Substance Abuse Research Articles

DepXGBoot: Depression detection using a robust tuned extreme gradient boosting model generator

In terms of severity and prevalence, depression is the worst. Suicide rates have risen because of this and are on the rise universally. Consequently, effective diagnosis and therapy must reduce the impact of depression. There is often more than one factor at play when determining why someone has been diagnosed with depression. In addition to alcohol and substance abuse, other possible causes include problems with physical health, adverse reactions to medications, life-changing events, and social circumstances. In this paper, exploratory data analysis is conducted to understand the insights of the sensorimotor database depression comprising depressive experiences in individuals who are either unipolar or bipolar. This study proposes a robust tuned extreme gradient boosting model generator to automatically predict the state of depression. The performance is optimized by determining the best combination of hyperparameters for the extreme gradient boosting model. By harnessing the power of advanced machine learning methodologies, this study underscores comparative analysis and the importance of data-driven innovation in mental health and clinical practice. Future developments for the robust tuned extreme gradient boosting model’s application and study to forecast depression in the sensorimotor database depression can be used to track changes in depressed states over time by integrating it with longitudinal and multimodal data.

Nonsedating anxiolytics.

Anxiety disorders are the most prevalent psychiatric pathology with substantial cost to society, but the existing treatments are often inadequate. This has rekindled the interest in the GABAA-receptor (GABAAR) positive allosteric modulator (PAM) compounds, which have a long history in treatment of anxiety beginning with diazepam, chlordiazepoxide, and alprazolam. While the GABAAR PAMs possess remarkable anxiolytic efficacy, they have fallen out of favor due to a host of adverse effects including sedation, motor impairment, addictive potential and tolerance development. A substantial effort was thus devoted to the design of GABAAR PAMs as anxiolytics with reduced sedative liabilities. Several non-benzodiazepine (BZD) GABAAPAMs progressed to clinical trials (bretazenil, abecarnil, alpidem, and ocinaplon) with alpidem obtaining regulatory approval as anxiolytic, but later withdrawn from market due to hepatotoxicity. Advances in molecular biology gave birth to a host of subtype selective GABAAR-PAMs which suffered from signs of sedation and motor impairment and only three compounds progressed to proof-of-concept studies (TPA-023, AZD7325 and PF-06372865). TPA-023 was terminated due to toxicity in preclinical species while AZD7325 and PF-06372865 did not achieve efficacy endpoints in patients. We highlight a new compound, KRM-II-81, that is an imidazodiazepine selective for GABAAR containing α2/3 and β3 proteins. In preclinical studies KRM-II-81 produced anxiolytic-like effects but with minimal sedation, respiratory depression, and abuse liability. Thus, KRM-II-81 is a newly discovered, non- BZD anxiolytic compound, which targets a selective population of GABAAR for improved therapeutic gain and reduced side effects.

The influence of social media on adolescent mental health and substance abuse patterns

Adolescents' widespread use of social media has become a serious public health issue, especially considering its effects on substance abuse and mental health. The aim of this review is to examine the complex relationship between the use of social media, mental health issues, and the rise in substance abuse among teenagers. An overview of social media engagement trends is given at the start, emphasising that teenagers are among the most frequent users and that platforms such as Instagram, TikTok, and Snapchat are essential to their social lives. According to recent studies, high social media use has been linked to a rise in mental health conditions, such as anxiety, depression, and low self-esteem. The prevalent behaviours of social comparison, cyberbullying, and validation-seeking in online interactions exacerbate mental health challenges. The review also explored the patterns of substance abuse among adolescents, with particular attention to the use of alcohol, tobacco, and illegal narcotics. Peer pressure, family dynamics, early substance exposure, and other factors have been identified as contributing factors to substance misuse. A critical analysis is conducted on the function that social media plays in normalising substance use, since media portrayals of substance use can glamourise these behaviours and make them seem socially acceptable to impressionable teens. The ways in which peer pressure and heightened stress are two of the methods through which social media impact substance abuse are examined, offering a thorough grasp of the difficulties that young people today face. The urgent need for multifaceted interventions that address social media use and mental health education is emphasised in the review's conclusion. Along with programs to promote digital literacy and ethical social media usage, recommendations are made for parents, schools, and policymakers to reduce the risks associated with social media use. The results highlight the need for additional investigation into the complex interactions among social media, mental health, and substance addiction and support cooperative endeavours aimed at safeguarding and enabling young people in the digital age.

