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Men and women differ substantially regarding height, weight, and body fat. Interestingly, previous work detecting genetic effects for waist-to-hip ratio, to assess body fat distribution, has found that many of these showed sex-differences. However, systematic searches for sex-differences in genetic effects have not yet been conducted. Therefore, we undertook a genome-wide search for sexually dimorphic genetic effects for anthropometric traits including 133,723 individuals in a large meta-analysis and followed promising variants in further 137,052 individuals, including a total of 94 studies. We identified seven loci with significant sex-difference including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were significant in women, but not in men. Of interest is that sex-difference was only observed for waist phenotypes, but not for height or body-mass-index. We found no evidence for sex-differences with opposite effect direction for men and women. The PPARG locus is of specific interest due to its link to diabetes genetics and therapy. Our findings demonstrate the importance of investigating sex differences, which may lead to a better understanding of disease mechanisms with a potential relevance to treatment options.
Dieser Artikel beschreibt die Inverted-Classroom-Methode(ICM) im Sinne einer Einführung in die Thematik und soll als Praxisleitleitfaden für diejenigen dienen, die diese Methode in der medizinischen Aus-, Fort- und Weiterbildung einsetzen möchten. Es handelt sich bei der ICM um einen Blended-Learning-Methode, bei dem eine Selbstlernphase (individuelle Phase) vor die Präsenzunterrichtsphase gesetzt wird. In der Online-Phase wird Faktenwissen vermittelt, das als Grundlage für die Präsenzphase dient. Die Präsenzphase soll anschließend dafür genutzt werden, das erlernte Wissen zu vertiefen und anzuwenden. Dem gegenüber stehen die traditionellen Kurskonzepte, in denen das Faktenwissen beispielsweise in Vorlesungen oder in anderen Präsenzunterricht-Formaten vermittelt wird und die Vertiefung dieses Wissens durch die Studierenden im Anschluss daran im Selbststudium stattfinden soll. Das Ziel der ICM ist die Verschiebung des passiven Lernens hin zum aktivierenden Lernen, um das Lernen auf kognitiv anspruchvollen Ebenen wie Analyse, Synthese und Evaluation zu unterstützen. Dabei haben die gestiegene Produktion und Nutzung von Screencasts und Lernvideos, die „Bewegung“ der „Open Educational Resources“ und die verbreitete Nutzung von „Massive Open Online Courses“ (MOOCs) zu einer gestiegenen Verbreitung der Inverted-Classroom-Methode beigetragen. Der Artikel soll als Einführung in die Thematik dienen und dabei eine kurze Übersicht über wichtige Projekte und Forschungsergebnisse in der medizinischen Ausbildung und in weiteren Gesundheitsberufen geben. Außerdem werden die Vor- und Nachteile der Methode und ihr potentieller Nutzen für die zukünftige medizinische Aus- und Weiterbildung dargestellt.
In light of increasing division of labour in healthcare, the training and acquisition of both profession-specific and interprofessional competencies have been attributed growing significance, creating the need to test and establish specific teaching formats. Despite ever more complex and interconnected healthcare systems, an increase in patients’ active self-responsibility and innumerable pedagogical and technological innovations, educational systems have not reacted adequately to these new demands. Many authors, not lease the German Council of Science and Humanities, have therefore urged a rethinking of traditional medical education. Student-centred learning activities, such as problem-based and research-based learning, are becoming increasingly significant in view of the numbers of students achieving unsatisfactory levels of competence in critical thinking, communication and writing abilities and complex clinical decision making, for example. The Council of Science and Humanities arrived at a positive evaluation of the various model and reformed courses of study attempting to effectuate a comprehensive reorganisation of medical studies in content and structure as well as methods and didactics. The persistent pervasiveness of instructor-centred learning formats is not only to be found in medical education but in all of the health professions. Although alternative teaching and instruction formats have already been designed and their effectiveness deemed positive in empirical evaluation, the lecture remains the most practised means of transmitting knowledge. In its essence, however, learning is not a question of transmitting information but, moreover, a question of processing information. In traditional instruction units, referred to as “chalk and talk classes” by Becker and Watts, the teaching party presents material in the form of a lecture. As appropriate, questions may be permitted or short processing periods for the students may be integrated into the lecture. The knowledge-assimilating and most essential analysis of the lecture’s contents takes place in the subsequent self-instruction phase, in which the student works alone on concrete tasks. It is during the transfer of knowledge conveyed in the lectures, however, that most questions arise. Of further disadvantage in the traditional lecture is the low level of motivation among students to attend lectures as well as their often heterogeneous knowledge. The Inverted Classroom Model seems to be an eligible instrument for greater facilitation of student-centred and interprofessional learning.
