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•Planning of new Benzimidazole N-acylhydrazones with antitrypanosomal activity.•Biological evaluation of the compounds against T. cruzi strains (Y and Tulahuen)•Biological evaluation ...of the compounds against L. amazonensis and L. infantum.
In this study, we present the design, synthesis, and cytotoxic evaluation of a series of benzimidazole N-acylhydrazones against strains of T. cruzi (Y and Tulahuen) and Leishmania species (L. amazonensis and L. infantum). Compound (E)-N’-((5-Nitrofuran-2-yl)methylene)-1H-benzodimidazole-2-carbohydrazide demonstrated significant activity against both trypomastigote and amastigote forms (Tulahuen strain), with an IC50/120 h of 0.033 μM and a selectivity index (SI) of 7680. This represents a potency 46 times greater than that of benznidazole (IC50/120 h = 1.520 μM, SI = 1390). Another compound (E)-N’-(2-Hydroxybenzylidene)-1H-benzodimidazole-2-carbohydrazide showed promising activity against both trypomastigote and amastigote forms (Tulahuen strain), with an IC50/120 h of 3.600 μM and an SI of 14.70. However, its efficacy against L. infantum and L. amazonensis was comparatively lower. These findings provide valuable insights for the development of more effective treatments against Trypanosoma cruzi.
Abstract Oil spills, intrinsically related to the petroleum production chain, represent a risk to the marine environment and a potential threat to humans through seafood consumption. We revised the ...NE Brazil oil spill and other accidents along the Brazilian coast, with a focus on seafood contamination, covering topics such as bioaccumulation, bioaccessibility, and risk analysis. Comprehensive knowledge of the impacts of spills helps in the interpretation of the dynamics of hydrocarbons released into the sea, contributing to actions to control their negative impacts. Currently, no legal limits have been established permanently in Brazil for PAHs in seafood edible tissues.
Several key evolutionary events marked the evolution of geminiviruses, culminating with the emergence of divided (bipartite) genomes represented by viruses classified in the genus Begomovirus. This ...genus represents the most abundant group of multipartite viruses, contributing significantly to the observed abundance of multipartite species in the virosphere. Although aspects related to virus‐host interactions and evolutionary dynamics have been extensively studied, the bipartite nature of these viruses has been little explored in evolutionary studies. Here, we performed a parallel evolutionary analysis of the DNA‐A and DNA‐B segments of New World begomoviruses. A total of 239 full‐length DNA‐B sequences obtained in this study, combined with 292 DNA‐A and 76 DNA‐B sequences retrieved from GenBank, were analysed. The results indicate that the DNA‐A and DNA‐B respond differentially to evolutionary processes, with the DNA‐B being more permissive to variation and more prone to recombination than the DNA‐A. Although a clear geographic segregation was observed for both segments, differences in the genetic structure between DNA‐A and DNA‐B were also observed, with cognate segments belonging to distinct genetic clusters. DNA‐B coding regions evolve under the same selection pressures than DNA‐A coding regions. Together, our results indicate an interplay between reassortment and recombination acting at different levels across distinct subpopulations and segments.
Background
Cardiorespiratory fitness and fatness (notably central obesity) are mediating factors of the metabolic syndrome (MetS) and consequent cardiovascular disease (CVD)/mortality risk. The ...fitness-fatness index (FFI) combines these factors and has been reported to be a better indicator of CVD and all-cause mortality risk, beyond the capacity of either fitness or fatness alone.
Objective
This study sought to investigate the effects of different exercise intensities on FFI in adults with MetS.
Methods
This was a sub-study of the ‘Exercise in the prevention of Metabolic Syndrome’ (EX-MET) multicentre trial. Ninety-nine adults diagnosed with MetS according to the International Diabetes Federation criteria were randomized to one of the following 16-week exercise interventions: i) moderate-intensity continuous training (MICT) at 60–70% HRpeak for 30 min/session (
n
= 34, 150 min/week); ii) 4 × 4 min bouts of high-intensity interval training at 85–95% HRpeak, interspersed with 3-min active recovery at 50–70% HRpeak (
n
= 34, 38 min/session, 114 min/week); and iii) 1 × 4 min bout of HIIT at 85–95% HRpeak (
n
= 31, 17 min/session, 51 min/week). Cardiorespiratory fitness (peak oxygen uptake, V̇O
2
peak) was determined via indirect calorimetry during maximal exercise testing and fatness was the ratio of waist circumference-to-height (WtHR). FFI was calculated as V̇O
2
peak in metabolic equivalents (METs) divided by WtHR. A clinically meaningful response to the exercise intervention was taken as a 1 FFI unit increase.
