Diabetes has been associated with cognitive changes and an increased risk of vascular dementia and Alzheimer's disease, but it is unclear whether there are associations between diabetes and early ...alterations in cognitive performance. The present study consisted of a cross-section analysis of 14,444 participants aged 35-74 years and from a developing country at baseline in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil); these participants were recruited between 2008 and 2010. We investigated whether there was an association between diabetes and early changes in the cognitive performance of this Brazilian population. To assess cognitive domains, we used the word-list learning, word-list delayed recall and word recognition tests along. Phonemic verbal fluency tests included semantic phonemic test (animals) and a phonemic test (words beginning with the letter F). Executive functions associated with attention, concentration and psychomotor speed were evaluated using the Trail Making Test B. The exposure variable in the study was defined as diabetes. Multiple linear regression was used to estimate the association between diabetes and cognitive performance. The results were adjusted for age, sex, education, hypertension, coronary disease, depression, physical activity, smoking, alcohol consumption, and the cholesterol/HDL-C ratio. We found a significant association between diabetes and decreased memory, language and executive function (attention, concentration and psychomotor speed) performance in this population from a country with a distinct epidemiological profile, even after adjusting for the main intervening variables.
The genotype-by-environment interaction (GxE) in beef cattle can be investigated using reaction norm models to assess environmental sensitivity and, combined with genome-wide association studies ...(GWAS), to map genomic regions related to animal adaptation. Including genetic markers from whole-genome sequencing in reaction norm (RN) models allows us to identify high-resolution candidate genes across environmental gradients through GWAS. Hence, we performed a GWAS via the RN approach using whole-genome sequencing data, focusing on mapping candidate genes associated with the expression of reproductive and growth traits in Nellore cattle. For this purpose, we used phenotypic data for age at first calving (AFC), scrotal circumference (SC), post-weaning weight gain (PWG), and yearling weight (YW). A total of 20,000 males and 7,159 females genotyped with 770k were imputed to the whole sequence (29 M). After quality control and linkage disequilibrium (LD) pruning, there remained \ 2.41 M SNPs for SC, PWG, and YW and \ 5.06 M SNPs for AFC. Significant SNPs were identified on Bos taurus autosomes (BTA) 10, 11, 14, 18, 19, 20, 21, 24, 25 and 27 for AFC and on BTA 4, 5 and 8 for SC. For growth traits, significant SNP markers were identified on BTA 3, 5 and 20 for YW and PWG. A total of 56 positional candidate genes were identified for AFC, 9 for SC, 3 for PWG, and 24 for YW. The significant SNPs detected for the reaction norm coefficients in Nellore cattle were found to be associated with growth, adaptative, and reproductive traits. These candidate genes are involved in biological mechanisms related to lipid metabolism, immune response, mitogen-activated protein kinase (MAPK) signaling pathway, and energy and phosphate metabolism. GWAS results highlighted differences in the physiological processes linked to lipid metabolism, immune response, MAPK signaling pathway, and energy and phosphate metabolism, providing insights into how different environmental conditions interact with specific genes affecting animal adaptation, productivity, and reproductive performance. The shared genomic regions between the intercept and slope are directly implicated in the regulation of growth and reproductive traits in Nellore cattle raised under different environmental conditions.
The aim of the study is to investigate whether adiposity markers, insulin resistance and prediabetes are associated with cognitive performance in middle-aged men and women without diabetes.
...Cross-sectional study with 11,115 adults without diabetes (34–64 years old). Cognitive performance was tested by word-list learning, word-list delayed recall, word recognition tests, semantic and phonemic verbal fluency tests and trail making test B. Linear regression models and generalized linear regression with logarithmic links between the cognitive tests and anthropometric indicators (body mass index BMI), insulin resistance (Homeostasis Model Assessment for Insulin Resistance HOMA-IR), and prediabetes (impaired glucose tolerance) were stratified by sex. The results were adjusted for age, education, comorbidities, health-related behaviors, waist circumference, and lipids.
Among women, higher BMI was associated with poorer performance on phonemic verbal fluency test (β-0.02 −0.04; −0.01) and memory tests (β-0.05 −0.07; −0.02). Higher HOMA-IR was associated with poorer cognitive performance in memory (β-0.11 −0.19; −0.01) and phonemic verbal fluency tests (β-0.12 −0.20; −0.04). In men, HOMA-IR (β-0.15 −0.25; −0.04) and prediabetes (β-0.35 −0.69; -0.03) were associated with poorer performance on memory tests.
We found a significant association of BMI and HOMA-IR with cognitive performance in young and middle-aged adult women without diabetes. In men, we found an association between HOMA-IR and prediabetes and poorer performance on memory tests.