Nosological delineation of congenital ocular motor apraxia type Cogan : an observational study
(2016)
Background: The nosological assignment of congenital ocular motor apraxia type Cogan (COMA) is still controversial. While regarded as a distinct entity by some authorities including the Online Mendelian Inheritance in Man catalog of genetic disorders, others consider COMA merely a clinical symptom.
Methods: We performed a retrospective multicenter data collection study with re-evaluation of clinical and neuroimaging data of 21 previously unreported patients (8 female, 13 male, ages ranging from 2 to 24 years) diagnosed as having COMA.
Results: Ocular motor apraxia (OMA) was recognized during the first year of life and confined to horizontal pursuit in all patients. OMA attenuated over the years in most cases, regressed completely in two siblings, and persisted unimproved in one individual. Accompanying clinical features included early onset ataxia in most patients and cognitive impairment with learning disability (n = 6) or intellectual disability (n = 4). Re-evaluation of MRI data sets revealed a hitherto unrecognized molar tooth sign diagnostic for Joubert syndrome in 11 patients, neuroimaging features of Poretti-Boltshauser syndrome in one case and cerebral malformation suspicious of a tubulinopathy in another subject. In the remainder, MRI showed vermian hypo-/dysplasia in 4 and no abnormalities in another 4 patients. There was a strong trend to more severe cognitive impairment in patients with Joubert syndrome compared to those with inconclusive MRI, but otherwise no significant difference in clinical phenotypes between these two groups.
Conclusions: Systematical renewed analysis of neuroimaging data resulted in a diagnostic reappraisal in the majority of patients with early-onset OMA in the cohort reported here. This finding poses a further challenge to the notion of COMA constituting a separate entity and underlines the need for an expert assessment of neuroimaging in children with COMA, especially if they show cognitive impairment.
Objective. We investigated the health-related quality of life (HRQoL) of patients with gastrointestinal stromal tumours (GIST). Methods: In the multicentre PROSa study, the HRQoL of adult GIST patients was assessed between 2017 and 2019 using the European Organisation for Research and Treatment of Cancer HRQoL questionnaire (EORTC QLQ-C30). We performed group comparisons and multivariate linear regressions. Results: Among 130 patients from 13 centres, the mean global HRQoL was 63.3 out of 100 points. Higher sores indicate better HRQoL. The highest restrictions were in emotional, social, role functioning, insomnia, fatigue, and pain. In multivariate linear regression, we found no significant differences between patients receiving tyrosine kinase inhibitor (TKI) treatment and those without TKI treatment as well as between patients treated with curative or with palliative intent. Patients who received multiple lines of TKI treatment had the most restrictions, notably in physical (unstandardized regression coefficient [B] = −15.7), role (B = −25.7), social (B = −18.4), and cognitive functioning (B = −19.7); fatigue (B = 15.93); general health (B = −14.23); and EORTC-sum score (B = −13.82) compared to all other patients. Conclusion: The highest HRQoL restrictions were in GIST patients receiving multiple lines of TKI therapy. Underlying causes need further investigation.
Sarcomas are rare cancers with high heterogeneity in terms of type, location, and treatment. The health-related quality of life (HRQoL) of sarcoma patients has rarely been investigated and is the subject of this analysis. Adult sarcoma patients and survivors were assessed between September 2017 and February 2019 in 39 study centers in Germany using standardized, validated questionnaires (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)). Associated factors were analyzed exploratively using multivariable linear regressions. Among 1113 patients, clinically important limitations and symptoms were most pronounced in emotional (63%, 95% CI 60–66%), physical (60%, 95% CI 57–62%), role functioning (51%, 95% CI 48–54%), and pain (56%, 95% CI 53–59%) and fatigue (51%, 95% CI 48–54%). HRQoL differed between tumor locations with lower extremities performing the worst and sarcoma types with bone sarcoma types being most affected. Additionally, female gender, higher age, lower socioeconomic status, recurrent disease, not being in retirement, comorbidities, and being in treatment were associated with lower HRQoL. Sarcoma patients are severely restricted in their HRQoL, especially in functioning scales. The heterogeneity of sarcomas with regard to type and location is reflected in HRQoL outcomes. During treatment and follow-up, close attention has to be paid to the reintegration of the patients into daily life as well as to their physical abilities and emotional distress.
