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OBJETIVO: Avaliar a influência da idade, da gravidade da doença e das intervenções terapêuticas na maior letalidade hospitalar do infarto agudo do miocárdio (IAM) em mulheres. MÉTODOS: Estudo de coorte retrospectivo, envolvendo 388 pacientes com IAM (50 óbitos). Foram avaliadas, como possíveis explicações para a associação entre sexo e letalidade hospitalar do IAM, as variáveis: idade ( ou = 60 anos), duração de sintomas, classe de Killip, tipo de IAM (com ou sem ondas Q), comorbidades, história de acidente vascular cerebral e intervenções terapêuticas para o IAM (ácido acetil-salicílico, betabloqueadores e agentes trombolíticos). Modelos de regressão logística foram usados para avaliar a influência de potenciais variáveis confundidoras na associação entre sexo e letalidade hospitalar do IAM. RESULTADOS: A letalidade hospitalar do IAM foi mais alta em mulheres (19,5% vs 9,4%) do que em homens (odds ratio (OR)= 2,34; IC 95%= 1,12-4,47). Embora as mulheres fossem significantemente (p

Objective: To identify, in the literature, the implications of gestational exposure to SARS-CoV-2 on neurodevelopment in the first postnatal year, focusing on changes in the motor, personal-social, socio-emotional, and communication and language domains., Method: Systematic review with narrative synthesis, considering neurodevelopmental outcomes, categorized according to gross and fine motor skills, personal-social interaction, socio-emotional aspects, and communication and language. Searches were conducted in PubMed, LILACS/BIREME, and EMBASE databases between January 2020 and June 2023. Two independent researchers performed selection by reading the title and abstract and applying the inclusion and exclusion criteria. Cohort studies that evaluated children up to one year old, exposed to SARS-CoV-2 in utero, were included. The Newcastle-Ottawa scale was used to assess methodological quality., Results: Seventeen articles were included, with methodological quality ranging from intermediate to good. The most frequently used instrument to characterize neurodevelopment was the Ages & Stages Questionnaires. Infants aged 0 to 3 months had lower scores for fine and gross motor skills. Infants aged 3 to 12 months had more fine motor, social and communication and language impairments., Conclusion: Most infants exposed to SARS-CoV-2 showed development as expected, however delays were identified in the motor, personal-social, socio-emotional and communication and language domains according to the age group.

In the search for more sustainable remediation strategies for PAH-contaminated soils, an integrated application of thermal remediation and bioremediation (TEB) may allow the use of less impacting temperatures by associating heating to biological degradation. However, the influence of heating on soil microbiota remains poorly understood, especially in soils from tropical regions. This work investigated the effects of low-temperature heating on creosote-contaminated soil bacteria. We used culture-dependent and 16 S rRNA sequencing methods to compare the microbial community of soil samples heated to 60 and 100 o C for 1 h in microcosms. Heating to 60 °C reduced the density of cultivable heterotrophic bacteria compared to control soil (p < 0.05), and exposure to 100 °C inactivated the viable heterotrophic community. Burkholderia-Caballeronia-Paraburkholderia (BCP) group and Sphingobium were the predominant genera. Temperature and incubation time affected the Bray-Curtis dissimilarity index (p < 0.05). At 60 °C and 30 days incubation, the relative abundance of Sphingobium decreased and BCP increased dominance. The network of heated soil after 30 days of incubation showed fewer nodes and edges but maintained its density and complexity. Both main genera are associated with PAH degradation, suggesting functional redundancy and a likely potential of soil microbiota to maintain biodegradation ability after exposure to higher temperatures. We concluded that TEB can be considered as a potential strategy to bioremediate creosote-contaminated soils, allowing biodegradation in temperature ranges where thermal remediation does not completely remove contaminants. However, we recommend further research to determine degradation rates with this technology., (© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Fatty acid profile, physicochemical composition, and carcass traits of 32 young Nellore bulls were assessed following the supplementation of Acacia mearnsii extract at levels of 0, 10, 30, and 50 g/kg of total dry matter (DM) in a completely randomized experiment with four treatments and eight replicates. Adding 50 g/kg DM of condensed tannins (CT) from Acacia mearnsii in the bulls' diet reduced DM intake, average daily gain, and meat lipid oxidation (P ≤ 0.05). The pH, centesimal composition, collagen, and meat color indexes of the longissimus muscle were not altered by the addition of Acacia mearnsii (P > 0.05). Cooling loss increased (P = 0.049) linearly. Including Acacia mearnsii in diet reduced the Warner-Bratzler shear force (WBSF, P = 0.018) of longissimus muscle of the bulls. The concentration of C16:0, C17:0, C24:0, t9,10,11,16-18:1, c9t11-18:2, C18:2n-6, C20:4n-6, 20:5n-3, 22:5n-3, and 22:6n-3 in the muscle increased due to the addition of Acacia in the diet (P ≤ 0.05), with the highest muscle concentrations caused by the addition of 10 to 30 g Acacia. c9-18:1 and t16-18:1 reduced linearly. ƩSFA, ƩBI, Ʃcis- and ƩMUFA, Ʃn-3, Ʃn-6, and ƩPUFA (P ≤ 0.05) quadratically increased at higher concentrations of addition of Acacia, above 30 g/kg DM. It is recommended to include Acacia mearnsii extract up to 30 g/kg total DM in diets for young bulls as it improves CLA, PUFA and TI and reduces lipid oxidation. Acacia mearnsii extract as source of CT at 50 g/kg DM negatively impacted the young bulls performance., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could have influenced the study reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Invasive species significantly impact biodiversity and ecosystem services, yet understanding these effects at large spatial scales remains a challenge. Our study addresses this gap by assessing the current and potential future risks posed by 94 invasive species to seven key ecosystem services in Europe. We demonstrate widespread potential impacts, particularly on outdoor recreation, habitat maintenance, crop provisioning, and soil and nitrogen retention. Exposure to invasive species was higher in areas with lower provision of ecosystem services, particularly for regulating and cultural services. Exposure was also high in areas where ecosystem contributions to crop provision and nitrogen retention were at their highest. Notably, regions vital for ecosystem services currently have low invasion suitability, but face an average 77% increase in potential invasion area. Here we show that, while high-value ecosystem service areas at the highest risk represent a small fraction of Europe (0-13%), they are disproportionally important for service conservation. Our study underscores the importance of monitoring and protecting these hotspots to align management strategies with international biodiversity targets, considering both invasion vulnerability and ecosystem service sustainability., (© 2024. The Author(s).)

Chitinases are widely studied enzymes that have already found widespread application. Their continued development and valorisation will be driven by the identification of new and improved variants and/or novel applications bringing benefits to industry and society. We previously identified a novel application for chitinases wherein the Candida albicans cell wall surface chitinase 3 (Cht3) was shown to have potential in vaccine applications as a subunit antigen against fungal infections. In the present study, this enzyme was investigated further, developing production and purification protocols, enriching our understanding of its properties, and advancing its application potential. Cht3 was heterologously expressed in Pichia pastoris and a 4-step purification protocol developed and optimised: this involves activated carbon treatment, hydrophobic interaction chromatography, ammonium sulphate precipitation, and gel filtration chromatography. The recombinant enzyme was shown to be mainly O-glycosylated and to retain the epitopes of the native protein. Functional studies showed it to be highly specific, displaying activity on chitin, chitosan, and chito-oligosaccharides larger than chitotriose only. Furthermore, it was shown to be a stable enzyme, exhibiting activity, and stability over broad pH and temperature ranges. This study represents an important step forward in our understanding of Cht3 and contributes to its development for application., (© 2023 Wiley-VCH GmbH.)

