The costs of preventing and treating chagas disease in Colombia

Background: The objective of this study is to report the costs of Chagas disease in Colombia, in terms of vector disease control programmes and the costs of providing care to chronic Chagas disease patients with cardiomyopathy. Methods: Data were collected from Colombia in 2004. A retrospective review of costs for vector control programmes carried out in rural areas included 3,084 houses surveyed for infestation with triatomine bugs and 3,305 houses sprayed with insecticide. A total of 63 patient records from 3 different hospitals were selected for a retrospective review of resource use. Consensus methodology with local experts was used to estimate care seeking behaviour and to complement observed data on utilisation. Findings: The mean cost per house per entomological survey was $4.4 (in US$ of 2004), whereas the mean cost of spraying a house with insecticide was $27. The main cost driver of spraying was the price of the insecticide, which varied greatly. Treatment of a chronic Chagas disease patient costs between$46.4 and $7,981 per year in Colombia, depending on severity and the level of care used. Combining cost and utilisation estimates the expected cost of treatment per patient-year is$1,028, whereas lifetime costs averaged $11,619 per patient. Chronic Chagas disease patients have limited access to healthcare, with an estimated 22% of patients never seeking care. Conclusion: Chagas disease is a preventable condition that affects mostly poor populations living in rural areas. The mean costs of surveying houses for infestation and spraying infested houses were low in comparison to other studies and in line with treatment costs. Care seeking behaviour and the type of insurance affiliation seem to play a role in the facilities and type of care that patients use, thus raising concerns about equitable access to care. Preventing Chagas disease in Colombia would be cost-effective and could contribute to prevent inequalities in health and healthcare.Wellcome Trus

Electrochemistry for biofuels waste valorization: vinasse as a reducing agent for Pt/C and its application to the electrolysis of glycerin and vinasse

Waste vinasse has been used, for the first time, as a reducing agent to prepare a 20 wt% Pt/C electrocatalyst. After alkalization and subsequent filtration, abundant cations such as Ca, Mg and Fe were effectively removed, precipitating as hydroxides and insoluble phosphates. Pt chemical reduction was carried out under reflux in the presence of Vulcan XC-72R carbon by the action of reductive species such as sugars and phenols present. Reduction was confirmed by thermal analysis and X-ray diffractograms displaying the typical Pt fcc structure formed by nanocrystals. In the transmission images, an irregular dispersion of the Pt nanoparticles was observed on the carbon support, with the presence of large agglomerations with a cotton-like structure. This structure was found to be very active for glycerol electrolysis in an alkaline membrane electrolysis cell, comparable to commercial materials. Finally, results for electrolysis of the vinasse were also presented, demonstrating the possibility of valorizing this residue by the production of hydrogen

Genomic characterization of orthobunyavirus of veterinary importance in America

During 2013, in Argentina, three new isolates of serogroup Bunyamwera virus (genus Orthobunyavirus, family Peribunyaviridae)were recovered from two horses with encephalitis, and from an aborted equine fetus. In the present study, we report the complete genome sequence, genetic characterization, and phylogenetic analysis of three new strains isolated in Argentina to clarifying their relationship within the Bunyamwera serogroup virus and to investigate the evolutionary history of viruses with segmented genomes.Fil: Tauro, Laura Beatriz. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: de Souza, William Marciel. Universidade de Sao Paulo; BrasilFil: Rivarola, María Elisa. Universidad Nacional de Córdoba. Facultad de Medicina. Laboratorio de Arbovirus y Arenovirus; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: de Oliveira, Rodrigo. Instituto Evandro Chagas; BrasilFil: Konigheim, Brenda Salome. Universidad Nacional de Cordoba. Facultad de Medicina. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Patroca Silva, Sandro. Instituto Evandro Chagas; BrasilFil: Lima, Clayton. Instituto Evandro Chagas; BrasilFil: Oliveira, Layanna. Instituto Evandro Chagas; BrasilFil: Vasconcelos, Janaina M.. Instituto Evandro Chagas; BrasilFil: Ferreira Cardoso, Jedson. Instituto Evandro Chagas; BrasilFil: Vianez Júnior, João Lídio. Instituto Evandro Chagas; BrasilFil: Teixeira Nunes, Márcio Roberto. Instituto Evandro Chagas; BrasilFil: Contigiani de Minio, Marta Silvia. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentin

Chrysoporthe puriensis sp. nov. from Tibouchina spp. in Brazil : an emerging threat to Eucalyptus