Objectives: It is known that transition, as a shift of care, marks a vulnerable phase in the adolescents’ lives with an increased risk for non-adherence and allograft failure. Still, the transition process of adolescents and young adults living with a kidney transplant in Germany is not well defined. The present research aims to assess transition-relevant structures for this group of young people. Special attention is paid to the timing of the process.
Setting: In an observational study, we visited 21 departments of paediatric nephrology in Germany. Participants were doctors (n=19), nurses (n=14) and psychosocial staff (n=16) who were responsible for transition in the relevant centres. Structural elements were surveyed using a short questionnaire. The experiential viewpoint was collected by interviews which were transcribedverbatim before thematic analysis was performed.
Results: This study highlights that professionals working within paediatric nephrology in Germany are well aware of the importance of successful transition. Key elements of transitional care are well understood and mutually agreed on. Nonetheless, implementation within daily routine seems challenging, and the absence of written, structured procedures may hamper successful transition.
Conclusions: While professionals aim for an individual timing of transfer based on medical, social, emotional and structural aspects, rigid regulations on transfer age as given by the relevant health authorities add on to the challenge.
Trial registration: number ISRCTN Registry no 22988897; results (phase I) and pre-results (phase II).
The COVID-19 pandemic has caused strains on health systems worldwide disrupting routine hospital services for all non-COVID patients. Within this retrospective study, we analyzed inpatient hospital admissions across 18 German university hospitals during the 2020 lockdown period compared to 2018. Patients admitted to hospital between January 1 and May 31, 2020 and the corresponding periods in 2018 and 2019 were included in this study. Data derived from electronic health records were collected and analyzed using the data integration center infrastructure implemented in the university hospitals that are part of the four consortia funded by the German Medical Informatics Initiative. Admissions were grouped and counted by ICD 10 chapters and specific reasons for treatment at each site. Pooled aggregated data were centrally analyzed with descriptive statistics to compare absolute and relative differences between time periods of different years. The results illustrate how care process adoptions depended on the COVID-19 epidemiological situation and the criticality of the disease. Overall inpatient hospital admissions decreased by 35% in weeks 1 to 4 and by 30.3% in weeks 5 to 8 after the lockdown announcement compared to 2018. Even hospital admissions for critical care conditions such as malignant cancer treatments were reduced. We also noted a high reduction of emergency admissions such as myocardial infarction (38.7%), whereas the reduction in stroke admissions was smaller (19.6%). In contrast, we observed a considerable reduction in admissions for non-critical clinical situations, such as hysterectomies for benign tumors (78.8%) and hip replacements due to arthrosis (82.4%). In summary, our study shows that the university hospital admission rates in Germany were substantially reduced following the national COVID-19 lockdown. These included critical care or emergency conditions in which deferral is expected to impair clinical outcomes. Future studies are needed to delineate how appropriate medical care of critically ill patients can be maintained during a pandemic.
Major mood disorders, which primarily include bipolar disorder and major depressive disorder, are the leading cause of disability worldwide and pose a major challenge in identifying robust risk genes. Here, we present data from independent large-scale clinical data sets (including 29 557 cases and 32 056 controls) revealing brain expressed protocadherin 17 (PCDH17) as a susceptibility gene for major mood disorders. Single-nucleotide polymorphisms (SNPs) spanning the PCDH17 region are significantly associated with major mood disorders; subjects carrying the risk allele showed impaired cognitive abilities, increased vulnerable personality features, decreased amygdala volume and altered amygdala function as compared with non-carriers. The risk allele predicted higher transcriptional levels of PCDH17 mRNA in postmortem brain samples, which is consistent with increased gene expression in patients with bipolar disorder compared with healthy subjects. Further, overexpression of PCDH17 in primary cortical neurons revealed significantly decreased spine density and abnormal dendritic morphology compared with control groups, which again is consistent with the clinical observations of reduced numbers of dendritic spines in the brains of patients with major mood disorders. Given that synaptic spines are dynamic structures which regulate neuronal plasticity and have crucial roles in myriad brain functions, this study reveals a potential underlying biological mechanism of a novel risk gene for major mood disorders involved in synaptic function and related intermediate phenotypes.
Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.
Principal findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10−6) and 14 (IGHV1-67 p = 7.9×10−8) which indexed novel susceptibility loci.
Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.