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Laboratorial diagnosis of tegumentary leishmaniasis (TL) is hampered by variable sensitivity and/or specificity of the tests, which are still hampered by blood́ invasive collection. In this context, in the present study, we develop a serum- and urine-based ELISA to TL diagnoses. A recombinant protein (rLiHyA), which was previously showed to be antigenic for the disease, as well as a B-cell epitope produced as synthetic peptide and a Leishmania antigenic extract (SLA), were used as antigens. A total of paired 205 urine and serum samples were used, which were comprised by samples from cutaneous (n = 30) and mucosal (n = 30) leishmaniasis patients, as well as from healthy individuals living in endemic region of disease (n = 45), of patients with Chagas disease (n = 30), leprosy (n = 35), malaria (n = 15) or HIV-infected (n = 20). Results showed that serum-based ELISA presented sensitivity of 24.0 %, 100 % and 41.0 %, when SLA, rLiHyA and synthetic peptide were used as antigens, and specificity of 98.4 %, 98.4 % and 98.4 %, respectively. The area under the curve (AUC) was calculated and results were 0.74, 1.0, and 0.71, respectively, when SLA, rLiHyA and synthetic peptide were used as antigens. Performing an urine-based ELISA, sensitivity was 28.0 %, 100 % and 75.0 %, respectively, when SLA, rLiHyA, and synthetic peptide were used, while specificity values were of 98.4 %, 98.4 % and 98.4 %, respectively. In addition, the AUC values were 0.82, 1.0, and 0.94, respectively. A significant drop in specific antibodies levels in both patientś serum and urine samples was found six months after treatment, suggesting a prognostic role of rLiHyA for TL. In conclusion, preliminary data suggest the potential of use patient urine to TL diagnoses., Competing Interests: Declaration of competing interest The 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., (Copyright © 2024. Published by Elsevier GmbH.)

Leptospirosis is a zoonotic disease with significant global impact and a challenging diagnosis. The utilization of adequately validated rapid tests is relevant for the opportune identification of the disease and for reduction in fatality rates. The present study analyzes the accuracy and reliability of the Dual Path Platform (DPP) assay -produced in Brazil by the Oswaldo Cruz Foundation (Fiocruz)- for diagnosing leptospirosis. Firstly, a serological panel was constructed in the Brazilian Reference Laboratory for Leptospirosis using samples routinely handled by reference laboratories of six Brazilian states. It consisted of 150 positive (according to MAT and IgM-ELISA) and 250 negative samples for leptospirosis. Subsequently, the panel samples were distributed to the reference laboratories for the performance of DPP assays in triplicate. Different measures were used in the assessment of diagnostic quality. Predictive values were estimated for different pre-test probability settings. Sensitivities varied between 67.33 % and 74.00 % and specificities between 93.20 % and 98.40 % in the states, and there were adequate agreements between them. Accuracies were lower for the samples of patients with less than 7 days of symptoms. In contexts of prevalence values up to around 25 %, positive and negative predictive values were around 90 %. However, in situations of high pre-test probabilities, NPVs were low. This study improves understanding of the use of DPP in diagnosing leptospirosis, particularly its application in healthcare settings. As long as the time of symptoms onset and clinical and epidemiological contexts are adequately considered for the interpretation of results, DPP is a valid option to be used in the leptospirosis diagnostic routine., Competing Interests: Declaration of competing interest The 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The aim of this study was to evaluate the in vitro cytotoxic, genotoxic, and mutagenic potential and to determine the in silico ADME parameters of two synthetic β-carboline alkaloids developed as prototypes of antitumor agents (NQBio-06 and NQBio-21). Additionally, acute toxicity of the compounds was evaluated in mice. The results from the MTT assay showed that NQBio-06 presented higher cytotoxicity in the ovarian cancer cell line TOV-21 G (IC 50 = 2.5 µM, selectivity index = 23.7). NQBio-21 presented an IC 50 of 6.9 µM and a selectivity index of 14.5 against MDA-MB-231 breast cancer cells. Comet assay results showed that NQBio-06 did not induce chromosomal breaks in vitro, but NQBio-21 was genotoxic with and without metabolic activation (S9 fraction). Micronucleus assay showed that both compounds were mutagenic. In addition, metabolic activation enhanced this effect in vitro. The in silico predictions showed that the compounds met the criteria set by Lipinski's rules, had strong prediction for intestinal absorption, and were possible substrates for P-glycoprotein. The in vivo results demonstrated that both the compounds exhibited low acute toxicity. These results suggest that the mechanisms underlying the cytotoxicity of NQBio-06 and NQBio-21 are related to DNA damage induction and that the use of S9 enhanced these effects. In vivo analysis showed signs of toxicity after a single administration of the compounds in mice. These findings highlight the potential of β-carboline compounds as sources for the development of new anticancer chemotherapeutic agents., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests Fernando de Pilla Varotti reports equipment, drugs, or supplies was provided by National Council for Scientific and Technological Development. Paulo Henrique de Almeida Campos Junior reports equipment, drugs, or supplies was provided by National Council for Scientific and Technological Development. Fernando de Pilla Varotti reports equipment, drugs, or supplies was provided by Minas Gerais State Foundation of Support to the Research. Paulo Henrique de Almeida Campos Junior reports equipment, drugs, or supplies was provided by Minas Gerais State Foundation of Support to the Research. Fernando de Pilla Varotti reports equipment, drugs, or supplies was provided by Minas Gerais State Foundation of Support to the Research. Kimberly Brito Tecchio reports equipment, drugs, or supplies was provided by Coordination of Higher Education Personnel Improvement. Gustavo Henrique Ribeiro Viana has patent pending to BR10201901777., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The diagnosis of tegumentary leishmaniasis (TL) is hampered by variable sensitivity and/or specificity of the tests. Serological assays are suitable to diagnose visceral leishmaniasis (VL); however, they present low performance for the detection of TL cases. Additionally, blood collection to obtain patient serum represents a challenge, as it is an invasive and uncomfortable procedure, requiring laboratorial infrastructure and trained professionals. In this context, the present study proposed to evaluate patient urine to detect TL, given that this analyte has proven to be effective in ELISA experiments for the detection of VL cases. For this, a Leishmania protein called LiHyV, two specific B-cell epitopes derived from protein amino acid sequence, and a Leishmania antigenic extract (SLA) were used as antigens. A total of 215 paired urine and serum samples were evaluated, and results showed that, when serum was employed as an analyte, rLiHyV, Peptide1, Peptide2, and SLA presented a sensitivity of 85 %, 29 %, 58 %, and 31 %, respectively, and a specificity of 97.5 %, 98 %, 100 %, and 97.5 %, respectively, in the diagnosis of TL. When urine was used, rLiHyV, Peptide1, Peptide2, and