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Communications Biology Jun 2024Tuberous sclerosis complex 2 (TSC2) crucially suppresses Rheb activity to prevent mTORC1 activation. However, mutations in TSC genes lead to mTORC1 overactivation,...
Tuberous sclerosis complex 2 (TSC2) crucially suppresses Rheb activity to prevent mTORC1 activation. However, mutations in TSC genes lead to mTORC1 overactivation, thereby causing various developmental disorders and cancer. Therefore, the discovery of novel Rheb inhibitors is vital to prevent mTOR overactivation. Here, we reveals that the anti-inflammatory cytokine IL-37d can bind to lysosomal Rheb and suppress its activity independent of TSC2, thereby preventing mTORC1 activation. The binding of IL-37d to Rheb switch-II subregion destabilizes the Rheb-mTOR and mTOR-S6K interactions, further halting mTORC1 signaling. Unlike TSC2, IL-37d is reduced under ethanol stimulation, which results in mitigating the suppression of lysosomal Rheb-mTORC1 activity. Consequently, the recombinant human IL-37d protein (rh-IL-37d) with a TAT peptide greatly improves alcohol-induced liver disorders by hindering Rheb-mTORC1 axis overactivation in a TSC2- independent manner. Together, IL-37d emerges as a novel Rheb suppressor independent of TSC2 to terminate mTORC1 activation and improve abnormal lipid metabolism in the liver.
Topics: Mechanistic Target of Rapamycin Complex 1; Ras Homolog Enriched in Brain Protein; Humans; Animals; Mice; Signal Transduction; Tuberous Sclerosis Complex 2 Protein; Liver Diseases, Alcoholic; Interleukin-1; Mice, Inbred C57BL; Male; HEK293 Cells
PubMed: 38907105
DOI: 10.1038/s42003-024-06427-8 -
Child Abuse & Neglect Jun 2024Effective classification of individuals who commit sexual offences is important for their assessment, treatment, and risk management. Victim age has often been used as a...
BACKGROUND
Effective classification of individuals who commit sexual offences is important for their assessment, treatment, and risk management. Victim age has often been used as a distinguishing factor between perpetrators.
OBJECTIVE
This study aimed to analyse the distinctive psychopathological and criminological characteristics of contact sexual offenders with adult and minor victims.
PARTICIPANTS AND SETTING
The study involved 97 adult males who were serving a prison sentence in Spain for at least one contact sexual offence against an adult or a minor.
METHODS
Researchers gathered data on criminological variables concerning the offender, victim, and modus operandi from prison records and interviews. Participants completed the Millon Clinical Multiaxial Inventory-III (MCMI-III) in a second session, and between-group differences were analysed.
RESULTS
Sex offenders with minor victims (SOMV) had significantly lower scores than sex offenders with adult victims (SOAV) on the Antisocial (r = -0.283, p = .005) and Sadistic (r = -0.209, p = .04) personality subscales, and on the Alcohol (r = -0.426, p < .001) and Drug dependence (r = -0.332, p = .001) syndrome subscales. SOAV were also more likely to use violence and/or intimidation, use a weapon, offend against female victims, offend against an intimate partner, commit their offences in public places, serve other ongoing prison sentences, and report a history of alcohol and substance abuse. SOMV were older and more likely to offend against family members.
CONCLUSIONS
These results suggest that there are key differences between SOAV and SOMV that should be considered in tailored prevention programmes for each subgroup of offenders.
PubMed: 38906041
DOI: 10.1016/j.chiabu.2024.106896 -
Medicine Jun 2024Gegensan (GGS) has been reported for the treatment of alcoholic liver disease (ALD), but its therapeutic mechanism is still unclear. This paper aims to determine the...
