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Zusammenfassung  Die depressive Störung gehört zu den häufigsten und schwerwiegendsten psychischen Erkrankungen. Trotz eines starken genetischen Einflusses blieb die Suche nach Kandidatengenen bisher von begrenztem Erfolg. Im Kontext komplexer, polygenetischer Erbgänge und heterogener, klinisch definierter Phänotypen wie der depressiven Störung scheint der Endophänotypansatz Erfolg versprechender zu sein. Die Entdeckung, dass eine genetische Risikovariante für Depressionen im Serotonintransportergen (5-HTTLPR) mit einer verstärkten Amygdalareaktivität auf aversive Reize assoziiert ist, legte den Grundstein für das Forschungsgebiet „imaging genetics“, welches durch die Wahl neurobiologischer Aktivierungsmuster als Endophänotyp charakterisiert ist. In der vorliegenden Übersicht werden bisherige Ergebnisse aus diesem rapide wachsenden Forschungsbereich diskutiert, wobei vor allem genetische Effekte auf die Funktion kortikolimbischer Netzwerke bei der Emotionsverarbeitung betrachtet werden. Es zeigt sich, dass mögliche Risikogenvarianten auch bei Gesunden zu funktionellen Veränderungen führen, die mit den Befunden bei depressiven Patienten vergleichbar sind. [ABSTRACT FROM AUTHOR]

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Zusammenfassung Das Erwerben von manuellen Fertigkeiten ist mit einer Lern- und Risikokurve verbunden. Zur Erzeugung von Lernkurven stehen verschiedene Techniken zur Verfügung: 1. Einfache graphische Aufzeichnungen der kumulierten Fehler, 2. das Generieren einer Lernkurve auf Basis eines binären Erfolgskriteriums mit einem Fit-Modell, 3. die sog.Kusum-Technik. Lernkurven ermöglichen es für das Erlangen einer kompetenten Anwendung einer manuellen Technik die notwendigen Fallzahlen zu bestimmen und entsprechend Trainingsprogramme auf eine rationale Basis zu stellen. Manuelle Fähigkeiten sind unterschiedlich schwer zu erwerben. Die institutionelle Umgebung beeinflusst die Lerngeschwindigkeit mit verschiedenen Faktoren. Lernkurven können dazu dienen, das individuelle Lernen und die Lernumgebung auch bei Verbesserungsmaßnahmen zu überprüfen. Allerdings ist nicht nur die technische Fertigkeit für eine sichere Anwendung von manuellen Verfahren erforderlich, sondern auch eine umfassende fachliche Kompetenz. Abstract Assessment in anaesthesia traditionally takes the form of written papers and oral examinations. These are important for assessing trainee''s knowledge and judgement, but do not test for competency in practical skills, which is essential for successful clinical practice. The presence of learning curves for practical skills in anaesthesia is now well recognized and they are useful tools to monitor a learning process. From these, estimates of the number of procedures that must be performed by trainees in order to reach an acceptable success rate can be produced. It is clear that these figures give some help for the rational design of training programs, however, numbers alone do not provide a sufficient basis to declare a trainee competent for a given procedure. Not only technical skills need to be taught, but also decisionmaking and even more important behavioral skills. In clinical practice there are often problems in providing all the necessary training on patients and by this reorganization of residency programs may be necessary. However, the role of medical simulation in the assessment of anesthetists in training is still unclear, and the introduction of simulator-based tests may be premature. [ABSTRACT FROM AUTHOR]

Field observations were made on the fl ower visiting behaviour of honeybee foragers in commercial fruit plantations of apricot, Japanese plums, sour cherry, apple and pear. The number of inspected cultivars was 18. The intensity of fl ower visiting by honey bees was markedly different when data of different fruit species are compared. Most intense bee activity was registered on the Japanese plums, somewhat less on apricots, the intensity diminished signifi cantly with apples and pears. Our data presented on the honeybee visitation of Japanese plums can be regarded as new fi nding because no information has been available so far on the relative attractiveness of this fruit species compared to European fruit tree species. Japanese plums were somewhat more attractive to honeybees than apricot and much more attractive than sour cherry, apple and pear. The behaviour of honeybees as visiting the blooming trees displayed specifi c differences according to the fruit species (apricot, sour cherry, pear), which coincide largely with earlier results. It is notable that the fl ower visiting behaviour of honeybees on Japanese plums has been found to be fairly similar to the same on European plums.

