Exploring therapeutic options for mild diabetic-related foot infections: a comparative in vitro study of cefditoren versus amoxicillin/clavulanic acid.

Skin and soft tissue infections (SSTIs), and particularly diabetic-related foot infections (DFI), present diagnostic and therapeutic complexities, often leading to severe complications. This study aims to evaluate the in vitro efficacy of cefditoren and amoxicillin/clavulanic acid against typical DFI pathogens. Clinical samples from 40 patients with mild SSTIs were analyzed, revealing a predominance of Staphylococcus spp. and Streptococcus spp. species. Cefditoren exhibited activity against 90% of isolates, with superior potency over amoxicillin/clavulanic acid. These findings underscore the utility of cefditoren in empirical treatment of DFI, although a larger sample size would be desirable for further validation.

Role of HLA-DQB1 alleles in the risk, signs and symptoms, and severity of celiac disease in a Venezuelan population.

INTRODUCTION AND AIMS: Celiac disease (CD) is a complex condition, whose main genetic determinant involves HLA molecules, specifically the HLA-DQ2 and/or HLA-DQ8 heterodimers. Nevertheless, the frequency of the alleles encoding those molecules has not been reported in Venezuelan celiac patients. Therefore, the aim of our study was to evaluate the frequency of the HLA-DQB1 alleles in individuals with symptoms suggestive of CD and define the diagnostic markers of the condition in a Venezuelan population. MATERIAL AND METHODS: A cross-sectional study included 516 individuals with symptoms suggestive of CD. Molecular typing of the HLA-DQB1 locus was performed using a polymerase chain reaction-sequence-specific oligonucleotide procedure (PCR-SSO). RESULTS: A total of 58.3% of the individuals with clinical manifestations consistent with CD presented with at least one risk allele (DQB1*0201 and/or DQB1*0302), and the diagnosis was confirmed in 40 of them. The patients with CD had a higher frequency of the DQB1*0201 risk allele (26.25%), followed by the DQB1*0302 (17.5%) allele. There was an association between the presence of risk alleles and the presence of lesions characteristic of CD (P = 0.001), and a correlation was found between the genetic predisposition to develop CD and the presence of anti-tissue transglutaminase antibodies (P = 0.0127). CONCLUSIONS: The results support the role of the DQB1*02 and DQB1*0302 alleles in CD susceptibility and the histologic alterations of the intestinal mucosa, in a Venezuelan population.

Black carbon and elemental characterization of PM2.5 in dense traffic areas in two cities in Fiji, a Small Island Developing State.

PM2.5 characterizations are essential in understanding its impact on the health of the exposed population. Sampled PM2.5 by Mani et al. (2020) was characterized to determine atmospheric metal concentration and inhalation health risk in Suva and Lautoka Cities, the only two cities in Fiji and one of the largest in the South Pacific Islands. Twenty-two elements (Al, As, Ba, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Mo, Na, Ni, P, Pb, S, Si, Sr, V, Zn) were analyzed using ICP-OES. Black Carbon (BC) sampling was also done at three different sites in Suva City, namely, Fiji National University Samabula Intersection site, Suva City Bus Station site and the Reservoir Road Community Settlement Site as well as at Lautoka City Bus Station. Mean BC concentrations over the sampling period were found to be 3.9 ± 2.9 (median = 3.3 µg/m3), 2.6 ± 2.7 µg/m3 (median = 1.7 µg/m3), 2.4 ± 2.3 µg/m3 (median = 1.7 µg/m3) and 4.0 ± 4.7 µg/m3 (median = 2.4 µg/m3) respectively. Health risk assessments (Carcinogenic Risk (CR) and Non-Carcinogenic Risk (HQ)) were also done to assess the risk of inhalation exposure in adults and children. The Hazard Index for children in Lautoka (HI = 1.03) was found to slightly exceed the safe level of 1. This study provides the first inventory of atmospheric particulate bound metal concentrations and diurnal BC profiles in Fiji and informs policy makers and scientists for further studies.

Risk of pacemaker implantation after radiotherapy for breast cancer: A study based on French nationwide health care database sample.

