What Chemsex does to the brain - neural correlates (ERP) regarding decision making, impulsivity and hypersexuality.

Chemsex describes the use of specific substances (methamphetamine, GHB/GBL, mephedrone, ketamine) which initiate or enhance sexual experiences and is mainly prevalent among men who have sex with men. Many Chemsex users experience somatic complications (for example sexually transmitted diseases) and sometimes adverse sociological, psychological, and neurological symptoms, such as depression, impulse control disorders or hypersexuality. Changes in impulsivity and deficits in executive functions have demonstrated to be associated with addiction and impulse control disorders as well as frontal brain dysfunction and behavioral control deficits. This study aims to explore the effects of neurophysiological correlates of inhibition and decision making in Chemsex users with an EEG paradigm using event-related potentials (N2, P3). 15 Chemsex users and 14 matched control subjects, all of them men who have sex with man, participated in an auditory Go/NoGo/Voluntary Selection EEG paradigm. In addition, clinical data (e.g. regarding depression), demographic information as well as measures of well-being and sexual behavior were collected. The results demonstrated that clinical symptoms, hypersexuality, and sexual risk behavior were more pronounced in Chemsex users compared to non-users. P3 amplitudes did not differ significantly between groups. However, the Chemsex users showed decreased electrophysiological N2 responses in fronto-central brain regions during decision-making, indicating compromised executive function and inhibitory control. The observed impairments may lead to increased risk behavior regarding drug abuse and hypersexuality. Understanding the neurobiological mechanisms can contribute to targeted interventions in order to mitigate the negative consequences of engaging in Chemsex and improve general well-being.

Small pouches, but high nicotine doses-nicotine delivery and acute effects after use of tobacco-free nicotine pouches.

Tobacco-free nicotine pouches are new nicotine products for oral consumption. They can contain very high nicotine amounts that have not been addressed with clinical studies yet. Thus, nicotine delivery, effects on craving, and side effects were assessed using pouches with up to 30 mg nicotine. In this single-center, five-arm, crossover study, 15 regular cigarette smokers consumed tobacco-free nicotine pouches from different brands with 6, 20, and 30 mg for 20 min. Comparators were nicotine-free pouches and tobacco cigarettes. At baseline and predefined time points over a study period of 240 min, plasma nicotine concentrations, effects on cigarette craving, and side effects were assessed. Cardiovascular parameters including arterial stiffness were measured using a MobilOGraph. Consumption of 30 mg nicotine pouches has led to a higher nicotine uptake compared with the cigarette (Cmax: 29.4 vs 15.2 ng/mL; AUC: 45.7 vs 22.1 ng/mL × h). Nicotine uptake in the acute phase was rapid during use of the 30 mg pouch and cigarette. Extraction rate of nicotine differed between pouches. Use of all products has reduced acute cigarette craving, even the nicotine-free pouch. During consumption of the cigarette and the pouches with 20 and 30 mg, heart rate increased about 27, 12, and 25 bpm, respectively. Parameters for arterial stiffness were elevated and all pouches have induced mouth irritations. The pouches with 30 mg nicotine had overall the strongest side effects and may induce addiction. As craving was also reduced by products with less nicotine, it is questionable whether such high nicotine contents should be allowed on the market. A limit of nicotine content is warranted. The nicotine release rate varies across products and needs to be known to estimate the nicotine delivery.

Smoking and quality of life in lung cancer patients: systematic review.

OBJECTIVES: Lung cancer (LC) accounts for the largest number of cancer deaths worldwide, with smoking being the leading cause for its development. While quality of life (QoL) is a crucial factor in the treatment of patients with LC, the impact of smoking status on QoL remains unclear. This systematic review aims to provide a comprehensive overview of available evidence on the relationship between smoking status and QoL among patients with LC. METHODS: A systematic search of Embase, Medline and Web of Science was conducted. Studies reporting the impact of smoking status on QoL among patients with LC were eligible for inclusion. Two reviewers independently assessed the eligibility of studies, extracted data and evaluated the risk of bias using the Critical Appraisal Skills Programme appraisal tool for cohort studies. A descriptive synthesis was performed due to the heterogeneity of the studies. RESULTS: A total of 23 studies met the inclusion criteria (17 studies providing cross-sectional and 6 longitudinal data). The studies included a total of 10 251 participants. The results suggested a tendency towards lower QoL among smokers compared with non-smokers. The effect of smoking cessation on QoL was insufficiently investigated in the included studies and therefore remains inconclusive. CONCLUSIONS: The findings of this review suggest that current smokers may experience worse QoL than former and never smokers. The results of this systematic review should, however, be viewed in the context of the difficulty of data collection in this patient group given the low survival rates and low performance status, among other factors and in light of the large variety of different QoL measures used. Future research requires uniform QoL measures, a holistic representation of all patients with LC as well as a comprehensive consideration of all potential determinants of QoL. The potential benefits of smoking cessation on QoL among patients with LC require investigation.

