchical linear regressions were conducted to test whether belonging at baseline predicted depression at six months and whether each identity variable moderated this association. Results: Analyses yielded significant main effects between belonging and depression. Hispanic nor first-generation status interacted with belonging in predicting depression. Sex interacted with belonging where higher belongingness was associated with lower levels of depression only among female students. Conclusion: Mental health providers should consider asking female students about their perceptions of belonging on college campuses to understand their vulnerability to depression.
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The first year of college is often marked by increased levels of alcohol consumption; first-year students also vary in their sense of fitting in on campus. Research has amply documented the links between social and enhancement drinking motives with various alcohol outcomes among college students. However, it is unclear how perceived levels of fitting in on campus potentially buffers or amplifies the relationship between drinking motives and drinking behavior. We explored whether perceptions of fitting in on campus moderated effects of social and/or enhancement drinking motives on drinks per week. A sample of 121 heavy drinking first year college students (50 % female, 58 % non-Latinx White, M = 18 years of age) were assessed twice in their first semester (baseline, 3 months) in the context of an alcohol-specific intervention. Hierarchical linear regressions were conducted to test whether drinking motives (social and enhancement) at baseline prospectively predicted drinks per week at 3 months. We hypothesized a positive association between both drinking motives and drinks per week; whether fitting in moderates these relationships was exploratory. Regression analyses yielded non-significant main effects of social motives, enhancement motives, and feelings of fitting in on drinks per week. There was no significant interaction for social motives, but the interaction between enhancement motives and fitting in was significant. Participants with a low sense of fitting in had a strong positive relationship between enhancement motives and drinks per week. Improving perceptions of fitting in for first-year college students may potentially reduce the association between enhancement drinking motives and drinks per week.
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Consumo de Álcool na Faculdade , Consumo de Bebidas Alcoólicas , Humanos , Feminino , Lactente , Masculino , Motivação , Estudantes , Emoções , Universidades , Etanol , Adaptação PsicológicaRESUMO
Purpose of review: Latinx sexual minority adolescents (LSMA) are at an intersection of ethnic and sexual minority (SM) status and may experience heighten risk of substance use and related problems. These youth may also hold unique protective factors that help mitigate the effects of minority stress and curb substance use. Little is known, however, about the intersectional minority stressors (i.e., due to ethnicity and SM status) and protective factors related to substance use among this population. Recent Findings: According to the minority stress model, there are unique minority stressors and resiliency factors that can help explain differences in behavioral health rates between white SM and SM of color. Research supports the notion that minority stressors (e.g., stigma/risk, homophobic bullying, and family rejection of SM status) confer risk for substance use among LSMA. In terms of resilience, less is known, but there may be some protective factors that have not been measured that could explain lower rates in some substances (i.e., club drugs and methamphetamine). Summary: Little is known about how the intersections of ethnicity and SM status are associated with substance use in adolescence. Future research should assess the temporal relationship of multilevel (i.e., intrapersonal, relational, and system), intersectional (i.e., ethnicity and SM status) minority stressors and protective factors unique to LSMA on substance use. We propose that the findings from these future studies will help to create socioculturally appropriate behavioral health treatments that consider the intersectional risks and strengths within the LSMA population.
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OBJECTIVE: Rates of heavy alcohol use among active-duty military personnel in the United States are high and negatively affect individuals within the service branches. This study tested the effectiveness of a military-focused screening, brief intervention, and referral to treatment (SBIRT) intervention for reducing risky alcohol use among active-duty patients. METHOD: We used a randomized, parallel, two-group design to test the effectiveness of the SBIRT intervention in a convenience sample of service members recruited from the emergency department of a military hospital. A total of 791 participants were randomized to the SBIRT or usual care conditions, and 472 participants (59.7%) completed a 6-month follow-up. Fifteen percent of the sample was female. Self-reported Alcohol Use Disorders Identification Test (AUDIT), controlled drinking self-efficacy (CDSE), and readiness to change drinking behaviors were assessed at baseline and follow-up. RESULTS: Among higher risk participants (i.e., AUDIT ≥8), results of a complete case analysis showed a significant reduction in scores on the AUDIT-C (consumption questions from the AUDIT) and a significant increase in CDSE. Null findings were observed for intent-to-treat analyses testing the effectiveness of the SBIRT intervention; significant decreases in AUDIT and AUDIT-C scores and significant increases in CDSE were observed over time, irrespective of condition assignment for both complete case and intent-to-treat analyses. CONCLUSIONS: Results of a complete case analysis provided some support for the effectiveness of the SBIRT intervention for higher risk participants. The results of the more conservative intent-to-treat analyses did not support any of the study hypotheses. Future SBIRT effectiveness trials should also test electronic SBIRT intervention approaches.
