Changes in epithelial tight junction protein expression and apoptosis increase epithelial permeability in inflammatory bowel diseases. The effect of the probiotic mixture VSL#3 on the epithelial barrier was studied in dextran sodium sulfate (DSS)-induced colitis in mice. Acute colitis was induced in BALB/c mice (3.5% DSS for 7 days). Mice were treated with either 15 mg VSL#3 or placebo via gastric tube once daily during induction of colitis. Inflammation was assessed by clinical and histological scores. Colonic permeability to Evans blue was measured in vivo. Tight junction protein expression and epithelial apoptotic ratio were studied by immunofluorescence and Western blot. VSL#3 treatment reduced inflammation (histological colitis scores: healthy control 0.94 +/- 0.28, DSS + placebo 14.64 +/- 2.55, DSS + VSL#3 8.43 +/- 1.82; P = 0.011). A pronounced increase in epithelial permeability in acute colitis was completely prevented by VSL#3 therapy [healthy control 0.4 +/- 0.07 (extinction/g), DSS + placebo 5.75 +/- 1.67, DSS + VSL#3 0.26 +/- 0.08; P = 0.003]. In acute colitis, decreased expression and redistribution of the tight junction proteins occludin, zonula occludens-1, and claudin-1, -3, -4, and -5 were observed, whereas VSL#3 therapy prevented these changes. VSL#3 completely prevented the increase of epithelial apoptotic ratio in acute colitis [healthy control 1.58 +/- 0.01 (apoptotic cells/1,000 epithelial cells), DSS + placebo 13.33 +/- 1.29, DSS + VSL#3 1.72 +/- 0.1; P = 0.012]. Probiotic therapy protects the epithelial barrier in acute colitis by preventing 1) decreased tight junction protein expression and 2) increased apoptotic ratio.

Background: Due to the substantial proportion of asymptomatic and mild courses many SARS-CoV-2 infections remain unreported. Therefore, assessment of seroprevalence may detect the real burden of disease. We aimed at determining and characterizing the rate of SARS-CoV-2 infections and the resulting immunity in a defined population. Methods: CoNAN is a population-based cohort study in the previously quarantined community Neustadt-am-Rennsteig, Germany six weeks after a SARS-CoV-2 outbreak with 49 cases identified by PCR screening of all 883 inhabitants. The primary objective of the study was to assess SARS-CoV-2 antibody seroconversion rate using six different IgG detecting immunoassays. Secondary objectives of the study were: i.) to determine the rate of seroconversion in children; ii.) to determine potential risk factors for symptomatic vs. asymptomatic Covid19 courses; iii.) to investigate the rate of virus persistence. Findings: We enrolled 626 participants (71% of the community population). All actual SARS-CoV-2 PCR tests were negative; while a total of 8.4% (52 of 620 tested) had antibodies against SARS-CoV-2 in at least two independent tests. Twenty of the antibody positive participants had previously a positive SARS-CoV-2 PCR. On the contrary, of those 38 participants with SARS-CoV-2 infection, only 20 (52.6%) were antibody positive. Interpretation: Several antibody tests conducted six weeks after an outbreak of SARS-CoV-2 did not detect all previously PCR-positive tested individuals. Cautious evaluation of antibody testing strategies to assess immunity against the infection is warranted.

Vaccination in the SARS-CoV-2 pandemic is important, especially to protect pregnant women and the unborn. In 2021, the messenger RNA (mRNA)-based vaccines BNT162b2 (BioNTech/Pfizer) and mRNA-1273 (Moderna), and the vector-based vaccine AZD1222 (AstraZeneca) were approved for use in Germany. 1 Vaccination for pregnant women was considered after weighing the individual benefits and risks of the vaccines without preference for a vaccine type. 1 After national guidelines discouraged the use of AZD1222 in those under 60 years of age, 1 mRNA-based boost vaccination was recommended. In this study we intend to evaluate antibody kinetics following heterologous vaccination in pregnant women in comparison to their newborns as well as to a healthy nonpregnant control group. STUDY DESIGN:We recruited 3 pregnant participants (gestational age at primary vaccination between 21 and 28 weeks) and 25 nonpregnant control participants at the Jena University Hospital. They were observed after prime vaccination with AZD1222 and boost vaccination 12 weeks thereafter with either BNT162b2 or mRNA-1273. Ethical approval was obtained for the same (Jena University Hospital ethics commission ref.: 2021-2078). The anti-Spike immunoglobulin G (IgG) antibody levels were determined in the serial serum samples (before and 1, 2, 3, 4, 5, 8, and 16 weeks after prime

