Wine yeast peroxiredoxin tsa1 plays a role in growth, stress response and trehalose metabolism in biomass propagation

Peroxiredoxins are a family of peroxide-degrading enzymes for challenging oxidative stress. They receive their reducing power from redox-controlling proteins called thioredoxins, and these, in turn, from thioredoxin reductase. The main cytosolic peroxiredoxin is Tsa1, a moonlighting protein that also acts as protein chaperone a redox switch controlling some metabolic events. Gene deletion of peroxiredoxins in wine yeasts indicate that TSA1, thioredoxins and thioredoxin reductase TRR1 are required for normal growth in medium with glucose and sucrose as carbon sources. TSA1 gene deletion also diminishes growth in molasses, both in flasks and bioreactors. The TSA1 mutation brings about an expected change in redox parameters but, interestingly, it also triggers a variety of metabolic changes. It influences trehalose accumulation, lowering it in first molasses growth stages, but increasing it at the end of batch growth, when respiratory metabolism is set up. Glycogen accumulation at the entry of the stationary phase also increases in the tsa1∆ mutant. The mutation reduces fermentative capacity in grape juice, but the vinification profile does not significantly change. However, acetic acid and acetaldehyde production decrease when TSA1 is absent. Hence, TSA1 plays a role in the regulation of metabolic reactions leading to the production of such relevant enological molecules

Efficiency of the cerebroplacental ratio in Identifying high-risk late-term pregnancies

Background and Objectives: Over the last few years, great interest has arisen in the role of the cerebroplacental ratio (CPR) to identify low-risk pregnancies at higher risk of adverse pregnancy outcomes. This study aimed to assess the predictive capacity of the CPR for adverse perinatal outcomes in all uncomplicated singleton pregnancies attending an appointment at 40–42 weeks. Materials and Methods: This is a retrospective cohort study including all consecutive singleton pregnancies undergoing a routine prenatal care appointment after 40 weeks in three maternity units in Spain and the United Kingdom from January 2017 to December 2019. The primary outcome was adverse perinatal outcomes defined as stillbirth or neonatal death, cesarean section or instrumental delivery due to fetal distress during labor, umbilical arterial cord blood pH < 7.0, umbilical venous cord blood pH < 7.1, Apgar score at 5 min < 7, and admission to the neonatal unit. Logistic mixed models and ROC curve analyses were used to analyze the data. Results: A total of 3143 pregnancies were analyzed, including 537 (17.1%) with an adverse perinatal outcome. Maternal age (odds ratio (OR) 1.03, 95% confidence interval (CI) 1.01 to 1.04), body mass index (OR 1.04, 95% CI 1.03 to 1.06), racial origin (OR 2.80, 95% CI 1.90 to 4.12), parity (OR 0.36, 95% CI 0.29 to 0.45), and labor induction (OR 1.79, 95% CI 1.36 to 2.35) were significant predictors of adverse perinatal outcomes with an area under the ROC curve of 0.743 (95% CI 0.720 to 0.766). The addition of the CPR to the previous model did not improve performance. Additionally, the CPR alone achieved a detection rate of only 11.9% (95% CI 9.3 to 15) when using the 10th centile as the screen-positive cutoff. Conclusions: Our data on late-term unselected pregnancies suggest that the CPR is a poor predictor of adverse perinatal outcomes

Consenso sobre el uso del monitor flash de glucosa de primera generación en pacientes menores de 18 años de edad con diagnóstico de diabetes mellitus tipo 1

Introducción: la diabetes mellitus tipo 1 (DM1) es una de las patologías endocrinas más frecuentes en la población pediátrica. La glucometría capilar, método de autocontrol más recomendado, se asocia con molestias que pueden disminuir la adherencia, lo que impulsó la creación de nuevas tecnologías que respondan a las necesidades de los pacientes. Objetivo: generar recomendaciones a partir del consenso de expertos acerca del uso del monitor flash de glucosa (MFG) en pacientes menores de 18 años con diagnóstico de DM1. Materiales y métodos: se realizó un consenso tipo Delphi modificado en el que participaron 8 especialistas en endocrinología pediátrica y un grupo desarrollador. A partir del análisis de los resultados, se presentaron las recomendaciones. Resultados: se obtuvieron recomendaciones acerca de indicaciones, frecuencia y modo de uso, perfil de seguridad e impacto de su uso en la calidad de vida. Conclusiones: el MFG tiene una precisión comparable con la glucometría capilar y se considera un dispositivo seguro, con la capacidad de impactar positivamente en la calidad de vida de los pacientes y sus cuidadores. Palabras clave: diabetes mellitus tipo 1, niño, adolescente, automonitorización de la glucosa sanguínea, sistema monitor flash glucosa

Risk of Fetal Loss After Chorionic Villus Sampling in Twin Pregnancy Derived from Propensity Score Matching Analysis