Background: Thrombotic Microangiopathy (TMA) is a syndrome characterized by the presence of anemia, thrombocytopenia and organ damage and has multiple etiologies. The primary aim is to develop an algorithm to classify TMA (TMA-INSIGHT score)., Methods: This was a single-center retrospective cohort study including hospitalized patients with TMA at a single center. We included all consecutive patients diagnosed with TMA between 2012 and 2021. TMA was defined based on the presence of anemia (hemoglobin level < 10 g/dL) and thrombocytopenia (platelet count < 150,000/µL), signs of hemolysis, and organ damage. We classified patients in eight categories: infections; Malignant Hypertension; Transplant; Malignancy; Pregnancy; Thrombotic Thrombocytopenic Purpura (TTP); Shiga toxin-mediated hemolytic uremic syndrome (STEC-SHU) and Complement Mediated TMA (aHUS). We fitted a model to classify patients using clinical characteristics, biochemical exams, and mean arterial pressure at presentation., Results: We retrospectively retrieved TMA phenotypes using automatic strategies in electronic health records in almost 10 years (n = 2407). Secondary TMA was found in 97.5% of the patients. Primary TMA was found in 2.47% of the patients (TTP and aHUS). The best model was LightGBM with accuracy of 0.979, and multiclass ROC-AUC of 0.966. The predictions had higher accuracy in most TMA classes, although the confidence was lower in aHUS and STEC-HUS cases., Conclusion: Secondary conditions were the most common etiologies of TMA. We retrieved comorbidities, associated conditions, and mean arterial pressure to fit a model to predict TMA and define TMA phenotypic characteristics. This is the first multiclass model to predict TMA including primary and secondary conditions., (© 2023. The Author(s).)

Different degrees in the biological activities of Canavalia rosea had been previously reported . In this study, our group assessed the cardioprotective effects of the ethyl acetate fraction (EAcF) of the Canavalia rosea leaves. Firstly, it was confirmed, by in vitro approach, that the EAcF has high antioxidant properties due to the presence of important secondary metabolites, as flavonoids. In order to explore their potential protector against cardiovascular disorders, hearts were previously perfused with EAcF (300 μg.mL-1) and submitted to the global ischemia followed by reperfusion in Langendorff system. The present findings have demonstrated that EAcF restored the left ventricular developed pressure and decreased the arrhythmias severity index. Furthermore, EAcF significantly increased the glutathiones peroxidase activity with decreased malondialdehyde and creatine kinase levels. EAcF was effective upon neither the superoxide dismutase, glutationes reductase nor the catalase activities. In addition, the Western blot analysis revealed that ischemia-reperfusion injury significantly upregulates caspase 3 protein expression, while EAcF abolishes this effect. These results provide evidence that the EAcF reestablishes the cardiac contractility and prevents arrhythmias; it is suggested that EAcF could be used to reduce injury caused by cardiac reperfusion. However more clinical studies should be performed, before applying it in the clinic.

Creosote is an organic pollutant formed by a complex mixture of highly toxic and carcinogenic compounds and classified as a dense non-aqueous phase liquid (DNAPL). Its migration depends on media and fluid properties that control the multiphase flow in the subsurface. Residual saturation and hydraulic conductivity are essential parameters to accurately simulate fluid displacement in porous media. This work shows the behavior of creosote in porous medium for sandy and clay soils, collected in a contaminated area in the state of São Paulo, Brazil. Creosote retention was evaluated and compared to water. The retention curve parameters were obtained based on van Genuchten and Brooks and Corey models. The hydraulic conductivities of creosote and water are presented for both soils. The results show that, in the clay soil, water was more retained than creosote, while in the sandy soil, creosote retention was higher. The hydraulic conductivity values obtained in the clay soil show a difference of two orders of magnitude between creosote and water. Although creosote is a viscous fluid, it presents considerable mobility in the clay soil, which is relevant in remediation processes. This study advances our knowledge about DNAPL behavior in clay and sand, and no other study of creosote parameters in these porous media was found. A more accurate estimate of the time required for a liquid spill to reach groundwater can then be predicted, so that appropriate actions can be taken and risk management can be carried out., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Quilombola communities are descended from African slaves who escaped in resistance to imperial rule in Brazil. Today, these communities suffer from inadequate health care and health promotion programs due to socioeconomic, geographic, and political factors. This generates greater vulnerability among these groups because they have limited information about prevention to improve their quality of life. This research aimed to analyze the sexuality of young quilombola adults and the impact on their quality of life through an observational, cross-sectional, quantitative study with descriptive and inferential analyses. Our study is the first to address these issues among quilombolas in the Eastern Amazon region. The participants were 79 individuals of both sexes, aged between 18 to 35 years, belonging to seven communities in the state of Pará. The questionnaires were designed to assess sexual behavior and satisfaction, values and beliefs about sexuality, prejudice regarding sexual and gender diversity, knowledge about sexually transmitted infections (STIs), beliefs about maternity, and quality of life. Women reported greater sexual dissatisfaction and lower quality of life than men. Men reported no dysfunctions; however, they were highly prejudiced towards sexual and gender diversity. Low education negatively impacts the health of quilombola populations, as knowledge about STIs and values and beliefs influence sexual behavior, exposing individuals to diseases. The research also confirms that, both among quilombolas and other groups, factors such as sexual satisfaction, values and beliefs about reproduction, and affectivity directly influence the quality of life.

Ecological processes are often spatially and temporally structured, potentially leading to autocorrelation either in environmental variables or species distribution data. Because of that, spatially-biased in-situ samples or predictors might affect the outcomes of ecological models used to infer the geographic distribution of species and diversity. There is a vast heterogeneity of methods and approaches to assess and measure spatial bias; this paper aims at addressing the spatial component of data-driven biases in species distribution modelling, and to propose potential solutions to explicitly test and account for them. Our major goal is not to propose methods to remove spatial bias from the modelling procedure, which would be impossible without proper knowledge of all the processes generating it, but rather to propose alternatives to explore and handle it. In particular, we propose and describe three main strategies that may provide a fair account of spatial bias, namely: (i) how to represent spatial bias; (ii) how to simulate null models based on virtual species for testing biogeographical and species distribution hypotheses; and (iii) how to make use of spatial bias - in particular related to sampling effort - as a leverage instead of a hindrance in species distribution modelling. We link these strategies with good practice in accounting for spatial bias in species distribution modelling., (© 2023. The Author(s).)

Invasive species pose a major threat to biodiversity and inflict massive economic costs. Effective management of bio-invasions depends on reliable predictions of areas at risk of invasion, as they allow early invader detection and rapid responses. Yet, considerable uncertainty remains as to how to predict best potential invasive distribution ranges. Using a set of mainly (sub)tropical birds introduced to Europe, we show that the true extent of the geographical area at risk of invasion can accurately be determined by using ecophysiological mechanistic models that quantify species' fundamental thermal niches. Potential invasive ranges are primarily constrained by functional traits related to body allometry and body temperature, metabolic rates, and feather insulation. Given their capacity to identify tolerable climates outside of contemporary realized species niches, mechanistic predictions are well suited for informing effective policy and management aimed at preventing the escalating impacts of invasive species., (© 2023. The Author(s).)