The composition of five pear varieties (‘Abate Fètel’, ‘Bosc’, ‘Williams’, ‘Conference’, ‘Packham’s Triumph’) grown in Nagykanizsa was investigated in three consecutive years (2008, 2009, 2010). A storage experiment was performed in 2008. Four winter pear cultivars were kept in an ULO store for four months and their parameters measured after two and four months. The parameters tested were: size, weight, water soluble solids, titratable acidity, glucose, fructose, sucrose, water soluble pectin, total polyphenols, free radical scavenging capacity, copper and zinc content. The fruits of ‘Conference’ and ‘Bosc’ varieties were found to contain the highest sucrose and total sugar content, while ‘Abate Fétel’ had the lowest sucrose and highest glucose levels among cultivars tested. ‘Williams’ pear was the most acidic. Brix, total sugar, sucrose and water soluble pectin were decreased during storage. Titratable acidity slightly decreased in fruits of Conference pear. Polyphenols and free radical scavenging capacity did not show a significant change during storage.

During a four yeas long experiment a simple bee shelterswas found to be a propermethod to increase the size ofmixed natural populations of the early season Osmia cornuta and O. rufa under practical farm conditions. Instead of the number of pesticide applications the earliness of the flowering of the fruit species in the orchards was found to be themost important factor in the rate of acceptance of reed as nestingmediumby Osmias in the bee shelter. This relationship was negative and highly significant (r = –0.829, p

We evaluated 285 pear genotypes (commercial cultivars, ancient local varieties, unnamed local strains, seedlings, wild seedlings) in the largest gene bank of pear in Hungary from the point of view of psylla resistance to explore their possible exploitation in organic farming. We have found some 10 new resistant types (Bókoló körte, Bôtermô Kálmán, Füge alakú körte, Nagyasszony körte, Nyári Kálmán, Rozs nyári körte, Viki körte, Pb-242, Pb-299, 0-632) and 7 highly tolerant ones (Cure-6, Kései Kálmán, Kieffer, Kieffer Éd, Steiner, Téli Kálmán, II. B-3- 6/4, 96-16/5) (Table 1). These made up 3.5 + 2.8 per cent of the investigated genotypes, while 93.7 per cent of them were susceptible to pear psylla damage. Taking earlier and present results into account we can list more than 30 European pear cultivars being resistant or highly tolerant to pear psylla infestation and damage. In fact, the list of resistant and highly tolerant cultivars may serve as a basis selecting pear cultivars fitting to the specific requirements of the organic farming. By the end we can conclude that there is some real hope to exploit some resistant or highly tolerant ancient or local cultivars in organic farming but further investigations are needed to estimate their yield capacity and fruit quality.

