Sharing knowledge: a new frontier for public-private partnerships in medicine

To help overcome the bottlenecks that limit the development of diagnostic and therapeutic products, academic and industrial researchers, patient organizations and charities, and regulatory and funding institutions should redefine the basis for sharing the knowledge collected in large-scale clinical and experimental studies

Myocardin is a bifunctional switch for smooth versus skeletal muscle differentiation

Skeletal and smooth muscle can mutually transdifferentiate, but little molecular insight exists as to how each muscle program may be subverted to the other. The myogenic basic helix–loop–helix transcription factors MyoD and myogenin (Myog) direct the development of skeletal muscle and are thought to be dominant over the program of smooth muscle cell (SMC) differentiation. Myocardin (Myocd) is a serum response factor (SRF) coactivator that promotes SMC differentiation through transcriptional stimulation of SRF-dependent smooth muscle genes. Here we show by lineage-tracing studies that Myocd is expressed transiently in skeletal muscle progenitor cells of the somite, and a majority of skeletal muscle is derived from Myocd-expressing cell lineages. However, rather than activating skeletal muscle-specific gene expression, Myocd functions as a transcriptional repressor of Myog, inhibiting skeletal muscle differentiation while activating SMC-specific genes. This repressor function of Myocd is complex, involving histone deacetylase 5 silencing of the Myog promoter and Myocd's physical contact with MyoD, which undermines MyoD DNA binding and transcriptional synergy with MEF2. These results reveal a previously unrecognized role for Myocd in repressing the skeletal muscle differentiation program and suggest that this transcriptional coregulator acts as a bifunctional molecular switch for the smooth versus skeletal muscle phenotypes

The effectiveness of blended versus regular Forensic Outpatient Systemic Therapy in the treatment of juvenile antisocial behavior: a study protocol of a randomized controlled trial

Background: Antisocial behavior during adolescence can have long-lasting negative effects and leads to high societal costs. Forensic Outpatient Systemic Therapy (Forensische Ambulante Systeem Therapie; FAST) is a promising treatment for juveniles aged 12–21 showing severe antisocial behavior. The intensity, content and duration of FAST can be adjusted to the needs of the juvenile and their caregiver(s), which is considered crucial for effective treatment. Next to the regular version of FAST (FASTr), a blended version (FASTb) in which face-to-face contacts are replaced by minimally 50% online contacts over the duration of intervention was developed during the Covid-19 pandemic. The current study will investigate whether FASTb is equally effective as FASTr, and through which mechanisms of change, for whom, and under which conditions FASTr and FASTb work. Methods: A randomized controlled trial (RCT) will be carried out. Participants (N = 200) will be randomly assigned to FASTb (n = 100) or FASTr (n = 100). Data collection will consist of self-report questionnaires and case file analysis, and include a pre-test at the start of the intervention, a post-test immediately after the intervention, and a six month follow-up. Mechanisms of change will be investigated using monthly questionnaires of key variables during treatment. Official recidivism data will be collected at two-year follow-up. Discussion: This study aims to improve the effectiveness and quality of forensic mental health care for juveniles with antisocial behavior by studying the effectiveness of blended care, which has not been studied before in treatment of externalizing behavior. If found to be at least as effective as face-to-face treatment, blended treatment can help meet the urgent need for more flexible and efficient interventions in this field. In addition, the proposed study aims to unravel what works for whom, knowledge urgently needed in mental health care for juveniles with severe antisocial behavior. Trial registration: This trial was registered at ClinicalTrials.gov on 07/11/2022, registration number NCT05606978

Breaking the chains? The effects of training a shelter dog in prison on criminal behavior and recidivism