Many species' distributions are being impacted by the acceleration of climate change. Amphibians in particular serve numerous ecosystem functions and are useful indicators of environmental change. Understanding how their distributions have been impacted by climate change and will continue to be impacted is thus important to overall ecosystem health. Plethodon cinereus (Eastern Red-Backed Salamander) is a widespread species of lungless salamander (Plethodontidae) that ranges across northeastern North America. To better understand future potential lungless salamander range shifts, we quantify environmental favorability, the likelihood of membership in a set of sites where environmental conditions are favorable for a species, for P. cinereus in multiple time periods, and examine shifts in the species' distribution. First, utilizing a large data set of georeferenced records, we assessed which bioclimatic variables were associated with environmental favorability in P. cinereus . We then used species distribution modeling for two time periods (1961-1980 and 2001-2020) to determine whether there was a regional shift in environmental favorability in the past 60 years. Models were then used to project future distributions under eight climate change scenarios to quantify potential range shifts. Shifts were assessed using fuzzy logic, avoiding thresholds that oversimplify model predictions into artificial binary outputs. We found that P. cinereus presence is strongly associated with environmental stability. There has been a substantial northward shift in environmental favorability for P. cinereus between 1961-1980 and 2001-2020. This shift is predicted to continue by 2070, with larger shifts under higher greenhouse gas emission scenarios. As climate change accelerates, it is differentially impacting species but has especially strong impacts on dispersal-limited species. Our results show substantial northward shifts in climatic favorability in the last 60 years for P. cinereus , which are likely to be exacerbated by ongoing climate change. Since P. cinereus is dispersal-limited, these models may imply local extirpations along the southern modern range with limited northward dispersal. Continued monitoring of amphibians in the field will reveal microclimatic effects associated with climate change and the accuracy of the model predictions presented here., Competing Interests: The authors declare that they have no conflict of interest., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Esophageal squamous cell carcinoma (ESCC) is a common type of cancer characterized by fast progression and high mortality rates, which generally implies a poor prognosis at time of diagnosis. Intricate interaction networks of cytokines produced by resident and inflammatory cells in the tumor microenvironment play crucial roles in ESCC development and metastasis, thus influencing therapy efficiency. As such, cytokines are the most prominent targets for specific therapies and prognostic parameters to predict tumor progression and aggressiveness. In this work, we examined the association between ESCC progression and the systemic levels of inflammatory cytokines to determine their usefulness as diagnostic biomarkers. We analyzed the levels of IL-1β, IL-6, IL-8, IL-10, TNF-α e IL-12p70 in a group of 70 ESCC patients and 70 healthy individuals using Cytometric Bead Array (CBA) technology. We detected increased levels of IL-1β, IL-6, IL-8, and IL-10 in ESCC patients compared to controls. However, multivariate analysis revealed that only IL8 was an independent prognostic factor for ESCC, as were the well-known risk factors: alcohol consumption, tobacco usage, and exposure to pesticides/insecticides. Importantly, patients with low IL-6, IL-8, TNM I/II, or those who underwent surgery had a significantly higher overall survival rate. We also studied cultured Kyse-30 and Kyse-410 cells in mice. We determined that the ESCC cell line Kyse-30 grew more aggressively than the Kyse-410 cell line. This enhanced growth was associated with the recruitment/accumulation of intratumoral polymorphonuclear leukocytes. In conclusion, our data suggest IL-8 as a valuable prognostic factor with potential as a biomarker for ESCC.

Soils and groundwater contamination modifies the physical-chemical conditions of the environment, altering natural biogeochemical processes of the ground. As a result, several mineral transformations occur, in which iron plays a decisive role. The presence of iron enables the study of magnetic properties, improving the understanding of the geophysical signatures of highly dynamic environments (e.g., biogeochemical hotspots and contamination plumes). In this work, we seek to identify creosote biodegradation related to the precipitation of magnetic minerals on sediments at a contaminated site in São Paulo, Brazil. Several rock magnetism analyses were carried out to provide the magnetic mineralogy of the samples in terms of their composition, size, and abundance. We conducted high-temperature thermomagnetic curves, frequency-dependent magnetic susceptibility, anesthetic remanent magnetization (ARM) and isothermal remanent magnetization (IRM) data, superparamagnetic concentration and dipole moment (SPCDM), and scanning electron microscopy (SEM) analyses. The magnetic signatures of the contaminated samples suggest an increase of superparamagnetic grains in the water table fluctuation zone if compared to the magnetic signatures of the uncontaminated samples. Thermomagnetic curves of contaminated samples showed a lower heterogeneity of the magnetic mineral phases than the uncontaminated ones. This work contributes to the advancement of the understanding of how natural biogeochemical processes are impacted by human actions, such as soil contamination, and even by climate change, which should affect soil redox conditions in periods of drought and flooding., (© 2022. The Author(s).)

We aimed to determine the optimal inclusion level of sunflower cake (0, 90, 180, and 270 g/kg total DM) as a partial replacement of soybean meal and corn ground in young bulls' diets by examining nutrient intake and digestibility, ingestive behavior, nitrogen balance, metabolic serum profile, growth performance, and carcass traits. Thirty-two intact Nellore bulls (BW 374 ± 42.5) were distributed in a completely randomized design. The experiment lasted 90 days. The final BW of the animals was 515.25 ± 24.7. There was a linear decrease effect in the intake of DM, crude protein and nonfibrous carbohydrates, eating and rumination efficiency, N-urinary, N-total excretion, and blood urea nitrogen. Sunflower cake did not affect the NDF digestibility, nitrogen (N)-fecal excretion, blood metabolites, Longissimus lumborum muscle area, or subcutaneous fat deposition. There were linear and quadratic effects on the eating and rumination time, microbial protein production and efficiency, gamma-glutamyl transferase and cholesterol serum concentrations, and muscle carcass tissue. There was a quadratic effect on ether extract intake, final BW, and total gain with the inclusion of sunflower cake in the young bull's diet. The replacement of soybean meal and corn ground with sunflower cake at the level of 90 g/kg of DM in the diet of young bulls is recommended because it reduces the DM intake and digestibility, increases microbial protein synthesis and muscle tissue deposition, and consequently improves the performance, feed efficiency, and carcass traits.

This study aims to evaluate the quality of salted sun-dried meat from young bulls (Nellore cattle) fed with a diet containing 0.0, 0.5, 1.0 and 1.5% of lauric acid in the total dry matter (DM). Thirty-two Nellore bulls with initial body weight of 368 ± 32 kg were used. A linear decrease (p < 0.05) in pH and protein content of the salted sun-dried meat was observed with the inclusion of lauric acid. The moisture, ash, lipid, collagen content, water-holding capacity, cooking loss, color indexes (L*, a*, b*, C*), and shear force were not affected. Lipid oxidation at 7 days of storage increased linearly in the salted sun-dried meat. Most of the fatty acid composition of the salted sun-dried meat from the semimembranosus muscle of young bulls was not influenced (p > 0.05) by the lauric acid inclusion in the bulls’ diet. However, there was a linear increase (p < 0.05) in the SFA lauric acid (C12:0), PUFAn-3 EPA (C20:5n − 3) and DHA (C22:6n − 3), and a quadratic increase in the PUFAn-6 arachidonic (C20:4n − 6) due to lauric acid addition from palm kernel oil in the diet. There was a liner increase (p < 0.05) in the total ∑PUFA, ∑n − 6, ∑n − 3 contents of salted sun-dried meat from the semimembranosus muscle of young bulls and the h:H health index of the level of lauric acid inclusion in bull’s diet. In contrast, the thrombogenicity health index (TI) and ∑n − 6:∑n − 3 ratio content in salted sun-dried meat from the semimembranosus muscle of young bulls presented a linear decrease (p < 0.05) due to lauric acid addition in the bulls’ diet. Lauric acid (C12:0) inclusion up to 1.5% in the diet of young Nellore bull improved the fatty acid composition of the salted sun-dried meat, increasing EPA, DHA, n − 6 and n − 3, TI, and h:H indexes, which are associated with a better lipid quality of meat products, and further improves tenderness at the highest concentration.