Developing a data-driven predictive model for substance abuse prevention among youth using behavioral analytics

Substance abuse among youth presents a critical public health challenge, necessitating innovative approaches for early intervention and prevention. This study proposes the development of a data-driven predictive model that leverages behavioral analytics to identify youth at risk of substance abuse. The model utilizes data from multiple sources, including social media activity, school performance records, and mental health screenings, to analyze behavioral patterns that may indicate a predisposition toward substance misuse. The core methodology integrates machine learning algorithms to process and analyze large datasets, uncovering correlations between specific behaviors and the likelihood of substance abuse. Predictive features such as changes in social engagement, academic performance fluctuations, and indicators of emotional distress are identified and incorporated into the model to enhance its accuracy. By applying supervised learning techniques, the model is trained to recognize patterns in historical data, allowing it to make predictions about future substance use risks. Furthermore, the model's design emphasizes real-time monitoring and adaptability, enabling health professionals and educators to receive timely alerts and intervene early when behavioral warning signs are detected. The application of behavioral analytics in this context offers a more proactive, personalized approach to prevention, targeting at-risk individuals before they develop harmful substance use habits. In addition to its predictive capabilities, the model also provides actionable insights into effective intervention strategies. By identifying the most influential behavioral factors, it informs tailored prevention programs that address specific risk behaviors among youth. These findings can support policymakers and healthcare providers in developing data-driven, evidence-based prevention initiatives that better allocate resources to high-risk populations.

EMPOWERING B40 YOUTH IN PENINSULAR MALAYSIA: RISK LITERACY FACTORS AND WELL-BEING

ABSTRACT The prevalence of drug abuse, self-injury, and juvenile delinquency highlights the concerning social risks faced by young people today. Hence, educating this group on risks or risk literacy is crucial. Risk literacy is perceiving risks to make rational decisions for healthier well-being. This study aims to determine risk literacy factors influencing the well-being of B40 youth. To achieve the study's objective, data was gathered from a survey involving 423 youths from the low-income group (B40) in Peninsular Malaysia. A two-stage sampling technique was employed, and data were analysed using partial least squares structural equation modelling (PLS-SEM). The study shows that thoughtful decision-making and effective risk communication are the main predictors of youth well-being. Being a risk-literate youth is essential to reduce the risk of poor decisions. The study's findings, which have the potential to significantly impact policy formulation, are crucial for assisting this group in escaping poverty. This, in turn, can enhance their overall well-being. Keywords: Decision-Making, Risk Literacy, Risk Communication, Youth, Well-Being

Opioid Use Following Open Reduction and Internal Fixation of Mandibular Fractures.

A mandible fracture is a common traumatic craniofacial injury for which surgery is sometimes indicated. Post-fracture and postoperative pain are often controlled through prescribed narcotics, which have received increased attention for potential abuse. The current work identified 90-day opioid prescribing patterns following surgically treated mandible fractures. Patients who underwent open reduction and internal fixation to treat a closed mandible fracture between 2011 and 2021 were identified in the PearlDiver Mariner165 database. Exclusion criteria included: (1) patients with records active for fewer than 180 days before the injury and 90 days post-fracture, (2) age younger than 18, and (3) those with long bone fracture within 30 days of mandible fracture. Variables associated with filling an opioid prescription and utilizing excess morphine milligram equivalents (MMEs) were identified through multivariate regression. Prescribing patterns between 2011 and 2021 were analyzed using simple linear regression. A total of 15,049 patients were identified. Of these patients, opioid prescriptions were filled by 10,389 (69.0%). Greater MMEs were filled for those with greater age, prior opioid use, and history of chronic pain (P < 0.01 for all). The proportion of patients who received opioids decreased from 2011 to 2021 (73.3% versus 61.9%) during which declines were also seen for median MMEs (225.0 versus 128.4) and mean number of filled prescriptions (4.1 versus 2.8). The present work identified age and preexisting risk factors as significantly associated with excess MMEs following open reduction and internal fixation-treated mandible fracture. The decreasing proportion of patients receiving opioids along with decreasing MMEs suggests more refined practice with regard to their use.