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Consumo de Bebidas Alcoólicas/prevenção & controle , Alcoolismo/diagnóstico , Programas de Rastreamento/métodos , Militares , Adulto , Aconselhamento , Intervenção em Crise , Serviço Hospitalar de Emergência , Feminino , Seguimentos , Humanos , Masculino , Encaminhamento e Consulta , Resultado do Tratamento , Estados Unidos , Adulto JovemRESUMO
Structural congenital heart disease (CHD) has not previously been linked to autoimmunity. In our study, we developed an autoimmune model of structural CHD that resembles hypoplastic left heart syndrome (HLHS), a life-threatening CHD primarily affecting the left ventricle. Because cardiac myosin (CM) is a dominant autoantigen in autoimmune heart disease, we hypothesized that immunization with CM might lead to transplacental passage of maternal autoantibodies and a prenatal HLHS phenotype in exposed fetuses. Elevated anti-CM autoantibodies in maternal and fetal sera, as well as IgG reactivity in fetal myocardium, were correlated with structural CHD that included diminished left ventricular cavity dimensions in the affected progeny. Further, fetuses that developed a marked HLHS phenotype had elevated serum titers of anti-ß-adrenergic receptor Abs, as well as increased protein kinase A activity, suggesting a potential mechanism for the observed pathological changes. Our maternal-fetal model presents a new concept linking autoimmunity against CM and cardiomyocyte proliferation with cardinal features of HLHS. To our knowledge, this report shows the first evidence in support of a novel immune-mediated mechanism for pathogenesis of structural CHD that may have implications in its future diagnosis and treatment.
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Autoimunidade/imunologia , Miosinas Cardíacas/imunologia , Síndrome do Coração Esquerdo Hipoplásico/imunologia , Animais , Autoanticorpos/imunologia , Western Blotting , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Cardiopatias Congênitas/imunologia , Cardiopatias Congênitas/patologia , Síndrome do Coração Esquerdo Hipoplásico/patologia , Imuno-Histoquímica , Ratos , Ratos Endogâmicos LewRESUMO
Cryptochrome (CRY) is the primary circadian photoreceptor in Drosophila. It resets the circadian clock by promoting light-induced degradation of the clock proteins Timeless and Period, as well as its own proteolysis. The E3 ligases that ubiquitylate Timeless and Period before degradation are known and it is known that Drosophila (d) CRY is degraded by the ubiquitin-proteasome system as well. To identify the E3 ligase for dCRY we screened candidates in S2 cells by RNAi. Knockdown of each of the 25 putative F-box proteins identified by bioinformatics did not attenuate the light-induced degradation of dCRY. However, knockdown of a WD40 protein, Bromodomain and WD repeat domain containing 3 (Brwd3) (CG31132/Ramshackle) caused strong attenuation of dCRY degradation following light exposure. We found that BRWD3 functions as a Damage-specific DNA binding protein 1 (DDB1)- and CULLIN (CUL)4-associated factor in a Cullin4-RING Finger E3 Ligase (CRL4) that mediates light-dependent binding of dCRY to CUL4-ROC1-DDB1-BRWD3, inducing ubiquitylation of dCRY and its light-induced degradation. Thus, this study identifies a light-activated E3 ligase complex essential for light-mediated CRY degradation in Drosophila cells.
