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Introduction: Glomerular diseases, encompassing primary and secondary forms, pose significant morbidity and mortality risks. Despite their impact, little is known about critically ill patients with primary glomerulopathy admitted to the intensive care unit (ICU)., Methods: We conducted a case‒control study of patients with primary glomerulopathy using the Medical Information Mart for Intensive Care IV database. Demographic, clinical, and outcome data were collected. Logistic regression and mediation analysis were performed to identify predictors of hospital and long-term mortality., Results: Among 50,920 patients, 307 with primary glomerulopathy were included. Infectious and cardiovascular-related causes were the main reasons for ICU admission, with sepsis being diagnosed in more than half of the patients during their ICU stay. The hospital mortality rate was similar to that of the control group, with a long-term mortality rate of 29.0% three years post-ICU discharge. Reduced urine output and serum albumin were identified as independent predictors of hospital mortality, while serum albumin and the Charlson comorbidity index were significantly associated with long-term mortality. Notably, although acute kidney injury was frequent, it was not significantly associated with mortality. Additionally, reduced urine output mediates nearly 25% of the association between serum albumin and hospital mortality., Conclusion: Critically ill patients with primary glomerulopathy exhibit unique characteristics and outcomes. Although hospital mortality was comparable to that of the control group, long-term mortality remained high. The serum albumin concentration and Charlson Comorbidity Index score emerged as robust predictors of long-term mortality, highlighting the importance of comprehensive risk assessment in this population. The lack of an association between acute kidney injury and mortality suggests the need for further research to understand the complex interplay of factors influencing outcomes in this patient population., (© 2024. The Author(s).)

We describe the geographical variation in tree species composition across Amazonian forests and show how environmental conditions are associated with species turnover. Our analyses are based on 2023 forest inventory plots (1 ha) that provide abundance data for a total of 5188 tree species. Within-plot species composition reflected both local environmental conditions (especially soil nutrients and hydrology) and geographical regions. A broader-scale view of species turnover was obtained by interpolating the relative tree species abundances over Amazonia into 47,441 0.1-degree grid cells. Two main dimensions of spatial change in tree species composition were identified. The first was a gradient between western Amazonia at the Andean forelands (with young geology and relatively nutrient-rich soils) and central-eastern Amazonia associated with the Guiana and Brazilian Shields (with more ancient geology and poor soils). The second gradient was between the wet forests of the northwest and the drier forests in southern Amazonia. Isolines linking cells of similar composition crossed major Amazonian rivers, suggesting that tree species distributions are not limited by rivers. Even though some areas of relatively sharp species turnover were identified, mostly the tree species composition changed gradually over large extents, which does not support delimiting clear discrete biogeographic regions within Amazonia., (© 2024. The Author(s).)

Objective: To evaluate the correlation between serum anti-Müllerian hormone (AMH) and the number of oocytes retrieved after controlled ovarian stimulation for in vitro fertilization treatments and determine cut-off values predictive of poor and high response to stimulation., Methods: It was performed a retrospective observational study that included 1003 cycles of controlled ovarian stimulation carried between February 2017 and December 2023 at a Medically Assisted Procreation Centre. The exclusion criteria were the following: serum AMH levels obtained more than 6 months prior to the start of the ovarian stimulation, the presence of a single ovary, non-Caucasian ethnicity, a controlled ovarian stimulation cycle performed for the purpose of oocyte donation or fertility preservation, a documented diagnosis of endometriosis, a documented history of ovarian surgery and the absence of essential data for the study in the medical records (absence of the number of oocytes obtained or the AMH value). Poor response to stimulation was defined as ≤ 3 oocytes retrieved, and high response was defined as > 15 oocytes. The correlation between variables was calculated using Spearman's correlation test and cut-off values were determined using ROC (Receiver Operating Characteristic) curves., Results: AMH exhibited a significantly positive correlation with the number of oocytes retrieved (Spearman's correlation coefficient = 0.60, p<0.01). The predictive cut-off for poor ovarian response was 0.72 ng/mL (specificity of 95.13%, sensitivity of 43.23%), and the predictive cut-off for high ovarian response was 4.77 ng/mL (specificity of 89.86%, sensitivity of 38.22%)., Conclusions: Serum AMH proved to be a good predictor of the ovarian response to controlled ovarian stimulation for in vitro fertilization treatments, which makes it useful in supporting clinical decision-making. However, it should not be used as an absolute discriminator of poor or high ovarian response.

Introduction: Cognitive decline is prevalent in maintenance hemodialysis patients. The blood-brain barrier has been implicated in cognitive decline. In this prospective cohort study, we investigated the associations between endothelium-related biomarkers and steeper cognitive decline in this population., Methods: Cognitive function was assessed using the Portuguese-adapted Cambridge Cognitive Examination (CAMCOG) with items of the Mini-Mental State Examination (MMSE). Endothelium-related biomarkers included syndecan-1, ICAM-1, VCAM-1 and angiopoietin-2 (AGPT2). Patients were followed up for 4 years, and cognitive assessments were repeated. Multinomial regression analyses were performed to evaluate associations between biomarkers and cognitive decline., Results: A total of 216 patients completed the test battery at baseline. After 4 years, 102 patients had follow-up data. There was a significant decrease in cognitive function according to the CAMCOG and MMSE scores: a change of -0.39 (95% CI -0.27 to -0.51) and -0.51 (95% CI -0.27 to -0.76) standard deviation (SD) of the baseline scores. Additionally, executive function but not memory significantly decreased. Syndecan-1 level was independently associated with steeper cognitive decline; each increase in the SD of the syndecan-1 level was associated with a decrease in the CAMCOG of 0.20 (95% CI 0.07-0.33) SD from baseline. Syndecan-1 was associated with a steeper decline in MMSE score (β 0.54, 95% CI 0.28-0.81) and executive function (β 0.17, 95% CI 0.02-0.32). Syndecan-1 predicted severe cognitive impairment with an area under the curve for receiver operating characteristic curves of 0.75 (95% CI 0.64-0.83)., Conclusion: Our findings highlight the potential of syndecan-1, a biomarker of endothelium glycocalyx derangement, as a predictor of steeper cognitive decline in prevalent hemodialysis patients., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Continuous kidney replacement therapy (CKRT) is a crucial intervention for hemodynamically unstable patients with acute kidney injury (AKI). Despite the recommendations to offer a CKRT dose of 20-25 mL/kg/h, the optimal CKRT dose remains uncertain, especially whether low-dose CKRT is associated with poor outcomes. This study investigated the association between low CKRT dosage and 90-day mortality using a marginal structural model (MSM)., Methods: Using the MIMIC-IV database, adult patients who received CKRT for more than 24 hours were included. Data on time-fixed and time-dependent variables were collected. Patients were categorized based on CKRT dose thresholds of 13 and 20 ml/kg/h., Results: Among the 1,329 patients, the 90-day mortality rate was 49.6%. The median age of the patients was 62 years (IQR: 52-72). Changes in CKRT dosing during treatment were frequent. Patients with a reduced delivered CKRT dose (<20 and < 13 ml/kg/h) generally exhibited low values during the initial days of CKRT, with an increase in the delivered CKRT dose. After adjusting only for baseline variables (traditional Cox regression model), patients receiving CKRT doses <13 ml/kg/h had significantly greater 90-day mortality (HR: 1.70, 95% CI 1.16-2.49) than those receiving CKRT doses ≥13 ml/kg/h. However, after adjusting for time-dependent variables, the CKRT dose was not significantly associated with mortality at either the 13 or 20 ml/kg/h threshold. Additionally, there were no significant associations between the delivered CKRT dose and 90-day mortality within the range of 5 to 40 ml/kg/h., Conclusion: This study highlights the impact of methodological approaches on the association between CKRT dose and mortality and that with personalized adjustments, there may not be a lower limit of the unsafe CKRT dose. However, lower CKRT doses were initially associated with higher mortality, and adjusting for time-dependent variables nullified this association., (Copyright © 2024 by the Shock Society.)