The discovery of Cryphonectriaceae and more specifically species related to the Eucalyptus canker pathogen Chrysoporthe cubensis on shrubs and trees in the Melastomataceae, has deepened our understanding of relevant, and potentially globally threatening tree pathogens. Recent isolations of Cryphonectriaceae associated with cankers on Tibouchina spp. in Brazil gave rise to an apparently undescribed species of Chrysoporthe associated with stem and branch cankers that lead to tree death. Cultures of this fungus were subjected to phylogenetic studies based on sequences for the ITS and β-tubulin gene regions. These analyses revealed a novel taxon that is described here as Chrysoporthe puriensis sp. nov., having both sexual and asexual states. Pathogenicity tests on two species of Tibouchina (T. granulosa, T. heteromalla) and hybrids of Eucalyptus grandis x E. urophylla showed that Chr. puriensis can infect and cause disease on all of these trees. It is clearly not only damaging on native Tibouchina spp. where environmental conditions are conducive to disease development, but also potentially threatening to non-native Eucalyptus spp., which form the basis of a major plantation forest industry.http://link.springer.com/journal/13313hj2022BiochemistryForestry and Agricultural Biotechnology Institute (FABI)GeneticsMicrobiology and Plant Patholog

Genetic variability in populations of Chrysoporthe cubensis and Chr. puriensis in Brazil

DATA AVAILABILITY STATEMENT: The data that support the findings will be available in NCBI Nucleotide at https://www.re3data.org/search?query=ncbi. The Genbank numbers are given in the text of the manuscript. The data is under embargo until a manuscript is accepted for publication. It will then be openly available.Chrysoporthe puriensis, a sibling species of the well-known Eucalyptus canker pathogen Chr. cubensis, has recently been described from Brazil. Both species are thought to be native to South America, but previous population genetic analyses were conducted prior to the ready availability of robust markers such as microsatellites to test this hypothesis. The objective of this investigation was to analyse the structure and genetic variability of Chr. cubensis and Chr. puriensis populations from non-native Myrtaceae and native Melastomataceae hosts in Brazil, using microsatellite markers developed for this purpose. The fungal isolates were obtained from Eucalyptus species, Corymbia citriodora and Tibouchina species in different regions of the country. Isolates were separated into sub-populations based on host families (Melastomataceae and Myrtaceae) and on region of origin. There was high genetic variability in all sub-populations with the highest levels detected within, rather than among sub-populations. Gene and genotypic diversities were higher for the isolates from the Melastomataceae than the Myrtaceae isolates. High levels of gene flow were found between sub-populations based on host and geographic distribution of the sub-populations. The presence of genetically diverse Chr. cubensis and Chr. puriensis populations on native hosts in Brazil supports a Latin American centre of origin for the two pathogens. Both undergo sexual and asexual reproduction and have a high potential for gene flow.The Tree Protection Co-operative Programme (TPCP) and the DST/NRF Centre of Excellence in Tree Health Biotechnology (South Africa). The FAPEMIG (Fundação de Amparo à Pesquisa do Estado de Minas Gerais), CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) for providing scholarships.https://link.springer.com/journal/13313hj2023BiochemistryForestry and Agricultural Biotechnology Institute (FABI)GeneticsMicrobiology and Plant Patholog

The impact of childhood abuse and recent stress on serum brain-derived neurotrophic factor and the moderating role of BDNF Val66Met

Contains fulltext : 98431.pdf (publisher's version ) (Open Access)RATIONALE: Recent findings show lowered brain-derived neurotrophic factor (BDNF) levels in major depressive disorder (MDD). Exposure to stressful life events may (partly) underlie these BDNF reductions, but little is known about the effects of early or recent life stress on BDNF levels. Moreover, the effects of stressful events on BDNF levels may in part be conditional upon a common variant on the BDNF gene (Val(66)Met; RS6265), with the Met allele being associated with a decrease in activity-dependent secretion of BDNF compared to the Val allele. METHODS: We investigated cross-sectionally in 1,435 individuals with lifetime MDD the impact of childhood abuse (CA) and recent life events on serum BDNF levels and assessed whether the impact of these events was moderated by the BDNF Val(66)Met polymorphism. RESULTS: Overall, BDNF Met carriers had reduced serum BDNF levels when exposed to CA in a dose-dependent way. Moreover, exposure to recent life events was also associated with decreases in BDNF levels, but this was independent of BDNF Val(66)Met. Moreover, when not exposed to CA, Met carriers had higher BDNF levels than the Val/Val individuals, who did not show decreases in BDNF associated with CA. Finally, these findings were only apparent in the MDD group without comorbid anxiety. CONCLUSIONS: These gene-environment interactions on serum BDNF levels suggest that Met carriers are particularly sensitive to (early) stressful life events, which extends previous findings on the moderating role of the BDNF Val(66)Met polymorphism in the face of stressful life events

Treatment for preventing tuberculosis in children and adolescents: a randomized clinical trial of a 3-month, 12-dose regimen of a combination of rifapentine and isoniazid

