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    Geburtsbezogene, medizinische und diagnostische Merkmale von Kindern und Jugendlichen mit der Störung mit Vermeidung oder Einschränkung der Nahrungsaufnahme (ARFID) in Abhängigkeit des Alters

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    Um die Lücke in der bisherigen Forschung zur Störung mit Vermeidung oder Einschränkung der Nahrungsaufnahme (engl. Avoidant/restrictive food intake disorder, ARFID) zu füllen, das Bewusstsein für altersspezifische Merkmale zu erhöhen und potentiell relevante ätiologische Faktoren zu erkennen, untersucht die Studie erstmalig Unterschiede in der Ausprägung geburtsbezogener, medizinischer und diagnostischer Faktoren bei N=51 Patient:innen mit ARFID zwischen zwei Altersgruppen. Dabei wurden sowohl prä- und perinatale Komplikationen als auch psychische und somatische Komorbiditäten zwischen Kindern mit ARFID zwischen 0 – 5 Jahren und Patient:innen zwischen 6 – 17 Jahren analysiert. Des Weiteren erfolgte eine deskriptive Untersuchung der altersabhängigen Verteilung der diagnostischen Kriterien sowie der Hauptmanifestationen der Erkrankung. Jüngere Patient:innen mit ARFID waren im Vergleich zu den Älteren signifikant häufiger Frühgeburten, litten öfter unter postnatalen Komplikationen und mussten häufiger nach der Geburt invasiv behandelt und versorgt werden. Sie zeigten mehr somatische Komorbiditäten, insbesondere kongenitale Anomalien, während Patient:innen zwischen 6 – 17 Jahren häufiger andere psychische Erkrankungen, darunter vor allem depressive Störungen, komorbid entwickelten.Background: Although avoidant/restrictive food intake disorder (ARFID) presents the replacement and extension of feeding disorders of infancy and childhood, previous research into ARFID concentrated mainly on older patients. While birth-related characteristics play an etiologic role in feeding disorders, virtually nothing is known so far in ARFID. Therefore, the first aim of the study was to identify differences in birth-related characteristics in younger vs. older children with ARFID. Second, differences in physical and mental comorbidities, and third, diagnostic features between age groups were analysed. Methods: Among N = 51 in- and outpatient treatment-seeking patients, n = 23 patients aged 0 – 5 years (30% girls) and n = 28 patients aged 6 – 17 years (57% girls) with an interview-based diagnosis of ARFID were included. Data on the pre- and perinatal period and mental and physical comorbidities were derived from patients’ medical records, while diagnostic criteria, main ARFID presentation, and sociodemographic variables were collected through diagnostic interview. Results: Significantly, younger patients with ARFID were born more preterm with well-known pre- and perinatal complications and a higher incidence of postnatal invasive procedures. Patients with ARFID aged 0 – 5 years presented significantly more physical comorbidities and conditions, especially congenital anomalies, while mental comorbidities, especially mood disorders were significantly more common in patients with ARFID aged 6 – 17 years. No age differences were found for the distribution of diagnostic criteria and main ARFID presentation. Conclusion: This is the first study which aimed to identify age-specific characteristics in patients with ARFID with potential relevance for diagnosis and treatment. Especially birth-related complications, including invasive procedures postnatally, may be associated with developing ARFID, highlighting the importance of a closer view on these potential risk factors of the disorder. Future research with longitudinal design and larger samples may allow more detailed information on further age-specific associations, symptom trajectories, and age-specific risk factors for ARFID

    Impact of High-Fat Diet and Exercise on Bone and Bile Acid Metabolism in Rats

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    Bile acids help facilitate intestinal lipid absorption and have endocrine activity in glucose, lipid and bone metabolism. Obesity and exercise influence bile acid metabolism and have opposite effects in bone. This study investigates if regular exercise helps mitigate the adverse effects of obesity on bone, potentially by reversing alterations in bile acid metabolism. Four-month-old female Sprague Dawley rats either received a high-fat diet (HFD) or a chow-based standard diet (lean controls). During the 10-month study period, half of the animals performed 30 min of running at moderate speed on five consecutive days followed by two days of rest. The other half was kept inactive (inactive controls). At the study’s end, bone quality was assessed by microcomputed tomography and biomechanical testing. Bile acids were measured in serum and stool. HFD feeding was related to reduced trabecular (−33%, p = 1.14 × 10−7) and cortical (−21%, p = 2.9 × 10−8) bone mass and lowered femoral stiffness (12–41%, p = 0.005). Furthermore, the HFD decreased total bile acids in serum (−37%, p = 1.0 × 10−6) but increased bile acids in stool (+2-fold, p = 7.3 × 10−9). These quantitative effects were accompanied by changes in the relative abundance of individual bile acids. The concentration of serum bile acids correlated positively with all cortical bone parameters (r = 0.593–0.708), whilst stool levels showed inverse correlations at the cortical (r = −0.651–−0.805) and trabecular level (r = −0.656–−0.750). Exercise improved some trabecular and cortical bone quality parameters (+11–31%, p = 0.043 to 0.001) in lean controls but failed to revert the bone loss related to the HFD. Similarly, changes in bile acid metabolism were not mitigated by exercise. Prolonged HFD consumption induced quantitative and qualitative alterations in bile acid metabolism, accompanied by bone loss. Tight correlations between bile acids and structural indices of bone quality support further functional analyses on the potential role of bile acids in bone metabolism. Regular moderate exercise improved trabecular and cortical bone quality in lean controls but failed in mitigating the effects related to the HFD in bone and bile acid metabolism