Introduction: The current definition of acute kidney injury (AKI) includes increased serum creatinine (sCr) concentration and decreased urinary output (UO). Recent studies suggest that the standard UO threshold of 0.5 ml/kg/h may be suboptimal. This study aimed to develop and validate a novel UO-based AKI classification system that improves mortality prediction and patient stratification., Methods: Data were obtained from the MIMIC-IV and eICU databases. The development process included (1) evaluating UO as a continuous variable over 3-, 6-, 12-, and 24-h periods; (2) identifying 3 optimal UO cutoff points for each time window (stages 1, 2, and 3); (3) comparing sensitivity and specificity to develop a unified staging system; (4) assessing average versus persistent reduced UO hourly; (5) comparing the new UO-AKI system to the KDIGO UO-AKI system; (6) integrating sCr criteria with both systems and comparing them; and (7) validating the new classification with an independent cohort. In all these steps, the outcome was hospital mortality. Another analyzed outcome was 90-day mortality. The analyses included ROC curve analysis, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and logistic and Cox regression analyses., Results: From the MIMIC-IV database, 35,845 patients were included in the development cohort. After comparing the sensitivity and specificity of 12 different lowest UO thresholds across four time frames, 3 cutoff points were selected to compose the proposed UO-AKI classification: stage 1 (0.2-0.3 mL/kg/h), stage 2 (0.1-0.2 mL/kg/h), and stage 3 (< 0.1 mL/kg/h) over 6 h. The proposed classification had better discrimination when the average was used than when the persistent method was used. The adjusted odds ratio demonstrated a significant stepwise increase in hospital mortality with advancing UO-AKI stage. The proposed classification combined or not with the sCr criterion outperformed the KDIGO criteria in terms of predictive accuracy-AUC-ROC 0.75 (0.74-0.76) vs. 0.69 (0.68-0.70); NRI: 25.4% (95% CI: 23.3-27.6); and IDI: 4.0% (95% CI: 3.6-4.5). External validation with the eICU database confirmed the superior performance of the new classification system., Conclusion: The proposed UO-AKI classification enhances mortality prediction and patient stratification in critically ill patients, offering a more accurate and practical approach than the current KDIGO criteria., (© 2024. The Author(s).)

This study evaluated the effect of different supportive treatments on PCV replacement of dairy calves naturally infected with tick fever (TF) agents, and treated with diminazene and enrofloxacin. Five products were tested as supportive treatments in four experiments. In these experiments, we used Girolando female calves (Gyr × Holstein, genetic ratio of 15 / 16 and 31 / 32 Holstein) four to six months old, raised in pasture, naturally infected with TF agents, and infested with R. microplus. Supportive treatment was administered once on day 0 of the study concurrently with specific treatment targeting TF agents. The animals were observed on days 0, 3, and 7. Oral or intravenous administration of a vitamin complex and mineral salts enhanced the increase in PCV and biochemical analytes present in the serum of calves naturally infected with TF agents. No positive effect on PCV values was observed with the administration of (1) invigorating tonic: calcium, casein-peptides and vitamin B12, (2) iron-based stimulant tonic and (3) metabolic tonic: vitamin A, vitamin D, and a fraction of polyunsaturated fatty acids. Supplementation by injection with Type III iron resulted in increased hemoglobin and PCV in treated animals. However, these results did not occur with iron citrate. Therefore, more studies with Type III iron need to be performed. Supportive treatment conferred no advantage in animals with no history of reduced PCV., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

This study evaluated the reproductive, productive and financial consequences of chronic Trypanosoma vivax infection in a dairy cattle herd located in a region without the cyclic vector during two years. Animals were categorized as either positive (chronically infected) or negative for T. vivax antibodies using a commercial rapid test. Additionally, serum samples from cows were analyzed for the presence of anti-Neospora caninum antibodies. Pregnancy diagnoses were performed through rectal palpation and ultrasonography after 30, 60 and every 21 days until the 144th day of pregnancy. If an abortion occurred in the final trimester, serology and cPCR were performed on calves for T. vivax and N. caninum. The breeding period, calving interval and pregnancy losses were recorded. The milk production of each animal during the 305 days of lactation was measured, and the annual financial impact of milk production was calculated using a revenue minus feed cost (RMFC) indicator. Out of 177 cows, 71.75 % were chronically infected, and 13.50 % were T. vivax-negative. No correlation (p = 0.8854) of co-infection between T. vivax and N. caninum was observed. Negative cows required fewer (p≤0.05) artificial inseminations than chronically infected ones. T. vivax was not significantly associated (p = 0.7893) with pregnancy loss up to 81 days of pregnancy. Cows chronically infected by T. vivax had 4-fold greater chance (p = 0.0280) of experiencing pregnancy loss between 82 and 144 days of gestation. Eighteen cows aborted, two were positive for T. vivax antibodies, and one for N. caninum antibodies. The calves were negative for T. vivax and N. caninum. Chronically infected cows and negative cows for T. vivax that experienced pregnancy loss (82-144 days of pregnancy) had a longer (p≤0.05) breeding period to become pregnant, and consequently a longer calving interval compared to cows that maintained pregnancy. The difference (p≤0.05) in milk production was evident when pregnancy loss occurred between 82 and 144 days of gestation in cows chronically infected by T. vivax. The RMFC indicated a negative impact of 38.2 % on the farm's annual milk revenue due to the presence of chronically infected cows., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The treatment for stage III melanoma has advanced significantly, nevertheless, a substantial proportion of patients experience relapse. Neoadjuvant immune checkpoint blockade has emerged as a promising approach, allowing early micrometastatic disease treatment, reduction of tumor burden before surgery, and enhanced tumor-specific T-cell responses. However, not all patients respond to treatment, highlighting the need for understanding immune mechanisms behind failure and identification of predictive markers. Here we performed a robust evaluation of systemic and tumoral immune profiles in a well-defined cohort of advanced melanoma patients treated with immune checkpoint inhibitors. Elevated CTACK and CXCL9 chemokines pre-treatment suggested their potential as predictive tools for treatment response. Furthermore, CD95 expression in CD8 + T lymphocytes surfaced as a favorable prognostic indicator, while PD-1, CD161, and PD-L2 exhibited correlations with worst outcomes. These findings shed light on the intricate interplay between immune markers and melanoma response to neoadjuvant immune checkpoint therapy, offering insights into personalized treatment strategies., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kenneth Gollob reports financial support, administrative support, article publishing charges, and equipment, drugs, or supplies were provided by GSK via the academic grant between FAPESP and GSK. Other authors, declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Introduction: Femoral fractures in elderly individuals present significant health challenges, often leading to increased morbidity and mortality. Acute kidney injury (AKI) during hospitalization further complicates outcomes, yet the interaction between AKI severity and comorbidities, as quantified by the Charlson Comorbidity Index (CCI), remains poorly understood in this population. This study aimed to assess the associations between AKI severity and the CCI and between AKI severity and one-year mortality postfemoral fracture in elderly patients., Methodology: This study utilized data from the Multiparameter Intelligent Monitoring in Intensive Care (MIMIC-IV) database and focused on elderly patients (> 65 years) admitted with hip fractures. Patients were categorized based on AKI stage according to the KDIGO criteria and CCI scores. The primary outcome assessed was all-cause mortality one year after hospital discharge. The statistical analyses included logistic regression, Cox proportional hazards regression and moderation analysis with the Johnson-Neyman technique to evaluate associations between AKI and long-term mortality and between the CCI and long-term mortality., Results: The analysis included 1,955 patients and revealed that severe AKI (stages 2 and 3) was independently associated with increased one-year mortality. Notably, the CCI moderated these associations significantly. A lower CCI score was significantly correlated with greater mortality in patients with severe AKI. The impact of severe AKI was greater for those with a CCI as low as 3, more than doubling the observed one-year mortality rate. In contrast, higher CCI scores (≥8) did not significantly impact mortality. Sensitivity analyses supported these findings, underscoring the robustness of the observed associations., Conclusion: This study elucidates the complex interplay between AKI severity and comorbidities and long-term mortality in elderly hip fracture patients. These findings underscore the importance of considering both AKI severity and comorbidity burden in prognostic assessments and intervention strategies for this vulnerable population. Targeted interventions tailored to individual risk profiles may help mitigate the impact of AKI on mortality outcomes, ultimately improving patient care and outcomes. Further research is warranted to explore the underlying mechanisms involved and refine risk stratification approaches in this population., (© 2024. The Author(s).)