BACKGROUND: Among cardiac complications of breast cancer radiotherapy (BC RT), there are very limited data on arrhythmia and conduction disorders, in particular severe cases requiring permanent pacemaker implantation (PPMI). Therefore, this exploratory study aimed to evaluate the risk of PPMI for BC patients treated with RT, compared with the general population and with BC patients not treated with RT. METHODS: The study was performed on a 1/97 representative sample of the French health care database (EGB database). Adult women with a first BC treated with or without RT between 2008 and 2016 were included, followed until 2018, and de novo PPMI were identified. We compared the PPMI incidence in BC cohort relative to the general population with standardized incidence ratio (SIR) and evaluated the risk of PPMI in RT patients compared to patients without RT with a competing risk survival analysis. RESULTS: A total of 3853 BCE patients were included. Among BC patients treated with RT, 28 PPMI cases were observed compared with 13 expected cases, corresponding to a SIR of 2.18 [95% CI: 1.45-3.06]. For BC patients not treated with RT, the SIR was 1.01 [95% CI: 0.40-1.90]. Patients treated with RT showed a borderline significant higher risk of PPMI compared with those not treated with RT (subdistribution Hazard Ratio = 2.08, 95% CI 0.87-4.97, p = 0.09). CONCLUSIONS: Our exploratory findings indicate that, over the last decade in France, BC patients treated with RT appeared to be at higher risk of PPMI than general population. Further studies are needed to expand on this topic.

Diabetes Remission and Relapse After Bariatric Surgery: a Nationwide Population-Based Study.

PURPOSE: The long-term impact of bariatric surgery on the remission of type 2 diabetes (T2DM) remains to be clarified through large nationally representative cohorts. The objectives were to determine the incidence of T2DM remission and relapse after bariatric surgery, to determine the factors associated with remission and to establish a profile for patients at risk for relapse. MATERIALS AND METHODS: We conducted a population-based cohort study using data from the French national health insurance database (Systeme national des données de santé [SNDS]). We had access to exhaustive regional data between 2013 and 2017 and to a national representative sample of the French population (EGB) from 2008 to 2018. Patients were included if they were adults and diabetics with incidental bariatric surgery. RESULTS: This study shows that 50% of patients are in remission from diabetes after bariatric surgery within a median of 2 to 4 months. Diabetes relapse was observed in 13-20% within 10 years. The factors favouring remission already described were noted (non-insulin-dependent diabetes) and original factors were also identified, in particular the advantage of bypass surgery over sleeve gastrectomy, with more remissions and fewer relapses. CONCLUSION: This study highlights a 50% prevalence of remission and a low prevalence of relapse. There are non-modifiable risk factors for remission and relapse (characteristics of diabetes, age, lipid-lowering therapy) and modifiable factors (type of surgery). Identifying these factors is essential for optimal management of patients. Additional data are essential to confirm the results of our analysis of the factors associated with relapse.

[Insufficient influenza vaccination coverage in giant cell arteritis. A French population-based study]. / Couverture vaccinale anti grippale insuffisante dans l'artérite à cellules géantes.

PURPOSE: To evaluate the rate of seasonal influenza vaccination coverage (IVC) in incident giant cell arteritis (GCA) patients compared with controls. METHODS: The vaccination rate was estimated from vaccine dispensation. IVC was compared between GCA and their controls using longitudinal multivariate Poisson regression. RESULTS: During the influenza campaigns from 2005-2006 to 2010-2011, the IVC rates in the GCA group and the control group ranged from 60.8 to 74.7% vs. 56.6 to 70.4%, respectively. Incident GCA influenza vaccination rate was 20% higher than controls (RR=1.20 ; IC 1.09 to 1.32, P<0.001). CONCLUSION: Although suboptimal, IVC in incident GCA was statistically better than controls.

Parents or Peers? Predictors of Prosocial Behavior and Aggression: A Longitudinal Study.

The aim of this longitudinal study was to determine the associations among peer attachment, warmth from the mother and father, strict control by the mother and father, prosocial behavior, and physical and verbal aggression in adolescence. Few longitudinal studies have examined how peer attachment and parenting styles of the mother and father relate to prosocial behavior and aggression. Participants were 192 boys and 255 girls (M = 14.70 years; SD = 0.68) in wave 1. In the study participated 11 schools. For three successive years, participants reported on their fathers' and mothers' warmth and strict control, peer attachment, prosocial behavior, and aggression. Structural equations modeling was employed to explore two longitudinal models. Results show the influence of the mother and father on prosocial and aggression during adolescence. In addition, strong peer attachment predicted prosocial behavior in subsequent years. Therefore, the findings indicate that despite the increasingly important role of friends during the transition from childhood to adolescence, parenting styles play a key role in the personal and social development of their children. Programs aimed at preventing aggression should be designed considering the importance of stimulating and strengthening prosocial behavior, peer attachment and a family environment of affect, support and communication.

