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We document mental and social distress of children, adolescents and adults, using data on 3 million calls to German helplines between January 2019 and May 2022. High-frequency data from crisis helpline logs offer rich information on the evolution of "revealed distress" among the most vulnerable, unaffected by researchers' study design and framing. Distress of adults, measured by the volume of calls, rose significantly after both the outbreak of the pandemic and the Russian invasion of Ukraine. In contrast, the overall revealed distress of children and adolescents did not increase during those crises. The nature of young people's concerns, however, changed more strongly than for adults after the COVID-19 outbreak. Consistent with the effects of social distancing, call topics of young people shifted from problems with school and peers to problems with family and mental health. We find the share of severe mental health problems among young people to have increased with a delay, in the second and third year of the pandemic., (© 2023. The Author(s).)

The frequency and severity of extreme events related to climate change have intensified worldwide in the last decades. It is documented that increasing extreme rainfall and flooding cause more nutrient runoff into waterbodies, initiating numerous harmful algal bloom (HAB) events, especially in fragile ecosystems. We analyze the dramatic economic damage of one of these episodes in Mar Menor, the largest salt-water lagoon in Europe. We show that when the public perceived the severity of environmental degradation, the return on housing investment was 43% lower in the surroundings than in similar neighboring zones 6 years after the HAB (2015). This represents a loss in housing wealth of more than 4000 million euros, around ten times the gains of changing from dry-farming to irrigated crops, which makes this ecosystem fragile. Hence, we quantify some of the economic consequences of ecological deterioration linked to episodes of Global Climate Change., (© 2023. The Author(s).)

Little is known about patients with sickle cell disease (SCD) who require intensive care unit (ICU) admission. The goals of this study were to assess outcomes in patients admitted to the ICU for acute complications of SCD and to identify factors associated with adverse outcomes. This multicenter retrospective study included consecutive adults with SCD admitted to one of 17 participating ICUs. An adverse outcome was defined as death or a need for life-sustaining therapies (non-invasive or invasive ventilation, vasoactive drugs, renal replacement therapy, and/or extracorporeal membrane oxygenation). Factors associated with adverse outcomes were identified by mixed multivariable logistic regression. We included 488 patients admitted in 2015-2017. The main reasons for ICU admission were acute chest syndrome (47.5%) and severely painful vaso-occlusive event (21.3%). Sixteen (3.3%) patients died in the ICU, mainly of multi-organ failure following a painful vaso-occlusive event or sepsis. An adverse outcome occurred in 81 (16.6%; 95% confidence interval [95% CI], 13.3%-19.9%) patients. Independent factors associated with adverse outcomes were low mean arterial blood pressure (adjusted odds ratio [aOR], 0.98; 95% CI 0.95-0.99; p = 0.027), faster respiratory rate (aOR, 1.09; 95% CI 1.05-1.14; p < 0.0001), higher haemoglobin level (aOR, 1.22; 95% CI 1.01-1.48; p = 0.038), impaired creatinine clearance at ICU admission (aOR, 0.98; 95% CI 0.97-0.98; p < 0.0001), and red blood cell exchange before ICU admission (aOR, 5.16; 95% CI 1.16-22.94; p = 0.031). Patients with SCD have a substantial risk of adverse outcomes if they require ICU admission. Early ICU admission should be encouraged in patients who develop abnormal physiological parameters., (© 2021. The Author(s).)

Rising temperature levels during spring and summer are often argued to enable lifting of strict containment measures even in the absence of herd immunity. Despite broad scholarly interest in the relationship between weather and coronavirus spread, previous studies come to very mixed results. To contribute to this puzzle, the paper examines the impact of weather on the COVID-19 pandemic using a unique granular dataset of over 1.2 million daily observations covering over 3700 counties in nine countries for all seasons of 2020. Our results show that temperature and wind speed have a robust negative effect on virus spread after controlling for a range of potential confounding factors. These effects, however, are substantially larger during mealtimes, as well as in periods of high mobility and low containment, suggesting an important role for social behaviour., (© 2021. The Author(s).)

Idiopathic pulmonary fibrosis is a progressive disease with unsatisfactory systemic treatments. Aerosol drug delivery to the lungs is expected to be an interesting route of administration. However, due to the alterations of lung compliance caused by fibrosis, local delivery remains challenging. This work aimed to develop a practical, relevant and ethically less restricted ex vivo respiratory model of fibrotic lung for regional aerosol deposition studies. This model is composed of an Ear-Nose-Throat replica connected to a sealed enclosure containing an ex vivo porcine respiratory tract, which was modified to mimic the mechanical properties of fibrotic lung parenchyma - i.e. reduced compliance. Passive respiratory mechanics were measured. 81m Kr scintigraphies were used to assess the homogeneity of gas-ventilation, while regional aerosol deposition was assessed with 99m Tc-DTPA scintigraphies. We validated the procedure to induce modifications of lung parenchyma to obtain aimed variation of compliance. Compared to the healthy model, lung respiratory mechanics were modified to the same extent as IPF-suffering patients. 81m Kr gas-ventilation and 99m Tc-DTPA regional aerosol deposition showed results comparable to clinical studies, qualitatively. This ex vivo respiratory model could simulate lung fibrosis for aerosol regional deposition studies giving an interesting alternative to animal experiments, accelerating and facilitating preclinical studies before clinical trials.

Neutrophil serine proteases (NSPs), like proteinase 3 (PR3) and neutrophil elastase (NE) are implicated in ischemia-reperfusion responses after lung transplantation (LTx). Cathepsin C (CatC) acts as the key regulator of NSP maturation during biosynthesis. We hypothesized that CatC inhibitors would reduce vascular breakdown and inflammation during reperfusion in pretreated lung transplant recipients by blocking NSP maturation in the bone marrow. An orthotopic LTx model in mice was used to mimic the induction of an ischemia-reperfusion response after 18 h cold storage of the graft and LTx. Recipient mice were treated subcutaneously with a chemical CatC inhibitor (ICatC) for 10 days prior to LTx. We examined the effect of the ICatC treatment by measuring the gas exchange function of the left lung graft, protein content, neutrophil numbers and NSP activities in the bone marrow 4 h after reperfusion. Pre-operative ICatC treatment of the recipient mice improved early graft function and lead to the disappearance of active NSP protein in the transplanted lung. NSP activities were also substantially reduced in bone marrow neutrophils. Preemptive NSP reduction by CatC inhibition may prove to be a viable and effective approach to reduce immediate ischemia reperfusion responses after LTx.

Enterococcus faecalis, an organism generally not pathogenic for healthy humans, has the potential to cause disease in susceptible hosts. While it seems to be equipped to interact with and circumvent host immune defense, most of the molecular and cellular mechanisms underlying the enterococcal infectious process remain elusive. Here, we investigated the role of the Enterococcal Leucine Rich protein A (ElrA), an internalin-like protein of E. faecalis also known as a virulence factor. ElrA was previously shown to prevent adhesion to macrophages. We show that ElrA does not inhibit the basic phagocytic process, but is able to prevent sensing and migration of macrophages toward E. faecalis. Presence or absence of FHL2, a eukaryotic partner of ElrA, does not affect the ElrA-dependent mechanism preventing macrophage migration. However, we highlight a partial contribution of FHL2 in ElrA-mediated virulence in vivo. Our results indicate that ElrA plays at least a dual role of which anti-phagocytic activity may contribute to dissemination of extracellular E. faecalis during infection.