Wine aromatic compound production and fermentative behaviour within different non-Saccharomyces species and clones.

AIMS: Twenty-five enological yeasts belonging to nine different species (Candida zeylanoides, Cryptococcus uzbekistanensis, Debaryomyces hansenii, Lachancea thermotolerans, Metschnikowia pulcherrima, Torulaspora delbrueckii, Williopsis pratensis, Zygosaccharomyces bailii and Saccharomyces cerevisiae) were screened for aroma formation and fermentative behaviour as part of a non-Saccharomyces yeast selection programme. METHODS AND RESULTS: Pure cultures were inoculated in pasteurized grape juice in order to perform alcoholic fermentations. Some non-Saccharomyces species did not ferment, others did not get established and none of them completed alcoholic fermentations. The physico-chemical parameters of the wines and the abundance of aromatic compounds at the end of alcoholic fermentation highlighted the notable differences in the aroma-forming ability and fermentative behaviour of the different non-Saccharomyces species, but not within clones. CONCLUSIONS: Lower diversity was detected within non-Saccharomyces species than that reported in S. cerevisiae with regard to enological behaviour and aromatic profiles. Metschnikowia pulcherrima and L. thermotolerans are the two species with higher possibilities to become an inoculum. SIGNIFICANCE AND IMPACT OF THE STUDY: Few significant differences were found within clones of the same species, but very important parameters in wine quality, such as volatile acidity, ethyl acetate and acetoin, which would justify selection programmes within those species. The results also demonstrated that T. delbrueckii and L. thermotolerans are two close species in their aromatic profiles.

Impact of an enhanced screening program on the detection of non-AIDS neoplasias in patients with human immunodeficiency virus infection.

BACKGROUND: The incidence of non-AIDS defining cancer (NADC) is higher in people living with HIV (PLWH) than in the general population, and it is already one of the leading causes of death in the HIV-infected population. It is estimated that the situation will be aggravated by the progressive aging of PLWH. Early diagnosis through intensive cancer screening may improve the ability for therapeutic interventions and could be critical in reducing mortality, but it might also increase expenditure and harms associated with adverse events. The aim of this study is to evaluate an enhanced screening program for early diagnosis of cancer in PLWH compared to standard practice. The specific objectives are (1) to compare the frequency of cancer diagnosed at an early stage, (2) to analyze safety of the enhanced program: adverse events and unnecessary interventions, (3) to analyze the cost-utility of the program, and (4) to estimate the overall and site-specific incidence of NADC in PLWH. METHODS: We will conduct a multicenter, non-blinded, randomized, controlled trial, comparing two parallel arms: conventional vs enhanced screening. Data will be recorded in an electronic data collection notebook. Conventional intervention group will follow the standard of care screening in the participating centers, according to the European AIDS Clinical Society recommendations, and the enhanced intervention group will follow an expanded screening aimed to early detection of lung, liver, anal, cervical, breast, prostate, colorectal, and skin cancer. The trial will be conducted within the framework of the Spanish AIDS Research Network Cohort (CoRIS). DISCUSSION: The trial will evaluate the efficacy, safety, and efficiency of an enhanced screening program for the early diagnosis of cancer in HIV patients compared to standard of care practice. The information provided will be relevant since there are currently no studies on expanded cancer screening strategies in patients with HIV, and available data estimating cost effectiveness or cost-utility of such as programs are scarce. An enhanced program for NADC screening in patients with HIV could lead to early diagnosis and improve the prognosis of these patients, with an acceptable rate of unnecessary interventions, but it is critical to demonstrate that the benefits clearly outweigh the harms, before the strategy could be implemented. TRIAL REGISTRATION: ClinicalTrials.gov NCT04735445. Registered on 25 June 2019.

Treatment of chronic he1patitis C genotype 1 with peginterferon-alpha2a (40 kDa) plus ribavirin under routine clinical practice in Spain: early prediction of sustained virological response rate.

BACKGROUND: Sustained virological response rates of up to 52% have been obtained with peginterferon alpha2a (40 kDa) plus ribavirin in patients suffering from chronic hepatitis C genotype 1 in randomized-controlled trials. AIM: To assess early virological response and its clinical utility in predicting an sustained virological response in patients suffering from chronic hepatitis C genotype 1 in routine clinical practice in Spain. METHODS: Treatment-naïve patients received pegylated interferon alpha2a (40 kDa) 180 microg/week plus ribavirin 1000/1200 mg/day for 48 weeks, and were followed for a further 24 weeks. Overall, 475 patients received at least one dose of medication and were included in the efficacy population. RESULTS: The overall sustained virological response rate was 48%. Of those with week 12 virological data, 83% had an early virological response. The negative predictive value of an early virological response was 93%. CONCLUSION: If sustained virological response is the goal, a treatment-decision based on a 12-week evaluation during routine clinical practice is feasible.