•The study evaluated the role of losartan in experimental arthritis.•Losartan reduced neutrophil infiltration and local cytokine levels.•Losartan also improved histological injury and pain in ...inflammated joints.•Losartan directly reduced leukocyte rolling and adhesion.•Angiotensin type 1 receptor antagonists emerge as potential therapeutic agents for arthritis.
Angiotensin (Ang) II and its AT1 receptors have been implicated in the pathogenesis of rheumatoid arthritis. Activation of the counter-regulatory Ang-(1–7)–Mas receptor axis may contribute to some of the effects of AT1 receptor blockers (ARBs). In this study, we have used losartan, an ARB, to investigate the role of and the mechanisms by which AT1 receptors participated in two experimental models of arthritis: antigen-induced arthritis (AIA) in mice and adjuvant-induced arthritis (AdIA) in rats. Treatment with losartan decreased neutrophil recruitment, hypernociception and the production of TNF-α, IL-1β and chemokine (C–X–C motif) ligand 1 in mice subjected to AIA. Histopathological analysis showed significant reduction of tissue injury and inflammation and decreased proteoglycan loss. In addition to decreasing cytokine production, losartan directly reduced leukocyte rolling and adhesion. Anti-inflammatory effects of losartan were not associated to Mas receptor activation and/or Ang-(1–7) production. Anti-inflammatory effects were reproduced in rats subjected to AdIA. This study shows that ARBs have potent anti-inflammatory effects in animal models of arthritis. Mechanistically, reduction of leukocyte accumulation and of joint damage was associated with local inhibition of cytokine production and direct inhibition of leukocyte–endothelium interactions. The anti-inflammatory actions of losartan were accompanied by functional improvement of the joint, as seen by reduced joint hypernociception. These findings support the use of ARBs for the treatment of human arthritis and provide potential mechanisms for the anti-inflammatory actions of these compounds.
A biodiesel process in a packed bed reactor was used as a model system to show the strong dependence of the reactor behavior on the developing of chemical environment within the reactor. Ethanolysis ...runs of babassu and macaw palm oils were carried out in a solvent-free system using Burkholderia cepacia lipase immobilized on silica–PVA matrix. The best performance was found for the reactor running on macaw palm oil, which resulted in a stable operating system and an average yield of 87.6±2.5%. This strategy also gave high biocatalyst operational stability, revealing a half-life of 478h.
•The potential of six non-edible feedstocks were assessed to yield biodiesel by enzymatic route.•Lipase from Burkholderia cepacia immobilized on silica-PVA was used as biocatalyst.•All feedstocks ...were found to be suitable for biodiesel production, attaining yields higher than 94.6%.•The high yields obtained enable the product to be classified as a fuel according to ASTM standards.
The focus of this work was to evaluate the potential of non-edible feedstocks to yield biodiesel by an enzymatic route. The ethanolysis of native oils from tropical crops, such as andiroba (Carapa guianensis), babassu (Orbignya sp.), jatropha (Jatropha curcas), macaw palm (Acrocomia aculeata), palm tree (Elaeis guineensis) and industrial waste (beef tallow) in solvent-free system was studied. All reactions were carried out with the microbial lipase from Burkholderia cepacia immobilized on a silica-polyvinyl alcohol matrix in a solvent-free system at 50°C for a maximum period of 24h. Under the conditions tested the biocatalyst was efficient in converting all fatty acids in the lipid feedstocks into the corresponding ethyl esters. Viscosity values for biodiesel samples obtained in each reaction (4.3 and 6.0mm2/s) showed consistent reduction in relation to their original feedstock material, which also confirms the high conversion of triglycerides to ethyl esters (>94.5%). This comparative study shows that the formation of ethyl esters from different non-edible feedstocks was feasible and can provide a considerable increase in the prospect of attaining an environmental sustainability of the process as a whole.
The effects of several natural antioxidants (copaiba oil, buriti oil, cocoa butter, tucuman butter, oregano and white thyme) were assessed in the enzymatic synthesis of monoglycerides (MAG) from the ...glycerolysis of babassu oil. The reactions were catalyzed by
Burkholderia cepacia
lipase immobilized on SiO
2
–PVA and the assays carried out in batch and continuous runs. Results were compared with those attained in the control reactions (without any strategy to avoid oxidation), and the best approach was tested in a continuous packed-bed reactor. The best performance was obtained using N
2
in the reaction medium (60 % of MAG) followed by buriti oil (57.6 % of MAG) and cocoa butter (56.6 % of MAG), preventing the oxidation of babassu oil in batch reaction. However, the incorporation of buriti oil in the medium influenced the MAG profile, leading to the largest formation of monoolein, unlike other runs. Similar results were obtained in continuous reactions, using inert atmosphere and cocoa butter (24–25 % of MAG). Thereby, among the tested antioxidant agents, cocoa butter was the most effective in both systems, because it did not interfere in the MAG profile and also reduced the cost of the process.