In tropical beef cattle production systems, animals are commonly raised on pastures, exposing them to potential stressors. The end of gestation typically overlaps with a dry period characterized by limited food availability. Late gestation is pivotal for fetal development, making it an ideal scenario for inter- and transgenerational effects of the maternal gestational environment. Intergenerational effects occur due to exposure during gestation, impacting the development of the embryo and its future germline. Transgenerational effects, however, extend beyond direct exposure to the subsequent generations. The objective of the present study was to verify these effects on the post-natal performance of zebu beef cattle. We extended the use of a reaction norm model to identify genetic variation in the animals' responses to transgenerational effects. The inter- and transgenerational effects were predominantly positive (-0.09% to 19.74%) for growth and reproductive traits, indicating improved animal performance on the phenotypic scale in more favourable maternal gestational environments. Additionally, these effects were more pronounced in the reproductive performance of females. On average, the ratio of direct additive genetic variances of the slope and intercept of the reaction norm ranged from 1.23% to 3.60% for direct and from 10.17% to 11.42% for maternal effects. Despite its relatively modest magnitude, this variation proved sufficient to prompt modifications in parameter estimates. The average percentage variation of direct heritability estimates ranged from 19.3% for scrotal circumference to 33.2% for yearling weight across the environmental descriptors evaluated. Genetic correlations between distant environments for the studied traits were generally high for direct effects and far from unity for maternal effects. Changes in EBV rankings of sires across different gestational environments were also observed. Due to the multifaceted nature of inter- and transgenerational effects of the maternal gestational environment on various traits of beef cattle raised under tropical pasture conditions, they should not be overlooked by producers and breeders. There were differences in the specific response of beef cattle to variations in the quality of the maternal gestational environment, which can be partially explained by transgenerational epigenetic inheritance. Adopting a reaction norm model to capture a portion of the additive variance induced by inter- or transgenerational effects could be an alternative for future research and animal genetic evaluations., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

This study aimed to investigate seven outbreaks of A. marginale infection in two regions of Brazil, affecting taurine, zebu, and crossbred cattle. We assessed the possible causes, treatment measures, and genetic diversity of A. marginale. These outbreaks occurred in two states (Goiás: outbreaks 1-7; Mato Grosso do Sul: outbreak 3), breeds (Holstein, Nellore, and crossbreed), age groups (beef cattle: 18-25 days old and 7-8 months; dairy cattle: 18-25 days old, 13-14 months, and cow after the first birth) and rearing systems (feedlot, pasture, pen in a wood shaving bedding system and compost bedded-pack barns). Metaphylactic or prophylactic treatments varied according to outbreak (imidocarb dipropionate: outbreaks 1-4 and 6; enrofloxacin: outbreaks 5 and 7; diminazene diaceturate: outbreak 5). In outbreaks 6 and 7, the packed cell volume was monitored. In all outbreaks, the practice of needle/syringe sharing was discontinued. For outbreaks 1-3, clinical signs and mortality (range, 4.8-13.3%) occurred 36-45 days after entry into the feedlot. In outbreak 4, A. marginale was diagnosed in 66.2% of the calves (bacteremia, 0-4.5%), with a mortality of 8.6%. Among nursing calves aged 60 days during outbreak 5, 53.8% were infected with A. marginale, with average bacteremia of 2.7% (range, 0-21.3%), and a mortality of 13.8%. In dairy heifers aged 14 months, raised in paddocks lacking vegetation cover and infested with R. microplus, then transitioned to a rotational grazing system also infested with R. microplus, the A. marginale bacteremia ranged from 3.2 to 6.7%, with a mortality of 20%. Before monitoring during outbreak 7, the mortality was 17.9%, but no further deaths were observed after monitoring initiation. In conclusion, possible causes triggering the outbreaks included primary tick infestation, needle/syringe sharing, and stress factors which may have affected the immunological statues of animals in the feedlots. Control measures performed in all outbreaks were effective. The partial msp4 gene sequences of A. marginale generated herein belonged to two haplotypes, but further research would be needed to investigate if this finding has any clinical significance., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Amazonia's floodplain system is the largest and most biodiverse on Earth. Although forests are crucial to the ecological integrity of floodplains, our understanding of their species composition and how this may differ from surrounding forest types is still far too limited, particularly as changing inundation regimes begin to reshape floodplain tree communities and the critical ecosystem functions they underpin. Here we address this gap by taking a spatially explicit look at Amazonia-wide patterns of tree-species turnover and ecological specialization of the region's floodplain forests. We show that the majority of Amazonian tree species can inhabit floodplains, and about a sixth of Amazonian tree diversity is ecologically specialized on floodplains. The degree of specialization in floodplain communities is driven by regional flood patterns, with the most compositionally differentiated floodplain forests located centrally within the fluvial network and contingent on the most extraordinary flood magnitudes regionally. Our results provide a spatially explicit view of ecological specialization of floodplain forest communities and expose the need for whole-basin hydrological integrity to protect the Amazon's tree diversity and its function., (© 2024. The Author(s).)

