Search

Abstract The enzymes performing protein post-translational modifications (PTMs) form a critical post-translational regulatory circuitry that orchestrates literally all cellular processes in the organism. In particular, the balance between cellular stemness and differentiation is crucial for the development of multicellular organisms. Importantly, the fine-tuning of this balance on the genetic level is largely mediated by specific PTMs of histones including lysine methylation. Lysine methylation is carried out by special enzymes (lysine methyltransferases) that transfer the methyl group from S-adenosyl-L-methionine to the lysine residues of protein substrates. Set7/9 is one of the exemplary protein methyltransferases that however, has not been fully studied yet. It was originally discovered as histone H3 lysine 4-specific methyltransferase, which later was shown to methylate a number of non-histone proteins that are crucial regulators of stemness and differentiation, including p53, pRb, YAP, DNMT1, SOX2, FOXO3, and others. In this review we summarize the information available to date on the role of Set7/9 in cellular differentiation and tissue development during embryogenesis and in adult organisms. Finally, we highlight and discuss the role of Set7/9 in pathological processes associated with aberrant cellular differentiation and self-renewal, including the formation of cancer stem cells.

Abstract Background Cases of mpox have been reported worldwide since May 2022. Limited knowledge exists regarding the long-term course of this disease. To assess sequelae in terms of scarring and quality of life (QoL) in mpox patients 4–6 months after initial infection. Methods Prospective observational study on clinical characteristics and symptoms of patients with polymerase chain reaction (PCR)-confirmed mpox, including both outpatients and inpatients. Follow-up visits were conducted at 4–6 months, assessing the Patient and Observer Scar Assessment Scale (POSAS), the Dermatology Life Quality Index (DLQI) and sexual impairment, using a numeric rating scale (NRS) from 0 to 10. Results Forty-three patients, age range 19–64 years, 41 men (all identifying as MSM) and 2 women, were included. Upon diagnosis, skin or mucosal lesions were present in 93.0% of cases, with 73.3% reporting pain (median intensity: 8, Q1-Q3: 6–10). Anal involvement resulted in a significantly higher frequency of pain than genital lesions (RR: 3.60, 95%-CI: 1.48–8.74). Inpatient treatment due to pain, superinfection, abscess or other indications was required in 20 patients (46.5%). After 4–6 months, most patients did not have significant limitations, scars or pain. However, compared to patients without such complications, patients with superinfection or abscess during the acute phase had significantly more extensive scar formation (median PSAS: 24.0 vs. 11.0, p = 0.039) and experienced a significantly greater impairment of their QoL (median DLQI: 2.0 vs. 0.0, p = 0.036) and sexuality (median NRS: 5.0 vs. 0.0, p = 0.017). Conclusion We observed a wide range of clinical mpox manifestations, with some patients experiencing significant pain and requiring hospitalization. After 4–6 months, most patients recovered without significant sequelae, but those with abscesses or superinfections during the initial infection experienced a significant reduction in QoL and sexuality. Adequate treatment, including antiseptic and antibiotic therapy during the acute phase, may help prevent such complications, and hence, improve long-term outcomes.

Abstract Background Dermatology teaching is fundamental for the promotion of young colleagues in our specialty. However, traditional teaching methods are being scrutinized by students of the ‘Generation Y and Z’, which can pose new challenges for teaching institutions. We therefore aimed to assess the motivational impact and reception of a newly created four-week curriculum containing modernized teaching methods integrated into clinical routine. Methods In this single-center study, 67 medical students completed this curriculum composed of weekly learning objectives including knowledge of morphological terms, 10 common dermatoses, communication and presentation skills. The participants provided information on their level of interest in dermatology each week as well as positive and negative aspects of the curriculum. Results During the curriculum a significant median increase in interest in dermatology was reported with no differences between the genders. Low initial interest could be improved, high initial interest maintained. Participants with an interest in scientific work (20.9%) were more motivated during the curriculum. The variety, quality of teaching and structure were the main aspects rated positively. Suggestions for improvement included the need for more teaching by senior doctors, transfer of responsibility, and a working environment updated to the latest technology standards. Conclusion The presented curriculum was well received by the participants and allowed to better define learning preferences of new generations which can be helpful to modernize traditional teaching methods. Interest in scientific work could be a factor to identify students with a particularly strong interest in dermatology.

Abstract Background This study examined whether the effects of a sit-stand desk (SSD) intervention on employees’ musculoskeletal complaints (i.e., intensity and prevalence) and activation (i.e., vigilance and vitality) persist or fade out and whether velocity and acceleration of health improvements can predict medium-term (six-month) and long-term (24-month) improvements. Drawing from dynamic models of self-regulation, as well as the psychological momentum theory, we hypothesized that velocity and acceleration of health improvements in the early stages of the intervention would predict medium-term health improvements, which sustain long-term. Methods We used data from a six-month seven-wave randomized controlled trial with employees in mostly sedentary occupations and supplemented this by follow-up data from the same participants 18 months later, resulting in eight waves. Results Bayesian structural equational modeling revealed no significant intervention effect after 24 months implying a fade-out. But more importantly, velocity and, partially, acceleration of health improvements at earlier stages predicted medium-term improvements in musculoskeletal complaints and long-term improvements in vigilance. Conclusion The findings of this study suggest that positive intervention effects fade out over time and health effects benefit from prompt progresses at the beginning of the intervention, warranting exploration in prolonged longitudinal studies.

