Background While childhood asthma prevalence is rising in Westernized countries, farm children are protected. The mitogen‐activated protein kinase (MAPK) pathway with its negative regulator dual‐specificity phosphatase‐1 (DUSP1) is presumably associated with asthma development. Objectives We aimed to investigate the role of MAPK signaling in childhood asthma and its environment‐mediated protection, including a representative selection of 232 out of 1062 children from two cross‐sectional cohorts and one birth cohort study. Methods Peripheral blood mononuclear cells (PBMC) from asthmatic and healthy children were cultured upon stimulation with farm‐dust extracts or lipopolysaccharide. In subgroups, gene expression was analyzed by qPCR (PBMCs, cord blood) and NanoString technology (dendritic cells). Protein expression of phosphorylated MAPKs was measured by mass cytometry. Histone acetylation was investigated by chromatin immunoprecipitation. Results Asthmatic children expressed significantly less DUSP1 (p = .006) with reduced acetylation at histone H4 (p = .012) compared with healthy controls. Farm‐dust stimulation upregulated DUSP1 expression reaching healthy levels and downregulated inflammatory MAPKs on gene and protein levels (PBMCs; p ≤ .01). Single‐cell protein analysis revealed downregulated pMAPKs upon farm‐dust stimulation in B cells, NK cells, monocytes, and T‐cell subpopulations. Conclusion Lower DUSP1 baseline levels in asthmatic children and anti‐inflammatory regulation of MAPK in several immune cell types by farm‐dust stimulation indicate a regulatory function for DUSP1 for future therapy contributing to anti‐inflammatory characteristics of farming environments.

Acute cytotoxic effects of tested compounds could be revealed. However, results were significantly different from each other with ATP assay being the most sensitive one under the conditions tested. Thus, acute cytotoxicity can be dramatically underestimated if only standard XTT test is used.

Representative, actively collected surveillance data on asymptomatic SARS-CoV-2 infections in primary schoolchildren remain scarce. We evaluated the feasibility of a saliva mass screening concept and assessed infectious activity in primary schools. During a 10-week period from 3 March to 21 May 2021, schoolchildren and staff from 17 primary schools in Munich participated in the sentinel surveillance, cohort study. Participants were tested using the Salivette® system, testing was supervised by trained school staff, and samples were processed via reverse transcription quantitative polymerase chain reaction (RT-qPCR). We included 4433 participants: 3752 children (median age, 8 [range, 6–13] years; 1926 girls [51%]) and 681 staff members (median age, 41 [range, 14–71] years; 592 women [87%]). In total, 23,905 samples were processed (4640 from staff), with participants representing 8.3% of all primary schoolchildren in Munich. Only eight cases were detected: Five out of 3752 participating children (0.13%) and three out of 681 staff members (0.44%). There were no secondary cases. In conclusion, supervised Salivette® self-sampling was feasible, reliable, and safe and thus constituted an ideal method for SARS-CoV-2 mass screenings in primary schoolchildren. Our findings suggest that infectious activity among asymptomatic primary schoolchildren and staff was low. Primary schools appear to continue to play a minor role in the spread of SARS-CoV-2 despite high community incidence rates.

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Context Endogenous Cushing’s syndrome (CS) leads to profound immunosuppression. Successful surgery induces biochemical remission and reversal of immunosuppression, which is characterized by clinical signs of glucocorticoid withdrawal and associated with increased susceptibility to infections and thromboembolic complications. Objective We hypothesized that the glucocorticoid withdrawal phase is characterized by low-grade inflammation that may be related to patient-relevant outcomes. Patients and methods In this retrospective observational study, we analyzed longitudinal data from 80 patients with CS prospectively enrolled in the German Cushing’s registry between 2012 and 2021. All enrolled patients underwent successful surgery. In a second step, a case control study was performed in 25 of the patients with age-, gender- and BMI-matched control patients in whom hypercortisolism was excluded. Analyses included the inflammatory markers C-reactive protein and interleukin-6, as well as body composition, muscle function testing and quality of life questionnaires. The patients were studied during active CS and in the postoperative remission phase 1, 3, 6, 12 and 24 months after surgery. Results Compared to the preoperative phase and matched controls, patients with CS had increased systemic inflammatory markers in the early remission phase. One month following surgery, median (IQR) C-reactive protein was 0.48 mg/dL (0.14; 0.90) vs. 0.10 mg/dL (0.06; 0.39) during active CS (p ≤ 0.001). Similarly, interleukin-6 one month after surgery was 7.2 pg/mL (3.3; 11.7) vs. 1.7 pg/mL (1.5; 2.5) during active CS (p ≤ 0.001). Obesity and HbA1c were associated with increased inflammation levels. This proinflammatory state lasted until one year following surgery. Moreover, inflammatory markers during early remission showed an inverse correlation with long-term muscle function. Conclusion The glucocorticoid withdrawal phase is associated with a low-grade inflammatory state, which is particularly pronounced in obese and hyperglycemic patients and related to lower muscle function.