SLA presented a sensitivity of 95 %, 74 %, 67 %, and 52 %, respectively, and a specificity of 100 %, 99 %, 98 %, and 86 %, respectively. In conclusion, preliminary data suggest that urine could be considered as an alternative biological sample for the detection of TL cases., Competing Interests: Declaration of competing interest The authors declare that no commercial or financial conflict of interest exist., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Malaria is one of most widespread infectious disease in world. The antimalarial therapy presents a series of limitations, such as toxicity and the emergence of resistance, which makes the search for new drugs urgent. Thus, it becomes necessary to explore essential and exclusive therapeutic targets of the parasite to achieve selective inhibition. Enoyl-ACP reductase is an enzyme of the type II fatty acid biosynthetic pathway and is responsible for the rate-limiting step in the fatty acid elongation cycle. In this work, we use hierarchical virtual screening and drug repositioning strategies to prioritize compounds for phenotypic assays and molecular dynamics studies. The molecules were tested against chloroquine-resistant W2 strain of Plasmodium falciparum (EC 50 between 330.05 and 13.92 µM). Nitrofurantoin was the best antimalarial activity at low micromolar range (EC 50 = 13.92 µM). However, a hit compound against malaria must have a biological activity value below 1 µM. A large number of molecules present problems with permeability in biological membranes and reaching an effective concentration in their target's microenvironment. Nitrofurantoin derivatives with inclusions of groups which confer increased lipid solubility (methyl groups, halogens and substituted and unsubstituted aromatic rings) have been proposed. These derivatives were pulled through the lipid bilayer in molecular dynamics simulations. Molecules 14, 18 and 21 presented lower free energy values than nitrofurantoin when crossing the lipid bilayer., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The advancement of nanobiocomposites reinforced with 2D nano-materials plays a pivotal role in enhancing bone tissue engineering. In this study, we introduce a nanobiocomposite that reinforces bovine collagen with 2D nano-talc, a recently exfoliated nano-mineral. These nanobiocomposites were prepared by blending collagen with varying concentrations of 2D nano-talc, encompassing mono- and few-layers talc from soapstone nanomaterial. Extensive characterization techniques including AFM, XPS, nano-FTIR, s-SNOM nanoimaging, Force Spectroscopy, and PeakForce QNM® were employed. The incorporation of 2D nano-talc significantly enhanced the mechanical properties of the nanobiocomposites, resulting in increased stiffness compared to pristine collagen. In vitro studies supported the growth and proliferation of osteoblasts onto 2D nano-talc-reinforced nanobiocomposites, as well as showed the highest mineralization potential. These findings highlight the substantial potential of the developed nanobiocomposite as a scaffold material for bone tissue engineering applications., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To develop a mortality risk score for COVID-19 patients admitted to intensive care units (ICU), and to compare it with other existing scores., Materials and Methods: This retrospective observational study included consecutive adult patients with laboratory-confirmed COVID-19 admitted to ICUs of 18 hospitals from nine Brazilian cities, from September 2021 to July 2022. Potential predictors were selected based on the literature review. Generalized Additive Models were used to examine outcomes and predictors. LASSO regression was used to derive the mortality score., Results: From 558 patients, median age was 69 years (IQR 58-78), 56.3 % were men, 19.7 % required mechanical ventilation (MV), and 44.8 % died. The final model comprised six variables: age, pO 2 /FiO 2 , respiratory function (respiratory rate or if in MV), chronic obstructive pulmonary disease, and obesity. The AB 2 CO had an AUROC of 0.781 (95 % CI 0.744 to 0.819), good overall performance (Brier score = 0.191) and an excellent calibration (slope = 1.063, intercept = 0.015, p-value = 0.834). The model was compared with other scores and displayed better discrimination ability than the majority of them., Conclusions: The AB 2 CO score is a fast and easy tool to be used upon ICU admission., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest concerning the research, authorship, and/or publication and/or competing financial of this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Cardiac in silico clinical trials can virtually assess the safety and efficacy of therapies using human-based modelling and simulation. These technologies can provide mechanistic explanations for clinically observed pathological behaviour. Designing virtual cohorts for in silico trials requires exploiting clinical data to capture the physiological variability in the human population. The clinical characterisation of ventricular activation and the Purkinje network is challenging, especially non-invasively. Our study aims to present a novel digital twinning pipeline that can efficiently generate and integrate Purkinje networks into human multiscale biventricular models based on subject-specific clinical 12-lead electrocardiogram and magnetic resonance recordings. Essential novel features of the pipeline are the human-based Purkinje network generation method, personalisation considering ECG R wave progression as well as QRS morphology, and translation from reduced-order Eikonal models to equivalent biophysically-detailed monodomain ones. We demonstrate ECG simulations in line with clinical data with clinical image-based multiscale models with Purkinje in four control subjects and two hypertrophic cardiomyopathy patients (simulated and clinical QRS complexes with Pearson's correlation coefficients > 0.7). Our methods also considered possible differences in the density of Purkinje myocardial junctions in the Eikonal-based inference as regional conduction velocities. These differences translated into regional coupling effects between Purkinje and myocardial models in the monodomain formulation. In summary, we demonstrate a digital twin pipeline enabling simulations yielding clinically consistent ECGs with clinical CMR image-based biventricular multiscale models, including personalised Purkinje in healthy and cardiac disease conditions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Julia Camps reports financial support was provided by Engineering and Physical Sciences Research Council. Blanca Rodriguez reports financial support was provided by Wellcome Trust Fellowship in Basic Biomedical Sciences. Zhinuo Jenny Wang reports financial support was provided by CompBioMed 2 Centre of Excellence in Computational Biomedicine. Kevin Burrage reports financial support was provided by Australian Research Council Centre of Excellence for Mathematical and Statistical Frontiers. Kevin Burrage reports financial support was provided by Australian Research Council Discovery Project. Leto Luana Riebel reports financial support was provided by BBSRC PhD scholarship in collaboration with AstraZeneca. Rodrigo Weber dos Santos reports financial support was provided by Coordination of Higher Education Personnel Improvement. Rodrigo Weber dos Santos reports financial support was provided by National Council for Scientific and Technological Development. Rafael Sebastian reports financial support was provided by Generalitat Valenciana., (Copyright © 2024. Published by Elsevier B.V.)