Gegensan (GGS) has been reported for the treatment of alcoholic liver disease (ALD), but its therapeutic mechanism is still unclear. This paper aims to determine the therapeutic mechanism and targets of action of GGS on alcoholic liver disease utilizing network pharmacology and bioinformatics. The active ingredients in GGS were screened in the literature and databases, and common targets of ALD were then obtained from public databases to construct the network diagram of traditional Chinese medicine-active ingredient targets. Based on the common targets, Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to find target enrichment pathways, and the core targets were screened out by combining differential analysis and protein-protein interaction network analysis. Molecular docking was performed to verify the binding effect between the core targets and the corresponding active ingredients. ALD and GGS have 84 common targets, corresponding to 91 active ingredients. After subsequent differential analysis and protein-protein interaction network analysis, 10 core targets were identified. Gene Ontology and KEGG enrichment analyses showed that the main BPs corresponding to the common targets included the response to lipopolysaccharide, inflammatory response, etc. The KEGG pathways involved in the regulation of the common targets included the lipid-atherosclerosis pathway and the alcoholic liver disease pathway, etc. Further molecular docking showed that the core targets CYP1A1, CYP1A2, CXCL8, ADH1C, MMP1, SERPINE1, COL1A1, APOB, MMP1, and their corresponding 4 active ingredients, Naringenin, Kaempferol, Quercetin, and Stigmasterol, have a greater docking potential. The above results suggest that GGS can regulate lipid metabolism and inflammatory response in the ALD process, and alleviate the lipid accumulation and oxidative stress caused by ethanol. This study analyzed the core targets and mechanisms of action of GGS on ALD, which provides certain theoretical support for the further development of GGS in the treatment of ALD, and provides a reference for the subsequent research on the treatment of ALD.
Topics: Liver Diseases, Alcoholic; Network Pharmacology; Humans; Molecular Docking Simulation; Drugs, Chinese Herbal; Computational Biology; Protein Interaction Maps; Medicine, Chinese Traditional; Gene Ontology
PubMed: 38905402
DOI: 10.1097/MD.0000000000038315 -
JAMA Network Open Jun 2024
Topics: Humans; United States; Clinical Trials as Topic; Consent Forms; Databases, Factual; Registries
PubMed: 38904965
DOI: 10.1001/jamanetworkopen.2024.18895 -
Cureus May 2024The abuse of inhalants like nitrous oxide (NO), readily available worldwide, has remained a prominent public health problem during the last few decades. Literature...
The abuse of inhalants like nitrous oxide (NO), readily available worldwide, has remained a prominent public health problem during the last few decades. Literature reveals increased use during the previous pandemic, particularly regarding recreational use. There is limited evidence-based data available to relate the abuse of NO with psychosis. Therefore, this case report of a 22-year-old adult with no previous psychiatry history, reportedly abusing 75-100 canisters of NO per day during the last pandemic COVID-19 lockdown, highlights the relationship between (NO) abuse and the symptoms evolved including delusions, auditory hallucinations, and disorganized cognition. All the laboratory findings and results from imaging modalities were inconsistent for any organic cause of the symptoms. The case then underwent treatment with antipsychotic medications and a multidisciplinary model, which improved the symptoms gradually. The case, in particular, discusses NO abuse, which is widespread in European Union countries, including the UK and the Republic of Ireland, and its chronic use puts one at a higher risk of developing psychosis, personality changes, affective lability, anxiety, depression, cognitive impairment, and myeloneuropathy. The sale of NO for its psychoactive properties is prohibited in many countries, including the Republic of Ireland, as per legislation. However, NO is not a controlled drug, meaning it is not a crime to possess NO. This case report manifests the psychopathy caused by abuse of NO, which would further attract specialists in the field to conduct epidemiological studies for prevention at the primary level.
PubMed: 38903353
DOI: 10.7759/cureus.60634 -
Enabling tobacco treatment for gastroenterology patients via a novel low-burden point-of-care model.BMC Health Services Research Jun 2024Smoking is a major risk factor for multiple gastrointestinal cancers, and adversely affects peptic ulcer disease, gastroesophageal reflux, pancreatitis and Crohn's...