This study evaluated the effects of palm kernel oil (PKO) in the diet of lambs on carcass characteristics, quality, and fatty acid profile of the meat. Forty uncastrated male Santa Inês lambs were used and divided among the treatments: PKOzero without inclusion; PKO1.3—added 1.3%; PKO2.6—added 2.6%; PKO3.9—added 3.9%; PKO5.2—added 5.2%. The carcass characteristics, the variables related to meat color, and the chemical composition of the Longissimus lumborum of lambs were not affected by the PKO inclusion. The weight of the carcasses at slaughter, hot and cold, half carcass, loin-eye area, and commercial cuts decreased linearly when PKO was added to the lamb diet (p < 0.01). CCY decreased linearly to the inclusion level of 2.66% PKO (RMSE 2.204). Total conjugated linoleic acid CLA and C18:3 n-3 GA concentrations remained stable until the inclusion levels of 3.44% PKO (RMSE 0.0956) and 2.17% (RMSE 0.0637), decreasing its concentrations as the increased level of PKO. The presence of PKO in the lambs’ diet up to the level of 5.2% did not change the meat quality characteristics; thus, from the point of view of lamb meat production and fatty acid profile, the inclusion of PKO is not beneficial.

Objective: Leprosy is a disabling infectious disease caused by Mycobacterium leprae. This study aimed to investigate the prevalence of leprosy among household contacts of leprosy patients., Methods: This study is a serological survey in household contacts of leprosy patients who had been treated or were undergoing treatment in the city of Presidente Prudente, São Paulo, Brazil, from 2006-2016, using clinical examination and screening for anti- Phenolic glycolipid-I antibodies with Mycobacterium leprae-flow serology., Results: A total of 263 index cases of leprosy were identified during the study period. Of these, 53 were approached, and among their household contacts, 108 were examined. The ML-flow test was positive in 2 (1.85%) individuals, but clinical examination revealed no signs or symptoms of leprosy in them. Therefore, they were considered to have a subclinical infection. Leprosy was not confirmed in any household contacts. In this study, a lower percentage of household contacts, when compared to that in the literature, had a positive Mycobacterium leprae-flow test result., Conclusion: The use of Mycobacterium leprae-flow should be encouraged during the follow-up of at-risk populations, such as the household contacts of leprosy patients.

Introduction: Although breast milk is the ideal food source for newborns during the first six months of life, a high percentage of children receive infant formulas. There is evidence that specific diet habits may influence individual metabolic profile. Therefore, in newborns, such profile can be influenced by the use of infantile formulas given the composition differences that display compared to human milk. Up to now, there are no reports in the literature that address this issue., Objectives: this work aims to compare the metabolic profile of full-term newborns that were feed with either breast milk (n = 32) or infantile formulas (n = 21). Methods: Metabolic profile was established based on urine analysis through gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance (H-NMR)., Results: our results evidenced a more gluconeogenic profile in breast-fed infants characterized by elevation of Kreb's cycle intermediaries like fumaric, succinic and ketoglutaric acids compared to infants receiving infant formula. In addition, infant formula fed infants presented urinary excretion of metabolites derived from specific compounds present in this type of diet that were not observed in breast-fed infants, for instance D-glucitol, and 4-deoxytetronic. Moreover, in infant formula fed infants there was excretion of basal levels of metabolites of clinical relevance like 3-hydroxy-3-methyl-glutaric, 2-methyl-3-keto-valeric and 3,4-dihydroxybutyric., Conclusion: These results show the importance of understanding the metabolic impact of diet in newborn population in normal and pathological contexts., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Control of tuberculosis depends on the rapid expression of protective CD4 + T-cell responses in the Mycobacterium tuberculosis (Mtb)-infected lungs. We have recently shown that the immunomodulatory cytokine IL-10 acts intrinsically in CD4 + T cells and impairs their parenchymal migratory capacity, thereby preventing control of Mtb infection. Herein, we show that IL-10 overexpression does not impact the protection conferred by the established memory CD4 + T-cell response, as BCG-vaccinated mice overexpressing IL-10 only during Mtb infection display an accelerated, BCG-induced, Ag85b-specific CD4 + T-cell response and control Mtb infection. However, IL-10 inhibits the migration of recently activated ESAT-6-specific CD4 + T cells into the lung parenchyma and impairs the development of ectopic lymphoid structures associated with reduced expression of the chemokine receptors CXCR5 and CCR7. Together, our data support a role for BCG vaccination in preventing the immunosuppressive effects of IL-10 in the fast progression of Mtb infection and may provide valuable insights on the mechanisms contributing to the variable efficacy of BCG vaccination., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ferreira, Micheli, Barreira-Silva, Barbosa, Resende, Vilanova, Silvestre, Cunha, Carvalho, Rodrigues, Correia-Neves, Castro and Torrado.)

Mammals are threatened worldwide, with ~26% of all species being included in the IUCN threatened categories. This overall pattern is primarily associated with habitat loss or degradation, and human persecution for terrestrial mammals, and pollution, open net fishing, climate change, and prey depletion for marine mammals. Mammals play a key role in maintaining ecosystems functionality and resilience, and therefore information on their distribution is crucial to delineate and support conservation actions. MAMMALS IN PORTUGAL is a publicly available data set compiling unpublished georeferenced occurrence records of 92 terrestrial, volant, and marine mammals in mainland Portugal and archipelagos of the Azores and Madeira that includes 105,026 data entries between 1873 and 2021 (72% of the data occurring in 2000 and 2021). The methods used to collect the data were: live observations/captures (43%), sign surveys (35%), camera trapping (16%), bioacoustics surveys (4%) and radiotracking, and inquiries that represent less than 1% of the records. The data set includes 13 types of records: (1) burrows | soil mounds | tunnel, (2) capture, (3) colony, (4) dead animal | hair | skulls | jaws, (5) genetic confirmation, (6) inquiries, (7) observation of live animal (8), observation in shelters, (9) photo trapping | video, (10) predators diet | pellets | pine cones/nuts, (11) scat | track | ditch, (12) telemetry and (13) vocalization | echolocation. The spatial uncertainty of most records ranges between 0 and 100 m (76%). Rodentia (n =31,573) has the highest number of records followed by Chiroptera (n = 18,857), Carnivora (n = 18,594), Lagomorpha (n = 17,496), Cetartiodactyla (n = 11,568) and Eulipotyphla (n = 7008). The data set includes records of species classified by the IUCN as threatened (e.g., Oryctolagus cuniculus [n = 12,159], Monachus monachus [n = 1,512], and Lynx pardinus [n = 197]). We believe that this data set may stimulate the publication of other European countries data sets that would certainly contribute to ecology and conservation-related research, and therefore assisting on the development of more accurate and tailored conservation management strategies for each species. There are no copyright restrictions; please cite this data paper when the data are used in publications., (© 2022 The Authors. Ecology © 2022 The Ecological Society of America.)

