Winners vs. losers: Schistosoma mansoni intestinal and liver eggs exhibit striking differences in gene expression and immunogenicity.

The eggs of the blood fluke Schistosoma mansoni are the main cause of the clinical manifestations of chronic schistosomiasis. After laying, the egg "winners" attach to the endothelium of the mesenteric vein and, after a period of development, induce the growth of a small granuloma, which facilitates their passage to the intestinal lumen. Egg "losers" carried by the bloodstream to non-specific tissues also undergo full development and induce large granuloma formation, but their life ends there. Although these trapped eggs represent a dead end in the parasite life cycle, the vast majority of studies attempting to describe the biology of the S. mansoni eggs have studied these liver-trapped "losers" instead of migrating intestinal "winners". This raises the fundamental question of how these eggs differ. With robust comparative transcriptomic analysis performed on S. mansoni eggs isolated 7 weeks post infection, we show that gene expression is critically dependent on tissue localization, both in the early and late stages of development. While mitochondrial genes and venom allergen-like proteins are significantly upregulated in mature intestinal eggs, well-described egg immunomodulators IPSE/alpha-1 and omega-1, together with micro-exon genes, are predominantly expressed in liver eggs. In addition, several proteases and protease inhibitors previously implicated in egg-host interactions display clear tissue-specific gene expression patterns. These major differences in gene expression could be then reflected in the observed different ability of liver and intestinal soluble egg antigens to elicit host immune responses and in the shorter viability of miracidia hatched from liver eggs. Our comparative analysis provides a new perspective on the biology of parasite's eggs in the context of their development and tissue localization. These findings could contribute to a broader and more accurate understanding of parasite eggs interactions with the host, which have historically been often restricted to liver eggs and sometimes inaccurately generalized.

Bsep/Abcb11 knockout ameliorates Schistosoma mansoni liver pathology by reducing parasite fecundity.

BACKGROUND AND AIMS: Schistosoma mansoni infection is one of the worldwide leading causes of liver fibrosis and portal hypertension. The objective of this study was to evaluate whether polyhydroxylated bile acids (BAs), known to protect mice from the development of acquired cholestatic liver injury, counteract S. mansoni-induced inflammation and fibrosis. METHODS: Adult FVB/N wild type (WT) and Abcb11/Bsep-/- mice were infected with either 25 or 50 S. mansoni cercariae. Eight weeks post infection, effects on liver histology, serum biochemistry, gene expression profile of proinflammatory cytokines and fibrotic markers, hepatic hydroxyproline content and FACS analysis were performed. RESULTS: Bsep-/- mice infected with S. mansoni showed significantly less hepatic inflammation and tendentially less fibrosis compared to infected WT mice. Despite elevated alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase levels in infected Bsep-/- mice, inflammatory cells such as M2 macrophages and Mac-2/galectin-3+ cells were reduced in these animals. Accordingly, mRNA-expression levels of anti-inflammatory cytokines (IL-4 and IL-13) were increased in Bsep-/- mice upon infection. Furthermore, infected Bsep-/- mice exhibited decreased hepatic egg load and parasite fecundity, consequently affecting the worm reproduction rate. This outcome could arise from elevated serum BA levels and lower blood pH in Bsep-/- mice. CONCLUSIONS: The loss of Bsep and the resulting changes in bile acid composition and blood pH are associated with the reduction of parasite fecundity, thus attenuating the development of S. mansoni-induced hepatic inflammation and fibrosis.

Single-dose SARS-CoV-2 vaccinations with either BNT162b2 or AZD1222 induce disparate Th1 responses and IgA production.

BACKGROUND: While vaccination programs against the severe acute respiratory syndrome virus 2 (SARS-CoV-2) are globally ongoing, disparate strategies for the deployment of spike antigen show varying effectiveness. METHODS: In order to explore this phenomenon, we sought to compare the early immune responses against AZD1222 and BNT162b2. SARS-CoV-2 seronegative participants received a single dose of either vaccine and were analyzed for immune cell, effector T cell, and antibody dynamics. RESULTS: AZD1222 induced transient leukopenia and major changes among innate and adaptive subpopulations. Both vaccines induced spike protein-specific effector T cells which were dominated by type 1 helper T cell responses following AZD1222 vaccination. A significant reduction of anti-inflammatory T cells upon re-stimulation was also restricted to AZD1222 vaccinees. While IgM and IgG were the dominant isotypes elicited by AZD1222, BNT162b2 led to a significant production of IgG and IgA. CONCLUSIONS: Our results suggest that the strategy for spike protein delivery impacts on how and to what extent immune priming against the main SARS-CoV-2 antigen proceeds.