Acute kidney injury (AKI) is a common condition in hospitalized patients who often requires kidney support therapy (KST). However, predicting the need for KST in critically ill patients remains challenging. This study aimed to analyze endothelium-related biomarkers as predictors of KST need in critically ill patients with stage 2 AKI. A prospective observational study was conducted on 127 adult ICU patients with stage 2 AKI by serum creatinine only. Endothelium-related biomarkers, including vascular cell adhesion protein-1 (VCAM-1), angiopoietin (AGPT) 1 and 2, and syndecan-1, were measured. Clinical parameters and outcomes were recorded. Logistic regression models, receiver operating characteristic (ROC) curves, continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used for analysis. Among the patients, 22 (17.2%) required KST within 72 h. AGPT2 and syndecan-1 levels were significantly greater in patients who progressed to the KST. Multivariate analysis revealed that AGPT2 and syndecan-1 were independently associated with the need for KST. The area under the ROC curve (AUC-ROC) for AGPT2 and syndecan-1 performed better than did the constructed clinical model in predicting KST. The combination of AGPT2 and syndecan-1 improved the discrimination capacity of predicting KST beyond that of the clinical model alone. Additionally, this combination improved the classification accuracy of the NRI and IDI. AGPT2 and syndecan-1 demonstrated predictive value for the need for KST in critically ill patients with stage 2 AKI. The combination of AGPT2 and syndecan-1 alone enhanced the predictive capacity of predicting KST beyond clinical variables alone. These findings may contribute to the early identification of patients who will benefit from KST and aid in the management of AKI in critically ill patients., (© 2024. The Author(s).)

Introduction: The use of clear aligners as an alternative to fixed orthodontic appliances has become popular due to the aesthetic demands of adult patients seeking orthodontic treatment. However, orthodontists' lack of knowledge about the legal consequences of their activities, and the lack of solid scientific evidence raise concerns regarding civil liability in this type of treatment. Marketing campaigns of manufacturing companies often exaggerate promises of results, and ignore the lack of scientific evidence. Patients, as consumers, are protected by the Consumer Protection Code, whereas orthodontists are considered treatment providers. Therefore, they can be held liable for damage caused to patients, whether by subjective or objective fault., Objective: This article aims to identify the civil responsibilities of orthodontists and aligner manufacturing companies, by means of a literature review, providing basic legal guidance to help professionals protect themselves from possible lawsuits related to treatment with orthodontic aligners., Conclusions: The study highlights the importance of knowledge of legal notions in treatments with orthodontic aligners by orthodontists, who should legally safeguard themselves through individual written contracts, avoiding obligation of results. In addition, in cases of legal claims, it is possible that the manufacturing companies are jointly and severally liable for possible damages claimed by the patient.

The study aimed to evaluate the antitumor and toxicogenetic effects of liposomal nanoformulations containing citrinin in animal breast carcinoma induced by 7,12-dimethylbenzanthracene (DMBA). Mus musculus virgin females were divided into six groups treated with (1) olive oil (10 mL/kg); (2) 7,12-DMBA (6 mg/kg); (3) citrinin, CIT (2 mg/kg), (4) cyclophosphamide, CPA (25 mg/kg), (5) liposomal citrinin, LP-CIT (2 μg/kg), and (6) LP-CIT (6 µg/kg). Metabolic, behavioral, hematological, biochemical, histopathological, and toxicogenetic tests were performed. DMBA and cyclophosphamide induced behavioral changes, not observed for free and liposomal citrinin. No hematological or biochemical changes were observed for LP-CIT. However, free citrinin reduced monocytes and caused hepatotoxicity. During treatment, significant differences were observed regarding the weight of the right and left breasts treated with DMBA compared to negative controls. Treatment with CPA, CIT, and LP-CIT reduced the weight of both breasts, with better results for liposomal citrinin. Furthermore, CPA, CIT, and LP-CIT presented genotoxic effects for tumor, blood, bone marrow, and liver cells, although less DNA damage was observed for LP-CIT compared to CIT and CPA. Healthy cell damage induced by LP-CIT was repaired during treatment, unlike CPA, which caused clastogenic effects. Thus, LP-CIT showed advantages for its use as a model of nanosystems for antitumor studies.

With global warming, there are growing challenges for raising taurine and composite beef cattle populations in tropical regions, including elevated temperatures, limited forage availability, parasite infestation, and infectious diseases. These environmental factors can trigger specific physiological responses in the developing fetus, which may have long-term implications on its performance. Therefore, the main objective of this study was to assess the influence of naturally induced thermal stress during the gestation period on the subsequent performance of tropical composite beef cattle progeny. Furthermore, we aimed to investigate the impact of genotype-by-gestational thermal environment interaction (G×Eg) on traits under selection pressure in the breeding population. A total of 157,414 animals from 58 farms located in various Brazilian states were recorded for birth weight (BW), preweaning weight gain (PWG), yearling weight (YW), hip height (HH), scrotal circumference (SC), and days to first calving (DFC). We first applied a linear regression model to the BW data, which revealed that the last 40 d of gestation were suitable for calculating the mean temperature humidity index (THIg). Subsequent regression analyses revealed that for every 10-unit increase in THIg, detrimental effects of approximately 1.13% to 16.34% are expected for all traits evaluated. Genetic parameters were estimated through a reaction norm model using THIg as the environmental descriptor. The posterior means of heritability estimates (SD) were 0.35 (0.07), 0.25 (0.03), 0.31 (0.03), 0.37 (0.01), 0.29 (0.07), and 0.20 (0.09) for the direct effect of BW, PWG, YW, HH, SC, and DFC, respectively. These estimates varied along the range of THIg values, suggesting a variable response to selection depending on the thermal environment during gestation. Genetic correlation estimates between more divergent THIg values were low or negative for YW, PWG, and DFC, indicating that the best-performing individuals at low THIg values may not perform as well at high THIg values and vice versa. Overall, thermal stress during gestation impacts the future performance of beef cattle offspring. Our results indicate the need for developing effective breeding strategies that take into account G×Eg effects and the re-ranking of breeding animals along the THIg scale, particularly for traits such as DFC that are highly sensitive to thermal stress., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Trees structure the Earth's most biodiverse ecosystem, tropical forests. The vast number of tree species presents a formidable challenge to understanding these forests, including their response to environmental change, as very little is known about most tropical tree species. A focus on the common species may circumvent this challenge. Here we investigate abundance patterns of common tree species using inventory data on 1,003,805 trees with trunk diameters of at least 10 cm across 1,568 locations 1-6 in closed-canopy, structurally intact old-growth tropical forests in Africa, Amazonia and Southeast Asia. We estimate that 2.2%, 2.2% and 2.3% of species comprise 50% of the tropical trees in these regions, respectively. Extrapolating across all closed-canopy tropical forests, we estimate that just 1,053 species comprise half of Earth's 800 billion tropical trees with trunk diameters of at least 10 cm. Despite differing biogeographic, climatic and anthropogenic histories 7 , we find notably consistent patterns of common species and species abundance distributions across the continents. This suggests that fundamental mechanisms of tree community assembly may apply to all tropical forests. Resampling analyses show that the most common species are likely to belong to a manageable list of known species, enabling targeted efforts to understand their ecology. Although they do not detract from the importance of rare species, our results open new opportunities to understand the world's most diverse forests, including modelling their response to environmental change, by focusing on the common species that constitute the majority of their trees., (© 2024. The Author(s).)

