University Medical Center Hamburg - Eppendorf

Our sense of agency, the subjective experience of controlling our actions, is a crucial component of self-awareness and motor control. It is thought to originate from the comparison between intentions and actions across broad cortical networks. However, the underlying neural mechanisms are still not fully understood. We hypothesized that oscillations in the theta-alpha range, thought to orchestrate long-range neural connectivity, may mediate sensorimotor comparisons. To test this, we manipulated the relation between intentions and actions in a tetraplegic user of a brain machine interface (BMI), decoding primary motor cortex (M1) activity to restore hand functionality. We found that the pre-movement phase of low-alpha oscillations in M1 predicted the participant’s agency judgements. Further, using EEG-BMI in healthy participants, we found that pre-movement alpha oscillations in M1 and supplementary motor area (SMA) correlated with agency ratings, and with changes in their functional connectivity with parietal, temporal and prefrontal areas. These findings argue for phase-driven gating as a key mechanism for sensorimotor integration and sense of agency.

Aims A systematic review and meta-analysis was conducted to investigate the prevalence and antecedents/outcomes of loneliness and social isolation among individuals with severe mental disorders (SMD), such as schizophrenia, schizoaffective disorder, bipolar disorder or major depressive disorder. Methods Five well-known electronic databases (PubMed, PsycINFO, CINAHL, Web of Science and Scopus) were searched (plus a hand search). Observational studies that report the prevalence and, if available, antecedents and consequences of loneliness/isolation among individuals with SMD were included. Key characteristics were extracted, and a meta-analysis was performed. Our systematic review was preregistered on PROSPERO (ID: CRD42024559043). The PRISMA guidelines were followed. The Joanna Briggs Institute (JBI) standardized critical appraisal tool developed for prevalence studies was applied to assess the quality of the included studies. Results The initial search yielded 4506 records, and after duplicate removal and screening, a total of 10 studies were finally included. The studies included used data from Europe, Asia, North America, and Oceania. Two studies employed a longitudinal design, while all other studies had a cross-sectional design. Most of the studies included between 100 and 500 individuals with SMD. All studies involved both male and female participants, with women typically comprising about 40% of the sample. The average age of participants often ranged from approximately 30 to 40 years. The estimated prevalence of loneliness was 59.1% (95% CI: 39.6% to 78.6%, I ² = 99.3, P < .001) among individuals with any diagnosis of SMD. Furthermore, the estimated prevalence of objective social isolation was 63.0% (95% CI: 58.6% to 67.4%) among individuals with schizophrenia or schizophrenia spectrum disorder. The quality of the studies was moderate to good. Subjective well-being and depressive symptoms in particular were found to contribute to loneliness in the included studies. Conclusions The present systematic review with meta-analysis identified high levels of loneliness and objective social isolation among those with SMD. These findings stress the importance of monitoring and addressing social needs in this vulnerable group, which may have a positive effect on the life quality of individuals with SMD. Future research in neglected regions (e.g. South America and Africa) is recommended. Different diagnoses within severe mental disorders should be distinguished in future studies. Furthermore, additional longitudinal studies are required to explore the antecedents and consequences of loneliness and social isolation among individuals with SMD.

Clinical research emphasizes the implementation of rigorous and reproducible study designs that rely on between-group matching or controlling for sources of biological variation such as subject’s sex and age. However, corrections for body size (i.e. height and weight) are mostly lacking in clinical neuroimaging designs. This study investigates the importance of body size parameters in their relationship with spinal cord (SC) and brain magnetic resonance imaging (MRI) metrics. Data were derived from a cosmopolitan population of 267 healthy human adults (age 30.1±6.6 years old, 125 females). We show that body height correlates with brain gray matter (GM) volume, cortical GM volume, total cerebellar volume, brainstem volume, and cross-sectional area (CSA) of cervical SC white matter (CSA-WM; 0.44≤r≤0.62). Intracranial volume (ICV) correlates with body height (r=0.46) and the brain volumes and CSA-WM (0.37≤r≤0.77). In comparison, age correlates with cortical GM volume, precentral GM volume, and cortical thickness (-0.21≥r≥-0.27). Body weight correlates with magnetization transfer ratio in the SC WM, dorsal columns, and lateral corticospinal tracts (-0.20≥r≥-0.23). Body weight further correlates with the mean diffusivity derived from diffusion tensor imaging (DTI) in SC WM (r=-0.20) and dorsal columns (-0.21), but only in males. CSA-WM correlates with brain volumes (0.39≤r≤0.64), and with precentral gyrus thickness and DTI-based fractional anisotropy in SC dorsal columns and SC lateral corticospinal tracts (-0.22≥r≥-0.25). Linear mixture of age, sex, or sex and age, explained 2±2%, 24±10%, or 26±10%, of data variance in brain volumetry and SC CSA. The amount of explained variance increased to 33±11%, 41±17%, or 46±17%, when body height, ICV, or body height and ICV, were added into the mixture model. In females, the explained variances halved suggesting another unidentified biological factor(s) determining females’ CNS morphology. In conclusion, body size and ICV are significant biological variables. Along with sex and age, body size should therefore be included as a mandatory variable in the design of clinical neuroimaging studies examining SC and brain structure; and body size and ICV should be considered as covariates in statistical analyses. Normalization of different brain regions with ICV diminishes their correlations with body size, but simultaneously amplifies ICV-related variance (r=0.72±0.07) and suppresses volume variance of the different brain regions (r=0.12±0.19) in the normalized measurements.

