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Background: Entering the Clinical Elective Year (CEY) is a challenging transition phase for undergraduate medical students. Students become members of a professional team, thereby taking over certain tasks, which are executed more or less independently. Factors which facilitate (or impede) this transition in the perception of students are not well described. We therefore wanted to explore, what students perceived to be helpful during the first phase of the CEY and possibly derive respective recommendations.Methods: We conducted semi-structured interviews with 5th year medical students after they had completed the first two months of their CEY. Students were asked which problems they had faced and how they felt prepared for the CEY. Interviews were audio-recorded, transcribed, and analysed by qualitative content analysis. Results: From 34 interviews, we included 28 into analysis. Overall, 24 students were satisfied or very satisfied with their start into the CEY. Satisfaction was expressed with respect to workplace experiences, learning progress, responsibilities and team integration. Especially, students appreciated if they were integrated as active members of the team, were given responsibility for certain units of work, and received well-structured formal teaching and supervision. Students had divergent opinions about the quality of teaching and supervision, about their own achievements, and the recognition they received. Students recommended improvements in respect to formal teaching and supervision by clinical supervisors, preparation of the CEY by university, and supporting structures in the hosting institution. Conclusion: Students in this study were generally satisfied with the first two months of their CEY. Facilitating factors were active and responsible involvement into routine patient care, and high quality formal teaching and supervision. Findings may inform universities, teaching hospitals, and students how to better shape the first phase of the CEY.

Introduction Melanomas exhibit tremendous intratumoral heterogeneity and phenotype plasticity, which allows them to switch between distinctive transcriptional programs in response to external stressors, including targeted therapies (1). These transcriptional phenotypes, [...], Virtually all patients with BRAF-mutant melanoma develop resistance to MAPK inhibitors largely through nonmutational events. Although the epigenetic landscape is shown to be altered in therapy-resistant melanomas and other cancers, a specific targetable epigenetic mechanism has not been validated. Here, we evaluated the corepressor for element 1-silencing transcription factor (CoREST) epigenetic repressor complex and the recently developed bivalent inhibitor corin within the context of melanoma phenotype plasticity and therapeutic resistance. We found that CoREST was a critical mediator of the major distinct melanoma phenotypes and that corin treatment of melanoma cells led to phenotype reprogramming. Global assessment of transcript and chromatin changes conferred by corin revealed specific effects on histone marks connected to epithelial-mesenchymal transition-associated (EMT-associated) transcription factors and the dual-specificity phosphatases (DUSPs). Remarkably, treatment of BRAF inhibitor-resistant (BRAFi-R) melanomas with corin promoted resensitization to BRAFi therapy. DUSP1 was consistently downregulated in BRAFi-R melanomas, which was reversed by corin treatment and associated with inhibition of p38 MAPK activity and resensitization to BRAFi therapies. Moreover, this activity was recapitulated by the p38 MAPK inhibitor BIRB 796. These findings identify the CoREST repressor complex as a central mediator of melanoma phenotype plasticity and resistance to targeted therapy and suggest that CoREST inhibitors may prove beneficial for patients with BRAFi-resistant melanoma.

Introduction: Implantation of minced cartilage is a one-step-procedure that leads to satisfactory results in osteochondral defects. Material and methods: A retrospective review was performed on a consecutive cohort of patients that received minced cartilage with fibrin (MCF), minced cartilage with membrane and fibrin (MCMF) and minced cartilage with the “AutoCart”-procedure (MCAC) between January 2019 and December 2023. Radiological outcome parameters were evaluated via Magnet-Resonance-Tomography (MRI) within one year using Ankle-Osteoarthritis-Scoring-System (AOSS). Results: Final data included 25 patients: 13 women and 12 men with a mean age of 28.2 years ± 10.9(range:18–51). Mean defect size was 103.6mm2 ± 59.0(95% CI = 79.2–128.0), mean depth 5.2 mm ± 3.6(3.7–6.6). Differences between groups in defect sizes were not significant (p = 0.999). MCF was carried out in 9(36.0%), MCMF in 7(28.0%) and MCAC in 9(36.0%) patients. Mean postoperative AOSS values were 2.6 ± 1.9(95%CI:1.1–4.1) for MCF-patients, 3.3 ± 2.9(0.6–5.9) for MCMF patients and 3.9 ± 2.8(1.7–6.1) for MCAC-patients, respectively. Differences were not significant (p = 0.639). Revision surgery because of symptomatic non-integration of the graft or ventral impingement occurred in 5(20%) of cases – all part of MCAC-patients that did not receive additional fibrin fixation as the top layer of transplant (p < 0.05). Conclusions: Autologous minced cartilage implantation seems to be sufficient as a viable, one-step treatment for osteochondral lesions of the talus. It leads to low complication rates and excellent AOSS values within a 12-month period whereas the application of fibrin as the last fixation layer seems to be advisory, which demands further investigation. [ABSTRACT FROM AUTHOR]

