Identification of human host factors required for beta-defensin-2 expression in intestinal epithelial cells upon a bacterial challenge.

The human intestinal tract is colonized with microorganisms, which present a diverse array of immunological challenges. A number of antimicrobial mechanisms have evolved to cope with these challenges. A key defense mechanism is the expression of inducible antimicrobial peptides (AMPs), such as beta-defensins, which rapidly inactivate microorganisms. We currently have a limited knowledge of mechanisms regulating the inducible expression of AMP genes, especially factors from the host required in these regulatory mechanisms. To identify the host factors required for expression of the beta-defensin-2 gene (HBD2) in intestinal epithelial cells upon a bacterial challenge, we performed a RNAi screen using a siRNA library spanning the whole human genome. The screening was performed in duplicate to select the strongest 79 and 110 hit genes whose silencing promoted or inhibited HBD2 expression, respectively. A set of 57 hits selected among the two groups of genes was subjected to a counter-screening and a subset was subsequently validated for its impact onto HBD2 expression. Among the 57 confirmed hits, we brought out the TLR5-MYD88 signaling pathway, but above all new signaling proteins, epigenetic regulators and transcription factors so far unrevealed in the HBD2 regulatory circuits, like the GATA6 transcription factor involved in inflammatory bowel diseases. This study represents a significant step toward unveiling the key molecular requirements to promote AMP expression in human intestinal epithelial cells, and revealing new potential targets for the development of an innovative therapeutic strategy aiming at stimulating the host AMP expression, at the era of antimicrobial resistance.

Pathologic Analysis of Twenty-one Appendices From Children With Multisystem Inflammatory Syndrome Compared to Specimens of Acute Appendicitis: A Cross-sectional Study.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a rare, severe complication of coronavirus disease 2019, commonly involving the gastrointestinal tract. Some children with MIS-C undergo appendectomy before the final diagnosis. There are several hypotheses explaining the pathomechanism of MIS-C, including the central role of the viral antigen persistence in the gut, associated with lymphocyte exhaustion. We aimed to examine appendectomy specimens from MIS-C patients and assess their pathologic features, as well as the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens. METHODS: In this cross-sectional study we included 21 children with MIS-C who underwent appendectomy. The control group included 21 sex- and age-matched children with acute appendicitis (AA) unrelated to SARS-CoV-2 infection. Histologic evaluation of appendiceal specimens included hematoxylin and eosin staining and immunohistochemical identification of lymphocyte subpopulations, programmed cell death protein-1 (PD-1) and SARS-CoV-2 nucleocapsid antigen. RESULTS: Appendices of MIS-C patients lacked neutrophilic infiltrate of muscularis propria typical for AA (14% vs. 95%, P < 0.001). The proportion of CD20+ to CD5+ cells was higher in patients with MIS-C (P = 0.04), as was the proportion of CD4+ to CD8+ (P < 0.001). We found no proof of SARS-CoV-2 antigen presence, nor lymphocyte exhaustion, in the appendices of MIS-C patients. CONCLUSIONS: The appendiceal muscularis of patients with MIS-C lack edema and neutrophilic infiltration typical for AA. SARS-CoV-2 antigens and PD-1 are absent in the appendices of children with MIS-C. These findings argue against the central role of SARS-CoV-2 persistence in the gut and lymphocyte exhaustion as the major triggers of MIS-C.

The anti-infective effect of ß-glucans in children.

Background: ß-glucans are bioactive ß-D-glucose polysaccharides of natural origin, presenting antimicrobial and immunomodulation properties, with a low risk of toxicity. Objectives: This scoping review aims to present the current knowledge on the anti-infective properties of ß-glucans in the pediatric population. Methods: We used the PRISMA Extension for Scoping Reviews Checklist to prepare this review. Studies were identified by electronic searches of Pubmed, Embase, and Cochrane databases up to May 2021. Results: The primary search allowed us to find 6232 studies, twelve of which were finally included in the analysis. Eight studies were designed as randomized, placebo-controlled trials, while in four studies the intervention outcome was compared with the pre-intervention period in the same group. The type of preparation and doses varied between studies: in five trials pleuran was administered (in dose 10 mg/5 kg of body weight/day), and in one study baker's yeast ß-glucan was used (in two doses: 35 mg/day and 75 mg/day). In six other studies, the analyzed preparation comprised ß-glucan and other substances. The shortest study lasted seven days, while the most prolonged intervention lasted six months, followed by six months of follow-up. Ten out of twelve trials demonstrated the effectiveness of ß-glucans in reducing respiratory tract infection incidence or alleviation of upper respiratory tract infection symptoms. Ten out of twelve studies have reported a good tolerance and safety profile. Conclusions: Good tolerance of ß-glucans shows a favorable benefit-risk ratio of this type of intervention. Nevertheless, further monitoring of their efficacy and safety in high-quality research is necessary.

Monte Carlo Regression for Evaluating Children's Role in the Pandemic Spread on the Example of Delta COVID-19 Wave.

BACKGROUND: The children's role in transmitting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the familial settings is uncertain. We aimed to assess how often children were the index cases transmitting SARS-CoV-2 into their households during the Delta wave, and to identify risk factors of children being the index case. METHODS: In this prospective survey study, we collected information regarding household members of SARS-CoV-2-positive children tested in a single tertiary hospital. Some patients were tested with polymerase chain reaction and those samples were typed and classified as Delta or non-Delta variant. We have used the Monte Carlo approach to assess predictors of children being the index case in the household. RESULTS: We surveyed 629 families and 515 of them fulfilled inclusion criteria. The child was the index case in 359 (69.71%) households. Attending childcare facilities in all age groups was positively associated with being the index case in the household [nursery, estimate = 1.456, 95% confidence interval (CI): 1.456-1.457, P < 0.001; kindergarten, estimate = 0.899, 95% CI: 0.898-0.900, P = 0.003; school, estimate = 1.23, 95% CI: 1.229-1.231, P = 0.001]. The same association was present in the subgroup of the families with the predominant Delta variant, but not in the subgroup with the predominant non-Delta variant. CONCLUSIONS: Attending childcare and educational facilities might be a significant predictor of a child being the SARS-CoV-2 index case in their household. Children's role in driving the SARS-CoV-2 pandemic changes in consecutive waves. The Monte Carlo approach can be applied to assess risk factors of infectious agents' spread in future epidemics.

Clinical efficacy of kinesiology taping in reducing edema of the lower limbs in patients treated with the ilizarov method--preliminary report.

INTRODUCTION: Postoperative edema of predominantly lymphatic origin is a significant hindrance to physiotherapy in patients subjected to limb lengthening by the Ilizarov method. New treatment methods are being sought, and Kinesiology Taping is one of them. MATERIAL AND METHODS: The study involved 24 patients of both sexes subjected to lower limb lengthening using the Ilizarov method who had developed edema of the thigh or crus of the lengthened extremity. The mean age of the patients was 21 years. The patients were randomized into two groups of twelve, which were then subjected to 10 days of standard physiotherapy. The study group was additionally treated with Kinesiology Taping (lymphatic application), while the control group received standard lymphatic drainage. Treatment results were assessed by comparing the linear circumferences of the lower limbs before and after the treatment. RESULTS: The application of Kinesiology Taping in the study group produced a decrease in the circumference of the thigh and crus statistically more significant than that following lymphatic drainage. CONCLUSIONS: 1. Both standard edema-reducing treatment in the form of lymphatic massage and Kinesiology Taping significantly reduced lower limb edema in patients treated by the Ilizarov method. 2. The application of Kinesiology Taping in the study group produced a significantly faster reduction of the edema compared to standard lymphatic massage.