Lipid supplementation through vegetable oils in diets for ruminants can be a nutritional strategy to increase energy density, manipulate ruminal fermentation and change the physicochemical composition and sensorial properties of meat. This study evaluated the optimal dietary inclusion of palm kernel oil (PKO) for Nellore bulls on meat quality. The diets consisted of 0.0, 11.5, 23.0, and 34.6 g/kg dry matter (DM) PKO levels. PKO inclusion did not influence the centesimal composition, pH, color indices, water holding capacity, cooking loss, or shear force of the beef. There were linear increases in the concentrations of lauric acid (C12:0) and myristic acid (C14:0) in the bull's meat. However, palmitic acid (C16:0), oleic acid (C18:0), vaccenic acid ( t -11-C18:1) and conjugated linoleic acid (CLA), ∑ n - 6, ∑ n - 3, ∑ n - 6/∑ n 3, the hypocholesterolemic: hypercholesterolemic ratio of the fatty acid content, and the thrombogenicity index were not affected. There were linear reductions in the oleic acid meat concentration ( c -9-C18:1) and elongated enzymatic activity when PKO was added to the bull diet. The atherogenicity index increased linearly due to PKO inclusion in the bull diet. No effect of the inclusion of PKO on meat flavor, perception of tenderness, juiciness, or global acceptance from the sensorial evaluation was recorded. The inclusion of PKO up to 34.6 g/kg DM can be recommended to supplement young bulls with no effects on meat composition and quality characteristics.

Vegetable oils can be used to increase energy density in diets; manipulate rumen fermentation; and alter the capacity for degradation, digestion and absorption of nutrients. Two experiments were conducted to evaluate palm kernel oil (PKO) in the diet of confined bulls with the inclusion of 0.0, 11.5, 23.0 and 34.6 g PKO/kg dry matter (DM). The first experiment evaluated nutrient intake, performance, ingestive behavior and carcass characteristics. In the second experiment, steers crossbred with a ruminal cannula were used to evaluate digestibility, nitrogen balance, microbial protein synthesis, short-chain fatty acid levels and protozoal counts. The results showed that the inclusion of PKO linearly reduced intake in kg/day (DM, crude protein-CP, neutral detergent fiber-NDF ap , nonfibrous carbohydrates-NFC and total digestible nutrient-TDN) and digestibility (DM, NDF ap and TDN). Ether extract intake increased quadratically with the predicted maximum intake of 15.4 g/kg DM. Regarding ingestive behavior, there was a quadratic increase in rumination time and a quadratic reduction in idle time. Nitrogen balance, nitrogen intake, nitrogen retention, microbial protein production, acetate, butyrate, acetate/propionate ratio and protozoa count showed linear decreases due to dietary PKO inclusion. Regarding the carcass characteristics, linear decreases were observed for the final weight, average daily gain, hot carcass weight, cold carcass weight, hot carcass yield, cold carcass yield, loin eye area and subcutaneous fat thickness. The inclusion of PKO at up to 34.6 g/kg DM in diets for confined bulls reduces intake, negatively affecting digestibility, performance and carcass characteristics.

The aim of this study was to evaluate the effects of the inclusion of palm kernel oil (PKO) in a lamb diet on nutrient intake, digestibility, ingestive behavior, nitrogen balance, blood metabolites, rumen fermentation parameters, and animal performance. Three experimental trials were conducted. The treatments consisted of varying levels of PKO included in the diet, with PKO zero = no PKO inclusion, PKO 1.3 = 1.3% addition, PKO 2.6 = 2.6% addition, PKO 3.9 = 3.9% addition, and PKO 5.2 = 5.2% addition, based on the total dry matter (DM) of the diet. With the inclusion of PKO in the diet, linear decreases in DM ( p < 0.001), crude ash ( p < 0.001), crude protein (CP) ( p < 0.001), neutral detergent fiber (NDF) ( p < 0.001), nonfibrous carbohydrate (NFC) ( p < 0.001), and total digestible nutrient (TDN) ( p = 0.021) intake were observed, as was an increase in ether extract (EE) intake ( p < 0.001). The digestibility coefficients of NDF and NFC were not affected by PKO addition to the diet. However, the digestibility of DM ( p = 0.035), EE ( p < 0.001), CP ( p < 0.001), and TDNs ( p < 0.001) increased when PKO was added to the lambs' diet. Reductions in N intake ( p < 0.001), fecal nitrogen excretion ( p < 0.001), and microbial protein production ( p < 0.001) were noted with increasing PKO levels. Serum cholesterol increased ( p < 0.001) while serum GGT enzyme concentrations in the blood decreased ( p = 0.048) with increasing PKO levels. PKO addition had no effect on total weight gain and average daily gain; however, feed conversion improved ( p = 0.001) with increasing PKO levels. The intake, digestibility, ingestive behavior, and growth performance of lambs with PKO 1.3 added to their diet were similar to animals that did not receive PKO, meaning that PKO could be an alternative energy source for growing lambs because it does not harm animal performance and can lower the cost of feed.

Abstract: Accumulating evidence indicates that transient receptor potential (TRP) channels are involved in the pathophysiological process in the heart, and monoterpenes, such as carvacrol, are able to modulate these channels activity. In this article, our purpose was to evaluate the direct cardiac effect of carvacrol on the contractility of cardiomyocytes and isolated right atria from spontaneously hypertensive and Wistar Kyoto rats. In this way, in vitro experiments were used to evaluate the ventricular cardiomyocytes contractility and the Ca2+ transient measuring, in addition to heart rhythm in the right atria. The role of TRPM channels in carvacrol-mediated cardiac activities was also investigated. The results demonstrated that carvacrol induced a significant reduction in ventricular cell contractility, without changes in transient Ca2+. In addition, carvacrol promoted a significant negative chronotropic response in spontaneously hypertensive and Wistar Kyoto rats' atria. Selective blockage of TRPM channels suggests the involvement of TRP melastatin subfamily 2 (TRPM2), TRPM4, and TRPM7 in the carvacrol-mediated cardiac effects. In silico studies were conducted to further investigate the putative role of TRPM4 in carvacrol-mediated cardiac action. FTMap underscores a conserved pocket in both TRPM4 and TRPM7, revealing a potential carvacrol binding site, and morphological similarity analysis demonstrated that carvacrol shares a more than 85% similarity to 9-phenanthrol. Taken together, these results suggest that carvacrol has direct cardiac actions, leading to reduced cellular contractility and inducing a negative chronotropic effect, which may be related to TRPM7 and TRPM4 modulation., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