BACKGROUND & AIM
Smoking is a major risk factor for multiple gastrointestinal cancers, and adversely affects peptic ulcer disease, gastroesophageal reflux, pancreatitis and Crohn's disease. Despite key recommendations for diagnosing and treating tobacco use disorder in healthcare settings, the degree to which this is implemented in Gastroenterology (GI) clinics is unknown. We aimed to assess our providers' practices, identify barriers for implementing evidence-based smoking cessation treatments, and address these barriers by implementing a novel low-burden point of care Electronic health record-enabled evidence-based tobacco treatment (ELEVATE), in GI clinics.
METHODS
An online survey was distributed to clinic gastroenterologists. ELEVATE module training was implemented in 1/2021. Data were evaluated during pre (7/2020-12/2020) and post (1/2021-12/2021) implementation periods to evaluate the reach and effectiveness of ELEVATE. Generalized estimating equations (GEE) were used to generate rate ratios (RR) to evaluate the intervention.
RESULTS
91% (20/22) of GI physicians responded to our survey, and only 20% often assisted patients who smoke with counseling. Lack of a systematic program to offer help to patients was reported by 80% of providers as an extremely/very important barrier limiting their smoking cessation practices. The proportion of current patients who smoke receiving cessation treatment increased from pre-ELEVATE to post-ELEVATE (14.36-27.47%, RR = 1.90, 95% CI 1.60-2.26, p < .001). Post-ELEVATE, 14.4% (38/264) of patients with treatment quit smoking, compared to 7.9% (55/697) of patients without treatment (RR = 1.89, 95% CI 1.26-2.82, p = .0021).
CONCLUSION
Smoking practices are frequently assessed in GI clinics but barriers limiting cessation treatment exist. The use of a low burden point of care EHR enabled smoking cessation treatment module has led to a significant improvement in the treatment of smoking and subsequent cessation in our clinics. This study sheds light on an often under-recognized source of morbidity in GI patients and identifies an efficient, effective, and scalable strategy to combat tobacco use and improve clinical outcomes in our patients.
Topics: Humans; Smoking Cessation; Male; Female; Point-of-Care Systems; Gastroenterology; Middle Aged; Adult; Surveys and Questionnaires; Electronic Health Records; Practice Patterns, Physicians'; Tobacco Use Disorder
PubMed: 38902682
DOI: 10.1186/s12913-024-11092-y -
Scientific Reports Jun 2024It is well-recognized that individuals with alcohol-related disorders often use other psychoactive substances; however, systematic research on this topic remains...
It is well-recognized that individuals with alcohol-related disorders often use other psychoactive substances; however, systematic research on this topic remains limited. The primary objective was to determine the prevalence of lifetime psychoactive substance use and describe the dependence between concurrent use of alcohol and other drugs on psychiatric comorbidities in the analyzed group. The secondary aim was to try to assess the frequency of seeking psychiatric treatment between individuals declaring the concurrent use of alcohol with other drugs and those declaring the use only alcohol. The study was designed as a retrospective cross-sectional analysis based on discharge reports from psychiatric patients admitted to the Regional Psychiatric Hospital in Olsztyn, Poland. 1015 cases were included and analyzed in the study. Data for the study were collected in specially designed monitoring cards from discharge reports including data from psychiatric examinations, especially anamnesis. The percentage of people declaring lifetime use of psychoactive substances was 17.6%. 2.8% of them were diagnosed with substance-related disorders (F11-19 according to ICD-10). The most frequently declared use was cannabis, followed by amphetamine-type substances, benzodiazepines and new psychoactive substances. In the group of people declaring the lifetime use of psychoactive substances, 13.4% were additionally diagnosed with mental disorders. It was, consequently, 8% in the group of people denying the lifetime use of psychoactive substances. People declaring lifetime use of psychoactive substances were significantly more likely to seek psychiatric treatment, i.e. they were admitted significantly more often on an emergency admission than on an elective one, these people were significantly more likely to have undergone psychiatric treatment in the past and were more often hospitalized in our center during the research period. People who concurrently use alcohol with other drugs significantly more often have psychiatric comorbidity than people who deny the use of other drugs. That group also visibly more often seeks psychiatric treatment than patients who deny taking psychoactive substances.