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Criptocromos/metabolismo , Proteínas Culina/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas do Olho/metabolismo , Luz , Proteólise , Fatores de Transcrição/metabolismo , Ubiquitinação/fisiologia , Animais , Criptocromos/genética , Proteínas Culina/genética , Proteínas de Drosophila/genética , Drosophila melanogaster , Proteínas do Olho/genética , Fatores de Transcrição/genética , Complexos Ubiquitina-Proteína Ligase , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação/efeitos da radiaçãoRESUMO
Photoacoustic tomography is a hybrid modality based on optical absorption excitation and ultrasonic detection. It is sensitive to melanin, one of the primary absorbers in skin. For cells that do not naturally contain melanin, melanin production can be induced by introducing the gene for tyrosinase, the primary enzyme responsible for expression of melanin in melanogenic cells. Optical resolution photoacoustic microscopy was used in the ex vivo study reported here, where the signal from transfected cells increased by more than 10 times over wild-type cells. A subsequent in vivo experiment was conducted to demonstrate the capability of photoacoustic microscopy to spectrally differentiate between tyrosinase-catalyzed melanin and various other absorbers in tissue.
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Genes Reporter , Microscopia/métodos , Imagem Molecular/métodos , Monofenol Mono-Oxigenase/metabolismo , Processamento de Sinais Assistido por Computador , Tomografia/métodos , Desenho de Equipamento , Células HEK293 , Hemoglobinas , Humanos , Melaninas/química , Melaninas/metabolismo , Microscopia/instrumentação , Oxiemoglobinas , Imagens de Fantasmas , Tomografia/instrumentação , Ultrassonografia/métodosRESUMO
Cryptochromes are a highly conserved class of UV-A/blue light photoreceptors. In Drosophila, cryptochrome is required for the normal entrainment of circadian rhythms to light dark cycles. The photocycle and molecular mechanism of animal cryptochrome photoreception are presently unknown. Drosophila cryptochrome undergoes light-dependent degradation when heterologously expressed in Schneider-2 cells. We have generated Drosophila luciferase-cryptochrome fusion proteins to more precisely monitor light-dependent cryptochrome degradation. We found that the luciferase-cryptochrome fusion protein undergoes light-dependent degradation with luciferase activity declining approximately 50% within 5 min of light exposure and approximately 85% within 1 h of light exposure. Degradation is inhibited by MG-132, consistent with a proteasomal degradation mechanism. Irradiance-response curves yield an action spectrum similar to absorption spectra for prokaryotic and eukaryotic cryptochromes with highest sensitivity in the UV-A. A luciferase-cryptochrome fusion protein lacking the terminal 15 amino acids is stably expressed in the dark but demonstrates increased sensitivity to light-induced degradation. The conferral of light-dependent degradation on a heterologous protein by fusion to cryptochrome may be a useful tool for probing protein function in cell expression systems.