An ultrafast, efficient, and eco-friendly method combining magnetic solid phase extraction and capillary electrophoresis with diode array detection have been developed to determine ractopamine residues in food samples. A restricted access material based on magnetic and mesoporous molecularly imprinted polymer has been properly synthesized and characterized, demonstrating excellent selectivity and high adsorbent capacity. Short-end injection capillary electrophoresis method was optimized: 75 mM triethylamine pH 7 as BGE, -20 kV, 50 mbar by hydrodynamic injection during 8 s, and capillary temperature at 25 °C; reaching ultrafast ractopamine analysis (∼0.6 min) with good peak asymmetry, and free from interfering and/or baseline noise. After sample preparation optimization, the conditions were: 1000 µL of sample at pH 6, 20 mg of adsorbent, stirring time of 120 s, 250 µL of ultrapure water as washing solvent, 1000 µL of methanol: acetic acid (7: 3, v/v) as eluent, and the adsorbent can be reused four times. In these conditions, the analytical method showed recoveries around to 100 %, linearity ranged from 9.74 to 974.0 µg kg -1 , correlation coefficient (r) ≥ 0,99 in addition to adequate precision, accuracy, and robustness. After proper validation, the method was successfully applied in the analysis ractopamine residues in bovine milk and bovine and porcine muscle., Competing Interests: Declaration of competing interest The 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

N-glycosylation at the antibody variable domain has emerged as an important modification influencing antibody function. Despite its significance, information regarding its role and regulation remains limited. To address this gap, we comprehensively explored antibody structures housing N-glycosylation within the Protein Data Bank, yielding fresh insights into this intricate landscape. Our findings revealed that among 208 structures, N-glycosylation was more prevalent in human and mouse antibodies containing IGHV1-8 and IGHV2-2 germline genes, respectively. Moreover, our research highlights the potential for somatic hypermutation to introduce N-glycosylation sites by substituting polar residues (Ser or Thr) in germline variable genes with asparagine. Notably, our study underscores the prevalence of N-glycosylation in antiviral antibodies, especially anti-HIV. Besides antigen-antibody interaction, our findings suggest that N-glycosylation may impact antibody specificity, affinity, and avidity by influencing Fab dimer formation and complementary-determining region orientation. We also identified different glycan structures in HIV and SARS-CoV-2 antibody proteomic datasets, highlighting disparities from the N-glycan structures between PDB antibodies and biological repertoires further highlighting the complexity of N-glycosylation patterns. Our findings significantly enrich our understanding of the N-glycosylation's multifaceted characteristics within the antibody variable domain. Additionally, they underscore the pressing imperative for a more comprehensive characterization of its impact on antibody function., Competing Interests: Declaration of competing interest The 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., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: Thrombin generation assay (TGA) is a laboratory method that provides the global evaluation of hemostasis. The association between thrombin generation and all-cause mortality is poorly investigated and results are contradictory. This study evaluated whether TGA parameters are associated with all-cause mortality in a prospective cohort., Methods: This study was conducted in 2,588 participants enrolled at baseline of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). TGA was performed using the Calibrated Automated Thrombogram (CAT) method, and its parameters lagtime, time-to-peak, peak, Endogenous Thrombin Potential (ETP) and normalized ETP (nETP) were evaluated according to the reference interval (RI). The association between TGA parameters and all-cause mortality was estimated by Cox regression and adjusted for confounders., Results: The mean follow-up time was 6.6 ± 2.7 years and 85 deaths occurred. After adjustment, time-to-peak values above the RI at low and high tissue factor (TF) concentrations were associated with higher risk of death [HR = 2.45 (95 % CI: 1.17-5.13) and HR = 2.24 (95 % CI: 1.02-4.93), respectively] and nETP and peak values below RI at high TF concentration were associated with higher risk of death [HR = 3.85 (95 % CI: 1.39-10.68) and HR = 2.56 (95 % CI: 1.17-5.61), respectively]., Conclusions: Delayed thrombin generation was associated with higher risk of all-cause mortality., Competing Interests: Declaration of competing interest The 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., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Barotrauma is a major cause of injury and mortality of fish as they pass through hydropower turbines. Current understanding of hydropower related barotrauma is biased towards northern temperate and southern subtropical species with single chambered swim bladders, specifically North American and Australian species, respectively. Today, unprecedented hydropower development is taking place in Neotropical regions where many species have complex multi-chambered swim bladder architecture. This study investigated barotrauma in two dual-chambered physostomous Neotropical fish (pacu, Piaractus mesopotamicus, and piracanjuba, Brycon orbignyanus) exposed to rapid (< 1 s) decompression at different Ratios of Pressure Change (RPC), using a hypo-hyperbaric chamber. The incidence and intensity (percentage surface area of organ affected) of injury and physiological and behavioural response (hereafter just response) of each species immediately after decompression was assessed. Twenty-two injury types (e.g. gill haemorrhage and exophthalmia) and eight response categories (e.g. rising to the surface and loss of orientation) were identified and the influence of: 1) species, 2) RPC, and 3) swim bladder rupture on each was quantified. There was considerable interspecific difference with emboli type injuries occurring more frequently in piracanjuba, but injury intensity tending to be higher in pacu. Both swim bladder chambers tended to rupture in piracanjuba but only the anterior chamber in pacu. RPC was positively correlated with response, incidence and intensity of several injury types for both species with some injuries occurring at very low RPC (e.g. 50 % probability of swim bladder rupture at 2.2 and 1.75 for piracanjuba and pacu, respectively). Multiple responses (e.g. loss of orientation) and injuries (e.g. eye haemorrhage) were correlated with swim bladder rupture suggesting gas venting into the body cavity likely causes secondary injury. When directly comparing our results with those available in the published literature, both pacu and piracanjuba appear to be more susceptible to barotrauma than previously studied subtropical and temperate species., Competing Interests: Declaration of competing interest The 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., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The 6-OHDA nigro-striatal lesion model has already been related to disorders in the excitability and synchronicity of neural networks and variation in the expression of transmembrane proteins that control intra and extracellular ionic concentrations, such as cation-chloride cotransporters (NKCC1 and KCC2) and Na+/K+-ATPase and, also, to the glial proliferation after injury. All these non-synaptic mechanisms have already been related to neuronal injury and hyper-synchronism processes., Objective: The main objective of this study is to verify whether mechanisms not directly related to synaptic neurotransmission could be involved in the modulation of nigrostriatal pathways., Methods: Male Wistar rats, 3 months old, were submitted to a unilateral injection of 24 µg of 6-OHDA, in the striatum (n = 8). The animals in the Control group (n = 8) were submitted to the same protocol, with the replacement of 6-OHDA by 0.9% saline. The analysis by optical densitometry was performed to quantify the immunoreactivity intensity of GFAP, NKCC1, KCC2, Na+/K+-ATPase, TH and Cx36., Results: The 6-OHDA induced lesions in the striatum, were not followed by changes in the expression cation-chloride cotransporters and Na+/K+-ATPase, but with astrocytic reactivity in the lesioned and adjacent regions of the nigrostriatal. Moreover, the dopaminergic degeneration caused by 6-OHDA is followed by changes in the expression of connexin-36., Conclusions: The use of the GJ blockers directly along the nigrostriatal pathways to control PD motor symptoms is conjectured. Electrophysiology of the striatum and the substantia nigra, to verify changes in neuronal synchronism, comparing brain slices of control animals and experimental models of PD, is needed., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Through density functional theory calculations was studied theoretically the formation process of a magnetic and mesoporous molecularly imprinted polymer for ractopamine (RAC), evaluating the molecular electrostatic potential map, functional monomers, functional monomer / template stoichiometry and crosslink agents. The results revealed that the best conditions for the synthesis were established with acrylic acid as functional monomer in a 1: 4 stoichiometry using acetonitrile as the solvent and ethylene glycol dimethacrylate as crosslink agent. It was observed that nine hydrogen bonds established between the RAC and acrylic acid play a key role on the pre-polymerization complex. In addition, three analytical methods using HPLC, UHPLC and CE instruments were optimized for rapid analysis. The adsorbent was experimentally synthesized considering the best conditions found at the molecular level and characterized by FTIR, DRX, TGA, SEM, TEM, surface analysis, and wettability. After that, the synthesized material was used in magnetic solid phase extraction combined with capillary electrophoresis in a preliminary RAC recovery study from milk samples. Finally, greenness metric with a score of 0.55 have been obtained for the sample preparation procedure using the online AGREEprep metric., Competing Interests: Declaration of Competing Interest The 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., (Copyright © 2023. Published by Elsevier B.V.)

