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

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

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)

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

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

A large geometric distortion in the first photointermediate of rhodopsin, determined by double-quantum solid-state NMR

Double-quantum magic-angle-spinning NMR experiments were performed on 11,12-C-13(2)-retinylidene-rhodopsin under illumination at low temperature, in order to characterize torsional angle changes at the C11-C12 photoisomerization site. The sample was illuminated in the NMR rotor at low temperature (similar to 120 K) in order to trap the primary photointermediate, bathorhodopsin. The NMR data are consistent with a strong torsional twist of the HCCH moiety at the isomerization site. Although the HCCH torsional twist was determined to be at least 40A degrees, it was not possible to quantify it more closely. The presence of a strong twist is in agreement with previous Raman observations. The energetic implications of this geometric distortion are discussed

Cardiac circRNAs Arise Mainly From Constitutive Exons Rather Than Alternatively Spliced Exons

Circular RNAs (circRNAs) are a relatively new class of RNA molecules, and knowledge about their biogenesis and function is still in its infancy. It was recently shown that alternative splicing underlies the formation of circular RNAs (circRNA) arising from the Titin (TTN) gene. Since the main mechanism by which circRNAs are formed is still unclear, we hypothesized that alternative splicing, and in particular exon skipping, is a major driver of circRNA production. We performed RNA sequencing on human and mouse hearts, mapped alternative splicing events, and overlaid these with expressed circRNAs at exon-level resolution. In addition, we performed RNA sequencing on hearts of Rbm20 KO mice to address how important Rbm20-mediated alternative splicing is in the production of cardiac circRNAs. In human and mouse hearts, we show that cardiac circRNAs are mostly (~90%) produced from constitutive exons and less (~10%) from alternatively spliced exons. In Rbm20 KO hearts, we identified 38 differentially expressed circRNAs of which 12 were produced from the Ttn gene. Even though Ttn appeared the most prominent target of Rbm20 for circularization, we also detected Rbm20-dependent circRNAs arising from other genes including Fan1, Stk39, Xdh, Bcl2l13, and Sorbs1. Interestingly, only Ttn circRNAs seemed to arise from Rbm20-mediated skipped exons. In conclusion, cardiac circRNAs are mostly derived from constitutive exons, suggesting that these circRNAs are generated at the expense of their linear counterpart and that circRNA production impacts the accumulation of the linear mRNA

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