The COVID-19 pandemic has caused strains on health systems worldwide disrupting routine hospital services for all non-COVID patients. Within this retrospective study, we analyzed inpatient hospital admissions across 18 German university hospitals during the 2020 lockdown period compared to 2018. Patients admitted to hospital between January 1 and May 31, 2020 and the corresponding periods in 2018 and 2019 were included in this study. Data derived from electronic health records were collected and analyzed using the data integration center infrastructure implemented in the university hospitals that are part of the four consortia funded by the German Medical Informatics Initiative. Admissions were grouped and counted by ICD 10 chapters and specific reasons for treatment at each site. Pooled aggregated data were centrally analyzed with descriptive statistics to compare absolute and relative differences between time periods of different years. The results illustrate how care process adoptions depended on the COVID-19 epidemiological situation and the criticality of the disease. Overall inpatient hospital admissions decreased by 35% in weeks 1 to 4 and by 30.3% in weeks 5 to 8 after the lockdown announcement compared to 2018. Even hospital admissions for critical care conditions such as malignant cancer treatments were reduced. We also noted a high reduction of emergency admissions such as myocardial infarction (38.7%), whereas the reduction in stroke admissions was smaller (19.6%). In contrast, we observed a considerable reduction in admissions for non-critical clinical situations, such as hysterectomies for benign tumors (78.8%) and hip replacements due to arthrosis (82.4%). In summary, our study shows that the university hospital admission rates in Germany were substantially reduced following the national COVID-19 lockdown. These included critical care or emergency conditions in which deferral is expected to impair clinical outcomes. Future studies are needed to delineate how appropriate medical care of critically ill patients can be maintained during a pandemic.

Interface dermatitis is a characteristic histological pattern that occurs in autoimmune and chronic inflammatory skin diseases. It is unknown whether a common mechanism orchestrates this distinct type of skin inflammation. Here we investigated the overlap of two different interface dermatitis positive skin diseases, lichen planus and lupus erythematosus. The shared transcriptome signature pointed toward a strong type I immune response, and biopsy-derived T cells were dominated by IFN-γ and tumor necrosis factor alpha (TNF-α) positive cells. The transcriptome of keratinocytes stimulated with IFN-γ and TNF-α correlated significantly with the shared gene regulations of lichen planus and lupus erythematosus. IFN-γ, TNF-α, or mixed supernatant of lesional T cells induced signs of keratinocyte cell death in three-dimensional skin equivalents. We detected a significantly enhanced epidermal expression of receptor-interacting-protein-kinase 3, a key regulator of necroptosis, in interface dermatitis. Phosphorylation of receptor-interacting-protein-kinase 3 and mixed lineage kinase domain like pseudokinase was induced in keratinocytes on stimulation with T-cell supernatant-an effect that was dependent on the presence of either IFN-γ or TNF-α in the T-cell supernatant. Small hairpin RNA knockdown of receptor-interacting-protein-kinase 3 prevented cell death of keratinocytes on stimulation with IFN-γ or TNF-α. In conclusion, type I immunity is associated with lichen planus and lupus erythematosus and induces keratinocyte necroptosis. These two mechanisms are potentially involved in interface dermatitis.

Purpose Evaluation of a lozenge for targeted micronutrition (holo-BLG), a new invention based on the farm effect, in house dust mite (HDM) allergic rhinoconjunctivitis (ARC) patients in a standardized allergen exposure chamber (AEC). Methods Eligible HDM allergic patients were exposed to HDM raw material in an AEC for 120 min before (V1) and after (V3) 3 months of holo-BLG supplementation. Nasal, conjunctival, bronchial and other symptoms were rated by the patients every 10 min and, wellbeing, peak nasal inspiratory flow (PNIF), and lung function parameters every 30 min. Primary endpoint was the change in median Total Nasal Symptom Score (TNSS) at V3 compared to V1 at 120 min of exposure. Secondary endpoints consisted of the exploratory analysis of the temporal evolution of symptom scores using linear mixed effects models. Results A total of 32 patients were included in the analysis. A significant improvement of 60% (p = 0.0034) in the primary endpoint TNSS (V1 2.5 [interquartile range, IQR 1–4], V3 1.0 [IQR 1–3]) was observed. 40% improvement was seen for the Total Symptom Score (V1 5.0 [IQR 3–9], V3 3.0 [IQR 2–4]; [Wilcoxon test: confidence interval 1.5–4.0, p < 0.0003]). The analysis of the temporal evolution of all symptom scores and the personal wellbeing revealed clinically meaningful improvement over time, manifested in a lower symptom increase during the final HDM exposure. No relevant differences were observed for PNIF and lung function parameters. Safety and tolerability were rated as excellent. Conclusions The effect of holo-BLG resulting in immune resilience might help to fight the allergy epidemic on a new front based on targeted micronutrition of immune cells. Trial registration The study was retrospectively registered at clinicaltrials.gov (NCT04477382).