Prevalence of M. tuberculosis infection and tuberculosis disease among HIV-infected people in Spain.

OBJECTIVE: To study the prevalence of Mycobacterium tuberculosis infection (MTBI) and past/current tuberculosis (TB) among human immunodeficiency virus (HIV) infected persons in Spain. DESIGN: Longitudinal study conducted between 2000 and 2003 at 10 HIV hospital-based clinics. Data were drawn from clinical records. Associations were measured using odds ratios (ORs) and their 95% confidence intervals (95%CI). RESULTS: Of the 1242 persons who met the eligibility criteria, most were male (75%), aged <40 years (75%) and unemployed (40%). HIV infection occurred through intravenous drug use (53%), heterosexual sex (29%) and sex between men (16%). In the initial evaluation, 315 subjects had evidence of MTBI: 84 (6.8%) had a history of TB, 23 (1.8%) current TB and 208 (16.8%) latent tuberculosis infection (LTBI). MTBI was associated with male sex, age 30-49 years, contact with a TB case, homelessness, poor education, and negatively with CD4 <100 cells/mm(3). Among subjects with MTBI, past/current TB was associated with retirement/disability (OR 6, 95%CI 1.6-22.5), CD4 <200 cells/mm(3) (OR 9.7, 95%CI 3.8-24.6), viral load >55,000 copies (OR 5.3, 95%CI 1.4-20.0), and negatively, with skilled work (OR 0.4, 95%CI 0.1-1.0) or administrative/managerial/professional work (OR 0.05, 95%CI 0.01-0.4). CONCLUSION: Social context has an impact on the effectiveness of HIV and TB control programmes even in industrialised countries with free access to health care.

Effects on grape amino acid concentration through foliar application of three different elicitors.

Elicitors play an important role in the defense against pathogens as an alternative to chemical pesticides by increasing secondary metabolites. Their effect on grape amino acid has been little investigated. Thus, the aim of this research was to study the influence of methyl jasmonate (MeJ), chitosan (CHT), and a yeast extract (YE) on grape amino acid composition, through foliar applications to grapevines. The must amino acid concentration was analyzed by HPLC. The results showed that CHT and YE treatments decreased the must concentration of several amino acids, affecting total amino acid content (from 2364 to 1961, and 1818mg/L, respectively). However, MeJ treatment had a slight effect on grape amino acid content, increasing the concentration of Met (from 8.95 to 12.13mg/L) and Phe (from 7.96 to 9.29mg/L). It seems to be that, the resistance induction through CHT and YE treatments results in physiological costs to grapevines associated with a decrease on grape amino acid concentration. Consequently, MeJ applications, as a viticultural practice, could be a better tool than CHT and YE treatments, because did not affect grape amino acid concentration.

Phenylalanine and urea foliar applications to grapevine: effect on wine phenolic content.

Phenolic compounds play a key role in the organoleptic properties of wines. Viticultural practices may influence grape and wine phenolic content, thus determining their quality. The objective of this study was to evaluate the effect of foliar applications of phenylalanine and urea, at two different doses, on wine phenolic composition. Grapes were harvested at their optimal technological maturity and their respective wines were elaborated at small scale. Wine detailed phenolic composition was determined. Results revealed that the content of several anthocyanins and flavonols was enhanced by the application of both phenylalanine doses and by the application of the low dose of urea. In contrast, flavanols and non-flavonoid compounds were less affected by the foliar treatments. The findings seem to be related to the time of application, since anthocyanins and flavonols are accumulated after veraison. In conclusion, nitrogen foliar fertilization increased the phenolic content of Tempranillo wines. This could be of interest since anthocyanins and flavonols are associated with wine quality, especially with its color.

Changes on grape phenolic composition induced by grapevine foliar applications of phenylalanine and urea.

Grapevines may require the input of nitrogen to grow and to guarantee an appropriate grape composition. Recently there has been a growing interest in foliar fertilization, which entails a fast and efficient assimilation of the products. The aim of this work was to study the influence of foliar applications of phenylalanine and urea, at two different doses, on grape anthocyanins, flavonols, flavan-3-ols, phenolic acids, and stilbenes. All treatments were applied at veraison and one week later at doses of 0.9 and 1.5 kg N/ha. The results showed that the synthesis of phenolic compounds was favoured by foliar applications of phenylalanine and urea. The application of the lowest dose of urea was the most effective treatment, increasing the content of several anthocyanins and flavonols. Moreover, none of the foliar treatments worsened the grape phenolic composition. In conclusion, foliar application of phenylalanine and especially urea, could be an interesting management tool for improving grape quality and their health-promoting properties.