Stayability (STAY) is a way to evaluate the productive longevity of females. Measuring the STAY at each cow calving allows earlier indicators of longevity to be obtained. Our objective with this study was to verify the association between STAY and consecutive calvings and traits potentially used as selection criteria in beef cattle, such as age at first calving (AFC), days to calving (DC), weaning weight (WW), and yearling weight (YW). Data from the Nelore, Angus/Brangus, and Hereford/Braford breeds were used. The estimation of variance components and subsequent prediction of breeding values were performed for all traits. The estimated breeding values (EBV) were used to analyse the association between STAY and the other traits. The Pearson's correlation estimated between the EBV for the intercept coefficient for STAY to consecutive calvings and those of AFC, DC, WW (direct and maternal effects), and YW was favourable and of low magnitude (<0.25) depending on the breed studied. The influence of the genetic merit of AFC on the chance of selection for STAY was favourable and relevant regardless of the intensity of selection and breed. DC and WW (maternal effect) traits were favourably influenced by the chance of selection for STAY, irrespective of breed. The WW (direct effect) did not affect the chance of selection for STAY for the Nelore and Hereford/Braford breeds and negatively influenced, but to a small extent, the Angus/Brangus breed. For YW, an increase in genetic merit affected the chances of selection for STAY, depending on the breed and selection intensity evaluated. The influence of the genetic merit for AFC, DC, and WW (maternal effect) on the chance of selection for STAY to consecutive calvings was favourable and relevant regardless of the selection intensity scenario evaluated. The WW (direct effect) did not influence the chance of selection for STAY. For the scenario with high selection intensity, the selection for YW favourably influenced the chance of selection for STAY in Angus/Brangus and Hereford/Braford breeds but not in Nelore., (© 2023 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

A role of IL-10 is down-regulating T-cell responses to schistosome antigens. Since SmATPDases can be correlated to modulation of the immune response, we evaluated the expression of enzymes in S. mansoni eggs. Faecal samples were collected from 40 infected individuals to detect coding regions of the SmATPDases. The cytokines were measured in supernatants of PBMC. The analysis was performed by the global median determination and set up high producers (HP) of cytokines. Six individuals expressed SmATPDase1, six expressed SmATPDase2 and six expressed both enzymes. The group who expressed only SmATPDase1 showed a high frequency of IFN-γ, TNF IL-4 HP; individuals who expressed only SmATPDase2 showed a high frequency of IFN-γ, IL-6 and IL-4 HP; and individuals who expressed both enzymes showed a high frequency of IL-10 HP. The comparison of the IFN-γ/IL-10 ratio presented higher indices in the group who had SmATPDase 2 expression than those who had the expression of both enzymes. The positive correlation between infection intensity and IL-10 levels remained only in the positive SmATPDase group. The IL-10 is the only cytokine induced by the expression of both enzymes. Our data suggest that the expression of both enzymes seems to be a factor that modulates the host immune response by inducing high IL-10 production., (© 2023 John Wiley & Sons Ltd.)

Ethnopharmacology and botanical taxonomy are valid criteria used to selecting plants for antimalarial bioprospection purposes. Based on these two criteria, ethanol extracts of 11 plants from Santarém City vicinities, Western Pará State, Brazilian Amazonia, had their in vitro antiplasmodial activity against chloroquine-resistant Plasmodium falciparum (W2 clone) assessed by the PfLDH method, whereas their cytotoxicity to HepG2-A16 cells was assessed through MTT assay. Acmella oleracea, Siparuna krukovii and Trema micrantha extracts disclosed the highest rate of parasite growth inhibition (90 %) in screening tests. In vivo antimalarial assays were conducted with these extracts against Plasmodium berghei (NK 65 strain) infected mice. Inhibition rate of parasite multiplication ranged from 41.4 % to 60.9 % at the lowest extract dose (25 mg/kg). HPLC-ESI-HRMS 2 analyses allowed the putative identification of alkylamides, fatty acids, flavonoid glycosides and alkaloids in ethanol extracts deriving from these three plant species. Results pointed towards A. oleracea flowers ethanol extract as the most promising potential candidate to preclinical studies aiming the development of antimalarial phytomedicine., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Experiments were conducted to evaluate the stability and degradation of NBPT under storage conditions and to quantify urease activity, ammonia losses by volatilization, and agronomic efficiency of urea treated with different urease inhibitors, measured in the field. Experiments included urea treated with 530 mg NBPT kg -1 (UNBPT) in contact with six P-sources (monoammonium phosphate-MAP; single superphosphate; triple superphosphate; P-Agrocote; P-Phusion; P-Policote), with two P-concentrations (30; 70%); the monitoring four N-technologies (SoILC; Limus; Nitrain; Anvol); and the application of conventional urea (U GRAN ) or urea treated with urease inhibitors as topdressing in three maize fields, at three N rates. It is concluded that: the mixture of UNBPT and P-fertilizers is incompatible. When MAP granules were coated to control P-release (P-Agrocote), the degradation of NBPT was moderate (approximately 400 mg kg -1 at the end of the storage test). SoILC and Limus solvent technologies extended the NBPT half-life by up to 3.7 and 4.7 months, respectively. Under field, each inhibition technology reduced urease activity, and lowered the intensity of ammonia emission compared to U GRAN by 50-62%. Our results show that the concentration of NBPT is reduced by up to 53.7% for mixing with phosphates. In addition, even with coatings, the storage of mixtures of urea with NBPT and phosphates should be for a time that does not reduce the efficiency of the inhibitor after application, and this time under laboratory conditions was 168 h. The reduction of NBPT concentration in urea is reduced even in isolated storage, our results showed that the half-life time is variable according to the formulation used, being 4.7, 3.7, 2.8 and 2.7 days for Limus, SoILC, Nitrain and Anvol, respectively. The results of these NBPT formulations in the field showed that the average losses by volatilization in the three areas were: 15%, 16%, 17%, 19% and 39% of the N applied, for SoILC, Anvol, Nitrain, Limus and urea, respectively. The rate of nitrogen application affected all agronomic variables, with varied effects in Ingaí. Even without N, yields were higher than 9200 kg ha -1 of grains. The increase in nitrogen rates resulted in linear increases in production and N removal in Luminárias and Ingaí, but in Lavras, production decreased above 95.6 kg ha -1 of N. The highest production in Lavras (13,772 kg ha -1 of grains) occurred with 100 kg ha -1 of N. The application of Anvol reduced the removal of N in Ingaí., (© 2023. The Author(s).)

Using 2.046 botanically-inventoried tree plots across the largest tropical forest on Earth, we mapped tree species-diversity and tree species-richness at 0.1-degree resolution, and investigated drivers for diversity and richness. Using only location, stratified by forest type, as predictor, our spatial model, to the best of our knowledge, provides the most accurate map of tree diversity in Amazonia to date, explaining approximately 70% of the tree diversity and species-richness. Large soil-forest combinations determine a significant percentage of the variation in tree species-richness and tree alpha-diversity in Amazonian forest-plots. We suggest that the size and fragmentation of these systems drive their large-scale diversity patterns and hence local diversity. A model not using location but cumulative water deficit, tree density, and temperature seasonality explains 47% of the tree species-richness in the terra-firme forest in Amazonia. Over large areas across Amazonia, residuals of this relationship are small and poorly spatially structured, suggesting that much of the residual variation may be local. The Guyana Shield area has consistently negative residuals, showing that this area has lower tree species-richness than expected by our models. We provide extensive plot meta-data, including tree density, tree alpha-diversity and tree species-richness results and gridded maps at 0.1-degree resolution., (© 2023. The Author(s).)