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Ritmo Circadiano/fisiologia , Proteínas de Drosophila/metabolismo , Flavoproteínas/metabolismo , Fotoperíodo , Complexo de Endopeptidases do Proteassoma/metabolismo , Sequência de Aminoácidos , Animais , Linhagem Celular , Criptocromos , Inibidores de Cisteína Proteinase/farmacologia , Proteínas de Drosophila/genética , Drosophila melanogaster , Flavoproteínas/genética , Expressão Gênica , Leupeptinas/farmacologia , Células Fotorreceptoras de Invertebrados/metabolismo , Inibidores de Proteassoma , Processamento de Proteína Pós-Traducional/efeitos da radiação , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Deleção de Sequência , Raios UltravioletaRESUMO
OBJECTIVE: To characterize temporal changes in mouse aortic wall gene expression associated with the development of experimental abdominal aortic aneurysms. METHODS: C57BL/6 mice underwent transient perfusion of the abdominal aorta with either elastase (n = 61) or heat-inactivated elastase as a control (n = 68). Triplicate samples of radiolabeled aortic wall complementary DNA were prepared at intervals of 0, 3, 7, 10, and 14 days, followed by hybridization to nylon microarrays (1181 genes). Autoradiographic intensity data were normalized by conversion to z scores, and differences in gene expression were defined by two-tailed z tests at a significance threshold of P < .01. RESULTS: Elastase perfusion caused a progressive increase in aortic diameter up to 14 days accompanied by transmural inflammation and destructive remodeling of the elastic media. No aneurysms occurred in the control group. Compared with healthy aorta, 336 genes exhibited significant alterations during at least 1 interval after elastase perfusion (135 at more than 1 interval and 14 at all intervals), with pronounced increases for interleukin 6, cyclin E2, interleukin 1beta, osteopontin, CD14/lipopolysaccharide receptor, P-selectin glycoprotein ligand 1, and gelatinase B/matrix metalloproteinase 9 (all >20-fold on day 3). Sixty-two genes exhibited synchronous alterations in the elastase and control groups, thus suggesting a nonspecific response. By direct comparisons between the elastase and control groups, there were 384 genes with significant differences in expression for at least 1 interval after aortic perfusion, including 234 with differential upregulation (eg, p44MAPK/ERK1, osteopontin, heat shock protein 84, hypoxia-inducible factor 1alpha, apolipoprotein E, monocyte chemotactic protein 3, MIG (monokine induced by gamma interferon), and interleukin 2 receptor gamma) and 163 with differential downregulation (eg, prothrombin, granzyme B, ataxia telangiectasia mutated, and interleukin-converting enzyme). CONCLUSIONS: Development of elastase-induced abdominal aortic aneurysms in mice is accompanied by altered aortic wall expression of genes associated with acute and chronic inflammation, matrix degradation, and vascular tissue remodeling. Knowledge of these alterations will facilitate further studies on the functional molecular mechanisms that underlie aneurysmal degeneration.
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Aneurisma da Aorta Abdominal/genética , Expressão Gênica/fisiologia , Músculo Liso Vascular/patologia , Animais , Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/patologia , Aortite/genética , Aortite/patologia , Sondas de DNA , DNA Complementar/genética , Modelos Animais de Doenças , Matriz Extracelular/genética , Matriz Extracelular/patologia , Expressão Gênica/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Análise de Sequência com Séries de Oligonucleotídeos , Elastase Pancreática , PerfusãoRESUMO
OBJECTIVE: To determine if treatment with hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) can influence the development of experimental abdominal aortic aneurysms (AAAs). SUMMARY BACKGROUND DATA: AAAs are associated with atherosclerosis, chronic inflammation, and matrix metalloproteinase (MMP)-mediated connective tissue destruction. Because statins exert antiinflammatory activities independent of their lipid-lowering effects, these agents may help suppress aneurysmal degeneration. METHODS: C57Bl/6 wild-type and hypercholesterolemic apoE-deficient mice underwent transient perfusion of the aorta with elastase followed by subcutaneous treatment with either 2 mg/kg simvastatin per day or vehicle. Aortic diameter (AD) was measured before and 14 days after elastase perfusion. The extent of aortic dilatation (DeltaAD) was determined with AAAs defined as DeltaAD >100%. RESULTS: Wild-type mice treated with simvastatin exhibited a 21% reduction in DeltaAD and a 33% reduction in AAAs compared with vehicle-treated controls. Suppression of AAAs in simvastatin-treated mice was associated with preservation of medial elastin and vascular smooth muscle cells, as well as a relative reduction in aortic wall expression of MMP-9 and a relative increase in expression of TIMP-1. In hypercholesterolemic apoE-deficient mice, treatment with simvastatin was associated with a 26% reduction in DeltaAD and a 30% reduction in AAAs. Treatment with simvastatin had no effect on serum cholesterol levels in either normal or hypercholesterolemic mice. CONCLUSIONS: Treatment with simvastatin suppresses the development of experimental AAAs in both normal and hypercholesterolemic mice. The mechanisms of this effect are independent of lipid-lowering and include preservation of medial elastin and smooth muscle cells, as well as altered aortic wall expression of MMPs and their inhibitors.