IMPORTANCE: Three months of a once-weekly combination of rifapentine and isoniazid for treatment of latent tuberculosis infection is safe and effective for persons 12 years or older. Published data for children are limited. OBJECTIVES: To compare treatment safety and assess noninferiority treatment effectiveness of combination therapy with rifapentine and isoniazid vs 9 months of isoniazid treatment for latent tuberculosis infection in children. DESIGN, SETTING, AND PARTICIPANTS: A pediatric cohort nested within a randomized, open-label clinical trial conducted from June 11, 2001, through December 17, 2010, with follow-up through September 5, 2013, in 29 study sites in the United States, Canada, Brazil, Hong Kong (China), and Spain. Participants were children (aged 2-17 years) who were eligible for treatment of latent tuberculosis infection. INTERVENTIONS: Twelve once-weekly doses of the combination drugs, given with supervision by a health care professional, for 3 months vs 270 daily doses of isoniazid, without supervision by a health care professional, for 9 months. MAIN OUTCOMES AND MEASURES: We compared rates of treatment discontinuation because of adverse events (AEs), toxicity grades 1 to 4, and deaths from any cause. The equivalence margin for the comparison of AE-related discontinuation rates was 5%. Tuberculosis disease diagnosed within 33 months of enrollment was the main end point for testing effectiveness. The noninferiority margin was 0.75%. RESULTS: Of 1058 children enrolled, 905 were eligible for evaluation of effectiveness. Of 471 in the combination-therapy group, 415 (88.1%) completed treatment vs 351 of 434 (80.9%) in the isoniazid-only group (P = .003). The 95% CI for the difference in rates of discontinuation attributed to an AE was -2.6 to 0.1, which was within the equivalence range. In the safety population, 3 of 539 participants (0.6%) who took the combination drugs had a grade 3 AE vs 1 of 493 (0.2%) who received isoniazid only. Neither arm had any hepatotoxicity, grade 4 AEs, or treatment-attributed death. None of the 471 in the combination-therapy group developed tuberculosis vs 3 of 434 (cumulative rate, 0.74%) in the isoniazid-only group, for a difference of -0.74% and an upper bound of the 95% CI of the difference of +0.32%, which met the noninferiority criterion. CONCLUSIONS AND RELEVANCE: Treatment with the combination of rifapentine and isoniazid was as effective as isoniazid-only treatment for the prevention of tuberculosis in children aged 2 to 17 years. The combination-therapy group had a higher treatment completion rate than did the isoniazid-only group and was safe

Diagnostic accuracy of a noninvasive hepatic ultrasound score for non-alcoholic fatty liver disease (NAFLD) in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

CONTEXT AND OBJECTIVE: Noninvasive strategies for evaluating non-alcoholic fatty liver disease (NAFLD) have been investigated over the last few decades. Our aim was to evaluate the diagnostic accuracy of a new hepatic ultrasound score for NAFLD in the ELSA-Brasil study.DESIGN AND SETTINGS: Diagnostic accuracy study conducted in the ELSA center, in the hospital of a public university.METHODS: Among the 15,105 participants of the ELSA study who were evaluated for NAFLD, 195 individuals were included in this sub-study. Hepatic ultrasound was performed (deep beam attenuation, hepatorenal index and anteroposterior diameter of the right hepatic lobe) and compared with the hepatic steatosis findings from 64-channel high-resolution computed tomography (CT). We also evaluated two clinical indices relating to NAFLD: the fatty liver index (FLI) and the hepatic steatosis index (HSI).RESULTS: Among the 195 participants, the NAFLD frequency was 34.4%. High body mass index, high waist circumference, diabetes and hypertriglyceridemia were associated with high hepatic attenuation and large anteroposterior diameter of the right hepatic lobe, but not with the hepatorenal index. The hepatic ultrasound score, based on hepatic attenuation and the anteroposterior diameter of the right hepatic lobe, presented the best performance for NAFLD screening at the cutoff point ≥ 1 point; sensitivity: 85.1%; specificity: 73.4%; accuracy: 79.3%; and area under the curve (AUC 0.85; 95% confidence interval, CI: 0.78-0.91)]. FLI and HSI presented lower performance (AUC 0.76; 95% CI: 0.69-0.83) than CT.CONCLUSION: The hepatic ultrasound score based on hepatic attenuation and the anteroposterior diameter of the right hepatic lobe has good reproducibility and accuracy for NAFLD screening

Genetic Determinants of Serum Testosterone Concentrations in Men

Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone's high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n = 871) and two de novo replication cohorts (n = 4,620) to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as <300 ng/dl. Two single-nucleotide polymorphisms at the sex hormone-binding globulin (SHBG) locus (17p13-p12) were identified as independently associated with serum testosterone concentration (rs12150660, p = 1.2×10−41 and rs6258, p = 2.3×10−22). Subjects with ≥3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (p = 5.6×10−16). The rs6258 polymorphism in exon 4 of SHBG affected SHBG's affinity for binding testosterone and the measured free testosterone fraction (p<0.01). Genetic variants in the SHBG locus and on the X chromosome are associated with a substantial variation in testosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery