lata seems to secrete a third type of chemical signal that amplifies basal immunity and might play a role in the context of consortia of mutually competing microorganisms. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email journals.permissions@oup.com.BACKGROUND The peptide hormone Insulin-like factor 3 (INSL3) is a marker for Leydig cell function and the clinical use of serum INSL3 measurements has been suggested by several groups. AIM i) To establish a reference range for LC-MS/MS of serum INSL3 in healthy boys and men and ii) to compare the associations of serum INSL3 and testosterone (T) to pubertal stage, life style factors, diurnal variation, body composition and human chorionic gonadotropin (hCG) stimulation. RESULTS In a reference range based on LC-MS/MS of serum from 1073 boys and men INSL3 increased from levels close to the detection limit (0.03 µg/L) in pre-pubertal boys to a maximum mean level of 1.3 µg/L (95% CI 0.9 - 2.7) in young men (19 - 40 years) and decreased slightly in older men (0.1 µg/L per decade). Serum T, but not INSL3, was associated with body mass index or body fat percentage and with alcohol consumption. Smoking was positively associated with serum T, but negatively associated with INSL3. There were significant diurnal variations in both INSL3 and T in men (p less then 0.001), but serum INSL3 varied substantially less, as compared to serum T (+/- 11% vs. +/- 26%). Mean serum INSL3 increased after hCG stimulation, but less than T (+ 17% vs. + 53%). In both healthy men and in patients suspected of testicular failure baseline serum INSL3 was closer associated to the hCG-induced increase in serum T, than baseline T itself. CONCLUSION Measurement of serum INSL3 by LC-MS/MS has promise as a marker of testicular disorders. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.Dengue endemicity varies but comparative, multi-country data are extremely limited. An improved understanding is needed to prioritize prevention, including vaccination, which is currently recommended only under specific epidemiological conditions. We used serological study data from 46 geographical sites in 13 countries to estimate dengue force of infection (FOI, the proportion of children seroconverting per year) under assumptions of either age-constant or age-varying FOI, and the age at which 50% and 80% of children had been infected. After exclusions, 13,661 subjects were included. Estimated constant FOI varied widely, from 1.7% (Singapore) to 24.1% (the Philippines). In the site-level analysis 44 sites (96%) reached 50% seroconversion, and 35 sites (75%) reached 80% seroconversion, by age 18, with significant heterogeneity. These findings confirm that children living in dengue-endemic countries receive intense early dengue exposure, increasing risk of secondary infection, and imply serosurveys at fine spatial resolutions are needed to inform vaccination campaigns. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.OBJECTIVES To describe the clinical presentation, treatments and prognosis of gastrointestinal (GI) involvement in adult IgA vasculitis (IgAV). METHODS Data from 260 adults with IgAV included in a French multicentre retrospective survey were analysed. Presentation and outcomes of patients with (GI+) and without (GI-) GI involvement were compared. RESULTS One hundred and thirty-seven (53%) patients had GI involvement. Initial manifestations were abdominal pain in 99%, intestinal bleeding in 31%, diarrhoea in 26% and acute surgical abdomen in only 4%. Abdominal imaging revealed thickening of intestinal wall in 61%, and endoscopies revealed abnormalities in 87%, mostly mucosal ulcerations. GI+ vs GI- patients were younger (46 ± 18 vs 54 ± 18 years; P = 0.0004), had more constitutional symptoms (43% vs 23%; P = 0.0005) and joint involvement (72 vs 50%; P = 0.0002), and higher CRP levels (3.7 vs 1.9 mg/dl; P = 0.001). Clinical response and relapse rates were comparable between groups, and all causes mortality (2 vs 4%) and IgAV-related mortality (1% vs 2%) as well. GI-related deaths were due to intestinal perforation and mesenteric ischaemia. CONCLUSION GI involvement is frequent in adult IgAV. GI involvement is frequent in adult IgAV. Mortality is not uncommon but does not seem to be specifically related to GI. Immunosuppressants should not be preferred as first-line therapy for GI+ patients but may be required in case of acute surgical abdomen. © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email journals.permissions@oup.com.Human noroviruses cause an estimated 685 million infections and 200,000 deaths annually worldwide. Although vaccines against GII.4 and GI.1 genotypes are under development, no information is available regarding vaccines or monoclonal antibodies to other noroviral genotypes. Here, we developed two variable-domain llama heavy-chain antibody fragment (VHHs) clones, 7C6 and 1E4, against GII.4 and GII.17 human noroviruses, respectively. Although 7C6 cross-reacted with virus-like particles (VLPs) of GII.17, GII.6, GII.3, and GII.4, it neutralized only GII.4 norovirus. In contrast, 1E4 reacted with and neutralized only GII.17 VLPs. Both VHHs blocked VLP binding to human iPSC-derived intestinal epithelial cells and carbohydrate attachment factors. Using these two VHHs, we produced a heterodimeric VHH fragment that neutralized both GII.4 and GII.17 noroviruses. Because VHH fragments are heat- and acid-stable recombinant monoclonal antibodies, the heterodimer likely will be useful for oral immunotherapy and prophylaxis against GII.4 and GII.17 noroviruses in young, elderly, or immunocompromised persons. © The Author(s) 2020. https://www.selleckchem.com/products/ABT-263.html Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.


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