Indigenous societies are known to have occupied the Amazon basin for more than 12,000 years, but the scale of their influence on Amazonian forests remains uncertain. We report the discovery, using LIDAR (light detection and ranging) information from across the basin, of 24 previously undetected pre-Columbian earthworks beneath the forest canopy. Modeled distribution and abundance of large-scale archaeological sites across Amazonia suggest that between 10,272 and 23,648 sites remain to be discovered and that most will be found in the southwest. We also identified 53 domesticated tree species significantly associated with earthwork occurrence probability, likely suggesting past management practices. Closed-canopy forests across Amazonia are likely to contain thousands of undiscovered archaeological sites around which pre-Columbian societies actively modified forests, a discovery that opens opportunities for better understanding the magnitude of ancient human influence on Amazonia and its current state.

The objective was to analyze the temporal effects of age, period, and cohort on mortality from all female homicides, and from female homicides and by firearms, in Brazil from 1980 to 2019. Data were accessed from Brazilian health records. There was an increase in the risk of death in the 2000s in the North and Northeast regions and a decrease in the Southeast, South, and Midwest. Younger women had a higher risk of death than women born between 1950 and 1954. The findings may be correlated with the inefficiency of the Brazilian state in protecting female victims of violence., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Is well known the taurine and zebuine susceptibility to Rhipicephalus microplus. Few are the reports regarding tick population dynamics between the same herd/breed, and because of this, two experiments were performed. In the 1st, the cattle tick population dynamics in dairy nursing calves (reared collective and individually), weaning calves (4-16 months), heifers (17-29 months), cows in lactation and dry cows (≥ 30 months) from the same herd, tick burden and milk production correlation were performed, for two years. R. microplus females (4.5-8.0 mm) counts and the milk production were performed every 28 and 14 days, respectively. In the 2nd experiment, bovines belonging to different categories/age (newborn without previous contact with tick; 12-13 months with tick contact since birth; and 23-24 months with tick contact since birth) were experimentally infested with 30,000 R. microplus larvae, to quantify the number of fully engorged females detached from these animals. In the 1st experiment, when the mean counts of tick were ≥ 30 all animals of the group were treated. Nursing calves showed 3-4 peaks of ticks, animals reared individually showed smaller (p ≤ 0.05) tick burden than those reared collectively. Weaning calves (4-8 months) showed 5 tick peaks/year and higher mean tick burden was found than other categories. On the other hand, animals with 17-29 months of age showed smallest (p ≤ 0.05) tick burden, with 3 tick peaks/year. When the animal become lactating the tick burden increase, and 5 peaks/year occurred, and decrease again in dry cows (p ≤ 0.05) showing 4-5 tick peaks/year. Weaning calves and lactating cows received more acaricide treatments (p ≤ 0.05), 18 and 15, respectively. Nursing calves reared individually, and heifers (21-29 months) were the categories that received two acaricide treatments. The more milk the cow produce, more ticks it has (p ≤ 0.05). In the 2nd experiment, more (p ≤ 0.05) fully engorged females were recovered from younger animals than older ones. So, different tick control strategies need to be adopted in different dairy cattle categories, and the tick burden should be considered, once the effect may be more inherent to the animal rather than the strategy adopted., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Aims: We analysed intestinal permeability in patients with chronic Chagas cardiomyopathy (CCC) and evaluated its association with clinical manifestations, haemodynamic parameters measured by echocardiogram, and disease outcome. Intestinal permeability was compared between CCC patients and a group of healthy controls., Background: Intestinal dysfunction may contribute to a more severe disease presentation with worse outcome in patients with CCC and heart failure., Methods: Fifty patients with CCC and left ventricular ejection fraction (LVEF) of less than 55% were prospectively selected and followed for a mean period of 18 ± 8 months. A group of 27 healthy volunteers were also investigated. One patient was excluded from the analysis since he died before completing the intestinal permeability test. Intestinal permeability was evaluated with the sugar probe drink test. It consists in the urinary recovery of previously ingested sugar probes: mannitol, a monosaccharide, and lactulose, a disaccharide., Results: Patient's mean age was 53.4 ± 10.4 years, and 31(63%) were male. Differential urinary excretion of lactulose/mannitol ratio did not differ significantly between healthy controls and CCC patients, regardless of clinical signs of venous congestion, haemodynamic parameters, and severity of presentation and outcome., Conclusions: The present study could not show a disturbance of the intestinal barrier in CCC patients with LVEF <55%, measured by lactulose/mannitol urinary excretion ratio. Further investigations are needed to verify if in patients with LVEF <40% intestinal permeability is increased., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Introduction: Up to 70% of intermittent hemodialysis (IHD) sessions in critically ill patients are complicated by hemodynamic instability. Although several clinical characteristics have been associated with hemodynamic instability during IHD, the discriminatory capacity of predicting such events during IHD sessions is less defined. In the present study, we aimed to analyse endothelium-related biomarkers collected before IHD sessions and their capacity to predict hemodynamic instability related to IHD in critically ill patients., Methods: In this prospective observational study, we enrolled adult critically ill patients with acute kidney injury who required fluid removal with IHD. We screened each included patient daily for IHD sessions. Thirty minutes before each IHD session, each patient had a 5-mL blood collection for measurement of endothelial biomarkers-vascular cell adhesion molecule-1 (VCAM-1), angiopoietin-1 and -2 (AGPT1 and AGPT2) and syndecan-1. Hemodynamic instability during IHD was the main outcome. Analyses were adjusted for variables already known to be associated with hemodynamic instability during IHD., Results: Plasma syndecan-1 was the only endothelium-related biomarker independently associated with hemodynamic instability. The accuracy of syndecan-1 for predicting hemodynamic instability during IHD was moderate [area under the receiver operating characteristic curve 0.78 (95% confidence interval 0.68-0.89)]. The addition of syndecan-1 improved the discrimination capacity of a clinical model from 0.67 to 0.82 ( P  < .001) and improved risk prediction, as measured by net reclassification improvement., Conclusion: Syndecan-1 is associated with hemodynamic instability during IHD in critically ill patients. It may be useful to identify patients who are at increased risk for such events and suggests that endothelial glycocalyx derangement is involved in the pathophysiology of IHD-related hemodynamic instability., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

In a time of rapid global change, the question of what determines patterns in species abundance distribution remains a priority for understanding the complex dynamics of ecosystems. The constrained maximization of information entropy provides a framework for the understanding of such complex systems dynamics by a quantitative analysis of important constraints via predictions using least biased probability distributions. We apply it to over two thousand hectares of Amazonian tree inventories across seven forest types and thirteen functional traits, representing major global axes of plant strategies. Results show that constraints formed by regional relative abundances of genera explain eight times more of local relative abundances than constraints based on directional selection for specific functional traits, although the latter does show clear signals of environmental dependency. These results provide a quantitative insight by inference from large-scale data using cross-disciplinary methods, furthering our understanding of ecological dynamics., (© 2023. The Author(s).)

Chicha gum is a natural polymer obtained from the Sterculia striata plant. The hydroxyl groups of its structure have a chemical affinity to form hydrogels, which favors the association with biologically active molecules, such as nerolidol. This association improves the biological properties and allows the material to be used in drug delivery systems. Chicha gum hydrogels associated with nerolidol were produced at two concentrations: 0.01 and 0.02 g mL -1 . Then, the hydrogels were characterized by thermogravimetry (TG), Fourier Transform Infrared spectroscopy (FTIR), and rheological analysis. The antibacterial activity was tested against Staphylococcus aureus and Escherichia coli . The cytotoxicity was evaluated against Artemia salina . Finally, an in vivo healing assay was carried out. The infrared characterization indicated that interactions were formed during the gel reticulation. This implies the presence of nerolidol in the regions at 3100-3550 cm -1 . The rheological properties changed with an increasing concentration of nerolidol, which resulted in less viscous materials. An antibacterial 83.6% growth inhibition effect was observed using the hydrogel with 0.02 g mL -1 nerolidol. The in vivo healing assay showed the practical activity of the hydrogels in the wound treatment, as the materials promoted efficient re-epithelialization. Therefore, it was concluded that the chicha hydrogels have the potential to be used as wound-healing products.

