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Treatment of adolescents with alcohol use problems can be as successful as in adults, but the success often is short-lived, with most treated adolescents relapsing within a few months. Developmental differences among adolescents may contribute to this high rate of relapse, and treatment approaches that pay direct attention to the patients' developmental status may improve outcomes. To date, studies assessing adolescent alcohol treatment rarely have investigated the association between developmental stage and outcome. In addition, even experts do not fully agree on the developmentally appropriate outcomes that should be evaluated in adolescent treatment studies. Research methods and variables used to assess the outcome of adolescent alcohol treatment often rely on those used in treatment studies of adults. Developmental factors that may directly influence adolescents' amenability to treatment, such as pubertal status, psychological development (e.g., executive mental functions), social relationships, and developmental transitions, have not been adequately investigated. Studies using concepts from developmental science are needed to determine how individual characteristics, various contextual influences (e.g., from peers, family, or the social environment), and the interactions of these factors influence alcohol use behavior, amenability to treatment, and treatment outcomes. Knowledge gained in studies directly examining developmental factors should help in the design of more effective treatment programs with lower relapse rates. [ABSTRACT FROM AUTHOR]

Alcohol and drug use is prevalent among juvenile offenders and many of the risk factors that predict delinquent behavior also predict adolescent drug use. This study examined the impact of self-reported risk factors on treatment outcomes and recidivism among Latino, Anglo, and African American juvenile offenders. Risk factors included family structure and interactions, peer influences, education, psychiatric history, substance abuse history, stressful life events experienced, and use of leisure time. Analyses yielded the following key findings: Older adolescents and males were more likely to have a greater number and severity of offenses; older adolescents were less likely to complete treatment successfully; a curvilinear relationship existed between time in treatment and positive treatment outcomes, with extremely long treatment time associated with poorer outcomes; and significant differences existed between Latino and African American youth in which risk factors predicted outcomes. Implications for social work practice and research are discussed. [ABSTRACT FROM AUTHOR]

Aims: To explore (1) the influence of pretreatment and treatment factors on treatment retention among a multi-ethnic sample of adolescents and (2) the potential differential influence of pretreatment and treatment factors on treatment retention within each ethnic subgroup. Participants: A multi-ethnic sample of 420 adolescent juvenile offenders in treatment for substance use problems (U.S.-born Hispanics n = 222; foreign-born Hispanics n = 94; African-Americans n = 66; and non-Hispanic Whites n = 38). Design: Cross-sectional data were examined using analysis of variance (ANOVA) testing putative differences in treatment retention for the entire sample (N = 420) for the following factors: (1) ethnicity, (2) psychiatric comorbidity, and (3) treatment variables. The second set of analyses examines differences in treatment retention associated with these factors within the ethnic subgroups. Finally, supplementary analyses were conducted to explore the potential influence on retention of the following cultural factors: (a) ethnic orientation, (b) perceived discrimination, and (c) acculturation level (for Hispanic youth only). Findings: Consistent with prior research, results indicated that non-Hispanic White adolescents had significantly higher treatment retention than the ethnic minority adolescents (p = .003). The particular factors related to treatment retention varied greatly across the four ethnic subgroups; however there were no differences in treatment retention by any of the cultural variables. Conclusions: Taken together, the results suggest that ethnic minority youth continue to drop out of treatment at higher rates than their non-Hispanic White counterparts, and the factors associated with treatment retention vary greatly across ethnic groups. [ABSTRACT FROM AUTHOR]