Background In connection with a hospital stay, patients have to make important health-related decisions. Adequately responding to the needs of patients requires good communication skills of healthcare professionals within healthcare organizations. The PIKoG project (As made for us – Improving professional health literacy in hospitals) aimed at improving professional health literacy by implementing participatory health literacy training and supporting measures in a hospital setting. This study aimed to analyze processes supporting and hindering the implementation of the complex intervention. Methods A mixed-methods study was conducted, including focus group interviews and a paper-pencil survey with healthcare professionals. Data was combined and analyzed using categories derived from the Medical Research Council’s guidance on process evaluation: (1) Implementation, (2) Mechanisms of impact, and (3) Context. Interview data were analyzed using structured qualitative content analysis according to Kuckartz. Survey data were analyzed descriptively. Results One of three on-site, full-day health literacy training sessions was offered weekly. Supporting measures were implemented step by step over the course of a year. Both the training and the supporting measures were rated positively overall, but they could not be effectively integrated into daily routines. The COVID-19 pandemic as well as resource constraints adversely affected implementation by altering workflows, increasing stress levels and shifting priorities. The participatory approach and individual change agents fostered the implementation of the complex intervention. Nurses were reached the most, while physicians engaged least in the interventions. Adaptations during the implementation increased the use of the implemented measures and gave rise to ideas for future improvements. Conclusion The study highlights the challenges involved in implementing a complex intervention supporting professional health literacy in an organization and stresses the importance of considering available resources, recruiting opinion leaders, and being responsive to the needs of different groups. While the participatory co-design development approach was found to be valuable, it does not guarantee successful organizational change in times when hospitals face multiple challenges. Subsequent studies should therefore focus on investigating the capacities of healthcare organizations for organization-wide improvement processes and identify how healthcare organizations can be innovative and patient-centered even in the presence of extremely difficult contextual conditions. Trial registration DRKS00019830, since 16th of April 2020.

Background The procedures and locations where patients are admitted to hospitals and subsequently diagnosed after out-of-hospital cardiac arrest (OHCA) in Germany exhibit considerable heterogeneity. Specifically, advanced imaging diagnostic methods via computed tomography (CT) show significant variation in both timing and execution. However, echocardiography (ECHO) is not an alternative to CT in this setting, as both modalities serve distinct diagnostic purposes. This study aimed to comprehensively analyze the status quo analysis of current procedures in German emergency departments (EDs) regarding early-phase (within the first six hours) CT imaging diagnostics after resuscitation and the treatment of critically ill patients in the ED resuscitation room. Methods An anonymized cross-sectional study was conducted from November 28, 2023, to February 18, 2024, using an online survey platform (https://www.surveymonkey.de) with a standardized questionnaire. The survey targeted 994 medical directors of German EDs and was distributed through the mailing lists of the German Society for Interdisciplinary Emergency and Acute Medicine (DGINA) and the German Interdisciplinary Association for Intensive Care and Emergency Medicine (DIVI). The Medical Faculty of Christian-Albrechts-University Kiel granted ethical approval (D 586/22). An expert panel reviewed the questionnaire to ensure validity and minimize bias. All statistical analyses, including both descriptive and inferential statistics, were conducted using R software. Results Out of 994 hospitals contacted, 182 hospitals from 15 German federal states participated, yielding a response rate of 18.3%. The overall completion rate for the whole questionnaire was 12.2% (n = 121/994). In the survey, 9.6% (n = 15/157) of hospitals reported having CT within the resuscitation room, while 70.1% (n = 119/157) had CT within a range of 50 m of the resuscitation room. A standard operating procedure (SOP)/postresuscitation protocol for patients suffering from OHCA was available for 61.1% (n = 88 yes, n = 56 no) of the hospitals. A specific postresuscitation CT protocol (postrCT protocol) was used by 30.0% (n = 48 yes, n = 93 no) of the hospitals, with 59.2% (n = 29) receiving a head-to-pelvis CT (whole-body CT). In hospitals without a CT protocol (n = 84), echocardiography (82.1%, n = 69), abdominal ultrasound (61.9%, n = 52), and non-contrast CT of the head (47.6%, n = 40) are used for distinctive diagnostics. Cardiac Arrest Center (CAC)-certified hospitals were significantly more likely to have a SOP/postresuscitation protocol (91.9 vs. 49.0%, p < 0.001) and a specific postrCT protocol (63.2 vs. 22.1%, p < 0.001) than noncertified hospitals. Conclusion Currently, there is no nationwide standardized protocol for imaging diagnosis in patients after OHCA in German EDs. Protocols are more often used in CAC hospitals in Germany then in non-certified hospitals. Given the limitations of survey-based research, results should be interpreted with caution regarding their representativeness across all German EDs and further prospective studies including mortality and neurological outcomes are warranted.