    Non-Syndromic and Syndromic Defects in Children with Extracranial Germ Cell Tumors: Data of 2610 Children Registered with the German MAKEI 96/MAHO 98 Registry Compared to the General Population

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    GCTs are developmental tumors and are likely to reflect ontogenetic and teratogenetic determinants. The objective of this study was to identify syndromes with or without congenital anomalies and non-syndromic defects as potential risk factors. Patients with extracranial GCTs (eGCTs) registered in MAKEI 96/MAHO 98 between 1996 and 2017 were included. According to Teilum’s holistic concept, malignant and benign teratomas were registered. We used a case–control study design with Orphanet as a reference group for syndromic defects and the Mainz birth registry (EUROCAT) for congenital anomalies at birth. Co-occurring genetic syndromes and/or congenital anomalies were assessed accordingly. Odds ratios and 95% confidence intervals were calculated and p-values for Fisher’s exact test with Bonferroni correction if needed. A strong association was confirmed for Swyer (OR 338.6, 95% CI 43.7–2623.6) and Currarino syndrome (OR 34.2, 95% CI 13.2–88.6). We additionally found 16 isolated cases of eGCT with a wide range of syndromes. However, these were not found to be significantly associated following Bonferroni correction. Most of these cases pertained to girls. Regarding non-syndromic defects, no association with eGCTs could be identified. In our study, we confirmed a strong association for Swyer and Currarino syndromes with additional congenital anomalies

    Novel Multiparametric Bioelectronic Measurement System for Monitoring Virus-Induced Alterations in Functional Neuronal Networks

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    Development and optimisation of bioelectronic monitoring techniques like microelectrode array-based field potential measurement and impedance spectroscopy for the functional, label-free and non-invasive monitoring of in vitro neuronal networks is widely investigated in the field of biosensors. Thus, these techniques were individually used to demonstrate the capabilities of, e.g., detecting compound-induced toxicity in neuronal culture models. In contrast, extended application for investigating the effects of central nervous system infecting viruses are rarely described. In this context, we wanted to analyse the effect of herpesviruses on functional neuronal networks. Therefore, we developed a unique hybrid bioelectronic monitoring platform that allows for performing field potential monitoring and impedance spectroscopy on the same microelectrode. In the first step, a neuronal culture model based on primary hippocampal cells from neonatal rats was established with reproducible and stable synchronised electrophysiological network activity after 21 days of cultivation on microelectrode arrays. For a proof of concept, the pseudorabies model virus PrV Kaplan-ΔgG-GFP was applied and the effect on the neuronal networks was monitored by impedance spectroscopy and field potential measurement for 72 h in a multiparametric mode. Analysis of several bioelectronic parameters revealed a virus concentration-dependent degeneration of the neuronal network within 24–48 h, with a significant early change in electrophysiological activity, subsequently leading to a loss of activity and network synchronicity. In conclusion, we successfully developed a microelectrode array-based hybrid bioelectronic measurement platform for quantitative monitoring of pathologic effects of a herpesvirus on electrophysiological active neuronal networks