Visceral leishmaniasis (VL) is a pressing public health problem in Brazil. The proper implementation of disease control programs in priority areas is a challenge for healthcare managers. The present study aimed to analyze the spatio-temporal distribution and identify high risk areas of VL occurrence in the Brazilian territory. We analyzed data regarding new cases with confirmed diagnosis of VL in Brazilian municipalities, from 2001 to 2020, extracted from the Brazilian Information System for Notifiable Diseases. The Local Index of Spatial Autocorrelation (LISA) was used to identify contiguous areas with high incidence rates in different periods of the temporal series. Clusters of high spatio-temporal relative risks were identified using the scan statistics. The accumulated incidence rate in the analyzed period was 33.53 cases per 100,000 inhabitants. The number of municipalities that reported cases showed an upward trend from 2001 onward, although there was a decrease in 2019 and 2020. According to LISA, the number of municipalities considered a priority increased in Brazil and in most states. Priority municipalities were predominantly concentrated in the states of Tocantins, Maranhão, Piauí, and Mato Grosso do Sul, in addition to more specific areas of Pará, Ceará, Piauí, Alagoas, Pernambuco, Bahia, São Paulo, Minas Gerais, and Roraima. The spatio-temporal clusters of high-risk areas varied throughout the time series and were relatively higher in the North and Northeast regions. Recent high-risk areas were found in Roraima and municipalities in northeastern states. VL expanded territorially in Brazil in the 21st century. However, there is still a considerable spatial concentration of cases. The areas identified in the present study should be prioritized for disease control actions., Competing Interests: Declaration of Competing Interest The 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., (Copyright © 2023. Published by Elsevier B.V.)

Brazilian Atlantic Forest is a biodiversity hotspot drastically fragmented due to different land use practices. Our understanding on the impacts of fragmentation and restoration practices on ecosystem functionality significantly increased during the last decades. However, it is unknown to our knowledge how a precision restoration approach, integrated with landscape metrics, will affect the decision-making process of forest restoration. Here, we applied Landscape Shape Index and Contagion metrics in a genetic algorithm for planning forest restoration in watersheds at the pixel level. We evaluated how such integration may configure the precision of restoration with scenarios related to landscape ecology metrics. The genetic algorithm worked toward optimizing the site, shape, and size of forest patches across the landscape according to the results obtained in applying the metrics. Our results, obtained by simulations of scenarios, support aggregation of forest restoration zones as expected, with priority restoration areas indicated where most of the aggregation of forest patches occurs. Our optimized solutions for the study area (Santa Maria do Rio Doce Watershed) predicted an important improvement of landscape metrics (LSI = 44 %; Contagion/LSI = 73 %). Largest shifts are suggested based on LSI (i.e., three larger fragments) and Contagion/LSI (i.e., only one well-connected fragment) optimizations. Our findings indicate that restoration in an extremely fragmented landscape will promote a shift toward more connected patches and with reduction of the surface:volume ratio. Our work explores the use of genetic algorithms to propose forest restoration based on landscape ecology metrics in a spatially explicit innovative approach. Our results indicate that LSI and Contagion:LSI ratio may affect the choice concerning precise location of restoration sites based on forest fragments scattered in the landscape and reinforce the usefulness of genetic algorithms to yield an optimized-driven solution for restoration initiatives., Competing Interests: Declaration of competing interest The 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., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The development of simple, efficient, and low-cost analytical methods is essential for the evaluation and monitoring of the main cannabinoids in Cannabis-based products. In this sense, the objectives of this study were to develop and validate an analytical method for obtaining and determining cannabinoids in a pool sample. Two extraction techniques were used, ultrasound and turbo-extraction, and two system-solvents, methanol:chloroform (9:1 v:v) and ethanol. The analytical method used and validated was carried out in High Performance Liquid Chromatography with Diodes Array Detector. The cannabidiol standard was characterized by a nuclear magnetic resonance. The use of the proposed method makes it possible to identify cannabinoids, both in the acid form and in the neutral form, in 7 min of analysis. The results confirmed high precision and accuracy. The detection and quantification limits were 0.19 μg/mL and 5 μg/mL, respectively. The method developed proved to be selective and robust for the evaluation of cannabinoids. It is hoped that the methods developed can be used to obtain and analyze cannabinoids, both for medicinal purposes and for forensic analysis., Competing Interests: Declaration of competing interest The 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., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: This study aimed to estimate five harmonized healthy aging indicators covering functional ability and intrinsic capacity among older women and men from Brazil and England and evaluate their association with loneliness., Study Design: This was a cross-sectional study., Methods: We used two nationally representative samples of men and women aged ≥60 years from the Brazilian Longitudinal Study of Aging (ELSI-Brazil) wave 2 (2019-2021; n = 6929) and the English Longitudinal Study of Aging wave 9 (2018-2019; n = 5902). Healthy aging included five separate indicators (getting dressed, taking medication, managing money, cognitive function, and handgrip strength). Loneliness was measured by the 3-item University of California Loneliness Scale. Logistic regression models stratified by sex and country were performed., Results: Overall, age-adjusted healthy aging indicators were worse in Brazil compared with England for both men and women. Considering functional ability, loneliness was negatively associated with all indicators (ranging from odds ratio [OR] = 0.26, [95% confidence interval (CI) 0.13-0.52] in English men regarding the ability to take medication to OR = 0.49 [95% CI 0.27-0.89] in Brazilian women regarding the ability to manage money). Considering intrinsic capacity, loneliness was negatively associated with a higher cognitive function (OR = 0.72; 95% CI 0.55-0.95 in English women) and a higher handgrip strength (OR = 0.61; 95% CI 0.45-0.83 in Brazilian women). Lonely women demonstrated lower odds