Psychological Characteristics of Fathers of People With Bulimia Nervosa: A Systematic Review.

Bulimia nervosa (BN) is a highly prevalent psychiatric disorder that has negative effects on the physical and psychological health of sufferers. Father-specific factors have been understudied in the context of BN. This systematic review aims to understand the psychosocial and psychopathological features of fathers of people with BN and their associations with the offspring's outcomes. A literature search on APA PsycINFO, ISI Web of Science, PubMed, Google Scholar, ResearchGate, and Open Science Framework yielded 2421 studies. These papers were independently evaluated based on the eligibility criteria. 29 studies were included in this review. The Joanna Briggs Institute Critical Appraisal Tools were used for the assessment of the methodological quality of the eligible studies. Across studies, no significant differences were found in perceptual body-size distortion, self-ideal discrepancy, eating-/weight-/body-related attitudes, several personality and ED traits, and general psychological functioning between fathers of the BN group and those of the comparison groups. However, significant differences were found in certain psychological aspects (e.g., impulse regulation) and ED-associated features (e.g., body dissatisfaction). Finally, significant relationships were found between the fathers' food attitudes, muscularity ratings, personality traits, and substance abuse and their offspring's risk of developing BN, greater body dissatisfaction, ED symptoms, and poor end-of-treatment outcome. Although the existing literature does not seem to strongly suggest a particular paternal factor pertaining to BN, several father-specific variables may be associated with the offspring's BN symptomatology and related characteristics. Further research is necessary to clearly understand paternal features in the context of BN.

Changing Pattern of Substance Abuse in Patients Attending a Regional Psychiatric Rehabilitation Center at Al-Qassim, Saudi Arabia

Background and Purpose The aim of this study was to record the prevalence and the characteristics of substance abusers from the year 2007 to 2017 and also to find the most prevalent form of substance abuse and association, if any, between the abusers and their demographic characteristics. Materials and Methods Descriptive and retrospective medical record review included patients of substance abuse attending a rehabilitation center in Buraidah from January 2007 to December 2017. A majority of 5,639 patients (63.6%) belonged to the age group of 31–50 years. Twenty-five and thirty-nine percent patients had secondary and higher education, respectively. Notably, more than half of them were unemployed. The commonly abused single drugs were amphetamine (40%), cannabis (11%), and alcohol (7%). High school goers’ cases have continuously spiked over the years. Substance abuse over the years from 2007 to 2017 was above 11% in 2007 and 2015. From 2009 to 2014, it was between 8 and 10%. However, the number of cases reported dropped to below 9% from 2016 onward. Amphetamine saw a downfall except peaking in 2010 and 2015. On the other hand, there was no substantial jump in the abuse of alcohol and cannabis over the years, but an increasing use from 2015 onward was visible. There was also a gradual rise over the years in the abuse of polysubstance (more than three drugs). Conclusion There is a growing trend in the use of polysubstance and the combination of two substances. There is a high incidence of drug abuse in high schoolers and also in patients in the age groups of 10–30 years.

Adjunctive Use of Gabapentinoids Increases Opioid Consumption Following 1- to 3-Level Anterior Lumbar Interbody Fusion with Posterior Fixation: A Propensity-Score Matched Analysis.