Inhaled endotoxin, lipopolysaccharide (LPS), has been shown to result in bronchial hyperresponsiveness (BHR) to endogenous bronchoconstrictive mediators such as histamine. To determine the role of sensory neuropeptides released from bronchopulmonary C-fibers in LPS-induced BHR, 24 guinea pigs were allocated randomly to the following four groups. Animals in Groups I and IV were challenged with intratracheal instillation of 100 microliters of saline vehicle, and those in Groups II and III with 1 mg of LPS (Escherichia coli, 0111:B4) in 100 microliters of saline. Groups III and IV also received a high dose capsaicin (HDC) treatment to deplete tachykinins from C-fibers 1-2 weeks prior to the experiment. Animals were anesthetized and paralyzed, and total lung resistance (RL) and compliance (Cdyn) were measured continuously during the experiment. Dose responses of RL and Cdyn to histamine (0-8 micrograms/kg, intravenously) and capsaicin (0-1.6 micrograms/kg, intravenously), a specific C-fiber stimulant, were obtained prior to and at 1, 2, and 3 h following LPS/saline vehicle challenge. At 2 h after LPS, delta RL caused by histamine (8 micrograms/kg) was significantly higher in Group II (1.145%) than that in Group I (280%; p < 0.05); similarly, delta RL caused by capsaicin (1.6 micrograms/kg) was also increased after LPS (Group I, 107%; Group II, 267%; p < 0.05). Although HDC treatment completely abolished the bronchomotor response to capsaicin in both Groups III and IV, it enhanced the LPS-induced BHR to histamine (8 micrograms/kg; Group III, 1.834%; p < 0.05). In conclusion, these results suggest that the role of tachykinins in LPS-induced BHR may be dependent upon the type and the route of administration of the bronchoactive substance studied.

Background: Infective endocarditis (IE) requires multidisciplinary management. We established an endocarditis team within our hospital in 2011 and a state-wide endocarditis network with referring hospitals in 2015. We aimed to investigate their impact on perioperative outcomes. Methods: We retrospectively analyzed data from patients operated on for IE in our center between 01/2007 and 03/2018. To investigate the impact of the endocarditis network on referral latency and pre-operative complications we divided patients into two eras: before (n = 409) and after (n = 221) 01/2015. To investigate the impact of the endocarditis team on post-operative outcomes we conducted multivariate binary logistic regression analyses for the whole population. Kaplan–Meier estimates of 5-year survival were reported. Results: In the second era, after establishing the endocarditis network, the median time from symptoms to referral was halved (7 days (interquartile range: 2–19) vs. 15 days (interquartile range: 6–35)), and pre-operative endocarditis-related complications were reduced, i.e., stroke (14% vs. 27%, p < 0.001), heart failure (45% vs. 69%, p < 0.001), cardiac abscesses (24% vs. 34%, p = 0.018), and acute requirement of hemodialysis (8% vs. 14%, p = 0.026). In both eras, a lack of recommendations from the endocarditis team was an independent predictor for in-hospital mortality (adjusted odds ratio: 2.12, 95% CI: 1.27–3.53, p = 0.004) and post-operative stroke (adjusted odds ratio: 2.23, 95% CI: 1.12–4.39, p = 0.02), and was associated with worse 5-year survival (59% vs. 40%, log-rank < 0.001). Conclusion: The establishment of an endocarditis network led to the earlier referral of patients with fewer pre-operative endocarditis-related complications. Adhering to endocarditis team recommendations was an independent predictor for lower post-operative stroke and in-hospital mortality, and was associated with better 5-year survival.