of a higher number of healthy aging indicators than men in both countries., Conclusions: Country-specific social environments should be targeted by public policies to decrease loneliness and promote healthy aging later in life., (Copyright © 2023 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Objective: Amygdala has been demonstrated as one of the brain sites involved in the control of cardiorespiratory functioning. The structural and physiological alterations induced by epileptic activity are also present in the amygdala and reflect functional changes that may be directly associated with a sudden unexpected death. Seizures are always associated with neuronal damage and changes in the expression of cation-chloride cotransporters and Na/K pumps. In this study, the authors aimed to investigate if these changes are present in the amygdala after induction of status epilepticus with pilocarpine, which may be directly correlated with Sudden Unexpected Death in Epilepsy (SUDEP)., Methods: Pilocarpine-treated wistar rats 60 days after Status Epilepticus (SE) were compared with control rats. Amygdala nuclei of brain slices immunostained for NKCC1, KCC2 and α 1 -Na + /K + -ATPase, were quantified by optical densitometry., Results: The amygdaloid complex of the animals submitted to SE had no significant difference in the NKCC1 immunoreactivity, but KCC2 immunoreactivity reduced drastically in the peri-somatic sites and in the dendritic-like processes. The α 1 -Na + /K + -ATPase peri-somatic immunoreactivity was intense in the rats submitted to pilocarpine SE when compared with control rats. The pilocarpine SE also promoted intense GFAP staining, specifically in the basolateral and baso-medial nuclei with astrogliosis and cellular debris deposition., Interpretation: The findings revealed that SE induces lesion changes in the expression of KCC2 and α1-Na+/K+-ATPase meaning intense change in the chloride regulation in the amygdaloid complex. These changes may contribute to cardiorespiratory dysfunction leading to SUDEP., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2022 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Studies about oxidative stress biomarkers revealed different phenotypes between early and late preeclampsia (PE). Despite that, there is extensive evidence of oxidative stress in investigations that combinate forms different of preeclampsia. This study reviews the oxidative stress profile in the PE subtypes and evaluates which markers are altered in the blood and placental tissue. A search was conducted in databases such as MEDLINE, EMBASE, LILACS, and Web of Science without restricting the year and language of publication. The quality of the studies was evaluated by the Newcastle-Ottawa scale and Joanna Briggs Institute for analytical Cross-Sectional Studies. After 13,319 screened records, 65 were included in the systematic review. The markers of stress oxidative of damage and reactive species were those selected, such as malondialdehyde (MDA), lipid peroxide, advanced protein oxidation products, carbonyl protein, 8-hydroxy-2'-deoxyguanosine, total oxidant status, hydrogen peroxide, nitric oxide (NO). We described the antioxidant activity, including the superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase, free glutathione, and total antioxidant capacity (TAC). We results demonstrated that oxidative stress is related to pathophysiology of PE, there were increased lipid peroxidation in the blood and placenta, and in blood a reduction of NO levels and of TAC, like lower enzymatic activity of GPx, CAT in PE, and SOD in mild PE. In addition, altered levels of MDA in the placenta and blood show that placental changes have repercussions on the clinical syndrome and are related to the severity of the disease., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Initially, a printed electrode was fabricated in a paper substrate using carbon nanotube ink, graphite pencil and silver nanoparticle ink. For that the electrode was modified with gold nanoparticles and a molecularly imprintedpolymer (MIP) using CA 15-3 as target molecule. The Atomic Force Microscopy (AFM) images exhibited the change in the morphology after each electrode modification. The roughness increasedafter the electropolymerization, and decreased after the extraction procedure. Next, slightly increased again associated to the interaction of CA 15-3 and the imprinted sites. Finally, the Fourier Transform Infrared Spectroscopy (FTIR) results suggested the extraction/rebinding of CA 15-3 in the MIP sensor and also indicated that the NIP sample do not have specific cavities for the CA 15-3. In short, under optimized conditions, the CNE/AuNP is incubated with CA 15-3 (40 U mL -1 ) for 2 h at 4 °C. Then the electropolymerization was carried out in the potential range of -0.2 to 1.0 V during 20 cycles at scan rate of 50 mV s -1 using a solution containing 15 mM of oPD. After electropolymerization, the sensor was washed with oxalic acid solution for 2 h, leading to the formation of imprinted cavities. The rebinding process was subsequently constructed for 1 h at 4 °C using CA 15-3 solution. The reproducibility and interference studies showed that the sensor can be reproducible and specific for CA 15-3. Then the sensor was applied in determination of CA 15-3 in samples of serum and saliva. The use in serum presented good recovery, but the application in saliva was not satisfactory. Therefore, the sensor CNE/AuNP/MIP could be used in the determination of CA 15-3 in serum samples., Competing Interests: Declaration of competing interest The 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., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: People with severe mental illness have a mortality rate higher than the general population, living an average of 10-20 years less. Most studies of mortality among people with severe mental illness have occurred in high-income countries (HICs). We aimed to estimate all-cause and cause-specific relative risk (RR) and excess mortality rate (EMR) in a nationwide cohort of inpatients with severe mental illness compared with inpatients without severe mental illness in a middle income country, Brazil., Methods: This national retrospective cohort study included all patients hospitalised through the Brazilian Public Health System (Sistema Único de Saúde [SUS]-Brazil) between Jan 1, 2000, and April 21, 2015. Probabilistic and deterministic record linkages integrated data from the Hospital Information System (Sistema de informações Hospitalares) and the National Mortality System (Sistema de Informação sobre Mortalidade). Follow-up duration was measured from the date of the patients' first hospitalisation until their death, or until April 21, 2015. Severe mental illness was defined as schizophrenia, bipolar disorder, or depressive disorder by ICD-10 codes used for the admission. RR and EMR were calculated with 95% CIs, comparing mortality among patients with severe mental illness with those with other diagnoses for patients aged 15 years and older. We redistributed deaths using the Global Burden of Diseases, Injuries, and Risk Factors Study methodology if ill-defined causes of death were stated as an underlying cause., Findings: From Jan 1, 2000, to April 21, 2015, 72 021 918 patients (31 510 035 [43·8%] recorded as male and 40 974 426 [56·9%] recorded as female; mean age 41·1 (SD 23·8) years) were admitted to hospital, with 749 720 patients (372 458 [49·7%] recorded as male and 378 670 [50·5%] as female) with severe mental illness. 