Retrospective cohort. To evaluate the impact of adjunctive gabapentinoid therapy on postoperative opioid consumption following 1-3 levels anterior lumbar interbody fusion (ALIF) with posterior fixation. Gabapentin and pregabalin are analogues of the inhibitory neurotransmitter Gamma-Aminobutyric Acid (GABA) and are frequently employed as adjuncts in multimodal anesthesia strategies for managing acute pain. However, the opioid-sparing effect of gabapentinoids in the context of spine surgery has yet to be consistently demonstrated. The PearlDiver Database was queried from 2010 to 2021 for patients who underwent primary 1-3 levels ALIF with posterior fixation. Patients with opioid or gabapentinoid use within 6 months prior to index surgery were excluded. Patients with both gabapentinoid and opioid treatment were propensity score-matched to patients with opioid-only treatment. The propensity score-matching resulted in two equal groups of 2,617 patients with and without adjunctive gabapentinoid treatment for pain management. Adjunctive use of gabapentinoids was associated with a modest 2.9% reduction in average Morphine Milligram Equivalent (MME) per day (Standardized Mean Difference (SMD) -1.33, 95% Confidence Interval (CI) [-2.657, -0.002], P=0.050). However, this was accompanied by a 37.1% increase in the total duration of opioid prescriptions (SMD 94.97, 95% CI [56.976, 132.967], P<0.001) and a 41.7% increase in total MME consumption per patient (SMD 4817.23, 95% CI [1864.410, 7770.044], P=0.001). Additionally, gabapentinoid use was associated with an increased risk of readmission due to pain (Relative Risk (RR) 1.10, 95% CI [1.002, 1.212], P=0.050) and the development of drug abuse (RR 1.37, 95% CI [1.016, 1.833], P=0.046). Despite the modest daily opioid-sparing effect observed, adjunctive gabapentinoid treatment appears to increase total opioid consumption due to prolonged opioid use and may compromise pain management in the context of ALIF with posterior fixation.

Gut microbiota profiling in injection drug users with and without HIV-1 infection in Puerto Rico

IntroductionThe full extent of interactions between human immunodeficiency virus (HIV) infection, injection drug use, and the human microbiome is unclear. In this study, we examined the microbiomes of HIV-positive and HIV-negative individuals, both drug-injecting and non-injecting, to identify bacterial community changes in response to HIV and drug use. We utilized a well-established cohort of people who inject drugs in Puerto Rico, a region with historically high levels of injection drug use and an HIV incidence rate disproportionately associated with drug use.MethodsUsing amplicon-based 16S rDNA sequencing, we identified amplicon sequence variants (ASVs) that demonstrated significant variations in the composition of microbial communities based on HIV status and drug use.Results and discussionOur findings indicate that the HIV-positive group exhibited a higher abundance of ASVs belonging to the genera Prevotella, Alloprevotella, Sutterella, Megasphaera, Fusobacterium, and Mitsuokella. However, Bifidobacteria and Lactobacillus ASVs were more abundant in injectors than in non-injectors. We examined the effect of drug use on the gut microbiome in both HIV-infected and non-infected patients, and found that multiple drug use significantly affected the microbial community composition. Analysis of differential of bacterial taxa revealed an enrichment of Bifidobacterium spp., Faecalibacterium spp., and Lactobacillus spp. in the multiple drug-injecting group. However, in the non-injecting group, Parabacteroides spp., Prevotella spp., Paraprevotella spp., Sutterella spp., and Lachnoclostridium spp. The presence of multiple drug-injecting groups was observed to be more prevalent. Our findings provide detailed insight into ASV-level changes in the microbiome in response to HIV and drug use, suggesting that the effect of HIV status and drug injection may have different effects on microbiome composition and in modulating gut bacterial populations.

PERAN BADAN KOORDINASI KEGIATAN KESEJAHTERAAN SOSIAL KALIMANTAN BARAT TERKAIT REHABILITASI NARKOBA

The purpose of this study was to determine the role of the West Kalimantan Social Welfare Coordinating Board in relation to drug rehabilitation. This study uses a qualitative method that aims to obtain a clear picture of a problem, which will be focused on collecting data or information on the object. The results of the study indicate that the drug rehabilitation places provided by the Government in West Kalimantan are still lacking. The results of the study stated that there are many cases in the community, of drug users who do not receive rehabilitation. BK3S has not played a role in drug rehabilitation but has carried out preventive education in the form of socialization to the community in preventing drugs. In the future, BK3S hopes to be able to carry out drug rehabilitation and have a sufficient budget to do so because drug rehabilitation requires a large budget.