Abstract Background Interest in the assessment of patient satisfaction with in-patient psychiatric treatment has steadily increased and several measurement tools are available for the quantification of patients’ experience. However, they are often uni-dimensional or focus mainly on therapeutic relationship and environment, and neglect other important issues such as information about treatment and participation. The BEST questionnaires were developed as comprehensive instruments that include items on all of the mentioned topics. The present study evaluates the psychometric properties of the BEST in a version for adolescents and for parents. Furthermore, the dimensionality of the satisfaction ratings is analyzed. Method Descriptive statistics were applied to data of 1582 adolescents (mean age = 15.0 years, SD = 1.65; 62.4% female) and 1998 parents/guardians assessed in seven in-patient units across Germany. The factorial structure of the BEST questionnaires was determined by exploratory and confirmatory factor analyses, including a bifactor model. Results The psychometric quality of the scales was strong. Correlations with another assessment instrument of patient satisfaction were good to high, indicating good convergent validity. Exploratory factor analyses revealed three factors in adolescents that were labelled as: Therapeutic relationship, environment, and general satisfaction and treatment success. For parents, the same three factors could be distinguished. Confirmatory bifactor models suggested that the vast majority of variance was accounted for by the general factor; the three specific factors provided some additional information. Agreement between the subscales of adolescents and their parents was only moderate. Parents were usually more satisfied. Conclusions The BEST questionnaires can be considered as reliable and valid instruments to not only assess the “classical” aspects of patient satisfaction, but to also assess newer fundamental topics such as children’s rights and treatment participation. For scientific usage, the total score seems superior because of the high explained variance by the general factor, but the subscale scores provide further information. The use of single items seems advantageous for quality management purposes.

Abstract Background With the “Artemis”-mission mankind will return to the Moon by 2024. Prolonged periods in space will not only present physical and psychological challenges to the astronauts, but also pose risks concerning the medical treatment capabilities of the crew. So far, no guideline exists for the treatment of severe medical emergencies in microgravity. We, as a international group of researchers related to the field of aerospace medicine and critical care, took on the challenge and developed a an evidence-based guideline for the arguably most severe medical emergency – cardiac arrest. Methods After the creation of said international group, PICO questions regarding the topic cardiopulmonary resuscitation in microgravity were developed to guide the systematic literature research. Afterwards a precise search strategy was compiled which was then applied to “MEDLINE”. Four thousand one hundred sixty-five findings were retrieved and consecutively screened by at least 2 reviewers. This led to 88 original publications that were acquired in full-text version and then critically appraised using the GRADE methodology. Those studies formed to basis for the guideline recommendations that were designed by at least 2 experts on the given field. Afterwards those recommendations were subject to a consensus finding process according to the DELPHI-methodology. Results We recommend a differentiated approach to CPR in microgravity with a division into basic life support (BLS) and advanced life support (ALS) similar to the Earth-based guidelines. In immediate BLS, the chest compression method of choice is the Evetts-Russomano method (ER), whereas in an ALS scenario, with the patient being restrained on the Crew Medical Restraint System, the handstand method (HS) should be applied. Airway management should only be performed if at least two rescuers are present and the patient has been restrained. A supraglottic airway device should be used for airway management where crew members untrained in tracheal intubation (TI) are involved. Discussion CPR in microgravity is feasible and should be applied according to the Earth-based guidelines of the AHA/ERC in relation to fundamental statements, like urgent recognition and action, focus on high-quality chest compressions, compression depth and compression-ventilation ratio. However, the special circumstances presented by microgravity and spaceflight must be considered concerning central points such as rescuer position and methods for the performance of chest compressions, airway management and defibrillation.

Abstract Background To improve national influenza vaccination recommendations, additional data on influenza A and B virus circulation are needed. Here, we describe the circulation of influenza A and B in the Czech Republic during 16 seasons. Methods This was a retrospective analysis of data collected from the 2000–2001 to 2015–2016 influenza seasons by the Czech Republic national influenza surveillance network. Influenza was confirmed and viral isolates subtyped by virological assays followed by antigen detection or by reverse transcriptase-polymerase chain reaction. Results Of 16,940 samples collected, 5144 (30.4%) were influenza-positive. Influenza A represented 78.6% of positive cases overall and accounted for more than 55.0% of all influenza cases in every season, except for 2005–2006 (6.0%). Both A/H1N1 and A/H3N2 were detected in most seasons, except for 2001–2002 and 2003–2004 (only A/H3N2), and 2007–2008 and 2009–2010 (only A/H1N1). Influenza B represented 21.4% of positive cases overall (range, 0.0–94.0% per season). Both influenza B lineages were detected in three seasons, a single B lineage in 11, and no B strain in two. For the 11 seasons where influenza B accounted for ≥20% of positive cases, the dominant lineage was Yamagata in six and Victoria in four. In the remaining season, the two lineages co-circulated. For two seasons (2005–2006 and 2007–2008), the B lineage in the trivalent influenza vaccine did not match the dominant circulating B lineage. Conclusions In the Czech Republic, during the 2000–2001 to 2015–2016 influenza seasons, influenza virus circulation varied considerably. Although influenza A accounted for the most cases in almost all seasons, influenza B made a substantial, sometimes dominant, contribution to influenza disease.

