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Introduction: Pathogenesis of cutaneous leishmaniases involves parasite growth, persistent inflammation, and likely participation of lipoproteins (LP). The cholesteryl ester transfer protein (CETP), involved in LP remodeling, has been shown to participate in the inflammatory response and the evolution of infectious conditions. Methods: We evaluated the impact of the presence of CETP on infection by Leishmania (L.) amazonensis in an experimental model of cutaneous leishmaniasis using C57BL6/J mice transgenic for human CETP (CETP), having as control their littermates that do not express the protein, wild-type (WT) mice. The progression of the lesion after infection in the footpad was monitored for 12 weeks. Two groups of animals were formed to collect the plantar pad in the 4th and 12th week post-infection. Results: The lesion increased from the 3rd week onwards, in both groups, with a gradual decrease from the 10th week onwards in the CETP group compared to the WT group, showing a reduction in parasitism and an improvement in the healing process, a reduction in CD68+ cells, and an increase in CD163+ and CD206, characterizing a population of M2 macrophages. A reduction in ARG1+ cells and an increase in INOS+ cells were observed. During infection, the LP profile showed an increase in triglycerides in the VLDL fraction in the CETP group at 12 weeks. Gene expression revealed a decrease in the CD36 receptor in the CETP group at 12 weeks, correlating with healing and parasite reduction. In vitro, macrophages derived from bone marrow cells from CETP mice showed lower parasite load at 48 h and, a reduction in arginase activity at 4 h accompanied by increased NO production at 4 and 24 h compared to WT macrophages, corroborating the in vivo findings. Discussion: The data indicate that the presence of CETP plays an important role in resolving Leishmania (L.) amazonensis infection, reducing parasitism, and modulating the inflammatory response in controlling infection and tissue repair.

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Importance: Matched placebo interventions are complex and resource intensive. Recent evidence suggests matched placebos may not always be necessary. Previous studies have predominantly evaluated potential bias of nonmatched placebos (ie, differing on dose, frequency of administration, or formulation) in pain and mental health, but to date no systematic examination has been conducted in infectious disease. Objective: To test for differences between nonmatched and matched placebo arms with respect to clinical outcome measures across multiple therapeutics for COVID-19. Design, Setting, and Participants: In a comparative effectiveness research study, a post hoc analysis was conducted of data on individual patients enrolled in a large, multiarm, platform randomized clinical trial in symptomatic adult outpatients with COVID-19 between January 15, 2021, to September 28, 2023, in which the outcomes of both matched and nonmatched placebo groups were reported. Bayesian and frequentist covariate-adjusted techniques were compared with 7 intervention-placebo pairs. Exposures: Seven matched and nonmatched placebo pairs (for a total of 7 comparisons) were evaluated throughout the primary platform trial. Comparisons were made between treatment and its associated matched (concurrent) placebo, as well as with nonmatched placebo (alone and in combination) assessed at a similar time point. Main Outcomes and Measures: Outcomes assessed included hospitalizations, EuroQol 5-Dimension 5-level scores, and PROMIS Global-10 scores. Results: A total of 7 intervention-control pairs (N = 2684) were assessed, including 1620 (60.4%) women, with mean (SD) age, 47 (15.2) years; the most common comorbidities were obesity (41.9%) and hypertension (37.9%). In a meta-analysis with decoupled SEs, accounting for overlapping placebo patients, the overall odds ratio (OR) of nonmatched compared with matched placebo was 1.01 (95% credible interval, 0.77-1.32), with posterior probability of equivalence, defined as 0.8 ≤ OR ≤ 1.2 (a deviation from perfect equivalence ie, OR = 1, by no more than 0.2) of 85.4%, implying no significant difference. Unadjusted analysis of the event rate difference between all nonmatched and matched placebo groups did not identify any notable differences across all 7 treatment-placebo combinations assessed. Similar analysis that was conducted for patient-reported quality of life outcomes did not yield statistically significant differences. Conclusions and Relevance: In this post hoc study of a randomized clinical platform trial, pooling matched and nonmatched placebo patient data did not lead to inconsistencies in treatment effect estimation for any of the investigational drugs. These findings may have significant implications for future platform trials, as the use of nonmatched placebo may improve statistical power, or reduce barriers to placebo implementation.

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Abstract Objective: To examine if the substitution of different screen time intervals with light physical activity (LPA), moderate to vigorous physical activity (MVPA) and sleep is associated with cardiovascular indicators and inflammatory markers in children. Methods: This is a cross-sectional study developed with 186 children aged between six and 11 years old from public schools in southern Brazil. CRF was measured with the 6-minute running and walking test, following the Brazil Sports Project procedures. The percentage of fat was evaluated through DXA. LPA and MVPA were measured using accelerometers. Sleep and screen time were assessed by questionnaires answered by parents. Leptin and C-reactive protein were measured by fasting blood collection. Systolic and diastolic blood pressure were determined through a digital sphygmomanometer. Isotemporal substitution models were used for statistical analysis. Results: Replacing 1 h of screen time with MVPA was associated with lower BMI, systolic and diastolic blood pressure, fat percentage, leptin, and C-reactive protein. When screen time was substituted for sleep time, lower waist circumference was observed. Regarding the substitution of 1 h of screen time with LPA, significant values were found only for leptin. Conclusion: The replacement of screen time with physical activities of different intensities and sleep time was associated with benefits in cardiovascular indicators and inflammatory markers in childhood.