Risk factors associated with the family care of people with serious mental illness.

BACKGROUND: The aim of the present study is to analyse the variables associated with the family care of people diagnosed with serious mental illness. MATERIAL AND METHODS: A cross-sectional study was carried out involving caregivers of people with serious mental illness (SMI) who were known to the mental health services in Valencia (España) and associations for those with SMI. The sample comprised 417 caregivers who completed a sociodemographic questionnaire and the Zarit Burden Interview. Bivariate analyses (t-test, analysis of variance and Pearson correlation) were performed, as was a multiple linear regression model. Values of p < .05 were considered significant. The study was carried out in accordance with the recommendations of the ethics committees of the participating institutions. RESULTS: The statistical analyses showed significant associations between the sociodemographic and clinical variables of the caregivers and patients and the burden felt by caregivers of people with SMI. The importance of both formal and informal social support stands out as a protective factor against the consequences of the illness's impact on the main caregiver. CONCLUSIONS: The role of spaces of mutual support is crucial. The results suggest that family psychoeducational programmes should be created, applied and evaluated in all mental healthcare services so as to reinforce training in mental health matters and provide support and assessment to caregivers in order to ease their burden.

Fear of cancer recurrence in Non- and Hodgkin lymphoma survivors during their first three years of survivorship among French patients.

The aim of this study was to measure the prevalence of FCR among a sample of French lymphoma survivors and to determine factors associated with clinical levels of FCR. The study was conducted with two cross-sectional measures: sociodemographic and anxiety, depression as well as health-related quality of life (HRQoL) scores were measured at the baseline of the post-cancer period and FCR was evaluated during the first 3 years of survivorship. The prevalence of clinical levels of FCR (≥13) was evaluated by the Fear of Cancer Recurrence Inventory - Short Form (FCRI-SF) among non- and Hodgkin lymphoma survivors undergoing prior first-line chemotherapy. Among 108 lymphoma survivors with an average follow-up of 1.6 years (range 0.3-3.0 years), clinical levels of FCR (≥13) were observed for 44.4% (n = 48). Multivariate analysis indicated that baseline anxiety and low quality of life were related to clinically significant FCR levels.

Optimization of fermentation-relevant factors: A strategy to reduce ethanol in red wine by sequential culture of native yeasts.

Current consumer preferences are determined by well-structured, full-bodied wines with a rich flavor and with reduced alcohol levels. One of the strategies for obtaining wines with reduced ethanol content is sequential inoculation of non-Saccharomyces and Saccharomyces cerevisiae yeasts. However, different factors affect the production of metabolites like ethanol, glycerol and acetic acid by inoculated yeasts. In order to obtain low alcohol wines without quality loss, the aims of our study were: i) to determine optimum conditions (fermentation temperature and time of permanence and initial inoculum size of the non-Saccharomyces population at the beginning of the process, prior to inoculation with S. cerevisiae); ii) to validate the optimized factors; and iii) to assess sensory quality of the wines obtained after validation. Two combinations of yeasts were used in this study: Hanseniaspora uvarum BHu9/S. cerevisiae BSc114 and Candida membranaefaciens BCm71/S. cerevisiae BSc114. Optimization of three fermentation factors that affect to non-Saccharomyces yeasts prior to S. cerevisiae inoculation was carried out using a Box-Behnken experimental design. Applying the models constructed by Response Surface Methodology, the lowest ethanol production by H. uvarum BHu9/S. cerevisiae BSc114 co-culture was obtained when H. uvarum BHu9 was inoculated 48 h 37 min prior to S. cerevisiae inoculation, at a fermentation temperature of 25 °C and at an initial inoculum size of 5 × 106 cells/mL. Lowest alcohol production with C. membranaefaciens BCm71/S. cerevisiae BSc114 was observed when C. membranaefaciens BCm71 was inoculated 24 h 15 min prior to S. cerevisiae at a fermentation temperature of 24.94 °C and at an initial inoculum size of 2.72 × 106 cells/mL. The optimized conditions of the two co-cultures were subsequently submitted to lab-scale validation. Both proposed strategies yielded ethanol levels that were significantly lower than control cultures (S. cerevisiae). Wines fermented with non-Saccharomyces/Saccharomyces co-cultures under optimized conditions were also associated with higher aromatic complexity characterized by the presence of red fruit aromas, whereas wines obtained with S. cerevisiae BSc114 were described by parameters linked with high ethanol levels.