Human serum activates the tegument of female schistosomes and supports recovery from Praziquantel.

Schistosomiasis is one of the most devastating parasitic disease in the world. Schistosoma spp. survive for decades within the vasculature of their human hosts. They have evolved a vast array of mechanisms to avoid the immune reaction of the host. Due to their sexual dimorphism, with the female worm lying within the gynecophoric canal of the male worm, it is the male that is exposed to the immediate environment and the soluble parts of the host's immune response. To understand how the worms are so successful in fending off the immune attacks of the host, comparative analyses of both worm sexes in human serum (with or without Praziquantel) were performed using scanning electron microscopy, transmission electron microscopy, and immunohistochemistry. Further, gene expression analyses of tegument-specific genes were performed. Following the incubation in human serum, males and females out of pairs show morphological changes such as an altered structure of the pits below the surface and an increased number of pits per area. In addition, female schistosomes presented a marked tuft-like repulsion of their opsonized surface. The observed resistance of females to Praziquantel seemed to depend on active proteins in the human serum. Moreover, different expression profiles of tegument-specific genes indicate different functions of female_single and male_single teguments in response to human serum. Our results indicate that female schistosomes developed different evasion strategies toward the host's immune system in comparison to males that might lead to more robustness and has to be taken into account for the development of new anti-schistosomal drugs.

[Challenges of the COVID-19 Pandemic for Schools in Mecklenburg-Vorpommern - First Results of a Prospective Case Study]. / Herausforderungen der COVID-19-Pandemie für Schulen in Mecklenburg-Vorpommern ­ erste Ergebnisse einer prospektiven Fallstudie.

BACKGROUND: The current risk of infection with SARS-CoV-2 in schools continues to be a subject of controversy. METHODOLOGY: "schugi-MV" collects data on the incidence of infection, hygiene management and other factors in structured inspections of schools in Mecklenburg-Western Pomerania. Recommendations for safe teaching are to be derived from the results. This article presents information on the first 10 schools visited between 18.12.2020 and 20.01.2021. RESULTS: At the schools visited, the ratio of the number of index cases among adults and children was 1:1.25. The inspections showed a great heterogeneity of schools and school buildings and the resulting possibilities for implementing infection control measures. CONCLUSION: Based on the present preliminary results, hygiene and infection control measures at schools in Mecklenburg-Western Pomerania cannot be standardised, but should leave room for design.

Inhibiting Interleukin 11 Signaling Reduces Hepatocyte Death and Liver Fibrosis, Inflammation, and Steatosis in Mouse Models of Nonalcoholic Steatohepatitis.

BACKGROUND & AIMS: We studied the role of interleukin 11 (IL11) signaling in the pathogenesis of nonalcoholic steatohepatitis (NASH) using hepatic stellate cells (HSCs), hepatocytes, and mouse models of NASH. METHODS: We stimulated mouse and human fibroblasts, HSCs, or hepatocytes with IL11 and other cytokines and analyzed them by imaging, immunoblot, and functional assays and enzyme-linked immunosorbent assays. Mice were given injections of IL11. Mice with disruption of the interleukin 11 receptor subunit alpha1 gene (Il11ra1-/-) mice and Il11ra1+/+ mice were fed a high-fat methionine- and choline-deficient diet (HFMCD) or a Western diet with liquid fructose (WDF) to induce steatohepatitis; control mice were fed normal chow. db/db mice were fed with methionine- and choline-deficient diet for 12 weeks and C57BL/6 NTac were fed with HFMCD for 10 weeks or WDF for 16 weeks. Some mice were given intraperitoneal injections of anti-IL11 (X203), anti-IL11RA (X209), or a control antibody at different timepoints on the diets. Livers and blood were collected; blood samples were analyzed by biochemistry and liver tissues were analyzed by histology, RNA sequencing, immunoblots, immunohistochemistry, hydroxyproline, and mass cytometry time of flight assays. RESULTS: HSCs incubated with cytokines produced IL11, resulting in activation (phosphorylation) of ERK and expression of markers of fibrosis. Livers of mice given injections of IL11 became damaged, with increased markers of fibrosis, hepatocyte cell death and inflammation. Following the HFMCD or WDF, livers from Il11ra1-/- mice had reduced steatosis, fibrosis, expression of markers of inflammation and steatohepatitis, compared to and Il11ra1+/+ mice on the same diets. Depending on the time of administration of anti-IL11 or anti-IL11RA antibodies to wild-type mice on the HFMCD or WDF, or to db/db mice on the methionine and choline-deficient diet, the antibodies prevented, stopped, or reversed development of fibrosis and steatosis. Blood samples from Il11ra1+/+ mice fed the WDF and given injections of anti-IL11 or anti-IL11RA, as well as from Il11ra1-/- mice fed WDF, had lower serum levels of lipids and glucose than mice not injected with antibody or with disruption of Il11ra1. CONCLUSIONS: Neutralizing antibodies that block IL11 signaling reduce fibrosis, steatosis, hepatocyte death, inflammation and hyperglycemia in mice with diet-induced steatohepatitis. These antibodies also improve the cardiometabolic profile of mice and might be developed for the treatment of NASH.

24-nor-ursodeoxycholic acid ameliorates inflammatory response and liver fibrosis in a murine model of hepatic schistosomiasis.

BACKGROUND & AIMS: Intrahepatic granuloma formation and fibrosis characterize the pathological features of Schistosoma mansoni infection. Based on previously observed substantial anti-fibrotic effects of 24-nor-ursodeoxycholic acid (norUDCA) in Abcb4/Mdr2(-/-) mice with cholestatic liver injury and biliary fibrosis, we hypothesized that norUDCA improves inflammation-driven liver fibrosis in S. mansoni infection. METHODS: Adult NMRI mice were infected with 50 S. mansoni cercariae and after 12 weeks received either norUDCA- or ursodeoxycholic acid (UDCA)-enriched diet (0.5% wt/wt) for 4 weeks. Bile acid effects on liver histology, serum biochemistry, key regulatory cytokines, hepatic hydroxyproline content as well as granuloma formation were compared to naive mice and infected controls. In addition, effects of norUDCA on primary T-cell activation/proliferation and maturation of the antigen-presenting-cells (dendritic cells, macrophages) were determined in vitro. RESULTS: UDCA as well as norUDCA attenuated the inflammatory response in livers of S. mansoni infected mice, but exclusively norUDCA changed cellular composition and reduced size of hepatic granulomas as well as TH2-mediated hepatic fibrosis in vivo. Moreover, norUDCA affected surface expression level of major histocompatibility complex (MHC) class II of macrophages and dendritic cells as well as activation/proliferation of T-lymphocytes in vitro, whereas UDCA had no effect. CONCLUSIONS: This study demonstrates pronounced anti-inflammatory and anti-fibrotic effects of norUDCA compared to UDCA in S. mansoni induced liver injury, and indicates that norUDCA directly represses antigen presentation of antigen presenting cells and subsequent T-cell activation in vitro. Therefore, norUDCA represents a promising drug for the treatment of this important cause of liver fibrosis.

Utilization of a highly adaptable murine air pouch model for minimally invasive testing of the inflammatory potential of biomaterials.

