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© 2020 Elsevier Ltd Melatonin and serotonin are bioactive compounds present in foods and beverages and related to neuroprotection and anti-angiogenesis, among other activities. They have been described in wines and the role of yeast in their formation is clear. Thus, this study evaluates the content of these bioactives and other related indolic compounds in beer. For this purpose, commercial beers were analyzed by a validated UHPLC-HRMS method and sample treatment optimized due to the low concentrations expected. Moreover, a wort was fermented with different commercial beer yeast (Abbaye, Diamond, SafAle, SafLager) in order to monitor the formation of these bioactives during the elaboration process. Results show that indolic compounds such as N-acetylserotonin and 3-indoleacetic acid are produced during the alcoholic fermentation of wort. Moreover, the occurrence of four indolic compounds (5-hydroxytryptophan, N-acetylserotonin, 3-indoleacetic acid, L-tryptophan ethyl ester) in commercial beers is reported for the first time.

Background: Since the 1918 influenza pandemic, non-randomised studies and small clinical trials have suggested that convalescent plasma or anti-influenza hyperimmune intravenous immunoglobulin (hIVIG) might have clinical benefit for patients with influenza infection, but definitive data do not exist. We aimed to evaluate the safety and efficacy of hIVIG in a randomised controlled trial. Methods: This randomised, double-blind, placebo-controlled trial was planned for 45 hospitals in Argentina, Australia, Denmark, Greece, Mexico, Spain, Thailand, UK, and the USA over five influenza seasons from 2013–14 to 2017–18. Adults (≥18 years of age) were admitted for hospital treatment with laboratory-confirmed influenza A or B infection and were randomly assigned (1:1) to receive standard care plus either a single 500-mL infusion of high-titre hIVIG (0·25 g/kg bodyweight, 24·75 g maximum; hIVIG group) or saline placebo (placebo group). Eligible patients had a National Early Warning score of 2 points or greater at the time of screening and their symptoms began no more than 7 days before randomisation. Pregnant and breastfeeding women were excluded, as well as any patients for whom the treatment would present a health risk. Separate randomisation schedules were generated for each participating clinical site using permuted block randomisation. Treatment assignments were obtained using a web-based application by the site pharmacist who then masked the solution for infusion. Patients and investigators were masked to study treatment. The primary endpoint was a six-category ordinal outcome of clinical status at day 7, ranging in severity from death to resumption of normal activities after discharge. The choice of day 7 was based on haemagglutination inhibition titres from a pilot study. It was analysed with a proportional odds model, using all six categories to estimate a common odds ratio (OR). An OR greater than 1 indicated that, for a given category, patients in the hIVIG group we

Melatonin (Mel), originally considered a neurohormone, has been detected in beverages and food‐fermented products in which yeast metabolism is highly important. This indolamine is synthesized from serotonin, with L‐tryptophan being the initial substrate of both. Regarding Mel metabolism, the biosynthetic pathway in mammals consists in four‐step reactions. However, six genes are implicated in the synthesis of Mel in plants, which suggest the presence of many pathways. The aim of this study was to provide new empirical data on the production of Mel and other indole‐related compounds in the yeast Saccharomyces cerevisiae (S. cerevisiae). To this end, we performed the addition of the pathway intermediates in S. cerevisiae cells in different growth stages (exponential and arrested cells) to follow the bioconversion and new indolic compound production from them. The different bioconverted indolic compounds tested (L‐tryptophan, 5‐hydroxytryptophan, tryptamine, serotonin, N‐acetylserotonin, 5‐methoxytryptamine, and Mel) were analyzed by UHPLC‐MS/MS from the extra‐ and intracellular contents. Our results showed that serotonin, in yeast, was prevalently formed via tryptophan decarboxylation, followed by tryptamine hydroxylation as in plants. Mel production from serotonin can be achieved by either N‐acetylation, followed by O‐methylation or O‐methylation, in turn followed by N‐acetylation. Accordingly, the classic pathway of Mel synthesis in vertebrates does not seems prevalent in yeast.

Background: Rapid screening for the detection of HLA-B*57:01 in the prevention of abacavir hypersensitivity in HIV-1-infected patients is a hallmark for clinical services. Objective: The aim of this work was to analyze the utility of flow cytometry with a new FITC-conjugated B-17 monoclonal antibody (mAb3E12) for HLA-B*57:01 screening in a Spanish cohort of 577 HIV-1+ individuals. Methods: Cryopreserved peripheral blood mononuclear cell samples from HIV-1+ individuals were analyzed by flow cytometry with the mAb 3E12 that recognizes both HLA-B*57 and HLA-B*58 alleles (members of the group specificity, HLA-B17). Patients' DNA samples had been previously typed for HLA-B*57:01 with PCR-SSO or PCR-SSP and additional DNA sequencing (EPI Study). The results obtained by flow cytometry were compared with the results obtained by the DNA-PCR techniques. Results: By flow cytometry, 46 samples (7.97%) were positive for HLA-B17, 530 (91.86%) were negative, and 1 (0.17%) was undetermined. All samples found negative by flow cytometry were negative for HLA-B*57:01 by DNA-PCR. Of the HLA-B17 positive samples, 31 (67.4%) were positive for HLA-B*57:01, 2 (3.25%) were positive for HLA-B*57:03, 11 (26.1%) were positive for HLA-B*58, and 2 (3.25%) were negative for both HLA-B*57 and HLA-B*58 antigens. The undetermined sample was negative for HLA-B*57 and HLA-B*58 alleles by DNA-PCR. Conclusions: This study shows that flow cytometry with mAb3E12 is a highly sensitive method (no false negatives) to implement prior to DNA-PCR analysis for rapid screening of HLA-B*57:01. Additional confirmation by molecular HLA typing method would be required in less than 10% of the cohort of HIV-1-infected individuals.

Objective: To evaluate the efficacy and safety of zidovudine (ZDV) and lymphoblastoid interferon (IFN)-[alpha] combination therapy compared with ZDV monotherapy in HIV-infected subjects with CD4+ cell counts between 150 and 500x106/1. Design: Open, randomized controlled trial with subjects stratified by the Centers for Disease Control and Prevention (CDC) 1986 classification of HIV disease (group 11/111 or IV). The study was amended to a sequential design in February 1992 to allow interim analyses to be conducted. Setting: Outpatient clinics in 45 hospitals in Europe, Australia and Canada. Participants: A total of 402 previously untreated subjects with symptomatic HIV infection (CDC group IV) and CD4+ count 150-500xT06/1 or asymptomatic HIV infection (CDC group 11/111) with CD4+ count 150-350 x 106/l. Interventions: ZDV 250 mg twice daily with or without 3 MU subcutaneous injections of lymphoblastoid IFN-[alpha] three times per week. Main outcome measures: Time to development of a study endpoint defined as: progression from CDC group 11/111 to group IV, group IV non-AIDS to AIDS, or group IV AIDS to a second AIDS-defining condition; also CD4+ count to < 50x 106/1 on two occasions at least 1 month apart or HIV-related death irrespective of CDC group on entry. Results: There was no reduction in the rate of disease progression for patients receiving ZDV plus IFN-[alpha] compared with patients receiving ZDV alone. No major differences between the groups were seen for CD4+ counts or percentages, or p24 antigenaemia. In a subset of 70 patients, a similar proportion from both dose groups showed evidence of ZDV resistance after 48 weeks of treatment. More adverse experiences were seen in the ZDV/IFN-a group. Conclusions: Combination therapy with low dose lymphoblastoid IFN-[alpha] and ZDV revealed no clinical benefit compared with ZDV monotherapy.