The semen microbiome and its relationship with local immunology and viral load in HIV infection

Semen is a major vector for HIV transmission, but the semen HIV RNA viral load (VL) only correlates moderately with the blood VL. Viral shedding can be enhanced by genital infections and associated inflammation, but it can also occur in the absence of classical pathogens. Thus, we hypothesized that a dysregulated semen microbiome correlates with local HIV shedding. We analyzed semen samples from 49 men who have sex with men (MSM), including 22 HIV-uninfected and 27 HIV-infected men, at baseline and after starting antiretroviral therapy (ART) using 16S rRNA gene-based pyrosequencing and quantitative PCR. We studied the relationship of semen bacteria with HIV infection, semen cytokine levels, and semen VL by linear regression, non-metric multidimensional scaling, and goodness-of-fit test. Streptococcus, Corynebacterium, and Staphylococcus were common semen bacteria, irrespective of HIV status. While Ureaplasma was the more abundant Mollicutes in HIV-uninfected men, Mycoplasma dominated after HIV infection. HIV infection was associated with decreased semen microbiome diversity and richness, which were restored after six months of ART. In HIV-infected men, semen bacterial load correlated with seven pro-inflammatory semen cytokines, including IL-6 (p = 0.024), TNF-α (p = 0.009), and IL-1b (p = 0.002). IL-1b in particular was associated with semen VL (r(2)  = 0.18, p = 0.02). Semen bacterial load was also directly linked to the semen HIV VL (r(2) = 0.15, p = 0.02). HIV infection reshapes the relationship between semen bacteria and pro-inflammatory cytokines, and both are linked to semen VL, which supports a role of the semen microbiome in HIV sexual transmission

Health-related quality of life and utilities in gastric premalignant conditions and malignant lesions: a multicentre study in a high prevalence country

BACKGROUND AND AIMS: A recent review of economic studies relating to gastric cancer revealed that authors use different tests to estimate utilities in patients with and without gastric cancer. Our aim was to determine the utilities of gastric premalignant conditions and adenocarcinoma with a single standardized health measure instrument. METHODS: Cross-sectional nationwide study of patients undergoing upper endoscopy (n=1,434) using the EQ-5D-5L quality of life (QoL) questionnaire. RESULTS: According to EQ-5D-5L, utilities in individuals without gastric lesions were 0.78 (95% confidence interval: 0.76-0.80), with gastric premalignant conditions 0.79 (0.77-0.81), previously treated for gastric cancer 0.77 (0.73-0.81) and with present cancer 0.68 (0.55-0.81). Self-reported QoL according to the visual analogue scale (VAS) for the same groups were 0.67 (0.66-0.69), 0.67 (0.66-0.69), 0.62 (0.59-0.65) and 0.62 (0.54-0.70) respectively. Utilities were consistently lower in women versus men (no lesions 0.71 vs. 0.78; premalignant conditions 0.70 vs. 0.82; treated for cancer 0.72 vs. 0.78 and present cancer 0.66 vs. 0.70). CONCLUSION: The health-related QoL utilities of patients with premalignant conditions are similar to those without gastric diseases whereas patients with present cancer show decreased utilities. Moreover, women had consistently lower utilities than men. These results confirm that the use of a single standardized instrument such as the EQ-5D-5L for all stages of the gastric carcinogenesis cascade is feasible and that it captures differences between conditions and gender dissimilarities, being relevant information for authors pretending to conduct further cost-utility analysis

Male circumcision significantly reduces prevalence and load of genital anaerobic bacteria

Male circumcision reduces female-to-male HIV transmission. Hypothesized mechanisms for this protective effect include decreased HIV target cell recruitment and activation due to changes in the penis microbiome. We compared the coronal sulcus microbiota of men from a group of uncircumcised controls (n = 77) and from a circumcised intervention group (n = 79) at enrollment and year 1 follow-up in a randomized circumcision trial in Rakai, Uganda. We characterized microbiota using16S rRNA gene-based quantitative PCR (qPCR) and pyrosequencing, log response ratio (LRR), Bayesian classification, nonmetric multidimensional scaling (nMDS), and permutational multivariate analysis of variance (PerMANOVA). At baseline, men in both study arms had comparable coronal sulcus microbiota; however, by year 1, circumcision decreased the total bacterial load and reduced microbiota biodiversity. Specifically, the prevalence and absolute abundance of 12 anaerobic bacterial taxa decreased significantly in the circumcised men. While aerobic bacterial taxa also increased postcircumcision, these gains were minor. The reduction in anaerobes may partly account for the effects of circumcision on reduced HIV acquisition. IMPORTANCE The bacterial changes identified in this study may play an important role in the HIV risk reduction conferred by male circumcision. Decreasing the load of specific anaerobes could reduce HIV target cell recruitment to the foreskin. Understanding the mechanisms that underlie the benefits of male circumcision could help to identify new intervention strategies for decreasing HIV transmission, applicable to populations with high HIV prevalence where male circumcision is culturally less acceptable

Monitoring Antibiotic Comsumption in the Surgery and Orthopaedics

A monitorização do consumo de antimicrobianos é um instrumento de interesse indiscutível e tem merecido uma atenção particular nos últimos anos, devido às crescentes preocupações com a emergência de estirpes microbianas multi-resistentes. Os objectivos do presente estudo consistiram, por um lado, na monitorização do consumo e na avaliação do impacto económico da prescrição hospitalar de antimicrobianos, em serviços de cirurgia e ortopedia. Por outro lado, pretendeu-se estudar e a relação indicação-prescrição terapêutica e profilática. Tendo presentes estes objectivos realizou-se um estudo-piloto longitudinal, com recolha de dados durante o mês de Maio de 2004, em seis Hospitais SA, incidindo numa amostra total de 1.122 doentes internados. Verificámos uma taxa de incidência de prescrição de 76,9%, com dispensa de 1.154 antimicrobianos, dos quais 71,2% se destinaram, em média, à profilaxia da infecção pós-cirúrgica, atestando a adesão geral à prática da profilaxia da infecção no local cirúrgico. O custo médio da antibioterapia foi mais elevado nos casos de “suspeita de infecção” (€9,09) ou “infecção declarada” (€8,74) e mais baixo quando utilizados para “profilaxia” (€5,67), facto relacionado com a menor duração média dos episódios de profilaxia. Os regimes de profilaxia utilizados apresentaram variações consideráveis entre os diferentes hospitais no que respeita ao tipo de antibiótico utilizado e uma duração média de 2,61 dias, com cerca de metade dos episódios de profilaxia prolongando-se por mais de 24 horas, sugerindo uma implementação insuficiente das actuais recomendações quanto ao tipo de fármaco a utilizar para esta prática, o que aponta para o necessidade duma avaliação da existência nas unidades hospitalares, de recomendações claras para a profilaxia da infecção do local cirúrgico, bem como da adesão dos clínicos a estas

Biocatalyzed flow oxidation of tyrosol to hydroxytyrosol and efficient production of their acetate esters

Tyrosol (Ty) and hydroxytyrosol (HTy) are valuable dietary phenolic compounds present in olive oil and wine, widely used for food, nutraceutical and cosmetic applications. Ty and HTy are endowed with a number of health-related biological activities, including antioxidant, antimicrobial and anti-inflammatory properties. In this work, we developed a sustainable, biocatalyzed flow protocol for the chemo-and regio-selective oxidation of Ty into HTy catalyzed by free tyrosinase from Agaricus bisporus in a gas/liquid biphasic system. The aqueous flow stream was then in-line extracted to recirculate the water medium containing the biocatalyst and the excess ascorbic acid, thus improving the cost-efficiency of the process and creating a self-sufficient closed-loop system. The organic layer was purified in-line through a catch-and-release procedure using supported boronic acid that was able to trap HTy and leave the unreacted Ty in solution. Moreover, the acetate derivatives (TyAc and HTyAc) were produced by exploiting a bioreactor packed with an immobilized acyltransferase from Mycobacterium smegmatis (MsAcT), able to selectively act on the primary alcohol. Under optimized conditions, high-value HTy was obtained in 75% yield, whereas TyAc and HTyAc were isolated in yields of up to 80% in only 10 min of residence time

Enzymatic Deglycosylation and Lipophilization of Soy Glycosides into Value-Added Compounds for Food and Cosmetic Applications

Soybean is one of the most important crops worldwide, being placed ninth on the chart of the most cultivated species. Its high level of production correlates with a huge amount of waste produced. These residues could be of great interest due to the presence of high-value-added molecules, including some glycosides (i.e., daidzin, genistin, glycitin) widely studied for their potent antioxidant properties. Due to their low bioavailability and limited solubility in lipidic media, lipophilization strategies have recently gained momentum to improve daidzin, genistin, and glycitin applications as multifunctional additives in the food, pharmaceutical, and cosmetic sectors. In this context, starting from soybean glycosides, we followed two parallel approaches, i.e., hydrolysis to obtain the corresponding aglycones possessing a better pharmacokinetic profile and esterification of the sugar primary alcohol with short-chain fatty acids. First, homemade extremophilic glycosidase (HOR) from Halothermothrix orenii has been employed for the preparation of aglycones (molar conversion 96-99%) in both water and biphasic media (water/2,2,5,5-tetramethyloxolane 1:1). Subsequently, lipophilization reactions with butanoic, hexanoic, and octanoic acids have been carried out using commercially available immobilized lipase B from Candida antarctica (CaLB) under flow conditions to produce modified glycosides with better physicochemical properties to be implemented in cosmetic preparations. Noteworthily, compared to the batch methodology, compound 1 (6-O-octanoildaidzin) was obtained with a drastic reduction in reaction time (30 min vs 18 h) and a consequent 9-fold increase in specific reaction rates (0.15 vs 0.017 mu mol/(ming))

Efficient Enzymatic Preparation of Flavor Esters in Water

A straightforward biocatalytic method for the enzymatic preparation of different flavor esters starting from primary alcohols (e.g., isoamyl, n-hexyl, geranyl, cinnamyl, 2-phenethyl, and benzyl alcohols) and naturally available ethyl esters (e.g., formate, acetate, propionate, and butyrate) was developed. The biotransformations are catalyzed by an acyltransferase from Mycobacterium smegmatis (MsAcT) and proceeded with excellent yields (80-97%) and short reaction times (30-120 min), even when high substrate concentrations (up to 0.5 M) were used. This enzymatic strategy represents an efficient alternative to the application of lipases in organic solvents and a significant improvement compared with already known methods in terms of reduced use of organic solvents, paving the way to sustainable and efficient preparation of natural flavoring agents