5 102 055 patient deaths (2 862 383 [56·1%] recorded as male and 2 314 781 [45·4%] as female) and 67 485 deaths in patients with severe mental illness (39 099 [57·9%] recorded as male and 28 534 [42·3%] as female) were registered. The RR for all-cause mortality in patients with severe mental illness was 1·27 (95% CI 1·27-1·28) and the EMR was 2·52 (2·44-2·61) compared with non-psychiatric inpatients during the follow-up period. The all-cause RR was higher for females and for younger age groups; however, EMR was higher in those aged 30-59 years. The RR and EMR varied across the leading causes of death, sex, and age groups. We identified injuries (suicide, interpersonal violence, and road injuries) and cardiovascular disease (ischaemic heart disease) as having the highest EMR among those with severe mental illness. Data on ethnicity were not available., Interpretation: In contrast to studies from HICs, inpatients with severe mental illness in Brazil had high RR for idiopathic epilepsy, tuberculosis, HIV, and acute hepatitis, and no significant difference in mortality from cancer compared with inpatients without severe mental illness. These identified causes should be addressed as a priority to maximise mortality prevention among people with severe mental illness, especially in a middle-income country like Brazil that has low investment in mental health., Funding: Bill and Melinda Gates Foundation, Fundação de Amparo a Pesquisa do Estado de Minas Gerais, FAPEMIG, and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil., Competing Interests: Declaration of interests All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Epidemiological studies of leishmaniasis in areas of great human influence and environmental change serve as important tools for the implementation of effective control plans. Mining is currently a major economic activity in Brazil with the municipality of Pains, in the state of Minas Gerais, being one of the main lime producing municipalities in the country. This study aimed to map areas of potential transmission risks within the municipality of Pains using an epidemiological approach in association with the ecological study of sand flies. Twelve samplings carried out between May 2015 and April 2016 collected a total of 12,728 sandflies, comprising 2,854 females (22.42%) and 9,874 males (77.58%), of 20 species belonging to ten genera. The most abundant species was Lutzomyia longipalpis (80%). Leishmania DNA was detected in seven pools of female sand flies with an infection rate of 0.37%. Geoprocessing and the use of maps revealed that vector sand flies are distributed throughout the urban area, as are cases of canine and human leishmaniasis. However, the greatest abundances of sand flies were at sampling points at the border of the urban area. Higher densities of sand flies and the presence of Leishmania DNA may be correlated with extensive degradation by limestone mining. Integrated and multidisciplinary research approaches are necessary to better understand how the impacts of environmental change influence these insect vectors of leishmaniasis., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Chagas disease is a zoonotic disease caused by the hemoflagellate Trypanosoma cruzi and transmitted primarily by triatomine vectors. Triatomines are hematophagous insects that feed on a variety of vertebrate hosts. The Chagas disease transmission cycle is closely related to the interactions between vectors, parasites, and vertebrate hosts. Knowledge of triatomine food sources is critical to understanding Chagas disease transmission dynamics. The aim of this study was to identify blood meal sources used by triatomines from different environments in the Brazilian Amazon. A total of 25 captures were conducted in four environments. Triatomine specimens were captured on palm trees and were identified by morphological and morphometric characters. Blood meal sources identification was conducted using a traditional PCR followed by Sanger sequencing of mtDNA cytb gene. Sequencing was successful in 167 specimens and a total of 21 blood meal sources were identified: two reptilians, six birds, and 13 mammals. Among these 21 species, three (Tamandua tetradactyla, Didelphis marsupialis and Rattus rattus) are considered reservoir of T. cruzi. Knowledge of the relationship between triatomines and possible reservoirs can help to elucidate the enzootic cycle of T. cruzi in the Amazon region and guide control strategies for Chagas disease transmission in that region., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Competing Interests: Conflicts of interest The authors declare no conflicts of interest.

Late in 2019, China identified a new type of coronavirus, SARS-CoV-2, and due to its fast spread, the World Health Organisation (WHO) declared a pandemic named COVID-19. Some variants of this virus were detected, including the Delta, which caused new waves of infections. This work uses an extended version of a SIRD model that includes vaccination effects to measure the impact of the Delta variant in three countries: Germany, Israel and Brazil. The calibrated models were able to reproduce the dynamics of the above countries. In addition, hypothetical scenarios were simulated to quantify the impact of vaccination and mitigation policies during the Delta wave. The results showed that the model could reproduce the complex dynamics observed in the different countries. The estimated increase of transmission rate due to the Delta variant was highest in Israel (7.9), followed by Germany (2.7) and Brazil (1.5). These values may support the hypothesis that people immunised against COVID-19 may lose their defensive antibodies with time since Israel, Germany, and Brazil fully vaccinated half of the population in March, July, and October. The scenario to study the impact of vaccination revealed relative reductions in the total number of deaths between 30% and 250%; an absolute reduction of 300 thousand deaths in Brazil due to vaccination during the Delta wave. The second hypothetical scenario revealed that mitigation policies saved up to 300 thousand Brazilians; relative reductions in the total number of deaths between 24% and 120% in the three analysed countries. Therefore, the results suggest that both vaccination and mitigation policies were crucial in decreasing the spread and the number of deaths during the Delta wave., Competing Interests: The 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., (© 2022 Elsevier B.V. All rights reserved.)