Plant extracts are complex mixtures that are difficult to characterize, and mass spectrometry is one of the main techniques currently used in dereplication processes. Fridericia chica is a species with medicinal uses in Latin American countries, used in the treatment of inflammatory and infectious diseases. Extracts of this plant species are characterized by the presence of anthocyanidins. In this study, using high-resolution mass spectrometry coupled with liquid chromatography, it was possible to determine the molecular formula of thirty-nine flavonoids. Fragmentation analysis, ultraviolet spectrum and nuclear magnetic resonance data allowed the partial characterization of the structures of these compounds. The spectral dataset allowed the identification of a series of flavones in addition to the desoxyanthocyanidins common in extracts of the species. The occurrence of some of the proposed structures is uncommon in extracts of species of the Bignoniaceae family, and they are reported for the first time in the extract of this species. Quantitative analyses of total flavonoids confirmed the high content of these constituents in the species, with 4.09 ± 0.34 mg/g of dry plant material. The extract under study showed low in vitro cytotoxicity with CC 50 ≥ 296.7 ± 1.4 µg/mL for Vero, LLC-MK2 and MRC-5 cell lines. In antiviral activity assays, inhibition of the cytopathic effects of Dengue, Zika and Mayaro viruses was observed, with EC 50 values ranging between 30.1 and 40.9 µg/mL. The best result was observed against the Mayaro virus, with an EC 50 of 30.1 µg/mL.

Data regarding parasitemia (blood smears), rectal temperature (RT), packed cell volume (PCV) and vaginal mucosa coloration (VMC) of Gyr x Holstein female calves between 3-7mo were accessed to evaluate different techniques for monitoring the bovine tick fever agents (TFA). The 1 st experiment determined the correlation between the TFA parasitemia with RT and PCV. The 2 nd , evaluated the associated risk of A. marginale parasitemia with RT and PCV in relation to the Gyr / Holstein genetic proportion ( 5 / 8 , 3 / 4 , 7 / 8 and 15 / 16 ) using Receiver Operating Characteristic Curve (ROC). The 3 rd , two groups were performed: cattle monitored by RT (T01) and by PCV (T02), during their 80-210 days of age, data regarding TFA parasitemia, RT, PCV, VMC and weight were registered. In 1st experiment, RT showed weak correlation with TFA parasitemia, while PCV showed a strong correlation with A. marginale and B. bigemina, but not with B. bovis parasitemia. In experiment 2, the ROC curve analysis showed that when the genetic proportion of B. t. taurus increased, least reliable RT was to monitor calves infected with A. marginale. The PCV for monitoring A. marginale was the best technique, showing sensitivity of 74.2% and specificity of 97.0% than other techniques that used RT and VCM as a monitoring tool. In general, calves monitored by PCV (T02) showed higher PCV values, lower A. marginale parasitemia, less pneumonia as co-infection and less salvation treatment were performed than in animals monitored by RT (T01). Furthermore, animals from T02 gained 23.5 kg more than those from T01. The low frequency of B. bovis and B. bigemina found in this study made impossible to compare the monitoring techniques for these pathogenic agents., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Shockwave therapy (SWT) has been successful in the management of musculoskeletal conditions. The limitations of the use of SWT in clinical practice regard a lack of familiarity with the device and the lack of uniformity in information reported in scientific publications. Standardization in the reporting of these parameters could facilitate the reproduction and interpretation of data in future studies. Most studies fail to offer a detailed description of the parameters. Therefore, the aim of the present paper is to prepare a report on how to standardize the presentation of this information and serve a reference guide to report physical parameters and procedures of SWT when used on patients with musculoskeletal disorders. The terms were selected from the Medical Subject Headings database of controlled vocabulary. An extensive process of systematic searching of databases was performed, after which experts met and discussed on the main findings, and a consensus was achieved. SWT parameters were described, including the physiological meaning and clinical relevance of each parameter. Also, the description of patient and equipment positioning was added. The consensus-based guideline on how to report SWT parameters for the treatment of musculoskeletal conditions was developed to help clinicians and researchers., Competing Interests: The authors have no conflicts of interest., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

The primary objective was to observe the relationship between serum levels of BNP, Ca-125, C-reactive protein and uric acid as prognostic and functional markers in patients with chronic Chagas cardiomyopathy (CCC). Circulating levels of cytokines: IL-1β, TNFα, IL-10, IL6, IL-8 and IL-12 were determined and investigated regarding their association with hemodynamic parameters, clinical signs of heart failure and outcome. Chagas is still a neglected disease that affects numerous individuals, many of them in their most productive years. CCC with left ventricular dysfunction is the most severe presentation of Chagas Disease. BNP is a well-recognized prognostic and clinical biomarker, not only in chronic heart failure patients but also in patients with CCC. Previous studies have shown Ca-125, C-reactive protein, and uric acid to be potentially good prognostic markers in heart failure (HF). Fifty patients with left ventricular fraction less (LVEF) than 55% were selected and followed for a mean period of 18 ± 8.3 months. Patient's mean age was 43.42 ± 10.3 years (32 male), their BNP was 293 (160-530) pg/mL, Ca-125 8.5 (5.5-16.75) U/mL, uric acid 6.2 ± 2 mg/dL, and C- reactive protein 4.5 (4.5-7.3) mg/L. Patients who had LVEF less than 35% had higher BNP ( p = 0.0023), Ca-125 ( p = 0.027) and uric acid ( p = 0.01) serum levels. Patients who died also showed higher BNP ( p = 0.01), uric acid ( p = 0.05) and a trend towards higher Ca-125 serum levels ( p = 0.056). All markers: BNP, Ca-125, uric acid and C-reactive had good predictability of death in Cox-regression univariate analysis, however, not on the final multivariate model. Of the inflammatory cytokines, IL-8 and IL-12 showed a relation to LVEF of less than 35%. IL-12 was related to adverse cardiovascular events and non-survival. IL-1β was a good predictor of mortality in the final Cox regression model. Determination of Ca-125, uric acid levels and C-reactive protein may add useful clinical and prognostic information and may help clinical decision making for patients with CCC.

Jewel tetra ( Hyphessobrycon eques ) is a freshwater fish found in several rivers and basins in South America. The present study is the first study to create a panel of microsatellite markers for detecting genetic diversity in H. eques and evaluating the application of these markers in Serrapinnus notomelas . In total, 44 individuals were genotyped from the natural (WIL, n  = 20) and stock in captivity (CAP, n  = 24) population. Moreover, 19 microsatellite markers were obtained, of which only 8 loci presented a high degree polymorphism. In total, 45 alleles were detected, ranging from 126 bp (Hype2G2) to 420 bp (Hype2E2). The Hardy-Weinberg equilibrium ( p  < 0.05) revealed significant difference in one locus in WIL (Hype1G4) and three loci in CAP (Hype1F4, Hype2C3, and Hype2G2). Null alleles ( p  < 0.05) were present in only one locus (Hype1G4). The WIL and CAP populations revealed high genetic diversity during F ST analysis. The cross-amplification test for S. notomelas revealed that only two loci (Hype2C3 and Hype2G2B) presented satisfactory transferability results. The developed microsatellite primers will be useful in studying the genetic diversity and population structure of H. eques in wild populations and fish farms in the Brazilian and other South American basins.