Information theory has deeply influenced the conceptualization of brain information processing and is a mainstream framework for analyzing how neural networks in the brain process information to generate behavior. Information theory tools have been initially conceived and used to study how information about sensory variables is encoded by the activity of small neural populations. However, recent multivariate information theoretic advances have enabled addressing how information is exchanged across areas and used to inform behavior. Moreover, its integration with dimensionality-reduction techniques has enabled addressing information encoding and communication by the activity of large neural populations or many brain areas, as recorded by multichannel activity measurements in functional imaging and electrophysiology. Here, we provide a Multivariate Information in Neuroscience Toolbox (MINT) that combines these new methods with statistical tools for robust estimation from limited-size empirical datasets. We demonstrate the capabilities of MINT by applying it to both simulated and real neural data recorded with electrophysiology or calcium imaging, but all MINT functions are equally applicable to other brain-activity measurement modalities. We highlight the synergistic opportunities that combining its methods afford for reverse engineering of specific information processing and flow between neural populations or areas, and for discovering how information processing functions emerge from interactions between neurons or areas. MINT works on Linux, Windows and macOS operating systems, is written in MATLAB (requires MATLAB version 2018b or newer) and depends on 4 native MATLAB toolboxes. The calculation of one possible way to compute information redundancy requires the installation and compilation of C files (made available by us also as pre-compiled files). MINT is freely available at https://github.com/panzerilab/MINT with DOI doi.org/10.5281/zenodo.13998526 and operates under a GNU GPLv3 license.

Background Healthy dietary patterns have been linked to reduced risks for cardiovascular diseases and dementia, making nutrition an essential part of a comprehensive approach for dementia prevention. Knowledge about factors associated with a healthy diet in people with increased dementia risk is scarce. Objective To analyze dietary habits and associated factors in older adults with increased dementia risk in Germany. Methods We used baseline-data of the AgeWell.de-trial (n = 1001, % female = 52.2, M age = 69.0, SD = 4.9). Nutrition was assessed using a composite score, comprising 11 components covered by national recommendations for a healthy diet (range = 0–11 points). Linear regressions assessed associations of sociodemographic, social, health-related and psychological factors with consumption of a healthy diet. Further, we assessed stages of change based on the transtheoretical model of behavior change. Results Consumption of a healthy diet was moderate (Median = 4, IQR = 2). Female sex (b = 0.64, 95% CI: 0.41, 0.88), higher levels of motivation for healthy eating (b = 0.22, 95% CI: 0.10, 0.34) and higher self-efficacy (b = 0.33, 95% CI: 0.20, 0.46) were linked to a healthy diet. Regarding the stages of behavior change, the majority were in the maintenance stage (45.2%), followed by the contemplation (21.5%) and precontemplation (21.2%) stages. Conclusions Results suggest room for improvement regarding a healthy diet in our sample. Lifestyle-based interventions in older adults should be tailored towards current levels of motivation and self-efficacy of participants. Including modules targeting motivation and self-efficacy might help maximize intervention effectiveness.