Objectives: This study investigates the simulation of the mechanical behavior of a bioceramic composite based on (Ce,Y)-TZP reinforced with equiaxed Al 2 O 3 and platelet-shaped hexaaluminate (H6A) grains using Finit Element Method (FEM)., Methods: A commercial (Ce, Y)-TZP/Al 2 O 3 ceramic powder was compacted into disc-shaped specimens that were sintered at 1500 °C for 2 h. The sintered samples were further subjected to hydrothermal degradation in an autoclave at 134 °C, 0.2 MPa, for 10 h and characterized according to their phase composition, microstructure, and relative density. Their flexural strength values were determined by the piston-on-three-ball test, and Weibull statistics was used to evaluate the results. Their hardness, fracture toughness and elastic parameters were also measured. Numerical simulations of the biaxial strength test were performed using the ABAQUS finite element code., Results: The sintered ceramic composite material presented relative density >99%, high resistance to hydrothermal degradation, average hardness of 1435 ± 35 HV, fracture toughness K IC of 9.7 ± 0.5 MPa m 1/2 , and average biaxial flexural strength of 952.6 ± 88 MPa. The numerical predictions of the biaxial flexural strength showed a consistently lower average biaxial flexural strength value of 880.9 MPa, ∼10% lower than the average experimental results., Conclusions: The differences observed are attributed to the complex coupled toughness mechanisms of this material, not included in the finite element simulations., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The genotoxicity of pyrene-polyethylene glycol-modified multi-walled carbon nanotubes (MWCNT-PyPEG), engineered as a nanoplatform for bioapplication, was evaluated. Toxicity was assessed in hamster lung fibroblast cells (V79-4). MTT and Cell Titer Blue methods were used to evaluate cell viability. Genotoxicity was measured by the comet assay and the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay, and fluorescence in situ hybridization (FISH) was used to test induction of structural chromosome aberrations (clastogenic activity) and/or numerical chromosome changes (aneuploidogenic activity). Exogenous metabolic activation enzymes were used in the CBMN-Cyt and FISH tests. Only with metabolic activation, the hybrids caused chromosomal damage, by both clastogenic and aneugenic processes., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Iron is a key element in cell function; however, its excess in iron overload conditions can be harmful through the generation of reactive oxygen species (ROS) and cell oxidative stress. Activity of Na,K-ATPase has been shown to be implicated in cellular iron uptake and iron modulates the Na,K-ATPase function from different tissues. In this study, we determined the effect of iron overload on Na,K-ATPase activity and established the role that isoforms and conformational states of this enzyme has on this effect. Total blood and membrane preparations from erythrocytes (ghost cells), as well as pig kidney and rat brain cortex, and enterocytes cells (Caco-2) were used. In E1-related subconformations, an enzyme activation effect by iron was observed, and in the E2-related subconformations enzyme inhibition was observed. The enzyme's kinetic parameters were significantly changed only in the Na + curve in ghost cells. In contrast to Na,K-ATPase α2 and α3 isoforms, activation was not observed for the α1 isoform. In Caco-2 cells, which only contain Na,K-ATPase α1 isoform, the FeCl 3 increased the intracellular storage of iron, catalase activity, the production of H 2 O 2 and the expression levels of the α1 isoform. In contrast, iron did not affect lipid peroxidation, GSH content, superoxide dismutase and Na,K-ATPase activities. These results suggest that iron itself modulates Na,K-ATPase and that one or more E1-related subconformations seems to be determinant for the sensitivity of iron modulation through a mechanism in which the involvement of the Na, K-ATPase α3 isoform needs to be further investigated., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Classified as the second most common neurodegenerative disorder associated with aging after Alzheimer's disease, Parkinson's disease (PD) is the most common movement disorder. In the last decade, despite advances in treatment, mortality rates linked with PD continued to reach significant figures. Available studies have shown that compared with healthy controls, patients with PD are accompanied by high rates of premature death. This is usually caused by factors such as pneumonia and cerebrovascular and cardiovascular diseases. Recently, it has been demonstrated that a significant proportion of patients with PD die suddenly. This is referred to as a sudden and unexpected death in PD (SUDPAR). Here, we focus on the magnitude of SUDPAR. Finally, it is important to learn more about SUDPAR for the implementation of effective prevention strategies., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2022 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Aquatic ecosystems are highly vulnerable to anthropogenic activities. However, it remains unclear how the microbiome responds to press disturbance events in these ecosystems. We examined the impact of the world's largest mining disaster (Brazil, 2015) on sediment microbiomes in two disturbed rivers compared to an undisturbed river during 390 days post-disturbance. The diversity and structure of the virulome and microbiome, and of antibiotic and metal resistomes, consistently differed between the disturbed and undisturbed rivers, particularly at day 7 post-disturbance. 684 different ARGs were predicted, 38% were exclusive to the disturbed rivers. Critical antibiotic resistance genes (ARGs), e.g., mcr and ereA2, were significantly more common in the disturbed microbiomes. 401 different ARGs were associated with mobile genetic elements (MGEs), 95% occurred in the disturbed rivers. While plasmids were the most common MGEs with a broad spectrum of ARGs, spanning 16 antibiotic classes, integrative conjugative elements (ICEs) and integrons disseminated ARGs associated with aminoglycoside and tetracycline, and aminoglycoside and beta-lactam, respectively. A significant increase in the relative abundance of class 1 integrons, ICEs, and pathogens was identified at day 7 in the disturbed microbiomes, 72-, 14- and 3- fold higher, respectively, compared with the undisturbed river. Mobile ARGs associated with ESKAPEE group pathogens, while metal resistance genes and virulence factor genes in nonpathogenic hosts predominated in all microbiomes. Network analysis showed highly interconnected ARGs in the disturbed communities, including genes targeting antibiotics of last resort. Interactions between copper and beta-lactam/aminoglycoside/macrolide resistance genes, mostly mobile and critical, were also uncovered. We conclude that the mud tsunami resulted in resistome expansion, enrichment of pathogens, and increases in promiscuous and mobile ARGs. From a One Health perspective, mining companies need to move toward more environmentally friendly and socially responsible mining practices to reduce risks associated with pathogens and critical and mobile ARGs., Competing Interests: Declaration of competing interest The 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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This study evaluated the in vitro antiplasmodial and cytotoxic effects of 26 extracts from nine marine sponges collected in Salvador, Bahia state, Brazil. All assayed extracts were found to be potently active against Plasmodium falciparum W2 strain, with IC 50 values ranging from 0.28 to 22.34 μg mL -1 , and weakly cytotoxic against the human cell line WI-26-VA4 with CC 50 values > 89 μg mL -1 , thus displaying selectivity indices (SI) equal or higher than 17. Interestingly, some SI values exceeded 1,000. The highly potent and selective antiplasmodial activity of the assessed marine sponges is reported for the first time in this study., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To investigate visual-related quality of life (VRQL) and prevalence and severity of depressive symptoms in Brazilian individuals with toxoplasmic retinochoroiditis (TRC)., Design: Comparative observational cross-sectional study. The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) and Beck Depression Inventory-II (BDI-II) were applied to respectively assess VRQL and depression in individuals consecutively seen at a uveitis referral center. Clinical/demographical data were collected. Descriptive/analytic statistics were employed, with P<0.05., Results: Patients and controls were comparable concerning age, sex and socioeconomic level. VRQL scores for all subscales were significantly lower in TRC when compared with controls, particularly associated (P<0.05) with female sex, history of ≥2 prior TRC recurrences, concomitant use of systemic corticosteroids, monocular vision and blindness. Depressive symptoms were more prevalent in TRC (55/188; 29.2%) than in controls (34/182; 18.7%) (P=0.023), also being associated with lower VRQL scores (P<0.001). Seropositive and seronegative controls for toxoplasmosis had similar VRQL scores and comparable