Identifying human diamine sensors for death related putrescine and cadaverine molecules

Pungent chemical compounds originating from decaying tissue are strong drivers of animal behavior. Two of the best-characterized death smell components are putrescine (PUT) and cadaverine (CAD), foul-smelling molecules produced by decarboxylation of amino acids during decomposition. These volatile polyamines act as 'necromones', triggering avoidance or attractive responses, which are fundamental for the survival of a wide range of species. The few studies that have attempted to identify the cognate receptors for these molecules have suggested the involvement of the seven-helix trace amine-associated receptors (TAARs), localized in the olfactory epithelium. However, very little is known about the precise chemosensory receptors that sense these compounds in the majority of organisms and the molecular basis of their interactions. In this work, we have used computational strategies to characterize the binding between PUT and CAD with the TAAR6 and TAAR8 human receptors. Sequence analysis, homology modeling, docking and molecular dynamics studies suggest a tandem of negatively charged aspartates in the binding pocket of these receptors which are likely to be involved in the recognition of these small biogenic diamines

Predictive power of the DSM-5 criteria for internet use disorder

$\bf Introduction:$ Although the majority of internet users enjoy the internet as a recreational activity, some individuals report problematic internet use behaviors causing negative psychosocial consequences. Therefore, it is important to have precise and valid diagnostic criteria to ensure suitable treatment for those affected and avoid over-pathologization. $\bf Methods:$ The aim of the present study was to determine which of the nine DSM-5 criteria of internet gaming disorder (IGD) are crucial in distinguish pathological from non-pathological internet use based on the questionnaire-based response behavior of the participants by applying the Chi-squared automatic interaction detection (CHAID) decision tree analysis. Under consideration of the nine DSM-5 criteria for IGD and according to the short-form scale to assess Internet Gaming Disorder (IGDS-SF9) the DSM-5 criteria were formulated as questions and applied to the broader concept of Internet Use Disorder (IUD). The nine questions were answered on a 5-point Likert scale from "never" to "very often". In accordance with the IGDS-SF9 participants were assigned to IUD-5plus if at least 5 of the 9 criteria were answered with "very often". The study was conducted in Germany ($\it N$ = 37,008; $\it mean age$: 32 years, $\it SD$ = 13.18, 73.8% male). $\bf Results:$ Although "loss of control", "continued overuse" and "mood regulation" were the most endorsed criteria, the analysis indicated that the criterion "jeopardizing" was found as the best predictor for IUD-5plus, followed by "loss of interest" and "continued overuse". Overall 64.9% of all participants who were in the IUD-5plus, could been identified by the fulfillment of the three criteria mentioned above. $\bf Discussion:$ The results found support for adjustment of the DSM-5 criteria of IGD in accordance to ICD-11. If the predictive power of the three criteria can be replicated in future representative studies, such a decision tree can be used as guidance for diagnostics to capture the particularly relevant criteria

Telemedicine as bridge to the offline world for person affected with problematic internet use or internet use disorder and concerned significant others

$\bf Introduction$ Internet use disorder is a disorder of the digital age and presents a growing problem worldwide. It appears that due to structural and personal barriers, many persons affected (PA) and Concerned Significant Others (CSO) do not reach the health care system so far and thus a chronification of the pathology can proceed. $\bf Methods$ A telemedicine counseling service for PA and CSO of PA unwilling to enter treatment with two webcam-based sessions of 60 minutes for each group was created with the aim of reaching out to PA and CSO to provide a low-threshold support and refer the participants to the local health care system. Motivational interviewing for PA and CRAFT (Community Reinforcement and Family Training) for CSO were used as methods. Participants answered questions about their Internet use and sociodemographic data and six months after participation, participants were asked via email if they entered the local health care system. CSO answered the questions for themselves and in a third-party rating for PA unwilling to enter treatment. $\bf Results$ 107 PA (34 years ($\it SD$ = 13.64), 86% male) and 38 CSO (53 years ($\it SD$ = 6.11), 28.9% male) participated in the two telemedicine sessions. After participation, 43.9% of the PA and 42.1% of the CSO reached the health care system. When there was consistency between the location of telemedicine consultation and treatment locally, over 90% of participants arrived (PA: 92.3%, CSO: 100%). $\bf Conclusion$ The results from this study reveal that telemedicine services could be a promising approach to address PA and CSO and build a bridge to the local health care system. Future studies should verify if these results can be replicated in randomized controlled trials

A short-term manual for webcam-based telemedicine treatment of Internet use disorders