The advent of disease-modifying therapies for neurodegenerative diseases may result in a growing demand for nuclear neuroimaging procedures presenting opportunities but also challenges to the nuclear medicine community. Whether capacity and expertise in Germany are sufficient to meet an increasing demand for nuclear neuroimaging is under discussion. Against this background, the Neuroimaging Working Group of the German Society of Nuclear Medicine initiated the first survey on the status of nuclear neuroimaging in Germany in 2023. 82 institutions participated in the survey: 33 practices, 15 community hospitals, 34 university hospitals. Primary findings were the following. In practices, brain scans are less frequently performed than in hospitals and are often limited to dopamine transporter SPECT. Brain PET is mainly performed in hospitals, and in community hospitals it is often restricted to FDG PET. Nevertheless, availability of amyloid PET with well-certified quality can be taken for granted. Thus, access to amyloid PET will not be a major bottleneck for new treatments of Alzheimer’s disease. Adequate reimbursement and clear anchoring in clinical guidelines have the greatest potential to advance nuclear neuroimaging in Germany. Clinical dopamine transporter SPECT is largely in agreement with procedure guidelines. An area for improvement is the limited availability of MR images to avoid misinterpretation of structural/vascular lesions as nigrostriatal degeneration. The survey provides the first systematic assessment of the status of nuclear neuroimaging in Germany. It underscores the capacity of the German nuclear medicine community to meet an increasing demand for neuroimaging procedures, its adherence to procedure guidelines and identifies topics for improvement.

Background Loss of chromosome Y (LOY) has recently been proposed to be associated with cancer aggressiveness, altered T-cell function, and poor prognosis in bladder carcinomas. Methods Chromosome Y was analyzed using fluorescence in-situ hybridization on a tissue microarray containing 2,071 urothelial carcinomas of the urinary bladder from male patients, including 487 patients who had undergone cystectomy for muscle-invasive disease and for whom follow-up data were available. Data on tumor microenvironment were obtained from a previous study. Results LOY was found in 26.0% of 1,704 analyzable cancers. In non-invasive cancers, LOY frequency was comparable in pTa G2 (22.8%) and pTa G3 (24.1%, p = 0.8036) carcinomas and slightly increased from pTa to pT2 - 4 carcinomas (23.1% for pTa and 27.2% for pT2 - 4) but these differences were not significant (p = 0.0794). In muscle-invasive cancers, LOY frequency slightly increased from pT2 (25.5%) to pT4 cancers (33.0%), but this association was not significant (p = 0.1814). Among pT2 - 4 cancers, LOY was associated with venous invasion (p = 0.0010) but unrelated to pT, pN, and L-status, as well as to overall, recurrence-free, and cancer-specific survival. Muscle-invasive urothelial carcinomas with and without LOY did not show significant differences in the number of CD8 positive lymphocytes, fraction of CD8 positive intraepithelial lymphocytes, number of macrophages and dendritic cells, and fraction of T helper and T regulatory cells. Conclusion The lack of a clear association of LOY with histopathological parameters of cancer aggressiveness, patient prognosis, and parameters describing the tumor microenvironment strongly argues against the driving role of LOY in bladder cancer progression and cancer-associated immune reactions.

Background Minimally invasive surgery (MIS) is the standard approach in bariatric surgery. The most common bariatric procedures are sleeve gastrectomy and Roux-en-Y-Gastric Bypass (RYGB). Simulation training, including virtual reality (VR), is useful when learning MIS. Training in pairs has proven beneficial in acquiring basic MIS skills. However, this has not been tested on more complex procedures such as MIS RYGB. The study aimed to assess the learning effects of training MIS RYGB on a VR trainer in pairs compared to solo training. Methods Medical students (n = 60) were randomized into the intervention group, trained in pairs (n = 30), and the control group, trained solo (n = 30). Both groups needed to train MIS RYGB on a VR trainer under the supervision of trained tutors until proficiency was reached. The MIS RYGB proficiency was defined as 105/110 points according to the Bariatric Objective Structured Assessment of Technical Skills (BOSATS) score. The primary outcome was the number of exercise repetitions until proficiency was reached. Secondary outcomes compared the BOSATS scores, bleeding incidents, and the validated score on current motivation. Results The intervention group achieved proficiency with significantly fewer repetitions than the control group (p = 0.002). Most participants in the intervention group reached proficiency by the fifth repetition, and none required an eighth repetition. The intervention group had better BOSATS scores than the control group after the second, fourth, and fifth MIS RYGB (91.1 ± 6.4 vs. 87.1 ± 7.0 points, p = 0.025; 104.0 ± 4.7 vs. 100.3 ± 6.1 points, p = 0.014; 106.2 ± 2.8 vs. 101.9 ± 5.8 points, p = 0.026), respectively. Additionally, the intervention group experienced fewer bleeding complications in the fifth and sixth MIS RYGB repetitions than the control group (2 vs. 10, p = 0.001; 0 vs. 8, p < 0.001, respectively). Conclusions Training MIS RYGB on a VR trainer in pairs enables trainees to reach procedural proficiency with fewer exercise repetitions than training alone.