Risk factors for bleeding, including platelet count threshold, in newly diagnosed immune thrombocytopenia adults.

Essentials Risk factors of bleeding in adult immune thrombocytopenia are not known. This multicenter study assessed risk factors of bleeding at immune thrombocytopenia onset. Platelet count thresholds associated with bleeding were < 20 × 109 L-1 and < 10 × 109 L-1 . Exposure to anticoagulants was a major risk factor of severe bleeding. SUMMARY: Background The aim of this cross-sectional study was to assess risk factors for bleeding in immune thrombocytopenia (ITP) adults, including the determination of platelet count thresholds. Methods We selected all newly diagnosed ITP adults included in the Cytopénies Auto-immunes Registre Midi-PyrénéEN (CARMEN) register and at the French referral center for autoimmune cytopenias. The frequencies of any bleeding, mucosal bleeding and severe bleeding (gastrointestinal, intracranial, or macroscopic hematuria) at ITP onset were assessed. Platelet count thresholds were assessed by the use of receiver operating characteristic curves. All potential risk factors were included in logistic regression models. Results Among the 302 patients, the frequencies of any, mucosal and severe bleeding were 57.9%, 30.1%, and 6.6%, respectively. The best discriminant threshold of platelet count for any bleeding was 20 × 109 L-1 . In multivariate analysis, factors associated with any bleeding were platelet count (< 10 × 109 L-1 versus ≥ 20 × 109 L-1 , odds ratio [OR] 48.2, 95% confidence interval [CI] 20.0-116.3; between 10 × 109 L-1 and 19 × 109 L-1 versus ≥ 20 × 109 L-1 , OR 5.2, 95% CI 2.3-11.6), female sex (OR 2.6, 95% CI 1.3-5.0), and exposure to non-steroidal anti-inflammatory drugs (NSAIDs) (OR 4.8, 95% CI 1.1-20.7). A low platelet count was also the main risk factor for mucosal bleeding. Exposure to anticoagulant drugs was associated with severe bleeding (OR 4.3, 95% CI 1.3-14.1). Conclusions Platelet counts of < 20 × 109 L-1 and < 10 × 109 L-1 were thresholds for major increased risks of any and mucosal bleeding. Platelet count, female sex and exposure to NSAIDs should be considered for assessment of the risk of any bleeding. Exposure to anticoagulant drugs was a major risk factor for severe bleeding.

[Propensity score: Interests, use and limitations. A practical guide for clinicians]. / Score de propension : intérêts, utilisation et limites. Un guide pratique pour le clinicien.

Propensity scores have been proposed in the early 1980s, and are increasingly used in epidemiology since the 2000s. They are is used to minimize the selection bias in observational studies, leading to a comparability between the exposure groups close to that observed in randomized trials. However, they have important limitations. Besides, new statistical techniques to improve the propensity score performances are more and more complex, while the build and the use of propensity score require a strict methodology to avoid bias, imprecision and non-reproducibility. This overview, designed for clinicians, is aimed at describing the advantages, techniques of use and limitations of propensity scores. A reading grid is provided in order to help interpreting studies using propensity scores.

Biomarkers of resistance to radiation therapy: a prospective study in cervical carcinoma.

