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Data Monitoring Committees (DMCs) have the important task to protect the safety of current and future patients during the conduct of a clinical study. Unfortunately, their work is often made difficult by voluminous DMC reports that are poorly structured and difficult to digest. In this article, we suggest improved solutions. Starting from a principled approach and building upon previous proposals, we offer concrete and easily understood displays, including related computer code. While leveraging modern tools, the most important is that these displays support the DMC’s workflow in answering the relevant questions of interest. We hope that the adoption of these proposals can ease the task of DMCs, and importantly, lead to better decision-making for the benefit of patients.

Treatment-resistant schizophrenia (TRS) is often accompanied by poor insight and impaired decision-making capacity (DMC), complicating the initiation of clozapine (CLZ) despite clear clinical indications. In Japan, CLZ utilization is markedly lower than in many foreign countries, partly due to concerns about adverse effects, mandatory blood monitoring, and difficulties in obtaining informed consent from patients with impaired DMC. Although CLZ can legally be initiated only with family consent, sustained treatment generally requires the patient's own agreement. Electroconvulsive therapy (ECT) may alleviate acute psychotic symptoms and temporarily improve DMC, thereby enabling informed participation in treatment decisions. A woman in her late thirties with TRS persistently refused CLZ. On readmission, her Clinical Global Impression-Severity (CGI-S) score was 7. Pseudo-TRS was partly ruled out using a long-acting injectable antipsychotic (LAI). Following a multidisciplinary case conference in the psychiatric department and family proxy consent, ECT was initiated during involuntary hospitalization for medical care and protection in accordance with clinical practice recommendations for ECT endorsed by the Japanese Society of Psychiatry and Neurology (JSPN). After three ECT sessions, the patient's DMC improved sufficiently to allow voluntary consent to CLZ initiation. Twelve ECT sessions were administered while CLZ was titrated to 225 mg/day. The CGI-S score improved to 3, no serious adverse events occurred, and she was discharged approximately 120 days after admission with stable outpatient follow-up. This case demonstrates that ECT can function as a capacity-restoring intervention enabling voluntary CLZ initiation in selected TRS patients who initially lack DMC. In the context of low CLZ utilization in Japan, a staged approach combining acute stabilization and pharmacological consolidation may provide a clinically and ethically acceptable pathway when supported by multidisciplinary review and procedural safeguards.

Background: Dyggve–Melchior–Clausen syndrome (DMC) is a rare autosomal recessive skeletal dysplasia characterized by dwarfism, coarse facial features, and intellectual disability. Caused by loss-of-function variants in the DYM gene, which encodes dymeclin, DMC is predominantly reported in consanguineous populations but remains poorly studied in South America. Methods: We report a 21-year-old Ecuadorian male with clinical features suggestive of DMC. Comprehensive clinical, radiological, and genetic evaluations were conducted, including clinical exome sequencing and Sanger sequencing, followed by an in silico analysis to assess the structural and functional consequences of the identified variant. Results: Exome sequencing identified a homozygous c.1878delA (p.Lys626fs) frameshift variant in the DYM gene, which was confirmed by Sanger sequencing as inherited from heterozygous parents. Variants of uncertain significance were detected in other skeletal dysplasia-related genes but did not correlate with the phenotype. A comprehensive review of reported DYM variants was also conducted. Conclusions: This report documents the first case of DMC in Ecuador and the second in South America, expanding the global understanding of DMC’s genetic diversity. It underscores the value of next-generation sequencing in rare disease diagnostics and highlights the critical need for inclusive genomic research in underrepresented populations to improve the understanding of genetic heterogeneity and rare disease epidemiology.

Directed motivational currents, unique and intense goal-directed motivational surges lasting over a period of time, have received increasing attention recently. This article reports the first systematic review of this phenomenon. A total of 21 reports appearing between 2013 and 2020 were included in the analysis. The results show that the majority of empirical reports were small-scale qualitative studies (median = 18 participants). The evidence on the three characteristics proposed as necessary and/or distinguishing conditions of directed motivational currents (vision, salient facilitative structure, and positive affect) is inconclusive due to the presence of directed motivational currents cases not exhibiting these features, and the absence of direct comparative analyses with non-directed motivational currents cases. A few intervention studies (N = 4) were conducted, but their results are also inconclusive due to a number of methodological limitations. Contrary to the claim that directed motivational current experiences are the “optimal form” of motivation, the results additionally showed that these experiences could lead to intense stress, anxiety, depression, sleeplessness, and panic attacks, thereby raising ethical concerns about deliberately inducing directed motivational currents in learners. We conclude that, although the concept of directed motivational currents is promising, more research is needed to reach a better understanding of its potential. We end this article by suggesting directions for future research into directed motivational currents, including renaming them as sustained flow.

Dyggve–Melchior–Clausen (DMC) syndrome is a rare autosomal recessive disorder characterized by the association of a progressive spondyloepimetaphyseal dysplasia and mental retardation ranging from mild to severe. The disorder results from mutations in the dymeclin ( DYM ) gene in the 18q12-12.1 chromosomal region. We report two siblings with classical clinical and radiological features of DMC and asymptomatic atlanto-axial dislocation. A novel homozygous splice-site mutation (IVS15+3G>T) was detected. Reverse transcriptase polymerase chain reaction (RT-PCR) confirmed that this mutation affects normal splicing. To the best of our knowledge, this is the first report of DMC from Saudi Arabia. The splice mutation noted in our patients was compared to the previously reported cases and supports the hypothesis that loss of DYM function is the likely mechanism of disease pathogenesis. In conclusion, distinction between this type of skeletal dysplasia and Morquio disease (MPS IV) is important for paediatricians and clinical geneticist in providing standard patient care and genetic counselling.

Background: Dyggve Melchior Clausen syndrome (DMC) is a severe autosomal recessive skeletal dysplasia associated with mental retardation. Direct sequencing of genomic DNA has identified causative mutations in the gene Dymeclin (chromosome 18q12–21), with the majority predicting the generation of a truncated protein product. Objective: To carry out molecular genetic studies in three DMC kindreds. Results: Two novel nonsense mutations and two complex genomic duplication events resulting in exon repetition were identified. Conclusions: Exon dosage assessment or mRNA analysis, in addition to direct genomic DNA sequencing, should be employed in the investigation of DMC affected individuals. Genomic duplication may be the causative mutation mechanism in other autosomal recessive disorders.