Objective: To estimate the risk of fetal loss associated with chorionic villus sampling (CVS) in twin pregnancy, using propensity score analysis. Methods: This was a multicenter cohort study of women with twin pregnancy undergoing ultrasound examination at 11-13 weeks' gestation, performed in eight fetal medicine units in which the leadership were trained at the Harris Birthright Research Centre for Fetal Medicine in London, UK, and in which the protocols for screening, invasive testing and pregnancy management are similar. The risk of death of at least one fetus was compared between pregnancies that had and those that did not have CVS, after propensity score matching (1:1 ratio). This procedure created two comparable groups by balancing the maternal and pregnancy characteristics that lead to CVS being performed, similar to how randomization operates in a randomized clinical trial. Results: The study population of 8581 twin pregnancies included 445 that had CVS. Death of one or two fetuses at any stage during pregnancy occurred in 11.5% (51/445) of pregnancies in the CVS group and in 6.3% (515/8136) in the non-CVS group (P < 0.001). The propensity score algorithm matched 258 cases that had CVS with 258 non-CVS cases; there was at least one fetal loss in 29 (11.2%) cases in the CVS group and in 35 (13.6%) cases in the matched non-CVS group (odds ratio (OR), 0.81; 95% CI, 0.48-1.35; P = 0.415). However, there was a significant interaction between the risk of fetal loss after CVS and the background risk of fetal loss; when the background risk was higher, the risk of fetal loss after CVS decreased (OR, 0.46; 95% CI, 0.23-0.90), while, in pregnancies with a lower background risk of fetal loss, the risk of fetal loss after CVS increased (OR, 2.45; 95% CI, 0.95-7.13). The effects were statistically significantly different (P-value of the interaction = 0.005). For a pregnancy in which the background risk of fetal loss was about 6% (the same as in our non-CVS population), there was no change in the risk of fetal loss after CVS, but, when the background risk was more than 6%, the posterior risk was paradoxically reduced, and when the background risk was less than 6%, the posterior risk increased exponentially; for example, if the background risk of fetal loss was 2.0%, the relative risk was 2.8 and the posterior risk was 5.6%. Conclusion: In twin pregnancy, after accounting for the risk factors that lead to both CVS and spontaneous fetal loss and confining the analysis to pregnancies at lower prior risk, CVS seems to increase the risk of fetal loss by about 3.5% above the patient's background risk. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.info:eu-repo/semantics/publishedVersio

Risk of miscarriage after chorionic villus sampling.

OBJECTIVE: To estimate the risk of miscarriage associated to chorionic villus sampling (CVS). METHODS: This was a retrospective cohort study performed in eight fetal-medicine units in Spain, Belgium and Bulgaria. Two populations were included: first, all singleton pregnancies attending to their first-trimester assessment in Murcia, Spain, and second, all singleton pregnancies having a CVS following first-trimester assessment at any of the participating centers. We used propensity score matching analysis to estimate the association between CVS and miscarriage. We compared risks of miscarriage of CVS and non-CVS groups after propensity score matching (1:1 ratio). This procedure creates two comparable groups balancing the maternal and pregnancy characteristics that lead to CVS, in a similar way in which randomization operates in a randomized clinical trial. RESULTS: The study population consisted of 22,250 participants in the non-CVS group and 3,613 in the CVS group. The incidence of miscarriage in the CVS group was 2.1% (77/3,613), which was significantly higher than the 0.9% (207/22,250) in the non-CVS group (p <0.001). The propensity score algorithm matched 2,122 CVS cases with 2,122 non-CVS cases including 40 (1.9%) and 55 (2.6%) miscarriages in the CVS and non-CVS groups, respectively (OR 0.72 [95% CI 0.48 to 1.10]; p = 0.146). However, we found a significant interaction between the CVS risk of miscarriage and the risk of aneuploidies, suggesting a different effect of the CVS for different baseline characteristics in such a way that, when the risk of aneuploidies is low, the risk after CVS increases (OR 2.87 [95% CI 1.13 to 7.30]) but when the risk is high, the risk after CVS is paradoxically reduced (OR 0.47 [95% CI 0.28 to 0.76]), presumably due to prenatal diagnosis and termination of major aneuploidies that would have otherwise resulted in spontaneous miscarriage. CONCLUSIONS: The risk of miscarriage in women having a CVS is about 1% higher than in women without CVS, although this excess risk is not entirely due to the invasive procedure but to some extent the demographic and pregnancy characteristics of the patient undergoing CVS. After accounting for these risk factors and confining the analysis to low-risk pregnancies, CVS seems to increase the risk of miscarriage about three times above the patient's background-risk. Although this is a substantial increase in relative terms, in pregnancies without risk factors, the risk of miscarriage after CVS will still remain low and similar to or slightly higher than that of the general population. For example, if her risk of aneuploidy is 1 in a 1,000 (0.1%), her risk of miscarriage after CVS will increase to 0.3% (0.2% higher)