Topics: Humans; Male; Female; Adult; Comorbidity; Substance-Related Disorders; Mental Disorders; Middle Aged; Cross-Sectional Studies; Retrospective Studies; Alcoholism; Poland; Patient Acceptance of Health Care; Prevalence; Psychotropic Drugs; Young Adult; Adolescent; Aged
PubMed: 38902395
DOI: 10.1038/s41598-024-65028-x -
JMIR Human Factors Jun 2024Young adults in the United States exhibit some of the highest rates of substance use compared to other age groups. Heavy and frequent substance use can be associated...
BACKGROUND
Young adults in the United States exhibit some of the highest rates of substance use compared to other age groups. Heavy and frequent substance use can be associated with a host of acute and chronic health and mental health concerns. Recent advances in ubiquitous technologies have prompted interest and innovation in using technology-based data collection instruments to understand substance use and associated harms. Existing methods for collecting granular, real-world data primarily rely on the use of smartphones to study and understand substance use in young adults. Wearable devices, such as smartwatches, show significant potential as platforms for data collection in this domain but remain underused.
OBJECTIVE
This study aims to describe the design and user evaluation of a smartwatch-based data collection app, which uses ecological momentary assessments to examine young adult substance use in daily life.
METHODS
This study used a 2-phase iterative design and acceptability evaluation process with young adults (aged 18-25 y) reporting recent alcohol or cannabis use. In phase 1, participants (8/15, 53%) used the data collection app for 14 days on their Apple Watches to report their substance use patterns, social contexts of substance use, and psychosocial risk factors (eg, affect). After this 14-day deployment, the participants completed a user experience survey and a semistructured interview to record their perspectives and experiences of using the app. Formative feedback from this phase informed feature modification and refinement of the app. In phase 2, an additional cohort (7/15, 47%) used the modified app for 14 days and provided feedback through surveys and interviews conducted after the app use period.
RESULTS
Analyses of overall app use patterns indicated high, consistent use of the app, with participants using the app for an average of 11.73 (SD 2.60) days out of 14 days of data collection. Participants reported 67 instances of substance use throughout the study, and our analysis indicates that participants were able to respond to ecological momentary assessment prompts in diverse temporal and situational contexts. Our findings from the user experience survey indicate that participants found the app usable and functional. Comparisons of app use metrics and user evaluation scores indicate that the iterative app design had a measurable and positive impact on users' experience. Qualitative data from the participant interviews highlighted the value of recording substance use patterns, low disruption to daily life, minimal overall burden, preference of platforms (smartphones vs smartwatches), and perspectives relating to privacy and app use in social contexts.
CONCLUSIONS
This study demonstrated the acceptability of using a smartwatch-based app to collect intensive, longitudinal substance use data among young adults. The findings document the utility of smartwatches as a novel platform to understand sensitive and often-stigmatized behaviors such as substance use with minimal burden.
Topics: Humans; Male; Feasibility Studies; Mobile Applications; Female; Adult; Young Adult; Adolescent; Substance-Related Disorders; Ecological Momentary Assessment; Smartphone; United States
PubMed: 38901024
DOI: 10.2196/50795 -
PloS One 2024Cigarette smoking is a persistent public health problem as it is a risk factor for many diseases. Previous studies on the role of illegal drug use in cigarette smoking... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Cigarette smoking is a persistent public health problem as it is a risk factor for many diseases. Previous studies on the role of illegal drug use in cigarette smoking have yielded disparate and inconclusive results, hindering the development of effective intervention strategies to address this issue. Therefore, this systematic review and meta-analysis aimed to estimate the pooled prevalence of cigarette smoking and its associated factors, with a specific focus on the influence of illegal drug use among students in Ethiopia.