Penetapan Batas Maksimal Bunga Pinjaman Pemegang Saham kepada Entitas Anak Perusahaan berbentuk Emiten atau Perusahaan Publik

In today's business activities, many companies in Indonesia choose to obtain funds from shareholders through loans from shareholders, compared to the mechanism of increasing issued and paid-up capital. Specific to subsidiaries with the status of public companies or issuers, the scheme of obtaining funds from shareholders through shareholder loans is considered relatively easier because it is an affiliate transaction. This study will further examine the appropriate form of regulation related to the determination of the maximum limit of shareholder loan interest to subsidiary entities in the form of issuers or public companies. Through a normative juridical approach with qualitative analysis methods, this study explores the existing regulatory framework, identifies gaps in implementation, and formulates comprehensive regulatory solutions. The results of the study revealed several important findings. First, the existing regulatory framework does not provide clear parameters regarding the maximum limit of interest on shareholder loans, causing inconsistencies in business practices. Second, the existing supervision and enforcement mechanisms have not been optimal in preventing potential abuse of shareholder loan schemes. Third, an integrative approach is needed that considers the legal aspects of the company, the capital market, and taxation in determining the maximum reasonable interest limit. This study recommends the establishment of a special regulatory framework that regulates the determination of the maximum limit of shareholder loan interest.

A bibliometric analysis of mental health among high school students

BackgroundIn recent years, with the increase in academic pressure and changes in social environment, especially after the outbreak of COVID-19, there has been a significant impact on the mental health of high school students. This trend, which is concerning, requires a systematic bibliometric analysis to develop effective preventive and remedial measures.ObjectiveThis study aims to identify and analysis the research hotspots, frontiers and emerging trends in the field of high school students’ mental health over the past two decades using CiteSpace software. These findings provide important insights that can shape future research agendas and guide targeted interventions to improve the mental health outcomes of this vulnerable group.MethodsThis study utilized the Web of Science Core Collection database as its data source to retrieve literature pertaining to high school students’ mental health from January 1, 2004, to January 1, 2023. The initial search yielded 1,764 relevant documents. After manually screening to exclude duplicates, conference proceedings, announcements, and irrelevant documents, a total of 1,748 relevant documents were retained. The research employed the CiteSpace 6.2.R4 tool to evaluate various bibliometric indicators of the included literature, including statistics on institutional and author publication volumes, as well as co-citation analysis.ResultsA total of 1,748 English-language documents were retrieved, showing an upward trend in publications on high school students’ mental health from 2004 to 2024. The research hotspots primarily focus on COVID-19 pandemic, depression, bullying, substance abuse, sexual behavior, Physical Education and their relationships with the mental health of high school students. Future research trends may focus on studies investigating the relationships between the use of electronic cigarettes, sleep disorders, internet addiction, and the mental health of high school students.ConclusionIn addition to the six major research hotspots of COVID-19 pandemic, Depression and stress, Suicidal ideation, Bullying, Sexual behavior and Physical education. Researches should pay more attention to the use of electronic cigarettes, sleep disorders, and Internet addiction among high school students.

Lifestyle and the Gut-Brain Axis Insights into Mental Health and Microbiome Interactions

Introduction: The intricate relationship between lifestyle factors and gut health has become a focus of recent research, emphasizing the significant role of the gut-brain axis (GBA) in regulating both physical and emotional well- being. Unhealthy lifestyle choices, including a diet high in ultra-processed foods, irregular sleep patterns, physical inactivity, and substance abuse, have been closely associated with gut dysbiosis, leading to gastrointestinal (GI) symptoms and mood disturbances such as anxiety and depression. The gut microbiota, through the production of neurotransmitters like serotonin and dopamine, as well as short-chain fatty acids (SCFAs), influences mood and mental health via the GBA. Maintaining a healthy lifestyle, characterized by balanced nutrition, regular physical activity, and good sleep quality, is critical in fostering a diverse and stable gut microbiome, which in turn supports emotional stability.  Aim: This review aims to examine the existing literature on the impact of lifestyle factors, such as diet, physical activity, sleep, smoking, alcohol consumption, and stress management, on gut health and emotional well-being. The goal is to highlight the importance of gut microbiota in mental health and the potential therapeutic strategies to enhance gut health for improved emotional outcomes.  Methodology: A comprehensive search of peer-reviewed journal articles was conducted using databases such as PubMed, Google Scholar, and Web of Science. Keywords like "lifestyle," "gut health," "emotional well-being," "dietary habits," "physical activity," "sleep patterns," and "gut-brain axis" were used to identify relevant studies. Inclusion criteria focused on human clinical trials and observational studies published within the last 16 years. Studies involving animal subjects, non-peer- reviewed articles, and outdated research were excluded.  Results: The literature shows that diets high in fiber and low in processed foods support a healthier gut microbiome, while high consumption of ultra-processed foods disrupts gut bacteria, leading to GI symptoms and mood disorders. Regular physical activity was found to enhance gut microbiota diversity, contributing to better emotional well-being. Conversely, poor sleep quality and chronic stress were linked to gut dysbiosis, which exacerbated mood disturbances. Smoking and excessive alcohol consumption further damaged gut health, contributing to mood dysregulation. Probiotic and prebiotic interventions, particularly synbiotics, were found to restore gut balance and improve both GI and mental health outcomes.  Conclusion: This review underscores the pivotal role of lifestyle choices in shaping gut health and emotional well-being. A balanced diet, regular exercise, sufficient sleep, and stress management are essential for maintaining a healthy gut microbiome, which, in turn, supports emotional stability. Therapeutic strategies involving prebiotics, probiotics, and synbiotics offer promising avenues for improving both gut health and mood. Addressing lifestyle factors and promoting gut health can potentially serve as an effective approach for enhancing overall well-being and preventing mood disorders.