Incidence and risk factors for developing cytomegalovirus retinitis in HIV-infected patients receiving protease inhibitor therapy. Spanish CMV-AIDS Study Group.

OBJECTIVE: To assess the incidence and risk factors for cytomegalovirus (CMV) retinitis in HIV-infected patients who initiated protease inhibitor-containing antiretroviral therapy. DESIGN AND SETTING: Prospective, multicentre study. PATIENTS: A cohort of 172 HIV-infected patients with a CD4 cell count below 100x10(6) cells/l at the time of protease inhibitor introduction. MAIN OUTCOME MEASURES: Confirmed CMV retinitis and mortality, according to CD4 cell count, HIV load, and CMV viraemia. RESULTS: The cumulative incidence of CMV retinitis was 5% at 1 year and 6% at 2 years. Only a positive CMV polymerase chain reaction (PCR) test at therapy initiation was significantly associated with the development of disease (relative hazard, 4.41; 95% confidence interval, 2.12-8.93; P<0.00001). The 12-month Kaplan-Meier CMV retinitis event rate was 38% in patients who were CMV PCR-positive compared with 2% in those who were CMV PCR-negative (P<0.001). Mean CMV load was significantly higher in those individuals who went on to develop CMV retinitis (3700 versus 384 copies/ml, P = 0.002). Only 2% of patients remained CMV PCR-positive after 3 months of protease inhibitor therapy, and CMV viraemia was not associated with a worse therapy response or shorter survival. Transient CMV positivity without a higher risk of disease was observed in 7% of patients at the first month on therapy. CONCLUSIONS: Protease inhibitor-containing antiretroviral therapy significantly reduces the incidence of CMV viraemia and disease. Although a positive CMV PCR test identifies those patients on therapy at highest risk of CMV retinitis, it is not associated with an increased risk of death or a worse response to protease inhibitor therapy.

Value of limited necropsy in HIV-positive patients.

We performed limited autopsy with histological examination of tissue cores obtained percutaneously using the Tru-Cut needle and the Jamshidi trocar in 150 adult HIV-positive patients. Data were compared retrospectively with the antemortem clinical diagnosis. Eighty-one percent of the patients were male, and 78% were intravenous drug users. Specimens were obtained from the brain, liver, lung, bone marrow, and kidney of most patients. The main findings included liver cirrhosis in 22 cases (associated with HCV infection in 81%), Pneumocystis carinii pneumonia in 21, Cytomegalovirus (CMV) infection in 19, Mycobacterium avium-intracellulaire (MAI) infection in 17, bacterial pneumonia in 14, tuberculosis in 12, and lymphoma in 13 cases. Forty-six (30.6%) patients had at least one clinical diagnosis that was confirmed by autopsy, i.e., there was 40.6% agreement between pre- and postmortem findings. Forty-six (30.6%) patients had at least one clinical diagnosis that was not confirmed at autopsy, whereas 41 (27.3%) had at least one AIDS-related or unrelated disease that was not suspected clinically. The results obtained by limited autopsy are principally comparable to those achieved by full necropsy, with the advantages of decreasing the contagious risk, saving cost and time, including a rapid final diagnosis, and easily obtaining the consent for postmortem examination so that necropsy studies may be performed on a larger number of patients, thus contributing to a better understanding of the spectrum of HIV infection in our environment.

Institutionwide pain management improvement through the use of evidence-based content, strategies, resources, and outcomes.

The Agency for Health Care Policy and Research pain guidelines and implementation theories were used in this improvement initiative to ensure that evidence-based pain management reached every provider and patient in a large tertiary care hospital. Implementation strategies, products, and outcome measures are described for use in the clinical setting. Critical success factors and implementation barriers are also addressed.

Study of the effects of proline, phenylalanine, and urea foliar application to Tempranillo vineyards on grape amino acid content. Comparison with commercial nitrogen fertilisers.

The aim of this work was to study the influence of foliar application of different nitrogen sources on grape amino acid content. The nitrogen sources applied to Tempranillo grapevines were proline, phenylalanine, urea, and two commercial nitrogen fertilisers, both without and with amino acids in their formulations. All treatments were applied at veraison and one week later. Proline treatment did not affect the must nitrogen composition. However, phenylalanine and urea foliar application enhanced the plants' synthesis of most of the amino acids, producing similar effects. In addition, the spray of commercial nitrogen fertilisers over leaves also induced a rise in grape amino acid concentrations regardless of the presence or absence of amino acids in their formulation. The most effective treatments were phenylalanine and urea followed by nitrogen fertilisers. This finding is of oenological interest for improved must nitrogen composition, ensuring better fermentation kinetics and most likely enhancing wine quality.

Effectiveness of chlorine washing disinfection and effects on the appearance of artichoke and borage.

