Warfarin genetic biomarkers in VKORC1 and CYP2C9*2 genes: Advancing personalized anticoagulant therapy using electrochemical genosensors

The genetic variants of vitamin K epoxide reductase complex (VKORC1) and in the cytochrome CYP2C9*2 genes have been identified to influence the anticoagulant warfarin and influence its plasmatic levels. Therefore, the pharmacogenetic information on these genes is useful for reducing warfarin adverse reaction. This work addresses the development of disposable electrochemical genosensors able of detecting single nucleotide polymorphism (SNP) in the VKORC1 and CYP2C9*2 genes. The genosensor methodology implied the immobilization of a mixed self-assembled monolayer (SAM) linear DNA-capture probe and mercaptohexanol (MCH) onto screen-printed gold electrodes (SPGE). To improve the genosensor’s selectivity and avoid strong secondary structures, that could hinder the hybridization efficiency, a sandwich format of the DNA allele was designed using a complementary fluorescein isothiocyanate-labelled signaling DNA probe and enzymatic amplification of the electrochemical signal. The developed electrochemical genosensors were able to discriminate between the two synthetic target DNA targets in both SNPs, as well as the targeted denatured genomic DNA. Several analytical parameters, such as DNA capture probe, 6-mercaptohexanol (as spacer) and antibody concentrations, as well as hybridization temperature and incubation time, were optimized. Using the best analytical conditions calibration curves employing increasing DNA target concentractions were ploted. Polymerase Chain Reaction (PCR), will be used for further validation of the electrochemical genosensor. Disposable electrochemical genosensors capable of detecting and distinguishing between two synthetic CYP2C9*2 and VKORC1 polymorphic sequences, with high selectivity and sensibility and in various concentrations, was developed. The functionality of these analytical approaches as alternative to the conventional genotyping methodologies can relieve the public health-care systems and, hopefully, prevent ADRs related to CDV episodes.info:eu-repo/semantics/publishedVersio

Controlling Bovine Brucellosis In The State Of São Paulo, Brazil: Results After Ten Years Of A Vaccination Program

A cross- sectional study was carried out, between May and November 2011, to estimate the situation of the bovine brucellosis in São Paulo State, 10 years after the commencement of the vaccination of the heifers with the S19 strain. The State was divided into seven regions and in each of them, 300 farms with reproductive activity were randomly chosen and considered as primary sample units. A fixed number of cows was randomly selected and tested for antibodies against Brucella spp. A farm was considered infected if at least one female tested positive. In the selected farms, an epidemiological questionnaire was administered which focused on herd traits as well as husbandry and sanitary practices that could be associated with the risk of infection. The prevalence (percentile, [95% confidence interval]) of infected herds was 10.2% [8.8-11.8] for the State, and for the regions, it varied from 7.3% [4.7-11.2] to 12.3% [8.8-16.8], not showing significant difference between different regions. The apparent prevalence of positive farms in the State and regions remained similar to the prevalence observed 10 years before. The prevalence of positive animals was 2.4% [1.8-3.1] in the State and varied from 1.1% [0.6-2] to 3.5% [1.7-7.1] in the regions, not showing significant difference between regions. Again, there was no difference in the prevalence of positive animals after 10 years of the vaccination program. The risk factors (odds ratio, 95% confidence interval) associated with bovine brucellosis in the State included number of cows = 24 (3.08, 2.22-4.27) and the acquisition of breeding animals (1.33, 0.95-1.87). The São Paulo State should conduct systematic vaccination coverage of above 80% of the eligible heifers with the S19 strain vaccine annually. Moreover, the State should emphatically use RB51 strain vaccine in females above 8 months of age not vaccinated with S19 strain vaccine. An efficient animal health education program to orientate farmers to test replacement animals for brucellosis prior to introduction in their herds should also be implemented.3753505351

Prevalence And Risk Factors For Bovine Tuberculosis In The State Of São Paulo, Brazil

