Medizinische Zentrum für Gesundheit

To reduce mental disorder prevalence, the understanding of resilience to stress-related disorder and its neurobiological mechanisms has come into the focus of biomedical research to develop both biologically rooted prevention and innovative therapeutic approaches for stress-related disorder. While some resilience mechanisms have been exemplified on the molecular, cellular, and brain-regional level, evidence on the neural systems level is rather sparse. We present the first translational evidence of adaptive plasticity in visual microcircuits and top-down modulation onto the visual system as a neurobiological resilience mechanism at the neural systems level in both humans and mice. In humans, we demonstrate that this adaptive microcircuit plasticity is linked to interactions between neurocognitive domains—executive and perceptual—and between brain regions—frontal and occipital—in specific oscillatory frequencies (β band in frontal inferior frontal gyrus and γ band in occipital V2). Additionally, expanding upon prior resilience research, our findings offer further evidence that phenotypic resilience is associated not only with macro- and microcircuit plasticity but also with better performance in neurocognitive functions central to resilience, i.e., perceptual discrimination in mice and cognitive control in humans. In mice, using awake 2-photon calcium imaging, we observed distinct resilient and susceptible network phenotypes in mouse visual cortex. Resilient animals surpassed both susceptible animals and nonstressed controls in their ability to encode visual afferents. This suggests an improved performance supporting the concepts of posttraumatic growth and stress inoculation on a neurobiological level. Resilience at the neural systems level involves active, dynamic processes rather than being merely passive responses to stress and constitutes a first example that neural network states of resilience are metastable, self-stabilizing, and noncontinuous entities that could serve as a target for new neural network interventions for fostering resilience.

Genomic sequencing leaves >50% of dystonia-affected individuals without a diagnosis. Where DNA-oriented approaches remain insufficient, integrating multiomics is essential to advance genome interpretation. Herein, we incorporated RNA sequencing (RNA-seq) data from 167 patients with dystonia across a range of ages and presentations. We leveraged an RNA-seq analysis pipeline, focused on the identification of expression and splicing aberrations, on RNA-seq from skin biopsies. The recruited patients had early-onset dystonia in 85.0%, non-focal dystonia in 92.2%, and coexisting features in 76.0%. Thirty-six patient samples with pre-identified variants (36/167, 21.6%) and 131 samples with no previously prioritized diagnostic candidates from genomic sequencing (131/167, 78.4%) were evaluated. We found that >80% of dystonia-associated genes were detected by fibroblast RNA-seq. Expression and splicing aberration analyses produced a manageable number of significant RNA defects affecting dystonia-associated genes. The approach was especially successful in validating pathogenic effects of loss-of-function variants, with disease-relevant RNA-underexpression detected for 66.7% (10/15). Studying aberrant expression and splicing in the context of other pre-identified variant types yielded relevant results in 28.6% (6/21 samples). We obtained a 6.9% (9/131) diagnostic uplift for patients without prior candidates, all of whom exhibited combined dystonia with autosomal recessive inheritance. The new diagnoses from RNA-seq and genomic reanalysis were based on previously neglected splice-region (3/9) and deep(er) intronic (6/9) variants. For the observed events, integration of new machine-learning scores predicted corresponding aberrant gene expression in the brain. Fibroblast-based RNA-seq in our selected cohort improved variant interpretation and offered a modest yield in patients without prior candidate variants. ANN NEUROL 2026.

Zusammenfassung Psychische Erkrankungen gehen für die Betroffenen und ihre Angehörigen mit erheblichen Belastungen und für die Gesellschaft mit besonders hohen Kosten einher. Früherkennung und Frühintervention haben das Potential, die Krankheitsverläufe und die soziale Inklusion der Betroffenen substanziell zu verbessern und die gesellschaftlichen Kosten dramatisch zu reduzieren

Recalled Parental Rearing Behavior is an important factor of socialization and vulnerability. Based on two representative surveys, Recalled Parental Rearing Behavior of fathers and mothers is compared between the eastern and the western German states from the perspectives of men and women in the years of 1994 and 2020. Participants, aged between 14 and 92 years, filled out the standardized Recalled Parental Questionnaire in 1994 (N=2948) and 2020 (N=2503). Results were compared by ANOVA according to time point, East-West-differences, sex and age. According to hypotheses, paternal and maternal rearing behavior was recalled in Germany as less punishing and warmer in 2020 compared to 1994. Parental rearing behavior of fathers and mothers was consistently reported less punishing and warmer in the eastern compared to the western states. Parental overprotection was more strongly recalled in 1994 in the western than the eastern states. As in the case of recalled warmth assessments in both regions converged over time. As in previous surveys, sons recalled their parents in east and west more punishing and less warm than daughters; daughters recalled their mothers only marginally warmer than sons. Older participants recalled parental rearing behavior consistently more negatively than younger ones. In the second survey assessments of the older cohorts were consistently more positive than in the previous survey with comparable age cohorts. Findings are discussed with regard to the impact of sociocultural characteristics on recalled parental rearing behavior under the aspects of cohort and age (e. g., convergence of sociocultural differences in East and West, gender roles, recall effects). On the background of robust associations with mental disorders, positive recollections of parental rearing behavior can be considered an important mental resource, reflecting multiple sociocultural influences and trends.

Zusammenfassung Hintergrund Das Ziel dieses Artikels ist es, die gesundheitlichen Veränderungen während der medizinischen Rehabilitation nach COVID-19 und potenzielle Determinanten für die Fatigue und ihre Genesung darzustellen. Materialien und Methoden Wir berichten quantitative Daten der Kohortenstudie einer multizentrischen Mixed-Methods-Studie. Rehabilitand*innen wurden zu 5 Zeitpunkten zu ihrer Gesundheit und Funktionsfähigkeit befragt und um ihre Zustimmung zur Analyse ihrer Klinikdaten gebeten. Vorliegend wurden die ersten zwei Messzeitpunkte analysiert: Mittels t-Tests und Effektstärken (Cohens d) erfolgte ein Vergleich zwischen Aufnahme (t0) und Entlassung (t1). In einer multiplen linearen Regression wurden mögliche Prädiktoren für die Fatigue und ihren Verlauf überprüft. ErgebnisseFür 267 Rehabilitand*innen lagen Daten für t0 und t1 sowie Klinikdaten vor. Wir fanden Verbesserungen in allen Dimensionen (Dyspnoe, motorische Funktionsfähigkeit, Depressivität, Ängstlichkeit,Lebensqualität und Erwerbsprognose) zum Ende der Rehabilitation. Ein höherer motorischer Funktionsstatus, höhere Lebensqualität, höheres Alter, geringere Depressivität und das männliche Geschlecht sind mit einer geringeren, eine schlechtere Erwerbsprognose mit einer höheren Erschöpfung bei t0 assoziiert. Bei t1 sind eine höhere Lebensqualität und motorische Leistungsfähigkeit mit einer geringeren Fatigue verbunden. Personen mit einer schlechteren Erwerbsprognose bei t0 haben eine stärkere Fatigue bei t1. Schlussfolgerungen Die Fatigue hat eine hohe Relevanz in der Post-COVID-Versorgung. Nur wenige untersuchte Faktoren zeigen während der medizinischen Rehabilitation einen statistischen Zusammenhang mit der Fatigue. Vermutlich existieren unentdeckte Prädiktoren, die weiter untersucht werden sollten, um die rehabilitative Versorgung Post-COVID-Betroffenen zu optimieren.

Effects of a Protein Optimized Diet Combined with Moderate Resistance Training on the Postoperative Course in Older Patients with Hip Fracture

A crucial aspect of a fair allocation of scarce resources in hospital is the close cooperation of hospital executives and physicians. This chapter has three aims. Firstly, it provides an analysis of basic elements of medical and hospital executives' ethics. Secondly, it discusses the role of concepts of justice in hospital decision-making. Thirdly, it reflects on process criteria and structures that might support coping with allocation conflicts in hospitals. While hospital executives mainly act according to economic, legal, and strategic considerations, physicians are traditionally obliged to professional ethics codes. These include patient welfare as the primary concern with economic aspects a secondary priority. Therefore, implementing and applying ethical principles for the allocation of scarce resources requires an ongoing constructive discourse between hospital managers and physicians. Furthermore, in order to build trust between the two stakeholders, an effective structure for solving ethical conflicts and a fair decision-making process is paramount.

Am 1. Februar 2010 ist das Gendiagnostikgesetz (GenDG) in Kraft getreten. Die Debatte um einige Regelungsbereiche, wie beispielsweise das Neugeborenenscreening, reist nicht ab. Ein Aspekt des Gesetzes ist im Rahmen der Debatte um die Praimplantationsdiagnostik (PID) in Deutschland unter neuen Vorzeichen zu diskutieren: Das – international bislang einzigartige – Verbot der pranatalen Diagnostik so genannter spatmanifestierender Erkrankungen, die erst nach der Vollendung des 18. Lebensjahres ausbrechen. In diesem Beitrag mochten wir Hinweise zur differenzierten Diskussion dieser in § 15(2) GenDG bestimmten Verbotsnorm liefern. Obgleich Argumente, insbesondere das Recht auf Nichtwissen des geborenen Kindes, fur ein solches Verbot sprechen, kommen wir aufgrund der medizinischen Sachlage und nach einer Analyse der Pro- und Kontraargumente aus ethischer und rechtlicher Sicht zu dem Schluss, dass ein generelles Verbot der pranatalen Diagnostik spatmanifestierender Erkrankungen im Sinne der Zielsetzung womoglich insuffizient ist sowie in der Begrundung Inkonsistenzen zum bereits bestehenden Regelwerk aufweist, und lenken daher den Blick auf unter Umstanden bessere Alternativen.