BACKGROUND: Clinical parameters and proteins have recently been suggested as possible causes of radiotherapy (RT) resistance in cervical carcinoma (CC). The objective of the present study was to validate prognostic biomarkers of radiation resistance. METHODS: The present prospective study included patients undergoing RT with curative intent for histologically proven locally advanced squamous cell CC. Tissues and blood samples were systematically collected before RT initiation. Immuno-histochemistry was performed (IGF-IR α and ß, GAPDH, HIF-1 alpha, Survivin, GLUT1, CAIX, hTERT and HKII). Response to radiation was assessed through tumour response 3 months after RT completion, through overall survival (OS) and through progression-free survival (PFS). RESULTS: One hundred forty nine patients with a mean age of 46 years were included, with FIGO IIB (n = 53) and FIGO IIIB (n = 96) CCs. 61 patients were treated with exclusive RT + brachytherapy and 88 underwent chemo-radiotherapy + brachytherapy. Our findings suggest an association between hemoglobin level (Hb) (>11 g/dL) and 3 months complete response (p = 0.02). Hb level < 11 g/dL was associated with decreased PFS (p = 0.05) and OS (p = 0.08). Overexpression of IGF-1R ß was correlated with a decreased OS (p = 0.007). Overexpression of GLUT1 was marginally correlated with reduced OS (p = 0.05). PFS and OS were significantly improved in patients undergoing chemoradiation versus exclusive radiotherapy (PFS: p = 0.04; OS: p = 0.01). CONCLUSIONS: IGF-1R ß overexpression and Hb level (≤11 g/dl) were associated with poor prognosis, and thus appear to be possible interesting biomarkers of radiation resistance. Our results corroborate previous pre-clinical studies suggesting IGF-1R and hypoxia to be part of the biological pathways leading to radio-resistance.

[Epidemiology and pharmacoepidemiology of immune thrombocytopenia]. / Épidémiologie et pharmacoépidémiologie du purpura thrombopénique immunologique.

During the last decade, the development of large clinical and population-based cohorts led to new findings in the epidemiology and the pharmacoepidemiology of immune thrombocytopenia (ITP). The incidence is estimated to 3-4 for 105 inhabitants/year, with a slight female predominance and peaks in children and patients after 60 years. The incidence rate is 9 for 105 inhabitants/year in males after 75 years. Variations across ethnic groups are discussed. In France, there is a North-South gradient and a peak of incidence during winter suggesting the role of viruses in ITP pathophysiology. Myelodysplastic syndromes are an emergent cause of secondary ITP. The incidence of intracranial bleeding is about 1% by year and the risk increases with aging. Exposure to splenectomy decreases while rituximab and thrombopoietin receptor agonists (TPO-RA) are the most used second-line drugs for persistent ITP. Mortality is slightly increased in primary ITP as compared with the general population. ITP patients have an increased risk of infection, thrombosis and hemorrhage. Aging, lung diseases, splenectomy, corticosteroids and rituximab are risk factors for infection while influenza and pneumococcal vaccines are associated with a 50% decrease of infection risk. Aging, cardiovascular risk factors, lupus anticoagulant and splenectomy are risk factors for thrombosis. The risk of thrombosis associated with corticosteroids and TPO-RAs must be further investigated.

Infections in non-splenectomized persistent or chronic primary immune thrombocytopenia adults: risk factors and vaccination effect.

Essentials The risk factors for infection in immune thrombocytopenia are not well known. We conducted a national pharmacoepidemiological study. Pulmonary disease, corticosteroids and rituximab were the main risk factors for infections. Pneumococcal and influenza vaccines were protective against infections. SUMMARY: Introduction Risk factors for infection and protective effect of vaccines in immune thrombocytopenia (ITP) patients in the era of rituximab therapy are unknown. Objectives To assess the risk factors for serious and non-serious infections (respectively, SIs and NSIs) in non-splenectomized adults treated for persistent or chronic primary ITP, including the effect of pneumococcal and influenza vaccines. Patients/Methods The population was the 2009-2012 FAITH cohort (n = 1805), which is the cohort of all incident (newly diagnosed) primary ITP adults treated > 3 months in France built into the national health insurance database (SNIIRAM). SIs were hospitalizations with any infection as the primary diagnosis code. NSIs were identified using out-of-hospital antibiotic dispensing. Cox models were performed. Results Incidence rates were 6.3/100 patient-years (95% confidence interval [CI], 5.4-7.4) for SIs (lower respiratory tract in 42.8% of the cases) and 100.5/100 patient-years (95% CI, 95.0-106.3) for NSIs. In multivariate analyses, increasing age and chronic pulmonary disease were associated with both SI and NSI occurrence. The hazard ratios (HRs) for corticosteroids and rituximab were, respectively, 3.83 (95% CI, 2.76-5.31) and 2.60 (95% CI, 1.67-4.03) for SIs and 2.46 (95% CI, 2.19-2.76) and 1.49 (95% CI, 1.28-1.74) for NSIs. Pneumococcal vaccine showed a protective effect for both SIs and NSIs (0.38 [95% CI, 0.20-0.73] and 0.52 [95% CI, 0.43-0.65], respectively), as did influenza vaccine (0.42 [95% CI, 0.27-0.64] and 0.49 [95% CI, 0.41-0.59], respectively). Conclusions Chronic pulmonary disease, corticosteroids and rituximab are the main risk factors for infections, whereas pneumococcal and influenza vaccines are protective against SIs and NSIs.

