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AimsBoth anticholinergic burden (ACB) and depression are known to increase fall risk in older persons, next to increasing morbidity and mortality. However, the effect of depression on fall risk associated with ACB is unclear. This is relevant because several antidepressants have anticholinergic effects to some extent. The aim of this study was to assess the relationship between ACB and falls, and the impact of depression on this relationship.MethodsWe cross‐sectionally examined the relationship between both ACB and clinical depression and falls in the past 12 months, in a harmonized cohort of Dutch community dwelling persons (n = 7884). For all analyses, we calculated adjusted odds ratios (ORs) and their 95% confidence intervals (CI). We also investigated the impact of depression on the relationship between ACB and falls, by calculating their interaction on both an additive and multiplicative scale.ResultsBoth a high ACB score (≥3) and clinical depression were independently significantly associated with falls in the past 12 months. Additionally, there was a statistically significant interaction (P = 0.038) between ACB and clinical depression on fall risk, both on an additive and multiplicative scale (1.13 and 1.44 respectively).ConclusionsIn older persons, the presence of clinical depression strengthened the association between ACB and falls. We discourage withholding pharmacological treatment to avoid falls, despite the ACB of antidepressants. In the case of depression, we recommend considering non‐pharmacological alternatives; choose pharmacological interventions with the lowest risk of adverse events; assess and treat other fall risk factors; and perform multidisciplinary medication review to minimize (accumulation of) ACB.

Autistic adults experience more daily stress compared to non-autistic adults. However, stress recognition is often delayed, potentially leading to chronic stress and significant (mental) health risks. We evaluated the effectiveness of Stress Autism Mate (SAM), a stress-monitoring mobile health application co-created with autistic individuals. We ran a two-arm, parallel, superiority randomized controlled trial. Autistic adults (n = 214) (mean age: 50.5 years; 66.4% female) were randomized to 1-month SAM usage or waitlist control. Participants self-reported on primary (Perceived Stress Scale; Warwick-Edinburgh Mental Wellbeing Scale), and secondary outcomes (Coping Self-Efficacy Scale) at baseline and 4 weeks later, after which the control group could start using the app. Hierarchical multiple regression analyses revealed that the intervention group had significantly lower perceived stress (d = 0.27), greater mental well-being (d = 0.35), and improved coping self-efficacy (d = 0.16) compared to the control group after 1 month. No intervention effect moderators could be identified. More frequent app usage was significantly associated with a stronger decrease in perceived stress (r = −0.293). However, 42.9% of app users indicated increased stress from app use, warranting further investigation. Our results suggest that SAM may be effective in reducing perceived stress and improving mental well-being for some autistic individuals. Further refinement and investigation are recommended.Lay abstractAutistic adults often experience more daily stress than non-autistic individuals, but they may not always recognize this stress timely, which can lead to long-term health problems. To help address this, we tested an app called Stress Autism Mate (SAM), which was designed together with autistic individuals to help autistic adults monitor and manage their stress. In our study, 214 autistic adults (average age: 50.5 years; 66.4% female) were randomly assigned to either use the app for 1 month or wait before using it. We asked participants to complete surveys before and after the 1-month period to measure changes in their stress levels, mental well-being, and confidence in coping. Results showed that participants who used the app reported lower stress, improved mental well-being, and better coping skills compared to those who did not use the app. We also found that the more often someone used the app, the more their stress levels decreased. However, 42.9% of users felt more stressed using the app, which needs further study. Overall, our findings suggest that SAM can help reduce stress and improve well-being for some autistic adults, but more work is needed to improve the app and better understand its effects.Trial registry ISRCTN Registry: ISRCTN17394910.