This article summarizes a symposium organized by Dr. Elizabeth D'Amico and presented at the 2004 Annual Meeting of the Research Society on Alcoholism in Vancouver, Canada. The four presentations illustrate the importance of creating substance use interventions that are developmentally appropriate for youth. They represent innovative approaches to working with preteens, teenagers, and young adults. Dr. D'Amico's paper describes her research on the development of a voluntary brief intervention targeting alcohol use among middle school students. Findings indicated that by using school and community input, she was able to obtain a diverse a sample of youth across grades, sex, ethnicity, and substance use status. Dr. Ellickson's paper describes her research on Project ALERT, a school-based prevention program for middle school youth. Her findings indicate that Project ALERT worked for students at all levels of risk (low, moderate, and high) and for all students combined. Dr. Wagner's Teen Intervention Project was a randomized clinical trial to test the efficacy of a standardized Student Assistance Program for treating middle and high school students with alcohol and other drug problems. The study provided a unique opportunity to begin to examine how development may impact response to an alcohol or other drug intervention. Dr. Turrisi's paper examined processes underlying the nature of the effects of a parent intervention on college student drinking tendencies. Findings suggested that the parent intervention seems to have its impact on student drinking by reducing the influence of negative communications and decreasing the susceptibility of influences from closest friends. Dr. Kim Fromme provided concluding remarks. [ABSTRACT FROM AUTHOR]

Group therapy is the most popular approach in the treatment of adolescent substance use problems. Recently, concerns have mounted about possible iatrogenic effects of group therapy based on studies on adolescents with conduct disorder. This paper reviews three possible contributors to response to group treatment among adolescents, and proposes a model of the relations among these variables, specifically in regard to how they independently and interactively contribute to outcomes among youth with conduct and substance use problems. [ABSTRACT FROM AUTHOR]

This cross-sectional study documents significant associations between patterns of sexual risk behaviors and psychiatric diagnoses in a multiethnic community sample of young adults (N = 1803) in South Florida. Self-report data regarding sexual behavior and psychiatric symptoms were collected in structured interviews in a follow-up of an earlier school-based study. Cluster analysis was used to group participants with regard to levels of sexual risk behaviors during the past year. Chi-square analysis and ANOVA identified significant associations between cluster membership and (a) lifetime and (b) past year diagnoses for affective disorders, conduct disorder, antisocial personality disorder, alcohol abuse/dependence, marijuana abuse/dependence, and other drug abuse/dependence. In addition, higher levels of sexual risk behaviors were associated with higher levels of cumulative lifetime psychiatric disorders. Implications for selected prevention of sexually transmitted diseases (STDs) and the treatment of psychiatric disorders in young adulthood are discussed. [ABSTRACT FROM AUTHOR]

Adolescents with substance use problems were classified into four distinct and meaninful subgroups based on patterns of depressive symptoms and motives for drinking before sex (i.e., avoidance, enhancement and social motives) using cluster analysis. Data were collected in face-to-face interviews from 120 adolescents and young adults (87 men, 33 women; mean age = 17.2 years) undergoing substance abuse treatment. Groups with higher and lower functioning were validated via significant group differences in conceptually relevant variables assessing psychological distress, alcohol use behaviors, and HIV-relevant risk behaviors. These analyses identified a subgroup of adolescents with high levels of depressive symptoms and drinking motives who are at elevated risk for HIV/STD exposure due to higher levels of risky sexual behavior and altered sexual behavior related to co-occuring alcohol use. Implications for morbidity, mortality and treatment effectiveness in this at-risk sample are discussed. [ABSTRACT FROM AUTHOR]

Efforts in the United States to eradicate drug use through supply reduction (that is, the War on Drugs) have increasingly violated the principles of social justice and human rights, both locally and globally. This has created ethical conflicts for social workers in policy making, practice, and research. Harm reduction has been conceptualized as a peace movement and is aligned with the humanistic values around which social work is organized. The authors examine how social workers may reduce the ethical conflicts associated with efforts to address substance abuse by adopting a harm reduction approach to policy, practice, and research. They examine current drug policies, the consequences of the policies, and, in particular, how the policies affect social workers as practitioners, agents of social control, and guardians of social justice. [ABSTRACT FROM AUTHOR]

Practical and methodological challenges in conducting research on community-based interventions for adolescent problems are described. First, a conceptual framework for the development of community-based interventions is provided, with an emphasis on the ecological and commonweal advantages of such interventions. Next, important issues that investigators confront when pursuing the dual goals of providing good community-based intervention and conducting rigorous intervention research are addressed. These issues include research design, intervention specification and integrity, participant concerns, changing clinical culture, community challenges, school challenges, and appropriate staffing. Finally, a summary of challenges to conducting good community-based intervention research and effective responses to these challenges is presented. [ABSTRACT FROM AUTHOR]