Cocaine-Induced DNA-Dependent Protein Kinase Relieves RNAP II Pausing by Promoting TRIM28 Phosphorylation and RNAP II Hyperphosphorylation to Enhance HIV Transcription

Drug abuse continues to pose a significant challenge in HIV control efforts. In our investigation, we discovered that cocaine not only upregulates the expression of the DNA-dependent protein kinase (DNA-PK) but also augments DNA-PK activation by enhancing its phosphorylation at S2056. Moreover, DNA-PK phosphorylation triggers the higher localization of the DNA-PK into the nucleus. The finding that cocaine increases the nuclear localization of the DNA-PK provides further support to our observation of enhanced DNA-PK recruitment at the HIV long terminal repeat (LTR) following cocaine exposure. By activating and facilitating the nuclear localization of the DNA-PK, cocaine effectively orchestrates multiple stages of HIV transcription, thereby promoting HIV replication. Additionally, our study demonstrates that the cocaine-induced DNA-PK promotes the hyper-phosphorylation of the RNA polymerase II (RNAP II) carboxyl-terminal domain (CTD) at Ser5 and Ser2 sites, enhancing both the initiation and elongation phases, respectively, of HIV transcription. The cocaine-mediated enhancement of transcriptional initiation is supported by its activation of cyclin-dependent kinase 7 (CDK7). Additionally, the induction of transcriptional elongation is marked by higher LTR recruitment and the increased phosphorylation of CDK9, which indicates the stimulation of positive transcriptional elongation factor b (P-TEFb). We demonstrate for the first time that cocaine, through DNA-PK activation, promotes the specific phosphorylation of TRIM28 at serine 824 (p-TRIM28, S824). This modification converts TRIM28 from a transcriptional inhibitor to a transactivator for HIV transcription. Additionally, we observed that the phosphorylation of TRIM28 (p-TRIM28, S824) promotes the transition from the pausing phase to the elongation phase of HIV transcription, thereby facilitating the production of full-length HIV genomic transcripts. This finding corroborates the previously observed enhanced RNAP II CTD phosphorylation at Ser2, a marker of transcriptional elongation, following cocaine exposure. Accordingly, upon cocaine treatment, we observed the elevated recruitment of p-TRIM28-(S824) at the HIV LTR. Overall, our results unravel the intricate molecular mechanisms underlying cocaine-induced HIV transcription and gene expression. These findings hold promise for the development of highly targeted therapeutics aimed at mitigating the detrimental effects of cocaine in individuals living with HIV.

Cognitive Impairments in Substance Addiction: Narrative Review

Cognition is an intricate mechanism governing the executive functions in the human body and undergoes a developmental process influenced by genetic, biological, and ecological factors. The addicted substance can be denoted as a trigger of deteriorated cognition, impacting memory, decision-making, attention, and reasoning. Specific examination of alcohol, nicotine, cannabis, cocaine, opioids, and amphetamines elucidates the unique ways each substance impairs cognitive functions, ranging from memory deficits to impaired attention and psychomotor skills. Hence the relevant information was gathered by referring to Google Scholar, PubMed, and Elsevier databases. To extract the updated information selected journals were filtered up to the previous ten years. Dopaminergic dysregulation arises as a central theme, influencing reward schemes, motivational drives, and memory pathways, disseminating compulsive behaviors, and obstructing substance cessation. This inclusive exploration highlights the urgency of addressing these complications for informed prevention strategies, effective public health initiatives, and targeted interventions. By elucidating the cognitive impairment in substance addiction, this review strives to emphasize the danger of substance usage.