Papel de las variantes GSTM1, GSTT1 y MnSOD en el desarrollo de enfermedad de Alzheimer de aparición tardía y su relación con el alelo 4 de APOE / Role of genes GSTM1, GSTT1, and MnSOD in the development of late-onset Alzheimer disease and their relationship with APOE*4

Introducción: Diversos estudios han descrito que en los cerebros de pacientes con enfermedad de Alzheimer (EA) hay una mayor oxidación de lípidos, proteínas y ADN. Además, en estos pacientes se ha observado diferencias en la actividad y polimorfismos de los genes que codifican las enzimas GST (T1 y M1) y MnSOD. En virtud de ello se planteó estudiar la variabilidad de los genes GSTT1, GSTM1 y MnSOD en individuos venezolanos sanos y con EA. Métodos: Se incluyeron 179 individuos venezolanos, no relacionados, agrupados en pacientes con EA (n = 79) e individuos sanos (n = 100). La presencia o ausencia de los genes GSTT1/GSTM1 se determinó por PCR-SSP y los polimorfismo de los genes MnSOD y APOE por PCR-RFLP. Resultados: El genotipo GSTT1+/GSTM1− parece favorecer el desarrollo de la EA (OR = 2,06; p = 0,01), siendo el riesgo mayor al estar en combinación con el alelo ε4 del gen APOE: GSTT1+/GSTM1−/ ε3 ε4 (OR = 3,07; p = 0,05), GSTT1+/GSTM1−/ ε4 ε4 (OR = 5,52; p = 0,02). El polimorfismo Ala-9Val por sí solo no parece estar relacionado con la EA, sin embargo, la presencia del genotipo Ala/Ala incrementa el riesgo que proporciona el alelo ε4 del gen APOE: AlaAla/ ε3 ε4 (OR = 3,47; p = 0,03), AlaAla/ ε4 ε4 (OR = 6,3; p = 0,01). Conclusiones: Los resultados apoyan la hipótesis de que el deterioro de la función mitocondrial y el aumento de daño oxidativo están involucrados en la patogénesis de la EA. Es importante estudiar otros genes relacionados con estrés oxidativo y vías antioxidantes, los cuales pudiesen estar involucrados en la susceptibilidad a desarrollar la EA

Introduction: Several studies have reported increased oxidation of lipids, proteins and DNA in the brains of patients with Alzheimer disease (AD). Moreover, these patients display differences in the activity and polymorphisms of the genes encoding the enzymes GST (T1, M1) and MnSOD. For these reasons, we designed a study of the variability in GSTT1, GSTM1, and MnSOD genes in healthy and AD groups from a Venezuelan population. Methods: We included 179 unrelated Venezuelan subjects classified as either AD patients (n = 79) or healthy individuals (n = 100). Presence or absence of the GSTT1/GSTM1 genes was determined using PCR-SSP, and polymorphisms of MnSOD and APOE genes were identified with PCR-RFLP. Results: The genotype GSTT1+/GSTM1− seems to favour development of AD (OR = 2.06, P = .01). The risk level is higher when it is combined with the ε4 allele of the APOE gene: GSTT1+/GSTM1−/ ε3 ε4 (OR = 3.07, P = .05), GSTT1+/GSTM1−/ ε4 ε4 (OR = 5.52, P = .02). The Ala-9Val polymorphism does not appear to be related to AD. However, the presence of the Ala/Ala genotype increases the risk provided by the ε4 allele of the APOE gene: AlaAla/_3_4 (OR = 3.47, P = .03), AlaAla/ ε4 ε4 (OR = 6.3, P = .01). Conclusions: The results support the hypothesis that impaired mitochondrial function and increased oxidative damage are involved in the pathogenesis of AD. It is important to study other genes related to oxidative stress and antioxidant pathways which could be involved in susceptibility to AD

Culture-dependent and independent techniques to monitor yeast species during cold soak carried out at different temperatures in winemaking.