rates of depressive symptoms., Conclusion: TRC affects VRQL in Brazilian individuals, particularly women, using systemic corticosteroids, with visual impairment and presenting recurrences of TRC. One-third of patients with TRC had evidence of depression, which was also associated with lower VRQL scores. Mental health issues in subjects with TRC should not be overlooked., Competing Interests: Declaration of Competing Interests None declared., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Infection caused by Mayaro virus (MAYV) is responsible for causing acute nonspecific fever, in which the majority of patients develop incapacitating and persistent arthritis/arthralgia. Mayaro fever is a neglected and underreported disease without treatment or vaccine, which has gained attention in recent years after the competence of Aedes aegypti to transmit MAYV was observed in the laboratory, coupled with the fact that cases are being increasingly reported outside of endemic forest areas, calling attention to the potential of an urban cycle arising in the near future. Thus, to mitigate the lack of information about the pathological aspects of MAYV, we previously described the involvement of oxidative stress in MAYV infection in cultured cells and in a non-lethal mouse model. Additionally, we showed that silymarin, a natural compound, attenuated MAYV-induced oxidative stress and inhibited MAYV replication in cells. The antioxidant and anti-MAYV effects prompted us to determine whether silymarin could also reduce oxidative stress and MAYV replication after infection in an immunocompetent animal model. We show that infected mice exhibited reduced weight gain, hepatomegaly, splenomegaly, anaemia, thrombocytopenia, leukopenia, increased liver transaminases, increased pro-inflammatory cytokines and liver inflammation, increased oxidative damage biomarkers, and reduced antioxidant enzyme activity. However, in animals infected and treated with silymarin, all these parameters were reversed or significantly improved, and the detection of viral load in the liver, spleen, brain, thigh muscle, and footpad was significantly reduced. This work reinforces the potent hepatoprotective, antioxidant, anti-inflammatory, and antiviral effects of silymarin against MAYV infection, demonstrating its potential against Mayaro fever disease., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The complexity and multifactorial characteristics of Chagas disease pathogenesis hampers the establishment of appropriate experimental/epidemiological sets, and therefore, still represents one of the most challenging fields for novel insights and discovery. In this context, we used a set of attributes including phenotypic, functional and serological markers of immune response as candidates to decode the genotype-specific immune response of experimental T. cruzi infection. In this investigation, we have characterized in C57BL/6 J mice, the early (parasitemia peak) and late (post-parasitemia peak) aspects of the immune response elicited by T. cruzi strains representative of TcI, TcII or TcVI. The results demonstrated earlier parasitemia peak for TcII/Y strain followed by TcVI/CL-Brener and TcI/Colombiana strains. A panoramic overview of phenotypic and functional features of the TCD4 + , TCD8 + and B-cells from splenocytes demonstrated that mice infected with TcI/Colombiana strain exhibited at early stages of infection low levels of most cytokine + cells with a slight increase at late stages of infection. Conversely, mice infected with TcII/Y strain presented an early massive increase of cytokine + cells, which decreases at late stages. The TcVI/CL-Brener strain showed an intermediate profile at early stages of infection with a slight increase later on at post-peak of parasitemia. The panoramic analysis of immunological connectivity demonstrated that early after infection, the TcI/Colombiana strain trigger immunological network characterized by a small number of connectivity, selectively amongst cytokines that further shade towards the late stages of infection. In contrast, the TcII/Y strain elicited in more imbricate networks early after infection, comprising a robust number of interactions between pro-inflammatory mediators, regulatory cytokines and activation markers that also decrease at late infection. On the other hand, the infection with TcVI/CL-Brener strain demonstrated an intermediate profile with connectivity axes more stable at early and late stages of infection. The analysis of IgG2a reactivity to AMA, TRYPO and EPI antigens revealed that at early stages of infection, the genotype-specific reactivity to AMA, TRYPO and EPI to distinguish was higher for TcI/Colombiana as compared to TcII/Y and TcVI/CL while, at late stages of infection, higher reactivity to AMA was observed in mice infected with TcVI/CL and TcII/Y strains. The novel systems biology approaches and the use of a flow cytometry platform demonstrated that distinct T. cruzi genotypes influenced in the phenotypic and functional features of the host immune response and the genotype-specific serological reactivity during early and late stages of experimental T. cruzi infection., (Copyright © 2021. Published by Elsevier B.V.)

Objectives: The majority of available scores to assess mortality risk of coronavirus disease 2019 (COVID-19) patients in the emergency department have high risk of bias. Therefore, this cohort aimed to develop and validate a score at hospital admission for predicting in-hospital mortality in COVID-19 patients and to compare this score with other existing ones., Methods: Consecutive patients (≥ 18 years) with confirmed COVID-19 admitted to the participating hospitals were included. Logistic regression analysis was performed to develop a prediction model for in-hospital mortality, based on the 3978 patients admitted between March-July, 2020. The model was validated in the 1054 patients admitted during August-September, as well as in an external cohort of 474 Spanish patients., Results: Median (25-75th percentile) age of the model-derivation cohort was 60 (48-72) years, and in-hospital mortality was 20.3%. The validation cohorts had similar age distribution and in-hospital mortality. Seven significant variables were included in the risk score: age, blood urea nitrogen, number of comorbidities, C-reactive protein, SpO 2 /FiO 2 ratio, platelet count, and heart rate. The model had high discriminatory value (AUROC 0.844, 95% CI 0.829-0.859), which was confirmed in the Brazilian (0.859 [95% CI 0.833-0.885]) and Spanish (0.894 [95% CI 0.870-0.919]) validation cohorts, and displayed better discrimination ability than other existing scores. It is implemented in a freely available online risk calculator (https://abc2sph.com/)., Conclusions: An easy-to-use rapid scoring system based on characteristics of COVID-19 patients commonly available at hospital presentation was designed and validated for early stratification of in-hospital mortality risk of patients with COVID-19., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Economic viability and eco-friendliness are important characteristics that make implants available to the population in a sustainable way. In this work, we evaluate the performance of a low-cost, widely available, and eco-friendly material (talc from soapstone) relative to reduced graphene oxide as reinforcement to brittle hydroxyapatite coatings. We employ a low-cost and straightforward technique, electrodeposition, to deposit the composite coatings on the titanium substrate. Corrosion, wear, and biocompatibility tests indicate that the reduced graphene oxide can be effectively replaced by talc without reducing the mechanical, anticorrosion, and biocompatible composite coatings properties. Our results indicate that talc from soapstone is a promising material for biomedical applications., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The potential use of nopal cladode flour (NC) as reinforcing/bioactive agent in cassava starch-based films was evaluated and compared with the use of propolis extract or lignin, which are commonly used for these purposes. Cassava starch-based films containing untreated NC (S-NC), NC treated at pH 12 (S-NC12), aqueous propolis extract at two different concentrations (SP1 or SP2), or lignin (S-L) were produced by the casting technique; glycerol was used as plasticizer. NC12 and NC affected the mechanical properties of the cassava starch-based film similarly as compared to propolis extract and lignin. Moreover, NC and NC12 had different performance as reinforcing and antioxidant agent in cassava starch-based film. Thus, S-NC12 film was more elongable (28.5 ± 6.5%), more hydrophobic (contact angle: 70.8° ± 0.1), less permeable to water vapor (0.8 ± 0.0 × 10 -10 g·m -1 ·s -1 ·Pa -1 ) and had better antioxidant activity by ABTS •+ (44.70 ± 0.3 μM Trolox·g -1 of film) than the S-NC film. SEM and TGA analysis of films showed that NC12 was better incorporated into the cassava starch matrix than NC, lignin and propolis extract. Overall, nopal cladode flour has potential use in the production of active biodegradable packaging for the food preservation with high oxidation rate., (Copyright © 2021 Elsevier B.V. All rights reserved.)