The effectiveness of Dutch Cell Dogs (DCD), a prison-based dog training program, in reducing criminal behavior and recidivism was assessed in a quasi-experimental study in twelve correctional facilities in the Netherlands (N = 241). DCD is a program in which incarcerated offenders train a shelter dog bi-weekly for eight weeks. Results demonstrated that DCD (n = 121) did not outperform treatment-as-usual (TAU; n = 120) in official recidivism outcomes and self-reported criminal behavior. However, subgroups based on age and detainees’ functioning responded differently in self-reported criminal behavior. Positive effects were found on self-reported criminal behavior for DCD participants who were older, had lower callous-unemotional traits, or had higher treatment motivation. In conclusion, findings provided initial evidence that subgroups may respond differently to a dog training program, however, more experimental research with larger sample sizes is needed

Alcohol use of immigrant youths in The Netherlands: The roles of parents and peers across different ethnic backgrounds

Contains fulltext : 179083.pdf (publisher's version ) (Closed access)Introduction and Aims. The aims of this study were to examine the roles of parental permissiveness toward alcohol use and affiliation with alcohol-using peers in alcohol use in youths from various ethnic backgrounds, and whether the role of peers was moderated by parental permissiveness. In addition, differences in these associations between native Dutch and non-Western immigrant youths were examined. Design and Methods. Cross-sectional data of 578 youths with Surinamese, Moroccan, Turkish, Antillean and Asian backgrounds and 81 native Dutch were used, all aged 15-24. Alcohol use, affiliation with alcohol-using peers and parental permissiveness were measured using self-report questionnaires. Regression models controlled for age, religiousness, education level and parental alcohol use. Because of very low levels of alcohol use, data from Turkish and Moroccan immigrants were aggregated, and logistic regression analyses were performed. Results. Parental permissiveness and affiliation with alcohol-using peers were positively related to level of alcohol use in youths with Surinamese, Antillean and Asian backgrounds and played an equally strong role in native Dutch youths with one exception. In Surinamese youths, parental permissiveness was more strongly related to alcohol use than in native Dutch youths. In youths with a Turkish/Moroccan background, parental permissiveness and affiliation with alcohol-using peers were strongly associated with any (versus no) alcohol use. Only parental permissiveness was, equally strong, associated with any alcohol use in native Dutch youths. Discussion and Conclusions. Irrespective of ethnic background and differences in level of alcohol use, parental permissiveness and affiliation with alcohol-using peers are related to youth alcohol use.8 p

The Effectiveness of School-Based Skills-Training Programs Reducing Performance or Social Anxiety: Two Randomized Controlled Trials

Background: Given that high levels of stress during adolescence are associated with negative consequences, it is important that adolescents with psychological needs are supported at an early stage, for instance with interventions at school. However, knowledge about the potential of school-based programs targeting adolescents with psychological needs, aimed at reducing school or social stress, is lacking. Objective: The current study aimed to investigate the effectiveness of two targeted school-based skills-training programs, addressing either skills to deal with performance anxiety or social skills. Methods: Two randomized controlled trials were performed with participants who self-selected to one of the programs. The sample comprised of N = 361 adolescents (Mage = 13.99 years, SD = 0.83) from various educational levels and ethnic identity backgrounds. The performance anxiety program included N = 196 participants (N = 95 in the experimental group), while the social skills program included N = 165 participants (N = 86 in the experimental group). MANCOVA’s were performed. Results: The performance anxiety program had a small effect on reducing adolescents’ test anxiety. Furthermore, for adolescents who attended more than half of the sessions, the program had small effects on reducing test anxiety and fear of failure. The program did not improve adolescents’ coping skills or mental health. The social skills program was not effective in improving social skills, social anxiety, and mental health. Conclusions: A relatively short, targeted program addressing skills to deal with performance anxiety can have the potential to reduce adolescents’ performance anxiety. Trial registration: International Clinical Trials Registry Platform (Netherlands Trial Register, number NTR7680). Registered 12 December 2018. Study protocol van Loon et al., (2019)

Hypercholesterolemia in young adult APOE−/− mice alters epidermal lipid composition and impairs barrier function