METHODS
We conducted a comprehensive search of international databases, including PubMed, Cochrane Library, Science Direct, CINAHL, African Journals Online, HINARI, Global Health, and Google and Google Scholar. Grey literature was also identified from various university digital libraries. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA) guidelines. Due to the high heterogeneity among the included studies (I2 = 98.6%; p-value <0.001), we employed a random-effects model with a 95% confidence interval (CI) to estimate the pooled effect using STATA 14 software. The publication bias was assessed using a statistical Egger regression test.
RESULTS
A total of 22 studies involving 18,144 students met the eligibility criteria for this systematic review and meta-analysis. The pooled prevalence of lifetime and current cigarette smoking among students in Ethiopia was 13.8% (95% CI: 9.90-17.82) and 9.61% (95% CI: 7.19-12.03), respectively. Students who used illegal drugs were twenty-three times more likely to smoke cigarettes compared to their counterparts (OR = 23.57, 95% CI: 10.87-51.1). Living in urban settings (OR = 2.9; 95% CI: 1.15-7.28) and the habit of alcohol consumption (OR = 4.79; 95% CI: 1.57-14.64) were also identified as factors associated with cigarette smoking.
CONCLUSIONS
We found that more than one in eight students in Ethiopia have engaged in lifetime cigarette smoking. Notably, students who used illegal drugs exhibited a significantly higher likelihood of cigarette smoking. In light of these findings, it is imperative to implement comprehensive public health interventions that target illegal drug use, cigarette smoking, and alcohol consumption, with a particular emphasis on urban residents.
Topics: Ethiopia; Humans; Students; Cigarette Smoking; Substance-Related Disorders; Prevalence; Illicit Drugs; Male; Female; Risk Factors
PubMed: 38900812
DOI: 10.1371/journal.pone.0304948 -
JMIR Infodemiology Jun 2024Prenatal alcohol exposure represents a substantial public health concern as it may lead to detrimental outcomes, including pregnancy complications and fetal alcohol...
BACKGROUND
Prenatal alcohol exposure represents a substantial public health concern as it may lead to detrimental outcomes, including pregnancy complications and fetal alcohol spectrum disorder. Although UK national guidance recommends abstaining from alcohol if pregnant or planning a pregnancy, evidence suggests that confusion remains on this topic among members of the public, and little is known about what questions people have about consumption of alcohol in pregnancy outside of health care settings.
OBJECTIVE
This study aims to assess what questions and topics are raised on alcohol in pregnancy on a web-based UK-based parenting forum and how these correspond to official public health guidelines with respect to 2 critical events: the implementation of the revised UK Chief Medical Officers' (CMO) low-risk drinking guidelines (2016) and the first COVID-19 pandemic lockdown (2020).
METHODS
All thread starts mentioning alcohol in the "Pregnancy" forum were collected from Mumsnet for the period 2002 to 2022 and analyzed using qualitative content analysis. Descriptive statistics were used to characterize the number and proportion of thread starts for each topic over the whole study period and for the periods corresponding to the change in CMO guidance and the COVID-19 pandemic.
RESULTS
A total of 395 thread starts were analyzed, and key topics included "Asking for advice on whether it is safe to consume alcohol" or on "safe limits" and concerns about having consumed alcohol before being aware of a pregnancy. In addition, the Mumsnet thread starts included discussions and information seeking on "Research, guidelines, and official information about alcohol in pregnancy." Topics discussed on Mumsnet regarding alcohol in pregnancy remained broadly similar between 2002 and 2022, although thread starts disclosing prenatal alcohol use were more common before the introduction of the revised CMO guidance than in later periods.
CONCLUSIONS
Web-based discussions within a UK parenting forum indicated that users were often unclear on guidance and risks associated with prenatal alcohol use and that they used this platform to seek information and reassurance from peers.
Topics: Humans; Pregnancy; Female; Alcohol Drinking; United Kingdom; COVID-19; Internet; Qualitative Research; Fetal Alcohol Spectrum Disorders; SARS-CoV-2; Social Media
PubMed: 38900536
DOI: 10.2196/58056