In recent decades, the number of people who experience their Internet use behavior as problematic has risen dramatically. In Germany, a representative study from 2013 estimated the prevalence of Internet use disorder (IUD) to be about 1.0%, with higher rates among younger people. A 2020 meta-analysis shows a global weighted average prevalence of 7.02%. This indicates that developing effective IUD treatment programs is more critical than ever. Studies show that motivational interviewing (MI) techniques are widely used and effective in treating substance abuse and IUDs. In addition, an increasing number of online-based health interventions are being developed to provide a low-threshold treatment option. This article presents a short-term online-based treatment manual for IUDs that combines MI techniques with therapy tools from cognitive behavioral therapy (CBT) and acceptance and commitment therapy (ACT). The manual includes 12 webcam-based therapy sessions, each lasting 50 min. Each session is framed by a standardized beginning, conclusion, outlook, and flexible session content. In addition, the manual contains example sessions to illustrate the therapeutic intervention. Finally, we discuss the advantages and disadvantages of online-based therapy compared to analog treatment settings and provide recommendations for dealing with these challenges. By combining established therapeutic approaches with an online-based therapeutic setting based on flexibility and motivation, we aim to provide a low-threshold solution for treating IUDs

Effects of an online-based motivational intervention to reduce problematic internet use and promote treatment motivation in internet gaming disorder and internet use disorder (OMPRIS)

$\it Introduction$ In May 2019, the WHO classified internet gaming disorder (IGD) as a mental disorder in the upcoming International Classification of Diseases 11th Revision. However, individuals affected by IGD or internet use disorders (IUDs) are often not provided with adequate therapy due to a lack of motivation or absence of adequate local treatment options. To close the gap between individuals with IUDs and the care system, we conduct an online-based motivational intervention to reduce problematic internet use and promote treatment motivation in internet gaming disorder and internet use disorder (OMPRIS). $\textit {Methods and analysis}$ Within the randomised controlled trial, a total of n=162 participants will be allocated by sequential balancing randomisation to the OMPRIS intervention or a waitlist control group. The study includes an extensive diagnostic, followed by a 4-week psychological intervention based on motivational interviewing, (internet-related) addiction therapy, behavioural therapy techniques and additional social counselling. The primary outcome is the reduction of problematic internet use measured by the Assessment of Internet and Computer Game Addiction Scale. Secondary outcomes include time spent on the internet, motivation for change (Stages of Change Readiness and Treatment Eagerness Scale for Internet Use Disorder), comorbid mental symptoms (Patient Health Questionnaire-9, Generalized Anxiety Disorder Screener-7), quality of life (EuroQoL Standardised Measure of Health-related Quality of Life–5 Dimensions, General Life Satisfaction-1), self-efficacy (General Self-Efficacy Scale), personality traits (Big Five Inventory-10), therapeutic alliance (Helping Alliance Questionnaire) and health economic costs. The diagnosis of (comorbid) mental disorders is carried out with standardised clinical interviews. The measurement will be assessed before (T0), at midpoint (T1) and after the OMPRIS intervention (T2), representing the primary endpoint. Two follow-up assessments will be conducted after 6 weeks (T3) and 6 months (T4) after the intervention. The outcomes will be analysed primarily via analysis of covariance. Both intention-to-treat and per-protocol analyses will be conducted. $\textit {Ethics and dissemination}$ Participants will provide written informed consent. The trial has been approved by the Ethics Committee of the Faculty of Medicine, Ruhr University Bochum (approval number 19-6779). Findings will be disseminated through presentations, peer-reviewed journals and conferences

Efficacy of a short-term webcam-based telemedicine treatment of internet use disorders (OMPRIS)

$\bf Background$ Evidence-based $\underline {treatments}$ for internet use disorders (IUDs) are limited, and online therapy approaches are poorly studied. We investigated the efficacy of a manualised therapist-guided online intervention (OMPRIS) to reduce IUD $\underline {symptoms}$ and improve psychological well-being. $\bf Methods$ In this multicentre, two-arm, single-blinded trial, individuals ≥16 years suffering from IUD symptoms were recruited in Germany from August 16, 2020, to March 11, 2022, through media advertisements and healthcare providers. Participants were randomly allocated by sequential balancing randomisation (1:1) to either the manualised webcam-based OMPRIS intervention or a waitlist control (WLC) group. OMPRIS provided strategies from motivational interviewing, behavioural therapy, and social counselling. The primary outcome at the end of treatment was a reduction in IUD symptoms as measured by the Assessment of Internet and Computer Scale (AICA-S). Follow-up assessments were conducted at 6 weeks and 6 months. Analyses were performed in the intention-to-treat population. This trial was registered (German $\underline {Clinical}$ $\underline {Trial}$ Register, DRKS00019925) and has been completed. $\bf Findings$ A total of 180 individuals were randomly assigned to the OMPRIS intervention (n = 89) or WLC (n = 91) arm. After treatment, 81 (91.0%) participants in the OMPRIS intervention group and 88 (96.7%) in the WLC group completed the outcome assessment. The $\underline {ANCOVA}$ model showed that OMPRIS participants had a significantly greater reduction in AICA-S scores from baseline (mean score 12.1 [SD 4.6]) to post-treatment (6.8 [5.2]) than those in the WLC group (from 12.6 [5.1] to 11.0 [5.4]; estimated mean difference −3.9; [95% CI −5.2 to −2.6]; p < 0.0001; d = 0.92). No adverse events were reported to the trial team. $\bf Interpretation$ Webcam-based OMPRIS therapy was effective and superior to waiting list conditions in reducing IUD symptoms. Webcam-based, specialised online therapy thus increases IUD treatment options