Glutaryl-CoA Dehydrogenase Misfolding in Glutaric Acidemia Type 1.

Glutaric acidemia type 1 (GA1) is a neurotoxic metabolic disorder due to glutaryl-CoA dehydrogenase (GCDH) deficiency. The high number of missense variants associated with the disease and their impact on GCDH activity suggest that disturbed protein conformation can affect the biochemical phenotype. We aimed to elucidate the molecular basis of protein loss of function in GA1 by performing a parallel analysis in a large panel of GCDH missense variants using different biochemical and biophysical methodologies. Thirteen GCDH variants were investigated in regard to protein stability, hydrophobicity, oligomerization, aggregation, and activity. An altered oligomerization, loss of protein stability and solubility, as well as an augmented susceptibility to aggregation were observed. GA1 variants led to a loss of enzymatic activity, particularly when present at the N-terminal domain. The reduced cellular activity was associated with loss of tetramerization. Our results also suggest a correlation between variant sequence location and cellular protein stability (p < 0.05), with a more pronounced loss of protein observed with variant proximity to the N-terminus. The broad panel of variant-mediated conformational changes of the GCDH protein supports the classification of GA1 as a protein-misfolding disorder. This work supports research toward new therapeutic strategies that target this molecular disease phenotype.

The transformation of masculinity orientations and work-related attitudes in men treated for depression (TRANSMODE): study protocol for a mixed-methods observational study.

BACKGROUND: Masculinity norms play a crucial role in men's help-seeking behaviors, service-use, and coping strategies for depression. While previous studies provided evidence for the association between gender role orientations, work related attitudes, stigmatization of men with depression and depressive symptoms, it remains unclear to what extent gender role orientations change over time and whether psychiatric and psychotherapeutic treatment have an impact on these transformations. Additionally, the role of partners in supporting depressed men and the impact of dyadic coping on these processes have not been explored. The aim of this study is to investigate how masculinity orientations and work-related attitudes change over time in men treated for depression, and to examine the role of their partners and dyadic coping in these transformation processes. METHODS: TRANSMODE is a prospective longitudinal mixed-methods study investigating the transformation of masculinity orientations and work-related attitudes in men treated for depression between the ages of 18 and 65 from different settings in Germany. The study will recruit 350 men from various settings for quantitative analysis. By applying a latent transition analysis, the primary outcome are changes in masculine orientations and work-related attitudes over time, measured at four times (t0, t1, t2, t3) with intervals of 6 months. Qualitative interview with a subsample of depressed men selected using latent profile analysis, will be conducted between t0 and t1 (a1) with a follow-up of 12 months (a2). In addition, qualitative interviews with the partners of depressed men will be conducted between t2 and t3 (p1). Qualitative data will be analysed using qualitative structured content analysis. DISCUSSION: A comprehensive understanding of the transformation processes of masculinity orientations over time including the impact of psychiatric/psychotherapeutic treatment and the role of partners can lead to the development of gender-sensitive depression treatment tailored to the unique needs of men with depression. Thus, the study can promote more effective and successful treatment outcomes and further contribute to reducing the stigma surrounding mental health issues among men and encourage them for mental health service use. TRIAL REGISTRATION: This study is registered in the German Clinical Trail Register (DRKS) and the WHO International Clinical Trials Registry Platform (ICTRP) under registration number DRKS00031065 (Date of registration 06 February 2023).

Lethal Lust: Suicidal Behavior and Chemsex-A Narrative Review of the Literature.