The current paper reviews the existing literature about smoking among teenage girls. We begin with a summary of recent epidemiological data concerning gender differences in the rates of various smoking behaviors among adolescents. We next focus on how gender may influence smoking initiation, maintenance, and cessation among adolescents. Specifically, we examine weight control motives, social influences, mood management motives, and image-related motives as particularly important factors in teenage girls' smoking. We then offer a brief review of some of the more popular adolescent smoking interventions. We conclude the paper with recommendations for ways in which the effectiveness of smoking prevention and intervention programs for girls may be improved. [ABSTRACT FROM AUTHOR]

Deregulation of transcription factors (TFs) leading to uncontrolled proliferation of tumor cells within the microenvironment represents a hallmark of cancer. However, the biological and clinical impact of transcriptional interference, particularly in multiple myeloma (MM) cells, remains poorly understood. The present study shows for the first time that MYC and JUNB, two crucial TFs implicated in MM pathogenesis, orchestrate distinct transcriptional programs. Specifically, our data revealed that expression levels of MYC, JUNB, and their respective downstream targets do not correlate and that their global chromatin-binding patterns are not significantly overlapping. Mechanistically, MYC expression was not affected by JUNB knockdown, and conversely, JUNB expression and transcriptional activity were not affected by MYC knockdown. Moreover, suppression of MYC levels in MM cells via targeting the master regulator BRD4 by either siRNA-mediated knockdown or treatment with the novel proteolysis targeting chimera (PROTAC) MZ-1 overcame bone marrow (BM) stroma cell/IL-6-induced MYC- but not MEK-dependent JUNB-upregulation and transcriptional activity. Consequently, targeting of the two non-overlapping MYC- and JUNB-transcriptoms by MZ-1 in combination with genetic or pharmacological JUNB-targeting approaches synergistically enhanced MM cell death, both in 2D and our novel dynamic 3D models of the BM milieu as well as in murine xenografts. In summary, our data emphasize the opportunity to employ MYC and JUNB dual-targeting treatment strategies in MM as another exciting approach to further improve patient outcomes., (© 2024. The Author(s).)

Alcohol and other drug (AOD) use problems among college students continue to represent a public health epidemic. In 2019, historically high rates of binge-drinking and marijuana use were reported among college-age adults, and the detrimental effects of excessive AOD use in college, such as poorer academic performance, sexual assault, injury or overdoses, and a range of other negative consequences, have been well-documented. Thus, there is a continued need for effective implementation of evidence-based, cost-effective interventions aimed at reducing risks associated with collegiate AOD use. Guided Self Change (GSC) is a brief intervention involving motivational enhancement and cognitive-behavioral strategies and has demonstrated effectiveness in reducing AOD use problems. Its brevity, client-driven style, and concrete here-and-now focus are appealing to individuals struggling with mild to moderate AOD use problems. In order to successfully intervene with collegians with AOD use problems attending minority-serving institutions, GSC requires developmental and cultural tailoring. The current report describes the developmental and cultural tailoring of GSC for emerging adult Latinx collegians, as well as our consumer-driven addition of mindfulness content. Key components of our GSC program are documented through qualitative feedback, quantitative results, and case vignettes.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death. HCC incidence is on the rise, while treatment options remain limited. Thus, a better understanding of the molecular pathways involved in HCC development has become a priority to guide future therapies. While previous studies implicated the Activator Protein-1 (AP-1) (Fos/Jun) transcription factor family members c-Fos and c-Jun in HCC formation, the contribution of Fos-related antigens (Fra-) 1 and 2 is unknown. Here, we show that hepatocyte-restricted expression of a single chain c-Jun~Fra-2 protein, which functionally mimics the c-Jun/Fra-2 AP-1 dimer, results in spontaneous HCC formation in c-Jun~Fra-2 hep mice. Several hallmarks of human HCC, such as cell cycle dysregulation and the expression of HCC markers are observed in liver tumors arising in c-Jun~Fra-2 hep mice. Tumorigenesis occurs in the context of mild inflammation, low-grade fibrosis, and Pparγ-driven dyslipidemia. Subsequent analyses revealed increased expression of c-Myc, evidently under direct regulation by AP-1 through a conserved distal 3' enhancer. Importantly, c-Jun~Fra-2-induced tumors revert upon switching off transgene expression, suggesting oncogene addiction to the c-Jun~Fra-2 transgene. Tumors escaping reversion maintained c-Myc and c-Myc target gene expression, likely due to increased c-Fos. Interfering with c-Myc in established tumors using the Bromodomain and Extra-Terminal motif inhibitor JQ-1 diminished liver tumor growth in c-Jun~Fra-2 mutant mice. Thus, our data establish c-Jun~Fra-2 hep mice as a model to study liver tumorigenesis and identify the c-Jun/Fra-2-Myc interaction as a potential target to improve HCC patient stratification and/or therapy., Competing Interests: Competing interests statement:The authors declare no competing interest.