Objective: To investigate the prediction ability of vascular injury biomarkers for haemodialysis requirement in patients with severe leptospirosis., Methods: Prospective study with severe leptospirosis patients hospitalised in Fortaleza, Brazil. Blood samples were collected hospital admission to quantify vascular injury biomarkers: syndecan-1, ICAM-1, VCAM-1, angiopoietin-2 and FGF-23. Two groups were evaluated according to haemodialysis requirement during hospital stay., Results: Twenty-seven patients were included, with a mean age of 39 ± 18 years. 88.9% were males. 53.8% needed haemodialysis and presented higher levels on hospital admission of syndecan-1 (572 [300-811] vs. 263 [106-421] ng/ml; p = 0.03), angiopoietin-2 (1.52 [0.72-2.72] vs. 0.63 [0.4-1.38] ng/ml; p = 0.01), and FGF-23 (291 [56-2031] vs. 10 [10-806] pg/ml; p = 0.021). Syndecan-1 showed significant correlation with creatinine (r = 0.546; p = 0.05) and total bilirubin levels (r = 0.534; p = 0.013) on hospital admission. Angiopoietin-2 showed significant correlation with creatinine levels (r = 0.513; p = 0.009) on hospital admission and with number of haemodialysis sessions (r = 0.406; p = 0.049). No significant correlation was found with FGF-23. Regarding prognostic performance, combined syndecan-1 and angiopoietin-2 levels had a better ability to predict haemodialysis need in patients with severe leptospirosis (AUC-ROC = 0.744 [95% CI: 0.545-0.943] p = 0.035)., Conclusion: Syndecan-1 and angiopoietin-2 were associated with haemodialysis need in patients with severe leptospirosis and may be useful to improve therapeutic approach and reduce mortality., (© 2022 John Wiley & Sons Ltd.)

The present work aimed to characterize the exopolysaccharide obtained from water kefir grains (EPSwk), a symbiotic association of probiotic microorganisms. New findings of the technological, mechanical, and biological properties of the sample were studied. The EPSwk polymer presented an Mw of 6.35 × 10 5 Da. The biopolymer also showed microcrystalline structure and characteristic thermal stability with maximum thermal degradation at 250 °C. The analysis of the monosaccharides of the EPSwk by gas chromatography demonstrated that the material is composed of glucose units (98 mol%). Additionally, EPSwk exhibited excellent emulsifying properties, film-forming ability, a low photodegradation rate (3.8%), and good mucoadhesive properties (adhesion Fmax of 1.065 N). EPSwk presented cytocompatibility and antibacterial activity against Escherichia coli and Staphylococcus aureus. The results of this study expand the potential application of the exopolysaccharide from water kefir as a potential clean-label raw material for pharmaceutical, biomedical, and cosmetic applications.

Cervical cancer is a public health issue with high disease burden and mortality in Brazil. The objectives of the present study were, firstly, to analyze age, period, and cohort effects on cervical cancer mortality in women 20 years old or older from 1980 to 2019 in the North, South, and Southeast Regions of Brazil; and secondly, to evaluate whether the implementation of a national screening program and the expansion of access to public health services impacted the examined period and reduced the risk of death compared with previous years and among younger cohorts. The effects were estimated by applying Poisson regression models with estimable functions. The highest mortality rate per 100,000 women was found in Amazonas (24.13), and the lowest in São Paulo (10.56). A positive gradient was obtained for death rates as women's age increased. The states in the most developed regions (South and Southeast) showed a reduction in the risk of death in the period that followed the implementation of the screening program and in the cohort from the 1960s onwards. The North Region showed a decreased risk of death only in Amapá (2000-2004) and Tocantins (1995-2004; 2010-2019). The findings indicate that health inequities remain in Brazil and suggest that the health system has limitations in terms of decreasing mortality associated with this type of cancer in regions of lower socioeconomic development.

Wounds are considered a clinically critical issue, and effective treatment will decrease complications, prevent chronic wound formation, and allow rapid healing. The development of products based on naturally occurring materials is an efficient approach to wound healing. Natural polysaccharides can mimic the extracellular matrix and promote cell growth, thus making them attractive for wound healing. In this context, the aim of this work was to produce a gel based on chicha gum, chitosan, and Mauritia flexuosa oil (CGCHO) for wound treatment. TG and DTG analyzed the thermal behavior of the materials, and SEM investigated the surface roughness. The percentages of total phenolic compounds, flavonoids, and antioxidants were determined, presenting a value of 81.811 ± 7.257 µmol gallic acid/g Mauritia flexuosa oil, 57.915 ± 0.305 µmol quercetin/g Mauritia flexuosa oil, and 0.379 mg/mL, respectively. The anti-inflammatory was determined, presenting a value of 10.35 ± 1.46% chicha gum, 16.86 ± 1.00% Mauritia flexuosa oil, 10.17 ± 1.05% CGCHO, and 15.53 ± 0.65% chitosan, respectively. The materials were tested against Gram-negative ( Klebsiella pneumoniae ) and Gram-positive ( Staphylococcus aureus ) bacteria and a fungus ( Candida albicans ). The CGCHO formulation showed better antimicrobial activity against Gram-positive bacteria. In addition, an in vivo wound healing study was also performed. After 21 days of treatment, the epidermal re-epithelialization process was observed. CGCHO showed good thermal stability and roughness that can help in cell growth and promote the tissue healing process. In addition to the good results observed for the antimicrobial, antioxidant, anti-inflammatory activities and providing wound healing, they provided the necessary support for the healing process, thus representing a new approach to the wound healing process.

Immune checkpoint inhibitors (ICI) have provided new hope for cancer patients, and in particular for patients with tumors that are immunologically active and classified as hot tumors. These tumors express antigenic and tumor microenvironment (TME) characteristics that make them potential candidates for therapy with checkpoint inhibitors that aim to reactivate the immune response such as anti-PD-1 and anti-CTLA-4. Examples of potentially responsive cancers are, melanoma, non-small cell lung cancer and several other metastatic or unresectable tumors with genetic instability: DNA mismatch repair deficiency (dMMR), microsatellite instability-high (MSI-H), or with a high tumor mutational burden (TMB). Immunotherapy using checkpoint inhibitors is typically associated with adverse events (AEs) that are milder than those with chemotherapy. However, a significant percentage of patients develop short-term immune-related AEs (irAEs) which range from mild (~70%) to severe cases (~13%) that can lead to modifications of the checkpoint inhibitor therapy and in some cases, death. While some studies have investigated immune mechanisms behind the development of irAEs, much more research is needed to understand the mechanisms and to develop interventions that could attenuate severe irAEs, while maintaining the anti-tumor response intact. Moreover, studies to identify biomarkers that can predict the likelihood of a patient developing severe irAEs would be of great clinical importance. Here we discuss some of the clinical ramifications of irAEs, potential immune mechanisms behind their development and studies that have investigated potentially useful biomarkers of irAEs development., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Immunology.)