Transformation of grape must into wine is a process that may vary according to the consumers' requirements. Application of cold soak prior to alcoholic fermentation is a common practice in cellars in order to enhance flavor complexity and extraction of phenolic compounds. However, the effect of this step on wine yeast microbiota is not well-known. The current study simultaneously analyzed the effect of different cold soak temperatures on the microbiological population throughout the process and the use of culture-dependent and independent techniques to study this yeast ecology. The temperatures assayed were those normally applied in wineries: 2.5, 8 and 12°C. PCR-DGGE allowed detection of the most representative species such as Hanseniaspora uvarum, Starmerella bacillaris and Saccharomyces cerevisiae. As could be expected, highest diversity indices were obtained at the beginning of each process, and survival of H. uvarum or S. bacillaris depended on the temperature. Our results are in agreement with those obtained with culture independent methods, but qPCR showed higher precision and a different behavior was observed for each yeast species and at each temperature assayed. Comparison of both culture-independent techniques can provide a general overview of the whole process, although DGGE does not reveal the diversity expected due to the reported problems with the sensitivity of this technique.

Insertion of Isocyanides into N-Si Bonds: Multicomponent Reactions with Azines Leading to Potent Antiparasitic Compounds.

Trimethylsilyl chloride is an efficient activating agent for azines in isocyanide-based reactions, which then proceed through a key insertion of the isocyanide into a N-Si bond. The reaction is initiated by N activation of the azine, followed by nucleophilic attack of an isocyanide in a Reissert-type process. Finally, a second equivalent of the same or a different isocyanide inserts into the N-Si bond leading to the final adduct. The use of distinct nucleophiles leads to a variety of α-substituted dihydroazines after a selective cascade process. Based on computational studies, a mechanistic hypothesis for the course of these reactions was proposed. The resulting products exhibit significant activity against Trypanosoma brucei and T. cruzi, featuring favorable drug-like properties and safety profiles.

Role of genes GSTM1, GSTT1, and MnSOD in the development of late-onset Alzheimer disease and their relationship with APOE*4. / Papel de las variantes GSTM1, GSTT1 y MnSOD en el desarrollo de enfermedad de Alzheimer de aparición tardía y su relación con el alelo 4 de APOE.

INTRODUCTION: Several studies have reported increased oxidation of lipids, proteins and DNA in the brains of patients with Alzheimer disease (AD). Moreover, these patients display differences in the activity and polymorphisms of the genes encoding the enzymes GST (T1, M1) and MnSOD. For these reasons, we designed a study of the variability in GSTT1, GSTM1, and MnSOD genes in healthy and AD groups from a Venezuelan population. METHODS: We included 179 unrelated Venezuelan subjects classified as either AD patients (n=79) or healthy individuals (n=100). Presence or absence of the GSTT1/GSTM1 genes was determined using PCR-SSP, and polymorphisms of MnSOD and APOE genes were identified with PCR-RFLP. RESULTS: The genotype GSTT1+/GSTM1- seems to favour development of AD (OR=2.06, P=.01). The risk level is higher when it is combined with the ɛ4 allele of the APOE gene: GSTT1+/GSTM1-/ɛ3ɛ4 (OR=3.07, P=.05), GSTT1+/GSTM1-/ɛ4ɛ4 (OR=5.52, P=.02). The Ala-9Val polymorphism does not appear to be related to AD. However, the presence of the Ala/Ala genotype increases the risk provided by the ɛ4 allele of the APOE gene: AlaAla/ɛ3ɛ4 (OR=3.47, P=.03), AlaAla/ɛ4ɛ4 (OR=6.3, P=.01). CONCLUSIONS: The results support the hypothesis that impaired mitochondrial function and increased oxidative damage are involved in the pathogenesis of AD. It is important to study other genes related to oxidative stress and antioxidant pathways which could be involved in susceptibility to AD.