The present work aimed to evaluate the expression profile of genes related to stem cells (SC) characteristics during the acquisition of the multidrug resistance (MDR) phenotype in the chronic myeloid leukemia (CML). For this, the K562 (non MDR) and FEPS (MDR) cell lines were used. K562 cells had resistance induced by exposure to daunorubicin (DNR), and induction was confirmed by flow cytometry with an increase in ABCB1 expression in K562 cells treated at the highest concentration. Real-time PCR gene expression analysis showed a direct relationship in the expression of OCT4 and ABCB1 genes, with an increase in ABCB1 expression after exposure to DNR, followed by an increase in OCT4 gene expression. This direct relationship was confirmed in the MDR FEPS cells that had the ABCB1 gene silenced. For the ALOX5 gene, we observed an inverse relationship with ABCB1, with a decrease in the expression of ALOX5 in the DNR-transformed K562 cells, and an increase in the expression of this gene when ABCB1 was silenced in the FEPS cells. Thus, during the acquisition of the MDR phenotype by the K562 cells, it was possible to observe that there is an increase in the expression of ABCB1, accompanied by the expression of OCT4, while the expression of ALOX5 is decreased., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Guided Self-Change (GSC) is a Motivational Interviewing (MI)-based early intervention program, infused with Cognitive Behavioral Therapy (CBT), for individuals with substance use problems. In this study, we implemented a 4-session GSC program with the innovative addition of mindfulness-based techniques at a minority-serving institution to reduce substance use and negative consequences among self-referred university students. We investigated processes that may be associated with behavior change, including perceived risk of use and self-efficacy ratings among university students who reported their primary substance of choice was cannabis ( n = 18) or alcohol ( n = 18). The sample of 36 participants ( M age = 24.4, SD age = 5, range 18-37) mostly identified as female (58.3%), then male (41.7%); 52.8% identified as Hispanic/Latine, 22.2% as Black or African American, and 19.5% as a sexual minority. Among cannabis primary using students, results indicated that the perceived risk of weekly cannabis use, confidence to change, and readiness to change showed statistically significant increases from pre- to post-assessment. Among alcohol primary using students, confidence to change and readiness to change showed statistically significant increases from pre- to post-assessments. All results yielded large effect sizes, which may be inflated due to the small sample size. Findings suggest that over the course of participation in a brief, 4-session targeted GSC program, there were significant increases in perceived risk and self-efficacy among minority university students who engage in primary cannabis or primary alcohol use., (© 2023 Authors et al.)