Results
Seventy-seven participants completed pre and post testing to determine FFI. While there was no significant between group difference (
p
= 0.30), there was a small group x time interaction effect on FFI
F
(2, 73) = 1.226;
η
2
= 0.01, with numerically greater improvements following HIIT (4HIIT, + 16%; 1HIIT, + 11%) relative to MICT (+ 7%). There was a greater proportion of participants who had a clinically meaningful change in FFI following high-volume HIIT (60%, 15/25) and low-volume HIIT (65%, 17/26) compared to MICT (38%, 10/26), but with no significant between-group difference (
p
= 0.12). A similar trend was found when a sub-analysis comparing the FFI between those with type 2 diabetes (MICT, 33%, 3/9; high-volume HIIT, 64%, 7/11; and low-volume HIIT, 58%, 7/12) and without type 2 diabetes (MICT, 41%, 7/17; high-volume HIIT, 57%, 8/14; low-volume HIIT, 71%, 10/14).
Conclusion
Although there were no statistically significant differences detected between groups, this study suggests that the response to changes in FFI in adults with MetS may be affected by exercise intensity, when numerical differences between exercise groups are considered. Further research is warranted.
Trial registration number and date of registration
: ClinicalTrials.gov NCT01676870; 31/08/2012.
•The ABC2-SPH mortality risk score employs seven variables upon hospital presentation•The model had high discriminatory value (AUROC 0.844, 95% CI 0.829 – 0.859)•External validation confirmed these ...results in Brazilian and Spanish cohorts•The ABC2-SPH outperformed other available scores•It is implemented in a freely available online risk calculator (https://abc2sph.com/)
The majority of available scores to assess mortality risk of coronavirus disease 2019 (COVID-19) patients in the emergency department have high risk of bias. Therefore, this cohort aimed to develop and validate a score at hospital admission for predicting in-hospital mortality in COVID-19 patients and to compare this score with other existing ones.
Consecutive patients (≥ 18 years) with confirmed COVID-19 admitted to the participating hospitals were included. Logistic regression analysis was performed to develop a prediction model for in-hospital mortality, based on the 3978 patients admitted between March–July, 2020. The model was validated in the 1054 patients admitted during August–September, as well as in an external cohort of 474 Spanish patients.
Median (25–75th percentile) age of the model-derivation cohort was 60 (48–72) years, and in-hospital mortality was 20.3%. The validation cohorts had similar age distribution and in-hospital mortality. Seven significant variables were included in the risk score: age, blood urea nitrogen, number of comorbidities, C-reactive protein, SpO2/FiO2 ratio, platelet count, and heart rate. The model had high discriminatory value (AUROC 0.844, 95% CI 0.829–0.859), which was confirmed in the Brazilian (0.859 95% CI 0.833–0.885) and Spanish (0.894 95% CI 0.870–0.919) validation cohorts, and displayed better discrimination ability than other existing scores. It is implemented in a freely available online risk calculator (https://abc2sph.com/).
An easy-to-use rapid scoring system based on characteristics of COVID-19 patients commonly available at hospital presentation was designed and validated for early stratification of in-hospital mortality risk of patients with COVID-19.
The majority of available scores to assess mortality risk of coronavirus disease 2019 (COVID-19) patients in the emergency department have high risk of bias. Therefore, this cohort aimed to develop ...and validate a score at hospital admission for predicting in-hospital mortality in COVID-19 patients and to compare this score with other existing ones.
Consecutive patients (≥ 18 years) with confirmed COVID-19 admitted to the participating hospitals were included. Logistic regression analysis was performed to develop a prediction model for in-hospital mortality, based on the 3978 patients admitted between March-July, 2020. The model was validated in the 1054 patients admitted during August-September, as well as in an external cohort of 474 Spanish patients.
Median (25-75th percentile) age of the model-derivation cohort was 60 (48-72) years, and in-hospital mortality was 20.3%. The validation cohorts had similar age distribution and in-hospital mortality. Seven significant variables were included in the risk score: age, blood urea nitrogen, number of comorbidities, C-reactive protein, SpO
/FiO
ratio, platelet count, and heart rate. The model had high discriminatory value (AUROC 0.844, 95% CI 0.829-0.859), which was confirmed in the Brazilian (0.859 95% CI 0.833-0.885) and Spanish (0.894 95% CI 0.870-0.919) validation cohorts, and displayed better discrimination ability than other existing scores. It is implemented in a freely available online risk calculator (https://abc2sph.com/).
An easy-to-use rapid scoring system based on characteristics of COVID-19 patients commonly available at hospital presentation was designed and validated for early stratification of in-hospital mortality risk of patients with COVID-19.
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