Inflammation, oxidative stress, and bioenergetic dysfunction are proposed underlying mechanisms of schizophrenia spectrum disorders (SSDs) and bipolar disorders (BDs), contributing to the largely untreated cognitive and negative symptoms in these conditions. Ketone bodies may offer a therapeutic option for these symptoms through their positive effects on the aforementioned mechanisms. Exogenous ketones like ketone esters (KEs) provide a means to quickly induce ketosis without dietary restrictions, though their effects on SSD and BD have not yet been investigated. This ongoing triple-blind, randomized controlled crossover trial investigates the effects of a single ingestion of KE on signs and symptoms of SSD and BD. A total of 24 patients (12 SSD and 12 BD) receiving inpatient care at Amsterdam University Medical Center (UMC) will be included in the study. Patients will ingest a single dose of KE ((R)-3-hydroxybutyl-(R)-3-hydroxybutyrate deltaG Ketones (dGK) and an isocaloric carbohydrate control with a washout period of 3 days between drinks. The primary outcome is the change in prepulse inhibition of the startle reflex induced by dGK ingestion compared with control. Secondary outcomes include resting-state electroencephalography, P3B amplitude, cognitive performance, and metabolic, immune, oxidative stress, and circadian rhythm parameters. Feasibility and potential side effects will also be assessed. N/A (study protocol). Our current study will offer valuable preliminary data on the effects of KE in patients with SSD and BD. It can provide the foundation for future research into the therapeutic potential of KE in alleviating symptoms and improving functional outcomes in these disorders.This trial was registered at www.clinicaltrials.gov as NCT06426134.

Research examining physical activity interventions for mental disorders has grown exponentially in the past decade. At this critical juncture, there is a need to synthesize the best evidence to guide researchers, clinicians and people with lived experience. This meta-review aimed to systematically identify and comprehensively evaluate the current evidence about: a) the efficacy of physical activity interventions on mental, cognitive and physical outcomes for individuals with mental disorders; b) the potential neurobiological, psychosocial and behavioral mechanisms underlying the observed effects; and c) the barriers and facilitators for individuals to successfully engage in these interventions. Our systematic search identified 13 meta-analyses of high methodological quality (i.e., A Measurement Tool to Assess Systematic Reviews, AMSTAR score ≥8) assessing outcomes of physical activity as an adjunctive treatment, which included 256 randomized clinical trials (RCTs) and 12,233 individuals. Large effect sizes were found for adjunctive physical activity interventions in improving attention in children and adolescents with attention-deficit/hyperactivity disorder (ADHD); reducing depressive symptoms in children, adolescents and adults with depressive disorders; and reducing body mass index in adults with schizophrenia. Moderate effect sizes were found for reductions of hyperactivity, impulsivity and anxiety, and improvements of executive and social functioning in children and adolescents with ADHD; reduction of anxiety symptoms in adults with anxiety disorders; improved physical and psychological quality of life and cardiovascular fitness in adults with depressive disorders; improved daily living skills, overall quality of life and cardiorespiratory fitness in adults with schizophrenia; reduction of depressive symptoms in older people with depressive disorders; and improvements in cognition and functional mobility in older people with dementia. There is, to date, no meta-analytic evidence for physical activity as a first-line treatment for people with a mental disorder. Five meta-analyses, including 89 RCTs and 4,575 individuals, investigated potential underlying mechanisms. There is a very preliminary evidence for an effect of physical activity on circulating levels of kynurenine, growth hormone, tumor necrosis factor-alpha and brain-derived neurotrophic factor in people with major depressive disorder. No meta-analytic evidence could be found for psychosocial or behavioral mechanisms. Based on 15 umbrella or systematic reviews, covering 432 studies and 48 guidelines, six implementation strategies, along with the most evidence-based behavioral change techniques to support them, were identified. Recommendations to support implementation research in this area were finally formulated.