Two JAMA studies delve into helping drug users with harm reduction

As harm reduction – with its varied definitions – becomes more mainstream, establishment medical journals are providing information to help clinicians. In the November 18 issue of the Journal of the American Medical Association (JAMA), one article focuses on how to tell patients who have opioid use disorder (OUD) about harm reduction and another provides an overview of different strategies to achieve this.

Neurotoxicity of Realgar: Crosstalk Between UBXD8-DRP1-Regulated Mitochondrial Fission and PINK1-Parkin-Mediated Mitophagy.

Realgar is a toxic mineral medicine containing arsenic that is present in many traditional Chinese medicines. It has been reported that the abuse of drugs containing realgar has potential neurotoxicity, but its mechanism of toxicity has not been fully clarified. In this study, we demonstrated that arsenic in realgar promoted mitochondrial fission via UBXD8-mediated DRP1 translocation to the mitochondria and activated mitophagy via PINK1-Parkin, resulting in mitochondrial dysfunction and nerve cell death in the rat cortex. We used PC12 cells and treated them with inorganic arsenic (iAs). Mdivi-1, a mitochondrial fission inhibitor, and the siRNA UBXD8 or PINK1 were used as interventions to verify the precise mechanism by which arsenic affects realgar-induced mitochondrial instability. The results revealed that the arsenic in realgar accumulated in the brain and led to neurobehavioral abnormalities in the rats. We demonstrated that arsenic in realgar-induced high expression of UBXD8 promoted the translocation of DRP1 to the mitochondria, where it underwent phosphorylation, which led to the over-fission of the mitochondria and mitochondria-mediated apoptosis. Moreover, the over-fission of the mitochondria activates mitophagy, which is self-protective but only partially alleviates apoptosis and mitochondria dysfunction. Our findings revealed the crosstalk between mitochondrial fission and mitophagy in realgar-induced neurotoxicity. These results highlight the role of the transposition of DRP1 by UBXD8 in realgar-induced mitochondrial dysfunction and provide new ideas and data for the study of the mechanism of realgar-induced neurotoxicity.

Adverse Childhood Experiences and Oral Health of Children and Adolescents: A Systematic Review and Meta-Analysis.

Adverse childhood experiences (ACEs) can be extremely traumatic, and their impact on health throughout the life course has been a public policy issue all around the world. Oral health conditions significantly influence quality of life, but its relationship with ACEs among children and adolescents is not well defined. This systematic review investigated the association between ACEs and oral health outcomes in children and adolescents. The search was conducted across six databases and the gray literature, with no restrictions. It included studies evaluating the association between ACEs and oral health outcomes (oral health condition, utilization of dental services, oral hygiene habits, or oral health related to quality of life) in individuals aged 0 to 19. Data of included studies were extracted and methodological quality was assessed. Meta-analysis was used for quantitative synthesis, and the Grading of Recommendations Assessment, Development and Evaluation approach assessed evidence certainty. From the 12 included studies, 11 had a cross-sectional design, and 1 was a cohort study. Seventeen types of ACEs were investigated, including neglect; violence between parents or caregivers; alcohol and substance abuse; and peer, community, and collective violence. The methodological quality compliance ranged between 38% and 100%. The meta-analysis revealed associations between ACEs and lower use of dental services, toothache, gingival bleeding, and dental cavities. Cumulative exposure to more than three ACEs was associated with poorer oral health. The certainty of the evidence varied from low to very low. These results highlight that children and adolescents with ACEs are more likely to present higher oral health problems, including decreased use of dental services.

Do we need additional indicators for the Sustainable Development Goal Target 3.5 on strengthening the prevention and treatment of substance abuse? An analysis of recent submissions to the UN Inter-Agency and Expert Group.

Do we need additional indicators for the Sustainable Development Goal Target 3.5 on strengthening the prevention and treatment of substance abuse? An analysis of recent submissions to the UN Inter-Agency and Expert Group.