Novel specific therapies for psoriasis and eczema have been developed, and they mark a new era in the treatment of these complex inflammatory skin diseases. However, within their broad clinical spectrum, psoriasis and eczema phenotypes overlap making an accurate diagnosis impossible in special cases, not to speak about predicting the clinical outcome of an individual patient. Here, we present a novel robust molecular classifier (MC) consisting of NOS2 and CCL27 gene that diagnosed psoriasis and eczema with a sensitivity and specificity of >95% in a cohort of 129 patients suffering from (i) classical forms; (ii) subtypes; and (iii) clinically and histologically indistinct variants of psoriasis and eczema. NOS2 and CCL27 correlated with clinical and histological hallmarks of psoriasis and eczema in a mutually antagonistic way, thus highlighting their biological relevance. In line with this, the MC could be transferred to the level of immunofluorescence stainings for iNOS and CCL27 protein on paraffin-embedded sections, where patients were diagnosed with sensitivity and specificity >88%. Our MC proved superiority over current gold standard methods to distinguish psoriasis and eczema and may therefore build the basis for molecular diagnosis of chronic inflammatory skin diseases required to establish personalized medicine in the field.

Background:The COVID-19 pandemic exposes individuals to multiple stressors, such as quarantine, physical distancing, job loss, risk of infection, and loss of loved ones. Such a complex array of stressors potentially lead to symptoms of adjustment disorder. Objective: This cross-sectional exploratory study examined relationships between risk and protective factors, stressors, and symptoms of adjustment disorder during the first year of the COVID-19 pandemic. Methods: Data from the first wave of the European Society of Traumatic Stress Studies (ESTSS) longitudinal ADJUST Study were used. N = 15,563 participants aged 18 years and above were recruited in eleven countries (Austria,

Distinct plasma miRNAs are differentially regulated both in murine and in human allergic asthma and were associated with clinical characteristics of patients. Thus, we suggest that miRNA levels in plasma might have future potential to subphenotype patients with asthma.

Plant growth and fertility strongly depend on environmental conditions such as temperature. Remarkably, temperature also influences meiotic recombination and thus, the current climate change will affect the genetic make-up of plants. To better understand the effects of temperature on meiosis, we followed male meiocytes in Arabidopsis thaliana by live cell imaging under three temperature regimes: at 21°C; at heat shock conditions of 30°C and 34°C; after an acclimatization phase of 1 week at 30°C. This work led to a cytological framework of meiotic progression at elevated temperature. We determined that an increase from 21°C to 30°C speeds up meiosis with specific phases being more amenable to heat than others. An acclimatization phase often moderated this effect. A sudden increase to 34°C promoted a faster progression of early prophase compared to 21°C. However, the phase in which cross-overs mature was prolonged at 34°C. Since mutants involved in the recombination pathway largely did not show the extension of this phase at 34°C, we conclude that the delay is recombination-dependent. Further analysis also revealed the involvement of the ATAXIA TELANGIECTASIA MUTATED kinase in this prolongation, indicating the existence of a pachytene checkpoint in plants, yet in a specialized form.

In human subjects imiquimod induces contact dermatitis with the distinctive feature that pDCs are the primary sensors, leading to an IL-23/T17 deviation. Despite these shortcomings, the human imiquimod model might be useful to investigate early pathogenic events and prove molecular concepts in patients with psoriasis.