Abstract Background Most psychiatric disorders in childhood and adolescence cause impairment in academic performance. Early interventions in school are thought to reduce the burden of disorder and prevent chronicity of disorder, while a delay in reachable help may result in more severe symptoms upon first time presentation, often then causing upon first-time presentation immediate need of inpatient care. Methods The study aims at reducing hospitalization rates and increasing social participation and quality of life among children and adolescents by establishing collaborations between schools, mental health care services and youth welfare services. CCSchool offers children and adolescents, aged six to 18 years, who present with psychiatric problems associated to school problems, a standardized screening and diagnostic procedure as well as treatment in school if necessary. Students can participate in CCSchool in three federal states of Germany if they a) show symptoms vindicating a mental health diagnosis, b) present with confirmed school problems and c) have a level of general functioning below 70 on the children global assessment of Functioning (C-GAF). Intervention takes place in three steps: module A (expected n = 901, according to power calculation) with standardized diagnostic procedures; module B (expected n = 428) implies a school-based assessment followed by a first intervention; module C (expected n = 103) offering school-based interventions with either four to six sessions (basic, 80% of patients) or eight to 12 sessions (intensive, 20% of patients). Primary aim is to evaluate the effectiveness of CCSchool, in reducing the need of hospitalization in children with mental health problems. The analyses will be conducted by an independent institute using mainly data collected from patients and their caregivers during study participation. Additionally, claims data from statutory health insurances will be analysed. Relevant confounders will be controlled in all analyses. Discussion Evaluation may show if CCSchool can prevent hospitalizations, enhance social participation and improve quality of life of children and adolescents with mental health problems by providing early accessible interventions in the school setting. Trial registration Deutsches Register Klinischer Studien, Trial registration number: DRKS00014838, registered on 6th of June 2018.

Abstract Background Integrating demography and adaptive evolution is pivotal to understanding the evolutionary history and conservation of great apes. However, little is known about the adaptive evolution of our closest relatives, in particular if and to what extent adaptions to environmental differences have occurred. Here, we used whole-genome sequencing data from critically endangered orangutans from North Sumatra (Pongo abelii) and Borneo (P. pygmaeus) to investigate adaptive responses of each species to environmental differences during the Pleistocene. Results Taking into account the markedly disparate demographic histories of each species after their split ~ 1 Ma ago, we show that persistent environmental differences on each island had a strong impact on the adaptive evolution of the genus Pongo. Across a range of tests for positive selection, we find a consistent pattern of between-island and species differences. In the more productive Sumatran environment, the most notable signals of positive selection involve genes linked to brain and neuronal development, learning, and glucose metabolism. On Borneo, however, positive selection comprised genes involved in lipid metabolism, as well as cardiac and muscle activities. Conclusions We find strikingly different sets of genes appearing to have evolved under strong positive selection in each species. In Sumatran orangutans, selection patterns were congruent with well-documented cognitive and behavioral differences between the species, such as a larger and more complex cultural repertoire and higher degrees of sociality. However, in Bornean orangutans, selective responses to fluctuating environmental conditions appear to have produced physiological adaptations to generally lower and temporally more unpredictable food supplies.

Abstract Background Molecular taxonomy studies and barcoding projects can provide rapid means of detecting cryptic diversity. Nevertheless, the use of molecular data for species delimitation should be undertaken with caution. Especially the single-gene approaches are linked with certain pitfalls for taxonomical inference. In the present study, recent and historical species descriptions based upon morphology were used as primary species hypotheses, which were then evaluated with molecular data (including in type and historical museum material) to form secondary species hypotheses. As an example of cryptic diversity and taxonomic controversy, the European Phoxinus phoxinus species complex was used. Results The results of the revision showed that of the fourteen primary species hypotheses, three were rejected, namely P. ketmaieri, P. likai, and P. apollonicus. For three species (P. strandjae, P. strymonicus, P. morella), further investigation with increased data sampling was suggested, while two primary hypotheses, P. bigerri and P. colchicus, were supported as secondary species hypotheses. Finally, six of the primary species hypotheses (P. phoxinus, P. lumaireul, P. karsticus, P. septimanae, P. marsilii and P. csikii) were well supported by mitochondrial but only limitedly corroborated by nuclear data analysis. Conclusion The approach has proven useful for revision of species complexes, and the study can serve as an overview of the Phoxinus genus in Europe, as well as a solid basis for further work.