    Entscheidungsbedauern von Krebspatienten nach einer Strahlentherapie

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    In dieser Dissertation wird das Entscheidungsbedauern von Krebspatienten nach einer Strahlentherapie untersucht. Die Untersuchung ist als Querschnittstudie an einem universitären radioonkologischen Zentrum aufgebaut und es wurden 207 Patienten mithilfe der Ottawa Decision Regret Scale sowie weiterer validierter Fragebögen zu Lebensqualität, psychischer Belastung, partizipativer Entscheidungsfindung, Zufriedenheit mit der medizinischen Behandlung, sozialer Unterstützung, Gesundheitskompetenz, Angst und Depression befragt. Dadurch sollten die Häufigkeit und Einflussfaktoren dieses Bedauerns analysiert werden. Kein Entscheidungsbedauern empfanden 43 % der Patienten, 38 % ein mildes und 18 % empfanden ein hohes Maß an Bedauern. Das Entscheidungsbedauern korrelierte negativ mit der Lebensqualität, sozialer Unterstützung, Zufriedenheit mit der Behandlung, Gesundheitskompetenz und wahrgenommener Beteiligung an der Entscheidungsfindung. Positiv korrelierte es mit Stress, Angst und Depression. Besonders gefährdet waren Patienten mit einem schlechtem Performance-Status, geringer sozialer Unterstützung, niedriger Behandlungszufriedenheit sowie Patienten mit Kopf-Hals-Tumoren. Die Studie deutet darauf hin, dass Entscheidungsbedauern ein relevantes Phänomen nach Strahlentherapie ist und psychosoziale Unterstützung sowie patientenzentrierte Entscheidungsprozesse wichtige Ansatzpunkte zur Reduktion darstellen können.:1 Einleitung 1.1 Krebs 1.2 Gemeinsame Entscheidungsfindung 1.3 Entscheidungsbedauern 1.4 Entscheidungsbedauern im Kontext einer Strahlentherapie 1.5 Messung von Entscheidungsbedauern mittels der Decision Regret Scale 1.6 Zusammenfassung 2 Publikation 3 Zusammenfassung der Arbeit 4 Literaturverzeichnis 5 Anlagen (Supplement Materials) 6 Darstellung des eigenen Beitrags 7 Erklärung über die eigenständige Abfassung der Arbeit 8 Lebenslauf 9 Danksagun

    ROBOCOP II (ROBOtic assisted versus conventional open partial nephrectomy) randomised, controlled feasibility trial: clinical trial protocol

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    Introduction Randomised controlled trials comparing robotic-assisted partial nephrectomy (RAPN) and open PN (OPN) are lacking. Therefore, we aim to report the study protocol and a trial update for a randomised controlled feasibility trial comparing RAPN versus OPN for renal neoplasms. Methods and analysis The ROBOtic assisted versus conventional Open Partial nephrectomy II trial is designed as a single-centre, randomised, open-label, feasibility trial. Participation will be offered to patients with renal neoplasms and deemed feasible for both, OPN and RAPN. We aim to enrol 50 patients within 15 months using a 1:1 allocation ratio. The primary endpoint of the trial is feasibility of recruitment and will be successful if one third of eligible patients agree to participate. Secondary endpoints include perioperative results, health-related quality of life, inflammatory response as well as surgical ergonomics of the operating team. If the primary outcome, feasibility of recruitment, is successful, the secondary results of the trial will be used for planning a confirmative phase III trial. Ethics and dissemination Ethical approval was obtained from the local institutional review board (Ethik-Kommission II at Heidelberg University: 2020-542N). Results will be made publicly available in peer-reviewed scientific journals and presented at appropriate congresses and social media

    Well-being, physical fitness and health profile of 10–12 years old boys in relation to leisure-time sports club activities: a cross-sectional study

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    Objectives This study investigated the correlation between sports club activities and well-being and physical health parameters in 10–12 years old boys. Design Cross sectional. Setting Danish schools. Participants 2293 boys took part in the study. Primary and secondary outcome measures Questionnaires on participation in sports clubs and well-being and testing of physical health profile through measurement of body composition, resting heart rate (RHR), blood pressure and postural balance, jump and Yo-Yo IR1C performance. Data were analysed by participation in sport and according to the five most frequently reported sports. Results Boys enrolled in sports clubs had higher physical well-being (51.7±9.7 vs 45.9±8.7) and psychological well-being (53.3±9.6 vs 51.4±10.0), experienced more peers and social support (50.9±9.9 vs 48.0±11.6), and had a more positive perception of the school environment (48.6±7.5 vs 45.9±8.1) than boys not involved in sports clubs. In addition, they showed better Yo-Yo IR1C (+46%), long jump (9%) and balance test performance (+20%). The boys active in sports clubs had higher relative muscle mass (+6%) and lower fat percentage (−3%), body mass index (−6%) and RHR (−5%) compared with boys not involved in sports clubs (p<0.05). Boys enrolled in football clubs had higher aerobic fitness compared with boys not active in clubs (+11%), handball players (+5%), swimmers (+8%) and badminton players (+7%). Moreover, the boys enrolled in football clubs had lower fat percentage (−17%) and higher relative muscle mass (+4%) than swimmers. Conclusion Boys participating in club-based sports showed markedly higher levels of well-being and better physical health profiles than boys not involved in sports club activities. Footballers had superior aerobic fitness and body composition compared with those active in other sports. Results suggest that sports club activities seem to be beneficial for young boys’ well-being, fitness and physical health profile, with the greatest benefits achieved by boys involved in football

