Admission rates and clinical profiles of children and youth with eating disorders treated as inpatients before and during the COVID-19 pandemic in a German university hospital.

Introduction: Children and youth at risk for mental health disorders, such as eating disorders (ED), were particularly affected by the COVID-19 pandemic, yet evidence for the most seriously affected and thus hospitalized youth in Germany is scarce. Methods: This crosssectional study investigated anonymized routine hospital data (demographic information, diagnoses, treatment modalities) of patients admitted (n = 2,849) to the Department of Child and Adolescence Psychiatry, Psychosomatics and Psychotherapy (DCAPPP) of a German University Hospital between 01/2016 and 02/2022. Absolute and relative number of inpatients with or without ED prior to (01/2016-02/2020) and during the COVID-19 pandemic (03/2020-02/2022) were compared. The effect of school closures as part of social lockdown measures for COVID-19 mitigation on inpatient admission rate was explored as it has been discussed as a potential risk factor for mental health problems in youth. Results: During the COVID-19 pandemic, ED inpatient admission rate increased from 10.5 to 16.7%, primarily driven by Anorexia Nervosa (AN). In contrast to previous reports, we found no change in somatic and mental disorder comorbidity, age or sexratio for hospitalized youth with ED. However, we did observe a shortened length of hospital stay (LOS) for hospitalized youth with and without ED. In addition, non-ED admissions presented with an increased number of mental disorder comorbidities. In contrast to our hypothesis, school closures were not related to the observed increase in ED. Discussion: In summary, the COVID-19 pandemic was associated with an increased rate of inpatient treatment for youth suffering from AN, and of youth affected by multiple mental disorders. Accordingly, we assume that inpatient admission was prioritized for individuals with a higher burden of disease during the COVID-19 pandemic. Our findings pinpoint the need for adequate inpatient mental health treatment capacities during environmental crises, and a further strengthening of child and adolescence psychiatry services in Germany.

Dynamic redistribution of paxillin in bovine osteoblasts stimulated with adenosine 5'-triphosphate.

Exposure to extracellular 5'-adenosine triphosphate (ATP) is known to induce membrane blebbing. In this study, we investigated the subcellular distribution of the cytoskeletal adaptor protein paxillin in primary bovine osteoblasts upon stimulation with ATP. Cells expressing a fusion protein of green fluorescent protein (GFP) and paxillin were followed by time-lapse video-microscopy after stimulation with 100 µM ATP. Within 100 s, GFP-paxillin became incorporated in numerous de novo formed focal aggregates localized at the cell periphery. The assembly of individual paxillin-containing aggregates occurred with a mean half-life time of <60 s, whereas their disassembly lasted twice as long. Despite the ongoing presence of ATP, the formation of paxillin aggregates was self-limiting within 25 min. Paxillin clustering was preceded by a transient rise in cytoplasmic calcium transients, which peaked already 20 s after adding ATP. The high mobility of paxillin was confirmed by measuring the dissociation rate of GFP-paxillin at mature focal adhesions, demonstrating the presence of a highly mobile fraction with a mean recovery half-life of 8.2 ± 1.2 s, followed by a slower phase (53 ± 20 s). Thus, both the exchange of paxillin at mature focal adhesions and the increase in intracellular calcium concentrations upon ATP stimulation are very rapid processes, which override the time course of ATP-induced paxillin membrane clustering by one to two orders of magnitude. Our data demonstrate that the transient recruitment of paxillin in membrane protuberances is based on the high intracytoplasmic mobility of unbound paxillin molecules and their rapid focal accumulation.

The additive effect of p53 Arg72Pro and RNASEL Arg462Gln genotypes on age of disease onset in Lynch syndrome patients with pathogenic germline mutations in MSH2 or MLH1.

p53 and the prostate-cancer-susceptibility gene RNASEL are tumour suppressor genes involved in apoptosis. We have previously reported that the common, functionally different variants Arg72Pro in p53 and Arg462Gln in RNASEL are associated with the age of disease onset of colorectal cancer in Lynch syndrome patients. To assess the combined effect of both variants, we screened 246 unrelated Lynch syndrome patients with a pathogenic germline mutation either in MSH2 (n=138) or in MLH1 (n=108) and colorectal cancer as first tumour, and 245 healthy controls. The global log rank test revealed significant differences in the age of disease onset for the genotypes of each variant (p=0.0176 for p53 and p=0.0358 for RNASEL) and for the combined genotypes of both variants (p=0.0174). The highest difference in median age of disease onset was seen between homozygotes for the wild-types in both genes (42years [range 22-75]) and homozygotes for the variant alleles in both genes (30years [range 26-47]). A multivariate Cox regression model indicated that only the p53 and RNASEL genotypes had a significant influence on age of disease onset (p=0.016 for p53 and p=0.014 for RNASEL) in an additive mode of inheritance, and that the effects of both variants are purely additive, which supports the notion that the p53 and RNaseL pathways do not interact. These findings may be relevant for preventive strategies in Lynch syndrome.

Arg462Gln sequence variation in the prostate-cancer-susceptibility gene RNASEL and age of onset of hereditary non-polyposis colorectal cancer: a case-control study.

BACKGROUND: RNASEL is thought to be a susceptibility gene for hereditary prostate cancer and encodes the endoribonuclease RNase L, which has a role in apoptosis and is a candidate tumour-suppressor protein. A common sequence variation in RNASEL, Arg462Gln, has been associated with hereditary and sporadic prostate cancer, and the Gln variant has about three-fold reduced RNase activity in vitro. In view of the association between the age of onset of hereditary non-polyposis colorectal cancer and functionally different variants of P53, which play a key part in the apoptotic pathway, we aimed to assess whether the Arg462Gln variation of RNASEL affects the age of onset of hereditary non-polyposis colorectal cancer. METHODS: We screened 251 patients with hereditary non-polyposis colorectal cancer who were unrelated, had pathogenic germline mutations in MSH2 (n=141) or MLH1 (n=110), and had colorectal carcinoma as the first tumour, for variation at codon 462 of RNASEL and compared them with 439 healthy controls. FINDINGS: The median age of onset was 40 years (range 17-75) for patients with an Arg/Arg genotype at codon 462, 37 years (13-69) for patients with an Arg/Gln genotype, and 34 years (20-49) for those with a Gln/Gln genotype (p=0.0198). Only the RNASEL genotype had a significant effect on age of onset (p=0.0062) in an additive mode of inheritance. Pair-wise comparisons between genotype groups showed that the two homozygous groups (ie, Arg/Arg vs Gln/Gln) differed significantly in age of disease onset (mean age difference 4.8 years [SD 1.7], p=0.0044). INTERPRETATION: A sequence variation in the prostate-cancer-susceptibility gene RNASEL has a role in a different, unassociated malignant disease. Genotypes at RNASEL codon 462 are associated with age of onset of hereditary non-polyposis colorectal cancer in a dose-dependent way, and might have a role in preventive strategies for this disease.