Although global life expectancy has increased over the past 20 years due to advancements in managing infectious diseases, one-fifth of people still die from infections. In response to this ongoing threat, significant efforts are underway to develop vaccines and antimicrobial agents. However, pathogens evolve resistance mechanisms, complicating their control. The COVID-19 pandemic has underscored the limitations of focusing solely on the pathogen-killing strategies of immunology and microbiology to address complex, multisystemic infectious diseases. This highlights the urgent need for practical advancements, such as microbiome therapeutics, that address these limitations while complementing traditional approaches. Our review emphasizes key outcomes in the field, including evidence of probiotics reducing disease severity and insights into host-microbiome crosstalk that have informed novel therapeutic strategies. These findings underscore the potential of microbiome-based interventions to promote physiological function alongside existing strategies aimed at enhancing host immune responses and pathogen destruction. This narrative review explores microbiome therapeutics as next-generation treatments for infectious diseases, focusing on the application of probiotics and their role in host-microbiome interactions. While offering a novel perspective grounded in a cooperative defense system, this review also addresses the practical challenges and limitations in translating these advancements into clinical settings. [ABSTRACT FROM AUTHOR]

OBJECTIVESFirst to determine the proportion of incompletely excised basal cell carcinomas (BCCs) treated by conventional excision by dermatologists, plastic surgeons and general practitioners. Second to identify characteristics of incomplete excised BCCs.METHODSAnalysis of pathology reports of 3005 primary BCC excisions by general practitioners (31%), dermatologists (34%) and plastic surgeons (35%) from an urbanized area in the South West of the Netherlands from 2008-2014. Chi-square test and independent T-tests were used to analyze the primary outcome. Logistic regression was used to determine the odds ratio for incomplete excision in the groups corrected for patients age, patients sex, site, size, subtype and specialism.OUTCOME MEASURESProportion of incompletely excised BCC per specialism, age and sex of patients, anatomical site, excision size (as a proxy for BCC size), and subtype.RESULTSDermatologists had a complete excision rate of 93.24%, plastic surgeons 83.33% and general practitioners 69.61% (p

Facioscapulohumeral muscular dystrophy (FSHD) is an inherited myopathy, characterized by progressive and asymmetric muscle atrophy, primarily affecting muscles of the face, shoulder girdle, and upper arms before affecting muscles of the lower extremities with age and greater disease severity. FSHD is a disabling condition, and patients may also present with various extramuscular symptoms. FSHD is caused by the aberrant expression of double homeobox 4 (DUX4) in skeletal muscle, arising from compromised epigenetic repression of the D4Z4 array. DUX4 encodes the DUX4 protein, a transcription factor that activates myotoxic gene programs to produce the FSHD pathology. Therefore, sequence-specific oligonucleotides aimed at reducing DUX4 levels in patients is a compelling therapeutic approach, and one that has received considerable research interest over the last decade. This review aims to describe the current preclinical landscape of oligonucleotide therapies for FSHD. This includes outlining the mechanism of action of each therapy and summarizing the preclinical results obtained regarding their efficacy in cellular and/or murine disease models. The scope of this review is limited to oligonucleotide-based therapies that inhibit the DUX4 gene, mRNA, or protein in a way that does not involve gene editing. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC), with its increasing prevalence globally, is emerging as a major health challenge. Hepatocellular carcinoma cells exhibit both significant homogeneity and heterogeneity, governed by complex epigenomic regulations. Recently, numerous single‐cell unimodal techniques have been used to study HCC at various levelswhich have already revealed a complex interplay at genomic, transcriptomic, spatial and epigenomic levels. However, the use of single‐cell multimodal techniques combining different unimodal layers in HCC remains quite limited, necessitating further studies focusing on these methods to uncover novel markers, and mechanisms at epigenetic levels. In this commentary, we highlight how integrating multimodal approaches with epigenetic modifications can provide new insights into HCC and foster future therapeutic advancements. [ABSTRACT FROM AUTHOR]