BACKGROUND AND OBJECTIVES The worldwide SARS-CoV-2 virus pandemic challenges adolescents’ mental health. The aim of this study was to compare the number of pediatric intensive care unit (PICU) admissions after suicide attempts during the first German lockdown and one year later during a second, prolonged lockdown with pre-pandemic years. METHODS A retrospective multicenter study was conducted among 27 German PICUs. Cases <18 years admitted to the PICU due to accidents or injuries between March 16th and May 31st of 2017-2021 were identified based on ICD-10 codes (German modification) and patient data entered into a database. This study is a subset analysis on suicide attempts in adolescents aged 12–17.9 years. The Federal Statistics Office was queried for data on fatal suicides, which were available only for 2020 in adolescents aged 10–17.9 years. RESULTS Total admissions and suicide attempts declined during the first lockdown in 2020 (standardized morbidity ratio (SMR) 0.74 (95% CI 0.58–0.92) and 0.69 (0.43–1.04), respectively) and increased in 2021 (2.14 (SMR 1.86–2.45) and 2.84 (2.29–3.49), respectively). Fatal suicide rates remained stable between 2017–2019 and 2020 (1.57 v. 1.48/100,000 adolescent years) with monthly numbers showing no clear trend during the course of 2020. CONCLUSIONS This study shows a strong increase in serious suicide attempts among adolescents during the course of the pandemic in Germany. More research is needed to understand the relation between pandemic prevention measures and suicidal ideation to help implement mental health support for adolescents.

Clostridioides (C.) difficile produces the exotoxins TcdA and TcdB, which are the predominant virulence factors causing C. difficile associated disease (CDAD). TcdA and TcdB bind to target cells and are internalized via receptor-mediated endocytosis. Translocation of the toxins’ enzyme subunits from early endosomes into the cytosol depends on acidification of endosomal vesicles, which is a prerequisite for the formation of transmembrane channels. The enzyme subunits of the toxins translocate into the cytosol via these channels where they are released after auto-proteolytic cleavage. Once in the cytosol, both toxins target small GTPases of the Rho/Ras-family and inactivate them by mono-glucosylation. This in turn interferes with actin-dependent processes and ultimately leads to the breakdown of the intestinal epithelial barrier and inflammation. So far, therapeutic approaches to treat CDAD are insufficient, since conventional antibiotic therapy does not target the bacterial protein toxins, which are the causative agents for the clinical symptoms. Thus, directly targeting the exotoxins represents a promising approach for the treatment of CDAD. Lately, it was shown that ambroxol (Ax) prevents acidification of intracellular organelles. Therefore, we investigated the effect of Ax on the cytotoxic activities of TcdA and TcdB. Ax significantly reduced toxin-induced morphological changes as well as the glucosylation of Rac1 upon intoxication with TcdA and TcdB. Most surprisingly, Ax, independent of its effects on endosomal acidification, decreased the toxins’ intracellular enzyme activity, which is mediated by a catalytic glucosyltransferase domain. Considering its undoubted safety profile, Ax might be taken into account as therapeutic option in the context of CDAD.

BackgroundPreterm newborns typically require supplemental oxygen but hyperoxic conditions also damage the premature lung. Oxygen-induced lung damages are mainly studied in newborn mouse models using oxygen concentrations above 75% and looking at short-term effects. Therefore, we aimed at the investigation of long-term effects and their dependency on different oxygen concentrations.MethodsNewborn mice were exposed to moderate vs. severe hyperoxic air conditions (50 vs. 75% O2) for 14 days followed by a longer period of normoxic conditions. Lung-related parameters were collected at an age of 60 or 120 days.ResultsSevere hyperoxia caused lower alveolar density, enlargement of parenchymal air spaces and fragmented elastic fibers as well as higher lung compliance with peak airflow limitations and higher sensitivity to ventilation-mediated damages in later life. However, these long-term lung structural and functional changes did not restrict the voluntary physical activity. Also, they were not accompanied by ongoing inflammatory processes, increased formation of reactive oxygen species (ROS) or altered expressions of antioxidant enzymes (superoxide dismutases, catalase) and lung elasticity-relevant proteins (elastin, pro-surfactant proteins) in adulthood. In contrast to severe hyperoxia, moderate hyperoxia was less lung damaging but also not free of long-term effects (higher lung compliance without peak airflow limitations, increased ROS formation).ConclusionsSevere but not moderate neonatal hyperoxia causes emphysematous lungs without persisting oxidative stress and inflammation in adulthood. As the existing fragmentation of the elastic fibers seems to play a pivotal role, it indicates the usefulness of elastin-protecting compounds in the reduction of long-term oxygen-related lung damages.

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