Long-term exposure to hypercholesterolemia induces the development of skin xanthoma's characterized by the accumulation of lipid-laden foam cells in humans and in mice. Early skin changes in response to hypercholesterolemia are however unknown. In this study, we investigated the skin lipid composition and associated barrier function in young adult low-density lipoprotein receptor knockout (LDLR−/−) and apolipoprotein E knockout (APOE−/−) mice, two commonly used hypercholesterolemic mouse models characterized by the accumulation of apolipoprotein B containing lipoproteins. No effects were observed on cholesterol content in the epidermis in LDLR−/− mice nor in the more extremely hypercholesterolemic APOE−/− mice. Interestingly, the free fatty acids in the APOE−/− epidermis shifted towards shorter and unsaturated chains. Genes involved in the synthesis of cholesterol and fatty acids were downregulated in APOE−/− skin suggesting a compensation for the higher influx of plasma lipids, most probably as cholesteryl esters. Importantly, in vivo transepidermal water loss and permeability studies with murine lipid model membranes revealed that the lipid composition of the APOE−/− skin resulted in a reduced skin barrier function. In conclusion, severe hypercholesterolemia associated with increased apolipoprotein B containing lipoproteins affects the epidermal lipid composition and its protective barrier.Biopharmaceutic

The effectiveness of Forensic Outpatient Systemic Therapy in the treatment of juvenile antisocial behavior: A study protocol of a Multiple Case Experimental Design

Background Juvenile antisocial behavior can have long-lasting and devastating effects for juveniles themselves, victims, and society. Evidence-based treatment is vital. Forensic Outpatient Systemic Therapy (Forensische Ambulante Systeem Therapie; FAST) is a promising treatment for juveniles showing severe antisocial behavior including aggression, (domestic) violence, and delinquent behavior. FAST has a flexible intensity and length, addresses individual and systemic risk and protective factors, and is responsive to the abilities of the client (system), intervention characteristics all considered crucial for effective treatment. The current study will investigate whether FAST is effective in reducing aggression of the juvenile, reaching client formulated subgoals, and improving family functioning. Processes of change will be examined, as well as mediation by reaching client formulated subgoals and improved family functioning. Methods A Multiple Case Experimental Design (MCED) with an ABC design will be performed (A = baseline, B = intervention, and C = follow-up). Juveniles with primary aggression and/or anger problems (N = 15) and their caregiver(s) will be recruited. Data collection will consist of self-report questionnaires and case file analysis. Participants fill out frequent short self-report questionnaires (twice a week during phase A, every other week during phase B, and every week during phase C) and two main questionnaires at the start of the intervention and immediately after intervention end, thereby covering a period of 5 to 11 months. Both visual and statistical analyses will be performed. Discussion This study will generate robust knowledge and inform clinical practice on the effectiveness, processes of change, and mediating mechanisms of FAST, aiming to improve the treatment of future families within youth forensic care. Trial registration This trial was registered at ClinicalTrials.gov on 28/08/2023, protocol ID 60-63600-98-1138a

Needs of Youth and Parents From Multi-Problem Families in the Search for Youth-Initiated Mentors

Youth-initiated mentoring is an innovative youth care approach in which youth recruit supportive adults from their social networks as a mentor for youth and a partner for parents and professionals. This qualitative interview study documents what youth (n = 15) and parents (n = 13) from multi-problem families look for in a mentor, what mentors (n = 8) believe they have to offer, and whether what mentors believe to offer matches youth’s and parents’ needs. Youth and parents indicated that a strong connection and trust were most important, or even prerequisites, as youth who were unable to find mentors did not have strong relationships of trust. Youth and parents also voiced preferences for an understanding, sensitive mentor who offered youth perspective by providing support and advice and (according to some) setting rules. What mentors believed to offer matched youth’s and parents’ needs, suggesting that most youth successfully recruited suitable mentors