This study aimed to compare the physicochemical characteristics, fatty acid composition, and sensory attributes of the meat from three genetic groups: Nellore (Nell), ½ Nellore × ½ Angus (NeAn), and ¼ Nellore × ¼ Angus × ½ Senepol (NASe). Longissimus lumborum muscle from 30 slaughtered bulls with a body weight of 549 ± 32.5 kg was used. The water holding capacity was greater for the Nell and NeAn groups than for the NASe group. Meat samples from the NASe group exhibited a higher L* index than those from the NeAn group and lower a* and b* color indexes than those from the Nell group. The meat fatty acid profiles showed that the Nell group had higher concentrations of 12:0, 14:0, 18:1 t11, 14:1 c9, 16:1 c9, 18:1 c9, 18:1 c11, 18:2 c9, t11 (conjugated linoleic acid (CLA)), and 20:3 n-6 polyunsaturated fatty acid (PUFA) than the NeAn and NASe groups. The total saturated (ΣSFA), unsaturated (ΣUFA), and monounsaturated (ΣMUFA) fatty acid concentrations were higher and the ΣPUFA:ΣSFA ratio was lower in the Nell group than in the NeAn group. The Δ 9 -desaturase C16 activity was significantly higher in the Nell and NASe groups than in the NeAn group. The atherogenicity index (AI) tended to be lower in the crossbreeds than in the Nell breed. The NASe group presented meat with better tenderness, juiciness, and overall acceptance than the Nell and NeAn groups and was therefore the best genetic group for beef production of the tested groups., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Cortical representation of the painful body region may be disrupted in several chronic pain conditions. The two-point discrimination test (TPDT) and the Left/Right Judgement Task (LRJT) have been used to identify changes in the cortical body schema in several chronic pain conditions. However, it is unclear if these changes are present for all chronic pain mechanisms., Objectives: To investigate the integrity of the body schema of the painful shoulder in patients with chronic unilateral nociceptive shoulder pain., Methods: The sample consisted of 52 individuals with chronic unilateral nociceptive shoulder pain. The TPDT was measured over the anterosuperior and lateral regions of both shoulders using a staircase method. Participants also performed judgment tests of shoulder and foot laterality. The comparison of the TPDT and LRJT was performed using the linear regression model with mixed effects., Results: There was no difference in TPDT in the anterosuperior and lateral regions when comparing the symptomatic and asymptomatic shoulders. There was no difference in the LRJT accuracy and response time between the symptomatic and asymptomatic shoulders. No differences were observed when comparing LRJT variables from symptomatic shoulder and foot., Conclusion: Therefore, results do not provide clear evidence of altered body schema in chronic nociceptive unilateral shoulder pain. This suggest that alterations in body representations may depend on the primary pain mechanism., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aims: Glucocorticoids (GC) in excess cause glucose intolerance and dyslipidemia due to their diabetogenic actions. Conceptually, antidiabetic drugs should attenuate these side effects. Thus, we evaluated whether the coadministration of metformin or sitagliptin (or both) with dexamethasone could attenuate GC-induced adverse effects on metabolism., Materials and Methods: Adult male rats were treated for 5 consecutive days with dexamethasone (1 mg/kg, body mass (bm), intraperitoneally). Additional groups were coadministered with metformin (300 mg/kg, bm, by oral gavage (og)) or sitagliptin (20 mg/kg, bm, og) or with both compounds in combination. The day after the last treatments, rats were submitted to glucose tolerance tests, pyruvate tolerance test, and euthanized for biometric, biochemical, morphologic, and molecular analyses., Key Findings: Dexamethasone treatment resulted in reduced body mass and food intake, increased blood glucose and plasma insulin, dyslipidemia, glucose intolerance, pyruvate intolerance, and increased hepatic content of glycogen and fat. Sitagliptin coadministration improved glucose tolerance compared with the control group, an effect paralleled with higher levels of active GLP-1 during an oral GTT. Overall, sitagliptin or metformin coadministration did not prevent any of the dexamethasone-induced metabolic disturbances., Significance: Coadministration of sitagliptin or metformin result in no major improvement of glucose and lipid metabolism altered by dexamethasone treatment in male adult rats., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Female mice (Black 6 strain) (C57BL/6) aged 6 weeks were subject to low dose streptozotocin (STZ) treatment for five consecutive days to mimic type 1 diabetes mellitus (T1DM) with insulitis. At two weeks after STZ injections, evaluation of the elevated glucose levels was used to confirm diabetes. The diabetic mice were then subject to the transplantation of pancreatic β-cells (MIN-6 line). Four groups of mice were studied. The first group was injected with saline-only acting as the placebo surgery control, also known as SHAM group, the second and third groups were injected with MIN-6 single cells and polyethylene glycol-modified dipalmitoyl-glycerol-phosphatidyl ethanolamine (PEG-DPPE) modified MIN-6 single cells (500 µg per 1.10 6 cells), respectively, while the fourth group was injected with hyaluronic acid (HA)-coated MIN-6 single cells (5 bilayers). At seven- and fourteen-days following transplantation, the mice were euthanised. The renal and pancreatic tissues were then collected and histologically analysed. The induction of diabetes in female mice, through five-consecutive daily STZ injections resulted in inconsistent glycaemic levels. Interestingly, this shows an incomplete diabetes induction in female mice, of which we attribute to sex dimorphism and hormonal interferences. Transplantation failure of free-floating encapsulated cells was unable to decrease blood glucose hyperglycaemia to physiological ranges. The result is attributed to deprived cell-cell interactions, leading to decreased β-cells functionality. Overall, we highlight the necessity of refining T1DM disease models in female subjects when using multiple low-dose STZ injections together with transplantation protocols. Considerations need to be made regarding the different developmental stages of female mice and oestrogen load interfering with pancreatic β-cells susceptibility to STZ. The use of pseudo islets, cell aggregates and spheroids are sought to improve transplantation outcome in comparison to free-floating single cells.

Cytokine-producing CD4+ T cells play a crucial role in the control of Mycobacterium tuberculosis infection; however, there is a delayed appearance of effector T cells in the lungs following aerosol infection. The immunomodulatory cytokine IL-10 antagonizes control of M. tuberculosis infection through mechanisms associated with reduced CD4+ T cell responses. Here, we show that IL-10 overexpression only before the onset of the T cell response impaired control of M. tuberculosis growth; during chronic infection, IL-10 overexpression reduced the CD4+ T cell response without affecting the outcome of infection. IL-10 overexpression early during infection did not, we found, significantly impair the kinetics of CD4+ T cell priming and effector differentiation. However, CD4+ T cells primed and differentiated in an IL-10-enriched environment displayed reduced expression of CXCR3 and, because they did not migrate into the lung parenchyma, their ability to control infection was limited. Importantly, these CD4+ T cells maintained their vasculature phenotype and were unable to control infection, even after adoptive transfer into low IL-10 settings. Together our data support a model wherein, during M. tuberculosis infection, IL-10 acts intrinsically on T cells, impairing their parenchymal migratory capacity and ability to engage with infected phagocytic cells, thereby impeding control of infection.

Tumor-infiltrating lymphocytes include heterogeneous populations of T lymphocytes that play crucial roles in the tumor immune response; importantly, their presence in the tumor tissue may predict clinical outcomes. Therefore, we herein studied the prognostic significance of the presence and location of CD3 + , CD8 + , and FoxP3 + T lymphocytes in colorectal cancer samples. In the intratumor analysis, our data did not reveal any association between lymphocyte infiltrations with clinical or pathological data. However, in the tumor margins, we found that the presence of high infiltrations of CD3 + , CD8 + , or FoxP3 + T lymphocytes were associated with TNM stages I-II ( p = 0.021, p = 0.022, and p = 0.012, respectively) and absence of lymph node metastases ( p = 0.010, p = 0.003, and p = 0.004, respectively). Despite these associations with good prognostic indicators, we were not able to find any statistically significant alterations in the overall survival of the patients, even though high infiltrations of FoxP3 + T lymphocytes in the tumor margins resulted in an increased overall survival of 14 months. Taken together, these data show that the presence of CD3 + , CD8 + , or FoxP3 + T lymphocyte infiltrates in the tumor margins are associated with the pathogenesis of CRC, but only high Foxp3 + T lymphocyte infiltrations in the tumor invasive margins are inclined to indicate favorable prognosis.