Chikungunya virus (CHIKV) is an Aedes mosquito-borne virus that has caused large epidemics linked to acute, chronic, and severe clinical outcomes. Currently, Brazil has the highest number of ...chikungunya cases in the Americas. We aimed to investigate the spatiotemporal dynamics and recurrence pattern of chikungunya in Brazil since its introduction in 2013.
In this epidemiological study, we used CHIKV genomic sequencing data, CHIKV vector information, and aggregate clinical data on chikungunya cases from Brazil. The genomic data comprised 241 Brazilian CHIKV genome sequences from GenBank (n=180) and the 2022 CHIKV outbreak in Ceará state (n=61). The vector data (Breteau index and House index) were obtained from the Brazilian Ministry of Health for all 184 municipalities in Ceará state and 116 municipalities in Tocantins state in 2022. Epidemiological data on laboratory-confirmed cases of chikungunya between 2013 and 2022 were obtained from the Brazilian Ministry of Health and Laboratory of Public Health of Ceará. We assessed the spatiotemporal dynamics of chikungunya in Brazil via time series, mapping, age–sex distribution, cumulative case-fatality, linear correlation, logistic regression, and phylogenetic analyses.
Between March 3, 2013, and June 4, 2022, 253 545 laboratory-confirmed chikungunya cases were reported in 3316 (59·5%) of 5570 municipalities, mainly distributed in seven epidemic waves from 2016 to 2022. To date, Ceará in the northeast has been the most affected state, with 77 418 cases during the two largest epidemic waves in 2016 and 2017 and the third wave in 2022. From 2016 to 2022 in Ceará, the odds of being CHIKV-positive were higher in females than in males (odds ratio 0·87, 95% CI 0·85–0·89, p<0·0001), and the cumulative case-fatality ratio was 1·3 deaths per 1000 cases. Chikungunya recurrences in the states of Ceará, Tocantins (recurrence in 2022), and Pernambuco (recurrence in 2021) were limited to municipalities with few or no previously reported cases in the previous epidemic waves. The recurrence of chikungunya in Ceará in 2022 was associated with a new East-Central-South-African lineage. Population density metrics of the main CHIKV vector in Brazil, Aedes aegypti, were not correlated spatially with locations of chikungunya recurrence in Ceará and Tocantins.
Spatial heterogeneity of CHIKV spread and population immunity might explain the recurrence pattern of chikungunya in Brazil. These results can be used to inform public health interventions to prevent future chikungunya epidemic waves in urban settings.
Global Virus Network, Burroughs Wellcome Fund, Wellcome Trust, US National Institutes of Health, São Paulo Research Foundation, Brazil Ministry of Education, UK Medical Research Council, Brazilian National Council for Scientific and Technological Development, and UK Royal Society.
For the Portuguese translation of the abstract see Supplementary Materials section.
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes acute, subacute, and chronic human arthritogenic diseases and, in rare instances, can lead to neurological complications and ...death. Here, we combined epidemiological, virological, histopathological, cytokine, molecular dynamics, metabolomic, proteomic, and genomic analyses to investigate viral and host factors that contribute to chikungunya-associated (CHIK) death. Our results indicate that CHIK deaths are associated with multi-organ infection, central nervous system damage, and elevated serum levels of pro-inflammatory cytokines and chemokines compared with survivors. The histopathologic, metabolite, and proteomic signatures of CHIK deaths reveal hemodynamic disorders and dysregulated immune responses. The CHIKV East-Central-South-African lineage infecting our study population causes both fatal and survival cases. Additionally, CHIKV infection impairs the integrity of the blood-brain barrier, as evidenced by an increase in permeability and altered tight junction protein expression. Overall, our findings improve the understanding of CHIK pathophysiology and the causes of fatal infections.
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•Host and viral factors that are associated with chikungunya fatalities are defined•Chikungunya deaths involve the infection of multiple organs and severe inflammation•Chikungunya virus crosses the blood-brain barrier•Chikungunya deaths are associated with dysregulated hemostasis and immune response
de Souza et al. show the complex factors behind fatal chikungunya cases, highlighting multi-organ infection, central nervous system damage, and severe inflammation. The findings suggest the chikungunya virus crosses the blood-brain barrier, contributing to central nervous system infection. This comprehensive study sheds light on chikungunya pathophysiology and fatal outcomes.
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