Introduction: The biocompatibility of an implanted material strongly determines the subsequent host immune response. After insertion into the body, each medical device causes tissue reactions. How intense and long-lasting these are is defined by the material properties. The so-called foreign body reaction is a reaction leading to the inflammation and wound healing process after implantation. The constantly expanding field of implant technology and the growing areas of application make optimization and adaptation of the materials used inevitable. Methods: In this study, modified liquid silicone rubber (LSR) and two of the most commonly used thermoplastic polyurethanes (TPU) were compared in terms of induced inflammatory response in the body. We evaluated the production of inflammatory cytokines, infiltration of inflammatory cells and encapsulation of foreign bodies in a subcutaneous air-pouch model in mice. In this model, the material is applied in a minimally invasive procedure via a cannula and in one piece, which allows material testing without destroying or crushing the material and thus studying an intact implant surface. The study design includes short-term (6 h) and long-term (10 days) analysis of the host response to the implanted materials. Air-pouch-infiltrating cells were determined by flow cytometry after 6 h and 10 days. Inflammation, fibrosis and angiogenesis markers were analyzed in the capsular tissue by qPCR after 10 days. Results: The foreign body reaction was investigated by macroscopic evaluation and scanning electron microscopy (SEM). Increased leukocyte infiltration was observed in the air-pouch after 6 h, but it markedly diminished after 10 days. After 10 days, capsule formations were observed around the materials without visible inflammatory cells. Discussion: For biocompatibility testing materials are often implanted in muscle tissue. These test methods are not sufficiently conclusive, especially for materials that are intended to come into contact with blood. Our study primarily shows that the presented model is a highly adaptable and minimally invasive test system to test the inflammatory potential of and foreign body reaction to candidate materials and offers more precise analysis options by means of flow cytometry.

Unisexual infection with Schistosoma mansoni in mice has the potential to boost the immune response against eggs after challenge infection.

Introduction: The complexity of the Schistosoma spp. life cycle and their effective immune evasion strategies, makes vaccine development challenging. Unisexual infection models, that excludes any immunomodulatory effects of the parasite eggs, may contribute to a better understanding of complex immunological processes and identification of new targets for vaccine research. We have recently shown that long-term unisexual infection with schistosomes in mice results in an unpolarized Th1/Th2 response associated with an abnormally enlarged spleen and diffuse liver inflammation. Herein, we investigated whether (i) unisexual worms can mate after three months of single sex infection and (ii) thus the Th2 response induced by oviposition can reverse or heal the described systemic inflammation. Methods: Therefore, we infected 6-8 weeks old female C57BL/6j mice with 100 male or female cercariae and reinfected with the opposite sex for the same period after 12 weeks. At 24 weeks after initial infection, we histologically examined worm mating, as evidenced by the presence of parasite eggs, infection-related pathology associated with eggs, and characterization of fibrosis in the livers. Results: Single worms are able to mate months after unisexual infection and start oviposition. Egg deposition has been associated with a typical Th2 immune response in the liver after unisexual reinfection, accompanied by increased recruitment of CD4+ T cells. Hepatic collagen levels were significantly increased in the reinfected groups compared to the naive and unisexually infected group. Discussion: Our results indicate that the eggs are able to restore the Th1/Th2 immune balance of a previous unisexual infection. However, the organ damage caused by the unisexual worms does not subside, but rather provides the baseline for the emerging egg-triggered inflammation and fibrosis. Since single schistosomes can mate even several weeks after unisexual infection and then accumulate worm- and egg-related organ damage, infection status without positive egg detection is very important, especially in areas with low prevalence.

Individually or as a Team-The Immunological Milieu in the Lung Caused by Migrating Single-Sex or Mixed-Sex Larvae of Schistosoma mansoni.

While the lung is considered an efficient site for stopping the larvae of the acute Schistosoma spp. infection phase from migrating through extensive inflammatory responses in the surrounding tissues, little is known about these processes. To date, the highest resistance to infection has been achieved in experimental studies with radiation-attenuated cercariae immunization, which elicits a strong Th1/Th2 response in the lung and results in up to 80% protection. Based on our own studies demonstrating a systemic, unpolarized Th1/Th2 response resulting from infection with male or female Schistosoma mansoni, we hypothesize that this atypical immune response is already detectable during the pulmonary passage of parasite larvae. Therefore, we examined the immune milieu in the lungs of mice caused by migrating schistosome larvae, either male or female (single-sex groups) or male + female (bisexual control), 4 and 16 days after infection in bronchoalveolar lavage and lung tissue by flow cytometry, qPCR, and multiplex analyzes. Our results show only minor differences in the inflammatory profile between the single-sex groups but significant differences compared with the bisexual control group. Both single-sex infected groups have increased expression of inflammatory markers in lung tissue, higher numbers of cytotoxic T cells (day 4 post-infection) and more T helper cells (day 16 post-infection), compared with the bisexual control group. A single-sex infection, regardless of whether it is an infection with male or female cercariae, causes an immune milieu in the lung that is clearly different from an infection with both sexes. In terms of identifying therapeutic targets to achieve resistance to re-infection, it is of great scientific interest to identify the differences in the inflammatory potential of male or female and male + female parasites.

Mimicking critical environment factors for a static in vitro biofilm formation model on blood-contact implant materials.

The prevention of implant infections is a major challenge for implant developers and clinicians. Understanding biofilm dynamics and favorable implant or environmental characteristics will help to prevent biofilm formation. Blood-contact implants, such as cardiovascular implants, are particularly susceptible to infections as the blood provides a favorable growth environment for bacteria due to its rich supply of micro- and macro substances, such as glucose and plasma proteins. In this context, Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecalis are the most reported causes accompanying foreign body-associated infections, mainly due to their ability to form an adherent, multilayered bacterial biofilm on a wide variety of surfaces. The present study demonstrates that the provision of glucose and human plasma to the growth medium or coating of the flask with human plasma differentially affects the biofilm formation of these three bacterial species, with human plasma being the most effective regulator. However, glucose supplementation promoted and stabilized biofilm formation of S. aureus and E. faecalis, while an opposite effect was observed for additional plasma. These findings highlight the urgent need to intensify studies on the impact of host soluble factors as risk factors promoting fitness and persistence of bacterial biofilms.

Bacterial Adhesion and Biofilm Formation of Enterococcus faecalis on Zwitterionic Methylmethacrylat and Polysulfones.

Biofilm-associated implant infections represent a major challenge for healthcare systems around the world due to high patient burden and enormous costs incurred. Enterococcus faecalis (E. faecalis) is the most prevalent enterococcal species identified in biofilm-associated infections. The steadily growing areas of application of implants demand a solution for the control of bacterial infections. Therefore, the development of modified anti-microbial implant materials and the testing of the behavior of different relevant bacterial strains towards them display an indispensable task. Recently, we demonstrated an anti-microbial effect of zwitterionic modified silicone rubber (LSR) against Staphylococcus aureus. The aim of this study was to evaluate bacterial colonization and biofilm formation of another clinically relevant strain, E. faecalis, on this material in comparison to two of the most commonly used thermoplastic polyurethanes (TPUs) and other modified LSR surfaces. By generating growth curves, crystal violet, and fluorescence staining, as well as analyzing the expression of biofilm-associated genes, we demonstrated no anti-microbial activity of the investigated materials against E. faecalis. These results point to the fact that anti-microbial effects of novel implant materials do not always apply across the board to all bacterial strains.

Sex-Specific Modulation of the Host Transcriptome in the Spleen of Schistosoma mansoni-Infected Mice.

Background: Schistosomiasis is a severe parasitic disease that is primarily driven by the host's immune response to schistosome eggs trapped in tissue and by the granulomatous inflammatory and fibrotic reaction they cause. Despite significant progress in understanding the complex immunological processes involved in the relationship between schistosomes and their host, neither an effective vaccine against the infection nor anti-fibrotic drugs currently exists, making the search for new targets for schistosome drugs and vaccine candidates even more important. In order to identify new molecular targets for defense against or elimination of the parasite, we investigate herein the interplay between the host and male or female schistosomes, clearly separating this from the action of the parasite eggs. Methods: For this purpose, we infected 6-8-week-old female NMRI mice with 100 male (M), female (F), or both (MF) S. mansoni cercariae and performed a comparative transcriptomic and flow cytometric analysis of their spleens. Results: Principal component analysis of a total of 22,207 transcripts showed a clear clustering of the experimental groups. We identified a total of 1,293 genes in group M, 512 genes in group F, and 4,062 genes in group MF that were differentially expressed compared to naive controls. The highest percentage of regulated genes (2,972; 65.9%) was found in group MF alone, but there was a large overlap between groups M and MF (798; 17.7%) and a small overlap between groups F and MF (91; 2.0%). Only 4.5% of genes (201) were revealed to be regulated in all experimental groups (M/F/MF). In addition, we were able to show that both worm sexes trigger immune responses in an egg-independent manner (non-polarized Th1 and Th2 response), with female worms exerting less regulatory influence than males. Conclusion: Our data show that adult schistosomes trigger sex-specific, egg-independent immune responses. The lists of genes regulated by adult female or male worms presented here may be useful in deciphering host-parasite interactions to identify targets for schistosome elimination.

A one-year unisexual Schistosoma mansoni infection causes pathologic organ alterations and persistent non-polarized T cell-mediated inflammation in mice.

In exhibiting gonochorism and phenotypic sexual dimorphism, Schistosoma spp. are unique among trematodes. Only females mating with male schistosomes can produce the highly immunogenic parasite eggs which determine the clinical picture of the disease schistosomiasis. The strong immune-modulatory effect of the eggs masks the influence of the adult worms. To shed light on the complexity of the immune response triggered by adult worms of Schistosoma mansoni, we performed a long-term unisexual infection experiment in mice. We were able to demonstrate that both male and female schistosomes can survive unpaired for one year in the murine host. Furthermore, unisexual S. mansoni infection leads to pronounced inflammation of the liver characterized by a non-polarized Th1/Th2 immune response, regardless of worm sex.

Comparative proteome analysis of the tegument of male and female adult Schistosoma mansoni.

The tegument, as the surface layer of adult male and female Schistosoma spp. represents the protective barrier of the worms to the hostile environment of the host bloodstream. Here we present the first comparative analysis of sex-specific tegument proteins of paired or virgin Schistosoma mansoni. We applied a new and highly sensitive workflow, allowing detection of even low abundance proteins. Therefore, a streptavidin-biotin affinity purification technique in combination with single pot solid-phase enhanced sample preparation was established for subsequent LC-MS/MS analysis. We were able to identify 1519 tegument proteins for male and female virgin and paired worms and categorized them by sex. Bioinformatic analysis revealed an involvement of female-specific tegument proteins in signaling pathways of cellular processes and antioxidant mechanisms. Male-specific proteins were found to be enriched in processes linked to phosphorylation and signal transduction. This suggests a task sharing between the sexes that might be necessary for survival in the host. Our datasets provide a basis for further studies to understand and ultimately decipher the strategies of the two worm sexes to evade the immune system.

Novel dalbavancin-PLLA implant coating prevents hematogenous Staphylococcus aureus infection in a minimally invasive mouse tail vein model.

Infective/bacterial endocarditis is a rare but life-threatening disease with a hospital mortality rate of 22.7% and a 1-year mortality rate of 40%. Therefore, continued research efforts to develop efficient anti-infective implant materials are of the utmost importance. Equally important is the development of test systems that allow the performance of new materials to be comprehensively evaluated. In this study, a novel antibacterial coating based on dalbavancin was tested in comparison to rifampicin/minocycline, and the suitability of a recently developed mouse tail vein model for testing the implant coatings was validated. Small polymeric stent grafts coated with a poly-L-lactic acid (PLLA) layer and incorporated antibiotics were colonized with Staphylococcus (S.) aureus before implantation into the tail vein of mice. The main assessment criteria were the hematogenous spread of the bacteria and the local tissue reaction to the contaminated implant. For this purpose, colony-forming units (CFU) in the blood, spleen and kidneys were determined. Tail cross sections were prepared for histological analysis, and plasma cytokine levels and expression values of inflammation-associated genes were examined. Both antibiotic coatings performed excellently, preventing the onset of infection. The present study expands the range of available methods for testing the anti-infectivity of cardiovascular implants, and the spectrum of agents for effective surface coating.

SARS-CoV-2 surveillance by RT-qPCR-based pool testing of saliva swabs (lollipop method) at primary and special schools-A pilot study on feasibility and acceptability.

BACKGROUND: Since the onset of the COVID-19 pandemic, children have been mentally and physically burdened, particularly due to school closures, with an associated loss of learning. Therefore, efficient testing strategies with high sensitivity are necessary to keep schools open. Apart from individual rapid antigen testing, various methods have been investigated, such as PCR-based pool-testing of nasopharyngeal swabs, gargle, or saliva samples. To date, previous validation studies have found the PCR-based saliva swab pool testing method to be an effective screening method, however, the acceptability and feasibility of a widespread implementation in the school-setting among stakeholders has not been comprehensively evaluated. METHODS: In this pilot study, SARS-CoV-2 saliva swab pool testing of up to 15 swabs per pool was conducted in ten primary and special schools in Mecklenburg-Western Pomerania, Germany, over a period of one month. Thereafter, parents, teachers and school principals of the participating schools as well as the participating laboratories were surveyed about the feasibility and acceptability of this method, its large-scale implementation and challenges. Data were analyzed quantitatively and qualitatively. RESULTS: During the study period, 1,630 saliva swab pools were analyzed, of which 22 tested SARS-CoV-2 positive (1.3%). A total of N = 315 participants took part in the survey. Across all groups, the saliva swab pool testing method was perceived as more child-friendly (>87%), convenient (>82%), and easier (>81%) compared to rapid antigen testing by an anterior nasal swab. Over 80% of all participants favored widespread, regular use of the saliva swab method. CONCLUSION: In school settings in particular, a high acceptability of the test method is crucial for a successful SARS-CoV-2 surveillance strategy. All respondents clearly preferred the saliva swab method, which can be used safely without complications in children six years of age and older. Hurdles and suggestions for improvement of an area-wide implementation were outlined.

In Vitro Study of the Interaction of Innate Immune Cells with Liquid Silicone Rubber Coated with Zwitterionic Methyl Methacrylate and Thermoplastic Polyurethanes.

The biocompatibility of medical devices, such as implants and prostheses, is strongly determined by the host's immune response to the implanted material. Monocytes and macrophages are main actors of the so-called foreign body reaction. The innate immune system macrophages (M) can be broadly classified into the pro-inflammatory M1-type and the anti-inflammatory, pro-healing M2-type. While a transient inflammatory initial state can be helpful during an infection, persistent inflammation interferes with proper healing and subsequent regeneration. The functional orientation of the immune response, mirrored by monocyte polarization, during interaction with different biomaterials has not yet been sufficiently explored. In implant manufacturing, thermoplastic polyurethane (TPU) represents the state-of-the-art material. The constantly growing areas of application and the associated necessary adaptations make the optimization of these materials indispensable. In the present study, modified liquid silicone rubber (LSR) were compared with two of the most commonly used TPUs, in terms of monocyte adhesion and M1/M2 polarization in vitro. Human monocytes isolated from venous blood were evaluated for their ability to adhere to various biomaterials, their gene expression profile, and their cytokine release. Based on the results, the different polymers exhibit different potential to bias monocytes with respect to early pro-inflammatory cytokine production and gene transcription. Furthermore, none of our test materials showed a clear trend towards M1 or M2 polarization. However, we were able to evaluate the inflammatory potential of the materials, with the classic TPUs appearing to be the most unreactive compared to the silicone-based materials.

Evaluation of a Murine Model for Testing Antimicrobial Implant Materials in the Blood Circulation System.

Medical device-related infections are becoming a steadily increasing challenge for the health care system regarding the difficulties in the clinical treatment. In particular, cardiovascular implant infections, catheter-related infections, as well as infective endocarditis are associated with high morbidity and mortality risks for the patients. Antimicrobial materials may help to prevent medical device-associated infections and supplement the currently available therapies. In this study, we present an easy-to-handle and simplified in vivo model to test antimicrobial materials in the bloodstream of mice. The model system is composed of the implantation of a bacteria-laden micro-stent scaffold into the murine tail vein. Our model enables the simulation of catheter-related infections as well as the development of infective endocarditis specific pathologies in combination with material testing. Furthermore, this in vivo model can cover two phases of the biofilm formation, including both the local tissue response to the bacterial biofilm and the systemic inflammatory response against circulating bacteria in the bloodstream that detached from a mature biofilm.