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The presence of Andean plant genera in moist forests of the Brazilian Atlantic Coast has been historically hypothesized as the result of cross-continental migrations starting at the eastern Andean flanks. Here we test hypotheses of former connections between the Atlantic and Andean forests by examining distribution patterns of selected cool and moist-adapted plant arboreal taxa present in 54 South American pollen records of the Last Glacial Maximum (LGM), ca. 19-23 cal ka, known to occur in both plant domains. Pollen taxa studied include Araucaria, Drimys, Hedyosmum, Ilex, Myrsine, Podocarpus, Symplocos, Weinmannia, Myrtaceae, Ericaceae and Arecaceae. Past connectivity patterns between these two neotropical regions as well as individual ecological niches during the LGM were explored by cluster analysis of fossil assemblages and modern plant distributions. Additionally, we examined the ecological niche of 137 plant species with shared distributions between the Andes and coastal Brazil. Our results revealed five complex connectivity patterns for South American vegetation linking Andean, Amazonian and Atlantic Forests and one disjunction distribution in southern Chile. This study also provides a better understanding of vegetation cover on the large and shallow South American continental shelf that was exposed due to a global sea level drop.

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BACKGROUND: Physical education classes are widely accepted as one of the most effective settings for promoting physical activity and health and have often been used to implement physical activity interventions. The aim of this pilot study was to test a physical education intervention program on physical activity levels and physical fitness in a sample of school-age children. METHODS: Participants were a convenience sample of 50 children (34 experimental group and 16 in the comparative group) aged between 6 and 11 years old (Mean = 8.28 years). A 21-week intervention was implemented, consisting of high-intensity and physical fitness-focused exercises, in addition to a once-a-month extra class nutritional education. The following variables were evaluated before and post-intervention: physical fitness, sedentary behavior (SB), light physical activity (LPA), moderate physical activity (MVA), and vigorous physical activity (VPA). Propensity score analyses calculated the average treatment effect on the treated (ATET) within a quasi-experimental framework. RESULTS: Physical fitness variables showed improvements after the intervention, specifically for agility (ATET = -0.67 s; p < 0.001), cardiorespiratory fitness (ATET = 89.27 m; p = 0.045), lower limbs power (ATET = 4.47 centimeters; p = 0.025), and speed (ATET = -1.06 s; p < 0.001). For physical activity and SB levels, there were no improvements after intervention implementation. CONCLUSION: The intervention program showed preliminary effectiveness to improve physical fitness of children, but not SB nor physical activity.

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OBJECTIVE: To examine if the substitution of different screen time intervals with light physical activity (LPA), moderate to vigorous physical activity (MVPA) and sleep is associated with cardiovascular indicators and inflammatory markers in children. METHODS: This is a cross-sectional study developed with 186 children aged between six and 11 years old from public schools in southern Brazil. CRF was measured with the 6-minute running and walking test, following the Brazil Sports Project procedures. The percentage of fat was evaluated through DXA. LPA and MVPA were measured using accelerometers. Sleep and screen time were assessed by questionnaires answered by parents. Leptin and C-reactive protein were measured by fasting blood collection. Systolic and diastolic blood pressure were determined through a digital sphygmomanometer. Isotemporal substitution models were used for statistical analysis. RESULTS: Replacing 1 h of screen time with MVPA was associated with lower BMI, systolic and diastolic blood pressure, fat percentage, leptin, and C-reactive protein. When screen time was substituted for sleep time, lower waist circumference was observed. Regarding the substitution of 1 h of screen time with LPA, significant values were found only for leptin. CONCLUSION: The replacement of screen time with physical activities of different intensities and sleep time was associated with benefits in cardiovascular indicators and inflammatory markers in childhood.

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The historical upland lake sediments in the Brazilian Amazon witnessed significant enrichment of total mercury (Hg). However, its spatio-temporal relationships between lakes and the main factors responsible for this enrichment are still poorly constrained. Given this, we geochemically investigated 12 radiometrically dated (extending back to ∼65 cal kyr BP) sediment cores from the Carajás plateau, Brazil. The Hg level in historical sediments presented a large temporal variability (from 1 to 3200 µg/kg), with maximum accumulation peaks observed between 30 and 45 cal kyr BP in core R2, LB3, and R1. However, the lack of the Hg peak in other cores (LV2 and LTI3) during the same period despite being proximity and non-correlation of these Hg peaks with the onset of major volcanic events indicates that this source has little bearing. Hg enrichment is highly dependent on the type of sedimentary facies, with higher values were associated with detritic facies (MI) and detritic+organic facies (P/M). Principal component analysis shows that aluminosilicate minerals and organic matter are essential hosts of Hg in sediments. The positive correlation between Al, Ti, and Hg in detritic facies and their strong coherence with Hg/TOC in R1, R5, LSL, ST02, and LB3 cores indicate that Hg is primarily of lithogenic origin. This can be substantiated by the higher background threshold value of Hg (574 µg/kg) in historical lake sediments compared to those in recent lake sediments (340 µg/kg). However, the most pronounced Hg peak (3200 µg/kg) in R2 around 45 cal kyr BP, which correlates positively with TOC, S, Se, As, and Mo indicates their diagenetic enrichment in organic-rich sediments under anoxic conditions. Thus, in addition to the lithogenic effect, it can be argued that diagenesis can play a significant role in prompting Hg enrichment in the Carajás lake sediments in Amazonia.