Alternative oxidase (AOX) is an enzyme that transfers electrons from reduced quinone directly to oxygen without proton translocation. When AOX from Ciona intestinalis is xenotopically expressed in mice, it can substitute the combined electron-transferring activity of mitochondrial complexes III/IV. Here, we used brain mitochondria from AOX-expressing mice with such a chimeric respiratory chain to study respiratory control bioenergetic mechanisms. AOX expression did not compromise the function of the mammalian respiratory chain at physiological conditions, however the complex IV inhibitor cyanide only partially blocked respiration by AOX-containing mitochondria. The relative fraction of cyanide-insensitive respiration increased at lower temperatures, indicative of a temperature-controlled attenuation of mammalian respiratory enzyme activity. As AOX does not translocate protons, the mitochondrial transmembrane potential in AOX-containing mitochondria was more sensitive to cyanide during succinate oxidation than during malate/pyruvate-supported respiration. High concentrations of cyanide fully collapsed membrane potential during oxidation of either succinate or glycerol 3-phosphate, but not during malate/pyruvate-supported respiration. This confirms AOX's electroneutral redox activity and indicates differences in the proton-translocating capacity of dehydrogenases upstream of the ubiquinone pool. Our respiration data refutes previous proposals for quinone partitioning within the supercomplexes of the respiratory chain, instead supporting the concept of a single homogeneous, freely diffusing quinone pool. Respiration with either succinate or glycerol 3-phosphate promotes reverse electron transfer (RET) towards complex I. AOX expression significantly decreased RET-induced ROS generation, with the effect more pronounced at low temperatures. Inhibitor-sensitivity analysis showed that the AOX-induced decrease in H 2 O 2 release is due to the lower contribution of complex I to net ROS production during RET. Overall, our findings provide new insights into the role of temperature as a mechanism to control respiration and highlight the utility of AOX as a genetic tool to characterize both the distinct pathways of oxygen reduction and the role of redox control in RET., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Mitochondrial bioenergetics in females and males is different. However, whether mitochondria from male and female brains display differences in enzymes of oxidative phosphorylation remains unknown. Therefore, we characterized mitochondrial complexes from the brains of male and female macaques (Macaca mulatta). Cerebral tissue from male macaques exhibits elevated content and activity of mitochondrial complex I (NADH:ubiquinone oxidoreductase) and higher activity of complex II (succinate dehydrogenase) compared to females. No significant differences between sexes were found in the content of α-ketoglutarate dehydrogenase or in the activities of cytochrome c oxidase and F 1 F o ATPase. Our results underscore the need for further investigations to elucidate sex-related mitochondrial differences in humans., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Infants face the constant challenge of selecting information for encoding and storage from a continuous incoming stream of data. Sleep might help in this process by selectively consolidating new memory traces that are likely to be of future relevance. Using a deferred imitation paradigm and an experimental design, we asked whether 15- and 24-month-old infants (N = 105) who slept soon after encoding a televised demonstration of target actions would show higher imitation scores (retention) after a 24-h delay than same-aged infants who stayed awake for ≥4 h after encoding. In light of infants' well-known difficulties in learning and remembering information from screens, we tested if increasing the relevance of the televised content via standardised caregiver verbalisations might yield the highest imitation scores in the sleep condition. Regardless of sleep condition, 24-month-olds exhibited retention of target actions while 15-month-olds consistently failed to do so. For 24-month-olds, temporal recall was facilitated by sleep, but not by parental verbalisations. Correlational analyses revealed that more time asleep within 4 h after encoding was associated with better retention of the target actions and their temporal order in 24-months-olds. These results suggest that sleep facilitates memory consolidation of screen-based content in late infancy and that this effect might not hinge on caregivers' verbal engagement during viewing., (© 2023 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Background: Individuals with anxiety disorders (ADs) often display hypervigilance to threat information, although this response may be less pronounced following psychotherapy. This study aims to investigate the unconscious recognition performance of facial expressions in patients with panic disorder (PD) post-treatment, shedding light on alterations in their emotional processing biases., Methods: Patients with PD (n=34) after (exposure-based) cognitive behavior therapy and healthy controls (n=43) performed a subliminal affective recognition task. Emotional facial expressions (fearful, happy, or mirrored) were displayed for 33 ms and backwardly masked by a neutral face. Participants completed a forced choice task to discriminate the briefly presented facial stimulus and an uncovered condition where only the neutral mask was shown. We conducted a secondary analysis to compare groups based on their four possible response types under the four stimulus conditions and examined the correlation of the false alarm rate for fear responses to non-fearful (happy, mirrored, and uncovered) stimuli with clinical anxiety symptoms., Results: The patient group showed a unique selection pattern in response to happy expressions, with significantly more correct "happy" responses compared to controls. Additionally, lower severity of anxiety symptoms after psychotherapy was associated with a decreased false fear response rate with non-threat presentations., Conclusion: These data suggest that patients with PD exhibited a "happy-face recognition advantage" after psychotherapy. Less symptoms after treatment were related to a reduced fear bias. Thus, a differential facial emotion detection task could be a suitable tool to monitor response patterns and biases in individuals with ADs in the context of psychotherapy., Competing Interests: ZQ received scholarships from the China Scholarships Council. MH, VA, H-UW, AS, CK, and TK have received research support from various sources, as detailed in Yang et al. 2020. The reviewer JM declared a past co-authorship with the author AOH to the handling editor. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Qian, Yang, Domschke, Gerlach, Hamm, Richter, Herrmann, Deckert, Arolt, Zwanzger, Lotze, Pfleiderer, Wittchen, Lang, Ströhle, Konrad, Rief, Suslow, Jansen, Kircher and Straube.)

During the COVID-19 pandemic, drastic measures to interrupt SARS-CoV-2 infection chains were implemented. In our study we investigated the consequences of pandemic related restrictions on the social, psychological, and physical well-being of institutionalized adults with intellectual and developmental disabilities. Methods: Online survey among professional caregivers in 71 residential groups, caring for 848 residents. Findings: (i.) A lack of participation concerning infection protection measures of the residents, their relatives, and their caregivers; (ii.) A 20% increase in doctor contacts during the pandemic; (iii.) A considerable deterioration in at least one item of the subdomains mood (49%), everyday skills (51%), social interaction (29%), exercise and coordination skills (12%), behavior (11%) and cognition and communication (7%); (iv.) A deterioration of the overall condition in 41%; Summery: Intensive attempts should be made to find individual and less categorical contra-infectious measures without questioning the basic everyday needs of people with intellectual and developmental disabilities., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li + PGS ) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li + PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi + Gen: N = 2367) and replicated in the combined PsyCourse (N = 89) and BipoLife (N = 102) studies. The associations of Li + PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P < 0.05. Li + PGS was positively associated with lithium treatment response in the ConLi + Gen cohort, in both the categorical (P = 9.8 × 10 - 12 , R 2  = 1.9%) and continuous (P = 6.4 × 10 - 9 , R 2  = 2.6%) outcomes. Compared to bipolar patients in the 1 st decile of the risk distribution, individuals in the 10 th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P = 3.9 × 10 - 4 , R 2  = 0.9%), but not for the continuous outcome (P = 0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li + PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment., (© 2023. The Author(s).)

Amyotrophic lateral sclerosis (ALS) is a devastating neuromuscular disease with limited therapeutic options. Biomarkers are needed for early disease detection, clinical trial design, and personalized medicine. Early evidence suggests that specific morphometric features in ALS primary skin fibroblasts may be used as biomarkers; however, this hypothesis has not been rigorously tested in conclusively large fibroblast populations. Here, we imaged ALS-relevant organelles (mitochondria, endoplasmic reticulum, lysosomes) and proteins (TAR DNA-binding protein 43, Ras GTPase-activating protein-binding protein 1, heat-shock protein 60) at baseline and under stress perturbations and tested their predictive power on a total set of 443 human fibroblast lines from ALS and healthy individuals. Machine learning approaches were able to confidently predict stress perturbation states (ROC-AUC ∼0.99) but not disease groups or clinical features (ROC-AUC 0.58-0.64). Our findings indicate that multivariate models using patient-derived fibroblast morphometry can accurately predict different stressors but are insufficient to develop viable ALS biomarkers., Competing Interests: Disclosure statement The authors have no actual or potential conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Existing guidelines recommend psychopharmacological treatment for the management of schizophrenia and bipolar disorder as part of holistic treatment concepts. About half of the patients do not take their medication regularly, although treatment adherence can prevent exacerbations and re-hospitalizations. To date, the relationship between medication adherence and cognitive performance is understudied. Therefore, this study investigated the relationship between medication adherence and cognitive performance by analyzing the data of 862 participants with schizophrenia-spectrum and bipolar disorders (mean [SD] age, 41.9 [12.48] years; 44.8% female) from a multicenter study (PsyCourse Study). Z-scores for three cognitive domains were calculated, global functioning was measured with the Global Assessment of Functioning Scale, and adherence was assessed by a self-rating questionnaire. We evaluated four multiple linear regression models and built three clusters with hierarchical cluster analyses. Higher adherence behavior (p < 0.001) was associated with better global functioning but showed no impact on the cognitive domains learning and memory, executive function, and psychomotor speed. The hierarchical cluster analysis resulted in three clusters with different cognitive performances, but patients in all clusters showed similar adherence behavior. The study identified cognitive subgroups independent of diagnoses, but no differences were found in the adherence behavior of the patients in these new clusters. In summary, medication adherence was associated with global but not cognitive functioning in patients with schizophrenia-spectrum and bipolar disorders. In both diagnostic groups, cognitive function might be influenced by various factors but not medication adherence., (© 2023. The Author(s).)

Background: Mitochondria generate energy through oxidative phosphorylation (OXPHOS). The function of key OXPHOS proteins can be altered by variation in mitochondria-related genes, which may increase the risk of mental illness. We investigated the association of mitochondria-related genes and their genetic risk burden with cognitive performance., Methods: We leveraged cross-sectional data from 1320 individuals with a severe psychiatric disorder and 466 neurotypical individuals from the PsyCourse Study. The cognitive tests analyzed were the Trail-Making Test, Verbal Digit Span Test, Digit-Symbol Test, and Multiple Choice Vocabulary Intelligence Test. Association analyses between the cognitive tests, and single-nucleotide polymorphisms (SNPs) mapped to mitochondria-related genes, and their polygenic risk score (PRS) for schizophrenia (SCZ) were performed with PLINK 1.9 and R program., Results: We found a significant association (FDR-adjusted p < 0.05) in the Cytochrome C Oxidase Assembly Factor 8 (COA8) gene locus of the OXPHOS pathway with the Verbal Digit Span (forward) test. Mitochondrial PRS was not significantly associated with any of the cognitive tests., Limitations: Moderate statistical power due to relatively small sample size., Conclusions: COA8 encodes a poorly characterized mitochondrial protein involved in apoptosis. Here, this gene was associated with the Verbal Digit Span (forward) test, which evaluates short-term memory. Our results warrant replication and may lead to better understanding of cognitive impairment in mental disorders., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)