Chemsex is described as the use of certain drugs-commonly methamphetamine, gamma-butyrolactone (GBL)/gammahydroxybutyrate (GHB), and mephedrone-before or during planned sexual activity primarily among men who have sex with men (MSM). Evidence shows that MSM who engage in chemsex are at increased risk of physical harm, such as sexually transmittable infections (STIs), and are more likely to experience mental health symptoms. To further assess this, we reviewed the recent literature to evaluate whether the psychological impact of chemsex behavior includes suicidal ideation and suicidal attempts. Pubmed/MEDLINE was searched for articles reporting suicidal ideation and behavior among chemsex users with the terms "chemsex", "sexualized drug use", "suicide", and "mental health". Twelve articles (three case reports and nine cross-sectional studies) were included in the final narrative review. Overall, we retrieved mixed results regarding the relationship between chemsex practice and suicidality outcomes. Considering the inhomogeneous nature of the studies, the findings indicate that suicidality could be an issue of concern among MSM in general but among chemsex users in particular. Possible risk factors for suicidality among chemsex participants may include adversities experienced due to one's sexual orientation and an increased risk for HIV and other STI infections and the resulting negative impact on mental well-being. These aspects warrant further investigations.

[Chemsex : A new challenge in addiction medicine and infectious diseases]. / Chemsex : Eine neue Herausforderung der Suchtmedizin und Infektiologie.

BACKGROUND: Recently there has been an increase in reports of the phenomenon called chemsex, a subform of sexualized substance use. Chemsex is a neologism consisting of the two terms "chemicals" and "sex". It describes the use of methamphetamine, γ­hydroxybutyrate/γ-butyrolactone (GHB/GBL), mephedrone and sometimes other substances in a sexual context, especially by men who have sex with men (MSM). Chemsex has been described as a significant risk factor for mental and physical diseases. OBJECTIVE: Due to the increasing importance of the phenomenon and the significantly increased number of publications on the subject, this article provides an overview of the current and relevant literature. The aim is to raise awareness on this topic among practitioners and researchers and thus to facilitate access to the help system for those affected. METHOD: A literature search was conducted in PubMed/Medline, Cochrane and Embase for the terms "chemsex", "sexualized drug use" and "slamming. A total of 22 articles were identified as being relevant. RESULTS: In the published literature on chemsex the current focus lies on somatic comorbidities. There is a significantly increased risk of sexually transmitted diseases. Mental illnesses such as depression, substance-induced psychosis and addiction also appear to be a significant consequence of chemsex. An individualized and specialized treatment approach is not yet established. DISCUSSION: The complexity of chemsex with its psychiatric and somatic aspects does not yet appear to be sufficiently reflected by the current data situation; however, due to the mutual influence of these different comorbidities, this patient clientele appears to be particularly at risk in the absence of a specialized treatment option, which is why further research on this topic is needed.

We Have a Lot to Do: Lack of Sexual Protection and Information-Results of the German-Language Online Survey "Let's Talk About Chemsex".

Background: The prevalence of chemsex and sexualized substance use is increasing in several European countries, particularly among men who have sex with men. In this subgroup, illegal substance use is associated with increased sexual risk behavior, which can result in severe physical and psychological impairments. The present study examined the incidence and prevalence of chemsex in German-speaking countries. Methods: To further describe the high-risk group of Chemsex users, participants (N = 429) were asked about their psychotropic substance use, sexual and health-related behavior, health status, and socio-demographic information by using an online questionnaire. Whether Chemsex has negative effects on well-being was measured with the WHO well-being index. Of additional interest was how informed Chemsex users are about the topic and what needs are placed on the practitioners. The online questionnaire consisted of 105 items, and data was collected from March to May 2019. Thousand forty seven datasets were saved with a dropout rate of 59%, 123 completed questionnaires fulfilled the criteria for chemsex users (n =123). Results: There were no significant differences in well-being between chemsex users and non-users. All participants protected themselves against sexually transmitted diseases irregularly or not at all. The majority of chemsex users reported intermittently using illegal substances (ketamine, methamphetamine, mephedrone, γ-butyrolactone/γ-hydroxy butyric acid). They viewed their sexual and substance use behavior as problematic, but few showed motivation for behavior change. Chemsex users clearly expressed a need for more information and advice centers. Conclusion: The results provide information on chemsex users that can be used for the future development of a therapy manual and thus contribute to improving health care for this group. The prevalence of chemsex is increasing and urgently needs more research to protect clients from health impairments and stigmatization.