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Although bat guano deposits have been proven to be excellent environmental archives for paleoecological and paleoclimate studies, the development of a standardized method specially catering to pollen extraction has received no attention so far. In general, the processing procedure is quite similar among published studies, but adjustments must be made regarding the proportion of organic and particulate matter in the guano deposit. In this study, we present step-by-step optimized sample processing methods for pollen analysis. These procedures first apply a chemical treatment for the removal of siliceous and organic material, followed by a sieving step to remove the remaining inorganic matter from those samples with high detrital content. Overall, our methods can efficiently remove particulate matter and improve the quality of the final residue, resulting in cleaner slides and better visualization of pollen and spores.•Remove humic acid and organic material with Potassium hydroxide.•Remove inorganic matter with hydrofluoric acid and sieving.•Concentrate and store the pollen residues in glycerin.

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BACKGROUND: Bovine leptospirosis is an important reproductive disease and abortion is a major sign, leading to economic impacts. Due to its multifactorial etiology, the proper diagnosis of the cause of the abortion is crucial. Necropsy of the fetuses followed by molecular analysis is recommended for diagnosis, and the investigation mainly occurs in the kidneys and liver. This study aimed to analyze unconventional sites for the presence of leptospiral DNA in bovine anicteric aborted fetuses. METHODS: Five fetuses of the same herd were received for necropsy and diagnosis. Conventional lipL32-PCR was performed in the fetuses' kidneys, livers, lungs, hearts, spleens, subcapsular kidney content, abomasal fluid, and in the cavity's hemorrhagic contents. To complete the investigation, the sera of 30 cows of the herd were collected to perform the serologic screening by Microscopic Agglutination Test. In addition, six subfertile non-pregnant cows from the same herd were selected due to their low reproductive performance, and genital samples (uterine fragment and cervicovaginal mucus) and urine were collected for lipL32-PCR. PCR-positive samples were submitted to a nested PCR of the secY gene and intended for sequencing. RESULTS: The herd presented seroreactive animals (11/30, 36.6%), all against the Sejroe serogroup, with titers between 200 and 1600. In necropsy, four fetuses showed hemorrhagic and anicteric lesions, while one fetus had no macroscopic lesions. Regarding molecular analysis, all the fetuses were positive in lipL32-PCR and the positive sites were the heart, lungs, subcapsular kidney content, thymus, kidneys, liver, and abomasal fluid. Only one fetus presented positive results in the kidney and liver, while three fetuses were positive in the abomasal fluid. Five of six cows were positive for lipL32-PCR, all being positive only in genital samples. Of the fetuses and the cows, seven sequences were obtained and all were identified as Leptospira interrogans serogroup Sejroe serovar Hardjoprajitno. CONCLUSIONS: In order to improve the diagnosis of leptospirosis in cows, it is recommended to perform a comprehensive analysis of the samples, beyond the kidneys and liver. Thus, we highly encourage testing multiple organs by PCR to investigate abortions suspected of bovine leptospirosis, particularly in anicteric fetuses.

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BACKGROUND: Staphylococcus aureus is one of the most frequently major mastitis pathogens that cause clinical and subclinical mastitis worldwide. Current antimicrobial treatments are usually ineffective, and the commercially available vaccines lack proven effectiveness. The immunological response elicited by the recombinant S. aureus-cure-associated proteins phosphoglycerate kinase (PGK), enolase (ENO), and elongation factor-G (EF-G) in combination with the granulocyte-macrophage colony-stimulating factor (GM-CSF) DNA vaccination was studied in this work. METHODS: Here, twenty-three C57BL/6 mice were divided into four groups and vaccinated with: G1: none (control); G2: GM-CSF DNA plasmid DNA vaccine; G3: the combination of EF-G+ENO+PGK; and G4: the combinations of EF-G+ENO+PGK proteins plus GM-CSF plasmid DNA vaccine. After 44 days, spleen cells were collected for immunophenotyping and lymphocyte proliferation evaluation by flow cytometry upon S. aureus stimulus. RESULTS: Immunization with the three S. aureus recombinant proteins alone resulted in a higher percentage of IL-17A+ cells among CD8+ T central memory cells, as well as the highest intensity of IL-17A production by overall lymphocytes indicating that the contribution of the combined lymphocyte populations is crucial to sustaining a type 3 cell immunity environment. CONCLUSION: The immunization with three S. aureus-cure-associated recombinant proteins triggered type 3 immunity, which is a highly interesting path to pursue an effective bovine S. aureus mastitis vaccine.