BackgroundResidents who do not internalize professional values may not be a good fit for their specialty and compromise the quality of their patient care. Research aimed at recognizing residents’ shortcomings in professionalism may help to prevent future shortcomings towards patients. The aim of this study was to increase insight into residents’ shortcomings in medical professionalism in light of professional values relevant within residency training.MethodsWe analyzed all law cases from the Dutch national conciliation board from 2011 to 2020 on the unprofessional behaviors described.ResultsDuring the period investigated, 61 dismissed residents challenged their dismissal. In 39 of 61 cases (64%), the program director named unprofessional behavior(s) as (one of the) reasons for dismissal. The most prevalent deficit of residents deemed unprofessional was poor self-awareness (80%); less prevalent deficits were: shortness of engagement and dishonest and disrespectful behavior (31% or less).ConclusionsWe describe perceived unprofessional behavior in residency, which was not about exceptional or abominable behaviors. For the most part, these behaviors concerned the accumulation of remediation-resistant day-to-day underperformance, discrediting trust and professional reliability. This finding encourages dedicated longitudinal assessment of professionalism and fuels the ethical debate about required professional values in hospital care.

This thesis investigated the structure and function of the human tRNA-like molecule mascRNA. By employing omics-level identification of associating protein complexes, this thesis demonstrates a systematic approach in understanding the ribonucleoprotein networks, where mascRNA functions are detected. In addition, this thesis includes an innovative approach to delete mascRNA from the human genome. Furthermore, this thesis includes a review on reported findings that pertain to the mechanistic features of tRNA-derived fragments in cardiac and skeletal muscle at the molecular level. Collectively, this thesis examined the roles of tRNA-related non-coding RNA species, with focused investigation on tRNA-like molecule mascRNA.

El mundo empresarial y financiero contemporáneo se encuentra en una etapa de transformación acelerada, impulsada por el avance tecnológico, la globalización y los cambios en las dinámicas de competitividad a nivel mundial. Este libro surge de la necesidad imperante de ofrecer una herramienta integral que aborde de manera holística los aspectos esenciales de la gestión empresarial, la competitividad, las finanzas, y el uso de tecnologías emergentes en la detección de fraudes internos, especialmente dentro del sector financiero. La obra se divide en varios ejes temáticos que permiten un abordaje multidimensional de los desafíos que enfrentan las organizaciones modernas. Desde la perspectiva empresarial, se explora con profundidad el concepto de competitividad, enfocándose particularmente en las MIPYMES, que constituyen un pilar fundamental de las economías en desarrollo y desarrolladas. A través de un análisis detallado, se desentrañan las múltiples dimensiones que influyen en la competitividad de estas pequeñas y medianas empresas, no solo desde una perspectiva interna, sino también en función de factores externos que condicionan su capacidad para sobrevivir y prosperar en entornos económicos cada vez más complejos y dinámicos.

BackgroundMonitoring cognitive side effects following electroconvulsive therapy (ECT) is crucial for balancing side effects and clinical effectiveness. Yet, evidence-based guidelines on cognitive testing following ECT are lacking. A frequently used test in global ECT practice is the Mini-Mental State Examination (MMSE). We examined the change of the MMSE score and its performance in identifying a decline in predefined neuropsychological measures sensitive to ECT-induced cognitive changes: verbal recall and verbal fluency. MethodsMean MMSE scores before and 1 week after ECT were compared using a Wilcoxon signed rank test. The Reliable Change Index was calculated for all cognitive measures to indicate whether a participant’s change in score from pre- to post-ECT was considered statistically significant. The sensitivity and specificity of the MMSE were calculated. ResultsA total of 426 patients with depression from 5 sites were included from the Dutch ECT Consortium. Mean (SD) MMSE score increased significantly from 26.2 (3.9) before ECT to 26.8 (3.8) after ECT (p = .002). After ECT, 36 patients (8.5%) showed a significant decline in MMSE score. The sensitivity of the MMSE in identifying patients who experienced a significant decline in verbal recall or verbal fluency ranged from 3.6% to 11.1%. The specificity of the MMSE in identifying patients who did not experience a significant decline in verbal recall or verbal fluency ranged from 95.6% to 96.6%. ConclusionsGiven the very low sensitivity of the MMSE, we propose reconsidering the prominence of the MMSE in ECT practice and cognitive monitoring guidelines, advocating for a more comprehensive approach to assess ECT-induced cognitive changes.