We performed a detailed analysis of immunophenotypic features of circulating leukocytes and spleen cells from cynomolgus macaques that had been naturally infected with Trypanosoma cruzi , identifying their unique and shared characteristics in relation to cardiac histopathological lesion status. T. cruzi- infected macaques were categorized into three groups: asymptomatic [CCC(-)], with mild chronic chagasic cardiopathy [CCC(+)], or with moderate chronic chagasic cardiopathy [CCC(++)]. Our findings demonstrated significant differences in innate and adaptive immunity cells of the peripheral blood and spleen compartments, by comparison with non-infected controls. CCC(+) and CCC(++) hosts exhibited decreased frequencies of monocytes, NK and NKT-cell subsets in both compartments, and increased frequencies of activated CD8 + T-cells and GranA + /GranB + cells. While a balanced cytokine profile (TNF/IL-10) was observed in peripheral blood of CCC(-) macaques, a predominant pro-inflammatory profile (increased levels of TNF and IFN/IL-10) was observed in both CCC(+) and CCC(++) subgroups. Our data demonstrated that cardiac histopathological features of T. cruzi -infected cynomolgus macaques are associated with perturbations of the immune system similarly to those observed in chagasic humans. These results provide further support for the validity of the cynomolgus macaque model for pre-clinical research on Chagas disease, and provide insights pertaining to the underlying immunological mechanisms involved in the progression of cardiac Chagas disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sathler-Avelar, Vitelli-Avelar, Mattoso-Barbosa, Pascoal-Xavier, Elói-Santos, Costa-Rocha, Teixeira-Carvalho, Dick, VandeBerg, VandeBerg and Martins-Filho.)

Purpose: Indirect evaluation tests of somatosensory integrity, such as the left/right judgment task and two-point discrimination thresholds, are used to complement a clinical evaluation facilitating tailored rehabilitation programs for patients with chronic pain. This study aimed to compare performance on the left/right judgment task and two-point shoulder discrimination thresholds between people with chronic shoulder pain and asymptomatic controls. The study's secondary objective was to investigate whether there is a relationship between pain intensity and the painful area with TPDT and LRJT., Materials and Methods: It is a cross-sectional study with a control group. Volunteers participated in the left/right judgment task using the Recognise Shoulder TM app, and two-point discrimination thresholds were performed using a Mitutoyo® digital caliper. The extent of the painful area, affectivity, and functionality were also determined to characterize the sample., Results: We assessed 52 symptomatic and 50 asymptomatic individuals. A between-group difference was observed in time response for the left/right judgment task (p = 0.025) and the two-point discrimination thresholds when tested over the shoulder's lateral region (p = 0.012). There was a significant positive weak correlation between pain intensity and TPDT test performance over the anterior shoulder (rs = 0.35; p = 0.01) and a positive weak correlation between pain area and LRJT response time (rs = 0.26; p = 0.04)., Conclusions: This study demonstrates a difference of small magnitude in the response time of the LRJT for the shoulder segment and TPDT in the lateral shoulder region between individuals with chronic shoulder pain and asymptomatic controls., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Wildlife roadkill hotspots are frequently used to identify priority locations for implementing mitigation measures. However, understanding the landscape-context and the spatial and temporal dynamics of these hotspots is challenging. Here, we investigate the factors that drive the spatiotemporal variation of bat mortality hotspots on roads along three years. We hypothesize that hotspot locations occur where bat activity is higher and that this activity is related to vegetation density and productivity, probably because this is associated with food availability. Statistically significant clusters of bat-vehicle collisions for each year were identified using the Kernel Density Estimation (KDE) approach. Additionally, we used a spatiotemporal analysis and generalized linear mixed models to evaluate the effect of local spatiotemporal variation of environmental indices and bat activity to predict the variation on roadkill hotspot locations and to asses hotspot strength over time. Between 2009 and 2011 we conducted daily surveys of bat casualties along a 51-km-long transect that incorporates different types of roads in southern Portugal. We found 509 casualties and we identified 86 statistically significant roadkill hotspots, which comprised 12% of the road network length and contained 61% of the casualties. Hotspots tended to be located in areas with higher accumulation of vegetation productivity along the three-year period, high bat activity and low temperature. Furthermore, we found that only 17% of the road network length was consistently classified as hotspots across all years; while 43% of hotspots vanished in consecutive years and 40% of new road segments were classified as hotspots. Thus, non-persistent hotspots were the most frequent category. Spatiotemporal changes in hotspot location are associated with decreasing vegetation production and increasing water stress on road surroundings. This supports our hypothesis that a decline on overall vegetation productivity and increase of roadside water deficit, and the presumed lower abundance of prey, have a significant effect on the decrease of bat roadkills. To our knowledge, this is the first study demonstrating that freely available remote sensing data can be a powerful tool to quantify bat roadkill risk and assess its spatiotemporal dynamics., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The immune system plays a critical role in preventing cancer development and progression. However, the complex network of cells and soluble factor that form the tumor microenvironment (TME) can dictate the differentiation of tumor-infiltrating leukocytes and shift the antitumor immune response into promoting tumor growth. With the advent of cancer immunotherapy, there has been a reinvigorated interest in defining how the TME shapes the antitumor immune response. This interest brought to light the microbiome as a novel player in shaping cancer immunosurveillance. Indeed, accumulating evidence now suggests that the microbiome may confer susceptibility or resistance to certain cancers and may influence response to therapeutics, particularly immune checkpoint inhibitors. As we move forward into the age of precision medicine, it is vital that we define the factors that influence the interplay between the triad immune system-microbiota-cancer. This knowledge will contribute to improve the therapeutic response to current approaches and will unravel novel targets for immunotherapy., (© 2021 S. Karger AG, Basel.)

Mexico is home to a large number of reptile species and has one of the greatest diversities of venomous snakes, among which the rattlesnakes pertaining to the Crotalus genus stand out. Out of more than 40 species in the country, nine are found in Zacatecas: C. aquilus , C. atrox , C. basiliscus , C. lepidus , C. molossus , C. polystictus , C. pricei , C. scutulatus and C. willardi . Although these reptiles are important, due to their relevance in terms of ecology, cultural use and public health, their conservation is impacted by multiple factors, such as habitat fragmentation and indiscriminate killing. Thus, most species within this genus are found in some type of risk category at both the national and international level. The purpose of this study was to determine the potential distribution and diversity of rattlesnakes at the municipal level in the understudied state of Zacatecas. To do this, we analyzed and described the global distribution of nine rattlesnake species by building species distribution models, which determined their potential distribution based on a set of ecological variables and presence records. The resulting models were used to assess the diversity of rattlesnake species potentially present in each municipality within the state. Thirty-nine (67.24 %) out of fifty-eight municipalities registered at least one rattlesnake species. Fresnillo, Sombrerete and Valparaíso were some of the municipalities showing greatest diversity. Moreover, C. atrox , C. lepidus , C. molossus and C. scutulatus were the most widely found species in the state. On the other hand, C. basiliscus , C. polystictus , C. pricei and C. willardi were rarely spotted and so, information on their distribution patterns within Zacatecas is limited. Finally, the areas having the largest potential for the distribution of these species were defined. These findings should make field work much more time- and cost-effective, facilitating the collection of in situ data that are useful for management and conservation plans of these species in Zacatecas., (Jesús Lenin Lara-Galván, Juan Felipe Martínez-Montoya, José Jesús Sigala-Rodríguez, Citlalli Edith Esparza-Estrada, Octavio César Rosas-Rosas, Lucía Ávila-Herrera, A. Márcia Barbosa.)