    Severe acute respiratory syndrome coronavirus-2 seroprevalence in non-vaccinated people living with HIV in Uganda during 2022

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    A cross-sectional study on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) seroprevalence among unvaccinated people living with HIV (PLWH) was conducted in Kampala, Uganda, in 2022. Data collection was done using a structured questionnaire. SARS-CoV-2 serologies were done using the Roche Elecsys Anti-SARS-CoV-2 S immunoassay, which assesses the adaptive humoral immune response to the SARS-CoV-2 Spike protein. A total of 575 PLWH (female n=355, 61.7%) with a median age of 49 years (IQR 39-55) were included. SARS-CoV-2 seroprevalence was 93%. The majority had antibody concentration levels ≥ 250 U/ml (n=383, 66.6%). Participants aged >55 years were significantly more likely to have lower antibody concentrations compared to younger participants (p-value < 0.001). A high BMI (≥ 30 kg/m2) was significantly associated with higher antibody concentrations (p-value 0.001). Concerning COVID-19 history, a small proportion of participants (n=79, 13.6%) reported contact with a known COVID-19 patient. Only 8.1% (n=47) had ever had a nasopharyngeal swab for SARS-CoV-2 RT-PCR done, and 3.1% (n=18) actually had a laboratory-confirmed SARS-CoV-2 infection in the past. SARS-CoV-2 seroprevalence was high among our study population, which may be attributed to the fact that the study took place right after all restrictions were lifted and the population was exposed to the dominant Omicron variant. Interestingly, only a small proportion of infections had been laboratory-confirmed

    International External Validation of Risk Prediction Model of 90-Day Mortality after Gastrectomy for Cancer Using Machine Learning

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    A 90-day mortality predictive model for curative gastric cancer resection based on the Spanish EURECCA Esophagogastric Cancer database was externally validated using the GASTRODATA registry. The externally validated model showed a modestly worse performance compared to the original model, nevertheless maintaining its discriminating ability in clinical practice.Background: Radical gastrectomy remains the main treatment for gastric cancer, despite its high mortality. A clinical predictive model of 90-day mortality (90DM) risk after gastric cancer surgery based on the Spanish EURECCA registry database was developed using a matching learning algorithm. We performed an external validation of this model based on data from an international multicenter cohort of patients. Methods: A cohort of patients from the European GASTRODATA database was selected. Demographic, clinical, and treatment variables in the original and validation cohorts were compared. The performance of the model was evaluated using the area under the curve (AUC) for a random forest model. Results: The validation cohort included 2546 patients from 24 European hospitals. The advanced clinical T- and N-category, neoadjuvant therapy, open procedures, total gastrectomy rates, and mean volume of the centers were significantly higher in the validation cohort. The 90DM rate was also higher in the validation cohort (5.6%) vs. the original cohort (3.7%). The AUC in the validation model was 0.716. Conclusion: The externally validated model for predicting the 90DM risk in gastric cancer patients undergoing gastrectomy with curative intent continues to be as useful as the original model in clinical practice

    Liver Phantoms Cast in 3D-Printed Mold for Image-Guided Procedures

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    Introduction: Image-guided invasive procedures on the liver require a steep learning curve to acquire the necessary skills. The best and safest way to achieve these skills is through hands-on courses that include simulations and phantoms of different complications, without any risks for patients. There are many liver phantoms on the market made of various materials; however, there are few multimodal liver phantoms, and only two are cast in a 3D-printed mold. Methods: We created a virtual liver and 3D-printed mold by segmenting a CT scan. The InVesalius and Autodesk Fusion 360 software packages were used for segmentation and 3D modeling. Using this modular mold, we cast and tested silicone- and gelatin-based liver phantoms with tumor and vascular formations inside. We tested the gelatin liver phantoms for several procedures, including ultrasound diagnosis, elastography, fibroscan, ultrasound-guided biopsy, ultrasound-guided drainage, ultrasound-guided radio-frequency ablation, CT scan diagnosis, CT–ultrasound fusion, CT-guided biopsy, and MRI diagnosis. The phantoms were also used in hands-on ultrasound courses at four international congresses. Results: We evaluated the feedback of 33 doctors regarding their experiences in using and learning on liver phantoms to validate our model for training in ultrasound procedures. Conclusions: We validated our liver phantom solution, demonstrating its positive impact on the education of young doctors who can safely learn new procedures thus improving the outcomes of patients with different liver pathologies

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