The age cohort referred to as emerging adults (ages 18-29 years old) demonstrates the most hazardous alcohol use in the United States (U.S.) Approximately one-third of emerging adults regularly engage in heavy episodic drinking (4/5 drinks in two hours females/males). Compared to their non-Latine White peers, Latine emerging adults in the U.S. report lower rates of heavy episodic drinking (HED) yet are at greater risk of developing a substance use disorder and experience more severe negative consequences from drinking alcohol. Despite their high-risk status, Latine emerging adults are less likely to seek treatment and have less access to innovative health-promoting resources, further exacerbating health inequities. Research has shown that practicing mindfulness can interrupt habituated cognitions, intrusive thinking, and automatic behaviors associated with hazardous drinking. However, Latine representation in MBI trials is minimal. This mini-review explores the potential value of mindfulness as an early intervention for hazardous alcohol use among Latine emerging adults. The review provides future directions for research, highlighting the need to design culturally and developmentally tailored MBIs that can provide a respectful, non-judgmental, and discrimination-free environment that appeals to Latine emerging adults. Additionally, conclusions are drawn regarding the possible benefits of pairing MBI with contingency management strategies to decrease attrition rates in MBI trials., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: The activator protein-1 (AP-1) transcription factor component c-Fos regulates chondrocyte proliferation and differentiation, but its involvement in osteoarthritis (OA) has not been functionally assessed., Methods: c-Fos expression was evaluated by immunohistochemistry on articular cartilage sections from patients with OA and mice subjected to the destabilisation of the medial meniscus (DMM) model of OA. Cartilage-specific c-Fos knockout (c-Fos ΔCh ) mice were generated by crossing c-fos fl/fl to Col2a1-CreERT mice. Articular cartilage was evaluated by histology, immunohistochemistry, RNA sequencing (RNA-seq), quantitative reverse transcription PCR (qRT-PCR) and in situ metabolic enzyme assays. The effect of dichloroacetic acid (DCA), an inhibitor of pyruvate dehydrogenase kinase (Pdk), was assessed in c-Fos ΔCh mice subjected to DMM., Results: FOS-positive chondrocytes were increased in human and murine OA cartilage during disease progression. Compared with c-Fos WT mice, c-Fos ΔCh mice exhibited exacerbated DMM-induced cartilage destruction. Chondrocytes lacking c-Fos proliferate less, have shorter collagen fibres and reduced cartilage matrix. Comparative RNA-seq revealed a prominent anaerobic glycolysis gene expression signature. Consistently decreased pyruvate dehydrogenase (Pdh) and elevated lactate dehydrogenase (Ldh) enzymatic activities were measured in situ , which are likely due to higher expression of hypoxia-inducible factor-1α, Ldha , and Pdk1 in chondrocytes. In vivo treatment of c-Fos ΔCh mice with DCA restored Pdh/Ldh activity, chondrocyte proliferation, collagen biosynthesis and decreased cartilage damage after DMM, thereby reverting the deleterious effects of c-Fos inactivation., Conclusions: c-Fos modulates cellular bioenergetics in chondrocytes by balancing pyruvate flux between anaerobic glycolysis and the tricarboxylic acid cycle in response to OA signals. We identify a novel metabolic adaptation of chondrocytes controlled by c-Fos-containing AP-1 dimers that could be therapeutically relevant., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Latinx youth with mental health disorders have worse outcomes when compared to their White (non-Hispanic) counterparts. Latinx youth also have less access to and lower utilization of mental health services. Emerging research supports the psychological and physical benefits of engaging in yoga and yoga may function as a complimentary treatment option for patients with mental health challenges. However, research assessing the efficacy of yoga and mindfulness is particularly sparse among Latinx youth, who may particularly benefit from mind body awareness activities given barriers to more traditional health approaches. The objective of this quasi-experimental study was to examine the effects of a 12-week Vinyasa flow-based yoga group intervention on anxiety, depression, empathy, and life satisfaction among adolescents receiving outpatient mental health treatment. Adolescents (n = 186; 12-17 years old) were recruited to an active intervention condition (Yoga); a subsequent group of participants (n = 91) were recruited in the same manner to an assessment-only comparison control condition (Comparison). The Yoga group participated in culturally and developmentally tailored group yoga classes for 12 weeks. Structural equation modelling was used to evaluate the main effect intervention response between participants in the two conditions. At the post-intervention assessment, after controlling for baseline levels of outcome variables (i.e., depression, anxiety, empathy, and life satisfaction), on average participants in the yoga condition reported: less depression symptoms (B = -1.54, p = 0.008), less anxiety symptoms (B = -0.75, p = 0.048), greater empathy (B = 1.32, p = 0.025) and greater life satisfaction (B = 0.30, p = 0.013) as compared to the Comparison condition. Yoga interventions can be an acceptable and feasible modality for promoting well-being and reducing mental health problems among Latinx youth., (© 2022 John Wiley & Sons Ltd.)

Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions. Here, the Nomenclature Committee on Cell Death (NCCD) gathered to critically summarize an abundant pre-clinical literature mechanistically linking the core apoptotic apparatus to organismal homeostasis in the context of disease., (© 2023. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

Racial and ethnic health disparities are more conspicuous in the United States since the start of the coronavirus disease 2019 (COVID-19) pandemic. While the urgency of these disparities was already alarming, the pandemic has exacerbated longstanding issues in health equity, disproportionate impacts, and social determinants of health. Vaccine hesitancy was a crucial factor during the U.S. COVID-19 vaccination campaign. We conducted a qualitative exploration of vaccine hesitancy through thematic analysis of four focus groups with Hispanic/Latine and African American/Black adults and senior citizens ( N =23). The focus groups were conducted between February and April of 2021, in both English and Spanish. All participants (mean age=66.2, female 78.3%) were recruited by community-based organizations in the South Florida area. We explored six categories: (1) barriers to prevention and preventive behaviors, (2) barriers to vaccination against COVID-19, (3) facilitators of prevention and preventative behaviors, (4) facilitators of vaccination against COVID-19, (5) trusted sources of information, and (6) suggested macrolevel measures. These categories are discussed vis-à-vis COVID-19 disparities among racial and ethnic minorities. Implications for public health policy and future vaccination campaigns are outlined and discussed., Competing Interests: The authors declare no relevant conflicts of interest or financial relationships, and there have been no previous presentations of the work., (© Robbert J. Langwerden et al., 2023; Published by Mary Ann Liebert, Inc.)

Previous studies have found increases in nonfatal opioid overdoses during the COVID-19 pandemic, which created difficult conditions for people with substance use disorders. We assessed changes in nonfatal opioid-related overdoses in Florida during the onset of the COVID-19 pandemic. Emergency medical service data was obtained from the Florida Department of Health. Naloxone administration with documented improvement was used as a proxy for nonfatal opioid-related overdoses. Age-adjusted rates were estimated per 100,000 population for April-September 2020 (n = 9,377) and compared to the same time period during 2019 (n = 6,765) using rate ratios. Age-adjusted rates were estimated by sex, race/ethnicity, and metro/nonmetro county classification, as well as county-level measures of medications for opioid use disorder (MOUD) availability, rates of COVID-19 deaths, and unemployment during 2020. The age-adjusted rate of nonfatal opioid-related overdoses increased from 32.41 (95 % CL: 31.64-33.19) during 2019 to 45.35 (95 % CL: 44.42-46.27) during 2020 (RR = 1.40; 95 % CL: 1.36-1.44). The rate for males increased most in metro counties (RR = 1.47, 95 % CL: 1.41-1.53); the rate for females increased most in nonmetro counties (RR = 1.51, 95 % CL: 1.10-2.06). The largest increases were observed among Hispanics (males: RR = 1.56, 95 % CL: 1.37-1.78; females: RR = 1.44, 95 % CL: 1.14-1.81), counties with no MOUD treatment options (RR = 1.66, 95 % CL: 1.14-2.44) and counties with the lowest rates of buprenorphine prescribers (RR = 1.70, 95 % CL: 1.29-2.22). Nonfatal opioid-related overdoses increased in Florida during the first six months of the COVID-19 pandemic. Expanding access to services that support treatment and recovery is critical to addressing the ongoing opioid crisis in Florida., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)