Aim: To report a case of a female patient with hemophagocytic lymphohistiocytosis (HLH) and to systematically review the available cases of the association between HLH and inflammatory bowel disease (IBD)., Methods: In accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, retrieval of studies was based on Medical Subject Headings and Health Sciences Descriptors, which were combined using Boolean operators. Searches were run on the electronic databases Scopus, Web of Science, MEDLINE (PubMed), Biblioteca Regional de Medicina, Latin American and Caribbean Health Sciences Literature, Cochrane Library for Systematic Reviews and Opengrey.eu. Languages were restricted to English, Spanish and Portuguese. There was no date of publication restrictions. The reference lists of the studies retrieved were searched manually., Results: The search strategy retrieved 223 references. In the final analysis, 28 references were included, with the report of 35 cases. The most common clinical finding was fever, 57% of patients had a cytomegalovirus infection and 30 patients were on thiopurines previously to HLH diagnosis. Most patients were treated with steroids and antiviral therapy. All-cause mortality was 22%., Conclusion: These findings suggest that there might be a connection of HLH to IBD, opportunistic viral infections and the use of thiopurines. Due to the severity of such disease, the clinical suspicion is paramount to early diagnosis and therapy., Competing Interests: The authors have nothing to disclose., (Copyright © 2020 by S. Karger AG, Basel.)

Tissue engineering aims to regenerate and restore damaged human organs and tissues using scaffolds that can mimic the native tissues. The requirement for modern and efficient biomaterials that are capable of accelerating the healing process has been considerably increased. In this work, a novel electrospun poly(lactic acid) (PLA) nanoporous membrane incorporated with niobium pentoxide nanoparticles (Nb 2 O 5 ) for biomaterial applications was developed. Nb 2 O 5 nanoparticles were obtained by microwave-assisted hydrothermal synthesis, and different concentrations (0, 1, 3, and 5% wt/wt) were tested. Chemical, morphological, mechanical, and biological properties of membranes were evaluated. Cell viability results demonstrated that the membranes presented nontoxic effects. The incorporation of Nb 2 O 5 improved cell proliferation without impairing the wettability, porosity, and mechanical properties of membranes. Membranes containing Nb 2 O 5 nanoparticles presented biocompatible properties with suitable porosity, which facilitated cell attachment and proliferation while allowing diffusion of oxygen and nutrients. This study has demonstrated that Nb 2 O 5 nanoparticle-loaded electrospun PLA nanoporous membranes are potential candidates for drug delivery and wound dressing applications., (© 2019 Wiley Periodicals, Inc.)

Background: The disturbance of host metabolic pathways by Leishmania parasites has crucial consequences for the activation status of immune cells and the outcome of infection. Glutamine has been described as an immunomodulatory amino acid, yet its role during Leishmania infection is still unknown., Methods: We performed transcriptomics in uninfected and L. donovani-infected macrophages 6 hours post-infection. Glutamine quantification by HPLC was assessed in the supernatant of macrophages throughout the infection course. For experimental L. donovani infections, mice were infected with 1.0 x 108 stationary L. donovani promastigotes. Glutaminase (GLS) chemical inhibition was performed using BPTES and glutamine was administered throughout infection. For combined therapy experiment, a daily administration of miltefosine and glutamine was performed by oral gavage. Parasite burden was determined using a Taqman-based assay. Immune cell phenotyping and cytotoxicity were performed in splenic cells using flow cytometry., Findings: We show that glutamine is essential for the control of L. donovani infection. Transcriptomic analysis of L. donovani-infected macrophages demonstrated an upregulation of genes involved in glutamine metabolism. Pharmacological inhibition of glutaminolysis significantly increased the susceptibility to infection, accompanied by an increased recruitment of anti-inflammatory myeloid cells and impaired T cell responses. Remarkably, the supplementation of glutamine to mice infected with L. donovani during miltefosine treatment potentiates parasite clearance through the development of a more effective anti-Leishmania adaptive immune response., Conclusions: Our data indicates that dietary glutamine supplementation may act as a promising adjuvant for the treatment of visceral leishmaniasis., Competing Interests: The authors have declared that no competing interests exist.

Hypoxia-inducible factor-1 alpha (HIF-1α) is considered a global regulator of cellular metabolism and innate immune cell functions. Intracellular pathogens such as Leishmania have been reported to manipulate host cell metabolism. Herein, we demonstrate that myeloid cells from myeloid-restricted HIF-1α-deficient mice and individuals with loss-of-function HIF1A gene polymorphisms are more susceptible to L. donovani infection through increased lipogenesis. Absence of HIF-1α leads to a defect in BNIP3 expression, resulting in the activation of mTOR and nuclear translocation of SREBP-1c. We observed the induction of lipogenic gene transcripts, such as FASN, and lipid accumulation in infected HIF-1α -/- macrophages. L. donovani-infected HIF-1α-deficient mice develop hypertriglyceridemia and lipid accumulation in splenic and hepatic myeloid cells. Most importantly, our data demonstrate that manipulating FASN or SREBP-1c using pharmacological inhibitors significantly reduced parasite burden. As such, genetic deficiency of HIF-1α is associated with increased lipid accumulation, which results in impaired host-protective anti-leishmanial functions of myeloid cells., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cardiomyopathies remain among the leading causes of death worldwide, despite all efforts and important advances in the development of cardiovascular therapeutics, demonstrating the need for new solutions. Herein, we describe the effects of the redox-active therapeutic Mn(III) meso -tetrakis( N -ethylpyridinium-2-yl)porphyrin, AEOL10113, BMX-010 (MnTE-2-PyP 5+ ), on rat heart as an entry to new strategies to circumvent cardiomyopathies., Methods: Wistar rats weighing 250-300 g were used in both in vitro and in vivo experiments, to analyze intracellular Ca 2+ dynamics, L-type Ca 2+ currents, Ca 2+ spark frequency, intracellular reactive oxygen species (ROS) levels, and cardiomyocyte and cardiac contractility, in control and MnTE-2-PyP 5+ -treated cells, hearts, or animals. Cells and hearts were treated with 20  μ M MnTE-2-PyP 5+ and animals with 1 mg/kg, i.p. daily. Additionally, we performed electrocardiographic and echocardiographic analysis., Results: Using isolated rat cardiomyocytes, we observed that MnTE-2-PyP 5+ reduced intracellular Ca 2+ transient amplitude, without altering cell contractility. Whereas MnTE-2-PyP 5+ did not alter basal ROS levels, it was efficient in modulating cardiomyocyte redox state under stress conditions; MnTE-2-PyP 5+ reduced Ca 2+ spark frequency and increased sarcoplasmic reticulum (SR) Ca 2+ load. Accordingly, analysis of isolated perfused rat hearts showed that MnTE-2-PyP 5+ preserves cardiac function, increases SR Ca 2+ load, and reduces arrhythmia index, indicating an antiarrhythmic effect. In vivo experiments showed that MnTE-2-PyP 5+ treatment increased Ca 2+ transient, preserved cardiac ejection fraction, and reduced arrhythmia index and duration. MnTE-2-PyP 5+ was effective both to prevent and to treat cardiac arrhythmias., Conclusion: MnTE-2-PyP 5+ prevents and treats cardiac arrhythmias in rats. In contrast to most antiarrhythmic drugs, MnTE-2-PyP 5+ preserves cardiac contractile function, arising, thus, as a prospective therapeutic for improvement of cardiac arrhythmia treatment., Competing Interests: The authors declare that I.B.H. is a consultant with and holds equities in BioMimetix JV LLC. I.B.H. and Duke University have patent rights and have licensed technologies to BioMimetix JV LLC., (Copyright © 2020 Andrezza M. Barbosa et al.)