AIM: Optimal conditions for chlorine application to obtain a reasonable decrease in the microbial counts without damaging the appearance of artichoke and borage have been established. METHODS AND RESULTS: The influence of chlorine concentration (0-200 mg l(-1)), pH, addition of organic acids, contact time and presence of protective structures on the microflora and vegetal appearance were studied. When pH was not controlled the effect of chlorine depended on its concentration until the pH increase caused by addition of chlorine reached 8.8. Any further increase in chlorine concentration was nullified by the pH increase. When pH was adjusted to 4.5 with acetic acid, the effectiveness increased with concentration. However, the use of citric acid to control pH caused a sharp decrease in effectiveness at concentration about 250 mg l(-1). The higher effectiveness of chlorine on homogenized plant extracts compared with the whole plant showed the impact of the vegetal structures on the resistance of the microorganisms. For artichoke, a relationship between the effectiveness of chlorine disinfection and its structures was also found. Extended washing times did not affect the total counts. However, in both vegetables, the appearance was affected by the extended contact times. CONCLUSIONS: The solutions rendering the highest microbial reduction with minimum damages were: 50 mg l(-1) free chlorine without pH control for artichoke and 100 mg l(-1) free chlorine at pH 7.0 for borage. SIGNIFICANCE AND IMPACT OF THE STUDY: Specific conditions for chlorine disinfection of artichoke and borage were determined to reduce the microorganisms in minimally processed artichoke and borage without damaging their appearance.

Poncet's disease and papulonecrotic tuberculid in a patient infected with the human immunodeficiency virus.

We report the case of a 27-year-old patient with the human immunodeficiency virus (HIV) infection who presented with a 2-week history of crops of painful, red papules over the trunk and extremities, together with a sterile, symmetric polyarthritis involving the small and large joints. Histologic study of a skin biopsy specimen demonstrated features of papulonecrotic tuberculid. Analytical and microbiologic studies ruled out tuberculous infection. Both the synovial and the skin processes were considered to be an immune response secondary to Mycobacterium tuberculosis infection. Specific treatment was established, and there was marked improvement in both the skin and joint symptoms. This case illustrates the complex relationship between the host and the HIV, suggesting an immune dysregulation cause for both the synovial and the skin lesions.

[Tuberculin test in HIV infection]. / Prueba de la tuberculina en infección por HIV.

BACKGROUND: Intravenous infected-HIV drug abusers (IDAP/HIV+) are known to have a higher risk of tuberculosis (TB) than others. The effectiveness of tuberculin testing (Mantoux) in the detection of the TB infection in HIV(+) patients is probably lower than HIV(-) individuals. The aim of this paper is to assess tuberculin testing in the active search of cases of TB infection in IDAP individuals and their differences between HIV(+) and HIV(-) ones. METHODS: We studied 332 patients with intravenous drug use belonging to a therapeutic community and to in-patients. Tuberculin testing was performed on all of them. They were examinated if had been previously vaccinated with BCG and we carried out the counting of linfocites CD4 in HIV(+) ones. In the cases of negative tuberculin skin test a second test was administered after 7 days. The patients were grouped in HIV(+) and HIV(-) and the variables were statistically assessed by the chi 2 and a logistic regression model. RESULTS: Tuberculin testing resulted positive in 16.9% IDAP/HIV(+) in comparison with 39.9% of IDAP/HIV(-). The induration size was significantly smaller in HIV(+) than HIV(-) individuals. In both cases, we found that in BCG vaccinated patients positive tuberculin testing was significantly lower than negative tuberculin. The booster effect was detected in 8.9% of HIV(+), whereas in HIV(-) not BCG vaccinated it was of 21.4% and in HIV(-) BCG vaccinated it increased to 30.9%. When the level of the linfocites CD4 exceeds 500/mm3 in HIV(+) the percentage of Mantoux test (+) equals HIV(-) individuals. CONCLUSIONS: A decrease in sensitivity of tuberculin testing in the diagnosis of TB infection in IDAP/HIV(+) was detected. A high percentage of booster effect in IDAP was also demonstrated. We recommend the performance of tuberculin testing at the beginning of HIV infection.

Atypical scabies in HIV-positive patients.

Five cases of Norwegian or keratotic scabies in HIV-positive patients are described. One of these patients was the source of an outbreak in a hospital, ultimately involving 72 persons. Three of our patients had a markedly pruritic eruption. This is unusual in crusted scabies in which pruritus is usually slight or absent. Two of the five patients had unusual CD4 counts of more than 200 cells per cubic millimeter. All our patients responded to lindane and keratolytic agents. When generalized papular, crusted, or eczematoid lesions are observed in HIV-positive patients, particularly if the CD4 count is less than 200/mm3, scabies should be included in the differential diagnosis.