A cross sectional study was carried out between May and November 2011 to investigate the epidemiological situation of bovine tuberculosis (bTB) in the state of São Paulo, Brazil. The state was divided into seven regions. Three hundred farms from each region, with reproductive activity, were randomly chosen and included as primary sample units. A fixed number of bovine females, older than 2 years of age, were randomly selected and tested, using the comparative cervical tuberculin test. An epidemiological questionnaire based survey was conducted in the selected farms. Our results show that in the state of São Paulo, the apparent prevalence of positive farms was 9% (95% confidence interval, 95% CI = 7.8 - 10.5%). The prevalence in the individual regions varied between 3.5% (95% CI = 1.7 - 6.8%) and 13.9% (95% CI = 10.2 - 18.8%). The apparent prevalence of positive animals in the state was 1.3% (95% CI = 0.9 - 1.7%) and varied from 0.3% (95% CI = 0.2 - 0.6%) to 2.5% (95% CI = 1.4 - 4.5%) in the regions. The risk factors associated with tuberculosis in the state were (i) number of adult females in a herd is = 24 (Odds ratio, OR = 1.91, 95% CI = 1.32 - 2.75), (ii) type of farm enterprise (dairy: OR = 2.70, 95% CI = 1.40 - 5.21; mixed: OR = 2.03, 95% CI = 1.08 - 3.82), (iii) milking process (milking parlor: OR = 4.12, 95% CI = 1.46 - 11.64; portable milking machine: OR = 2.94, 95% CI = 1.42 - 6.09), and (iv) pasture sharing (OR = 1.58, 95% CI = 1.07 - 2.33). The state of São Paulo should implement a structured surveillance system to detect and mitigate the disease. Further, an efficient animal health education program, which encourages the farmers to test replacement animals for bTB prior to introduction in their herds and to avoid pasture sharing with farms of unknown sanitary conditions should also be implemented.3753673368

Recovery of dialysis patients with COVID-19 : health outcomes 3 months after diagnosis in ERACODA

Background. Coronavirus disease 2019 (COVID-19)-related short-term mortality is high in dialysis patients, but longer-term outcomes are largely unknown. We therefore assessed patient recovery in a large cohort of dialysis patients 3 months after their COVID-19 diagnosis. Methods. We analyzed data on dialysis patients diagnosed with COVID-19 from 1 February 2020 to 31 March 2021 from the European Renal Association COVID-19 Database (ERACODA). The outcomes studied were patient survival, residence and functional and mental health status (estimated by their treating physician) 3 months after COVID-19 diagnosis. Complete follow-up data were available for 854 surviving patients. Patient characteristics associated with recovery were analyzed using logistic regression. Results. In 2449 hemodialysis patients (mean ± SD age 67.5 ± 14.4 years, 62% male), survival probabilities at 3 months after COVID-19 diagnosis were 90% for nonhospitalized patients (n = 1087), 73% for patients admitted to the hospital but not to an intensive care unit (ICU) (n = 1165) and 40% for those admitted to an ICU (n = 197). Patient survival hardly decreased between 28 days and 3 months after COVID-19 diagnosis. At 3 months, 87% functioned at their pre-existent functional and 94% at their pre-existent mental level. Only few of the surviving patients were still admitted to the hospital (0.8-6.3%) or a nursing home (∼5%). A higher age and frailty score at presentation and ICU admission were associated with worse functional outcome. Conclusions. Mortality between 28 days and 3 months after COVID-19 diagnosis was low and the majority of patients who survived COVID-19 recovered to their pre-existent functional and mental health level at 3 months after diagnosis

Crustal evolution between 2.0 and 3.5 Ga in the southern Gavião block (Umburanas-Brumado-Aracatu region), São Francisco Craton, Brazil: A 3.5-3.8 Ga proto-crust in the Gavião block?

International audienc

The geological roots of South America: 4.1 Ga and 3.7 Ga zircon crystals discovered in N.E. Brazil and N.W. Argentina

International audienceWe present new LA-ICP-MS in situ geochronological results for seven Eoarchean zircons dated at 3.7 Ga coming from Cretaceous ash layers of NW Argentina and one Hadean single crystal sampled within the São Francisco Craton in NE Brazil. This zircon comprises a zoned magmatic core dated at 4.1 Ga surrounded by a 1.9 Ga overgrowth related to Paleoproterozoic reworking. This Hadean age is consistent with previously published Nd model ages on orthogneisses from the same domain. These two results represent among the oldest geological witnesses discovered to date in South America, which demonstrates the occurrence of a primitive crust. The contrasting age patterns recorded in both samples and localities indicate that at least two different nuclei of early crust survived in the continental domain. The São Francisco Craton in Brazil can be now considered as one of the very few areas where rare occurrences of Hadean zircon record the early evolution of the Earth