Normas percebidas por estudantes universitários sobre seus companheiros e uso de drogas: um estudo multicêntrico em cinco países da América Latina

Este estudio transversal se comparó la percepción que se tiene del consumo de los pares con el uso real de drogas, en una muestra de estudiantes universitarios de América Latina. Los estudiantes de nueve universidades en cinco países (Brasil, Chile, Colombia, Honduras y Perú) respondieron a un cuestionario que abordaba el uso de tabaco, alcohol, marihuana y cocaína. El análisis se concentró en la comparación de la percepción y el consumo real de drogas. Los resultados en gran medida, aunque no completamente, confirmaron que los estudiantes sobreestiman el uso de drogas entre sus pares. Los resultados inesperados fueron los relacionados con el alcohol. Mientras que los estudiantes generalmente sobrestimaron el consumo de tabaco, marihuana y cocaína entre sus pares, los mismos estimaron con bastante precisión o subestimaron el uso de alcohol entre sus pares. Además de los resultados inesperados en relación al alcohol, este estudio muestra que la percepción del uso de drogas en América Latina se comporta de manera similar a otros lugares. Los resultados también apoyan la sugerencia respecto a que la retroalimentación normativa sería útil para fortalecer los programas de prevención de drogas dirigidos a jóvenes en América Latina.Este estudo transversal comparou a percepção dos companheiros de usuários de drogas em uma amostra de estudantes universitários da América Latina. Os estudantes de nove universidades, localizadas em cinco países (Brasil, Chile, Colômbia, Honduras e Peru) responderam questionário que abordou questões sobre o tagagismo, álcool, maconha e cocaína. A análise foi focalizada na comparação da percepção e da realidade dos atuais usuários de drogas. Os resultados confirmaram, de forma geral, a ideia de que os estudantes superestimam o uso de drogas. Resultados inesperados foram identificados em relação ao uso de álcool. Enquanto os estudantes geralmente superestimam o uso de tabaco, maconha e cocaína, entre seus pares, estimaram com bastante precisão ou subestimaram o uso de álcool entre seus pares. Apesar desse resultado inesperado, este estudo mostra que a percepção do uso de drogas entre estudantes universitários da América Latina se comporta de maneira similar ao uso de drogas em outras localidades. Os resultados também apóiam a sugestão de que intervenções, usando retroalimentação normativa, seriam úteis para fortalecer os programas de prevenção ao uso de drogas, dirigidos aos jovens da América Latina.This cross-sectional study compared perceived peer drug use and actual drug use in a sample of Latin American university students. Students from nine universities in five countries (Brazil, Chile, Colombia, Honduras and Peru) completed a questionnaire that addressed the use of tobacco, alcohol, marijuana and cocaine. Analysis focused on comparing perceptions to actual drug use. The findings largely, but not completely, confirmed the idea that students overestimate peer drug use. The unexpected findings were those relating to alcohol. While students generally overestimated peer use of tobacco, marijuana and cocaine, they accurately estimated or underestimated peer use of alcohol. Apart from the anomalous findings with regard to alcohol, this study shows that perceived drug use relates to actual drug use in Latin America as it does elsewhere. The results also support the suggestion that interventions using normative feedback would be useful to strengthen drug use prevention programs aimed at youth in Latin America

Yeast thioredoxin reductase Trr1p controls TORC1-regulated processes

The thioredoxin system plays a predominant role in the control of cellular redox status. Thioredoxin reductase fuels the system with reducing power in the form of NADPH. The TORC1 complex promotes growth and protein synthesis when nutrients, particularly amino acids, are abundant. It also represses catabolic processes, like autophagy, which are activated during starvation. We analyzed the impact of yeast cytosolic thioredoxin reductase TRR1 deletion under different environmental conditions. It shortens chronological life span and reduces growth in grape juice fermentation. TRR1 deletion has a global impact on metabolism during fermentation. As expected, it reduces oxidative stress tolerance, but a compensatory response is triggered, with catalase and glutathione increasing. Unexpectedly, TRR1 deletion causes sensitivity to the inhibitors of the TORC1 pathway, such as rapamycin. This correlates with low Tor2p kinase levels and indicates a direct role of Trr1p in its stability. Markers of TORC1 activity, however, suggest increased TORC1 activity. The autophagy caused by nitrogen starvation is reduced in the trr1Δ mutant. Ribosomal protein Rsp6p is dephosphorylated in the presence of rapamycin. This dephosphorylation diminishes in the TRR1 deletion strain. These results show a complex network of interactions between thioredoxin reductase Trr1p and the processes controlled by TOR

Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1