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Christian Quijia Quezada,1,2 Clênia S Azevedo,1 Sébastien Charneau,3 Jaime M Santana,1 Marlus Chorilli,2 Marcella B Carneiro,4 Izabela Marques Dourado Bastos11Pathogen-Host Interface Laboratory, Department of Cell Biology, Institute of Biology, University of Brasilia, Brasília, Brazil; 2Department of Drugs and Medicines, São Paulo State University (UNESP), Araraquara, São Paulo, Brazil; 3Laboratory of Protein Chemistry and Biochemistry, Department of Cell Biology, Institute of Biology, University of Brasilia, Brasília, Brazil; 4Electron Microscopy Laboratory, Department of Cell Biology, Institute of Biology, University of Brasilia, Brasília, BrazilAbstract: Chagas disease is one of the most important public health problems in Latin America due to its high mortality and morbidity levels. There is no effective treatment for this disease since drugs are usually toxic with low bioavailability. Serious efforts to achieve disease control and eventual eradication have been unsuccessful to date, emphasizing the need for rapid diagnosis, drug development, and a reliable vaccine. Novel systems for drug and vaccine administration based on nanocarriers represent a promising avenue for Chagas disease treatment. Nanoparticulate systems can reduce toxicity, and increase the efficacy and bioavailability of active compounds by prolonging release, and therefore improve the therapeutic index. Moreover, nanoparticles are able to interact with the host’s immune system, modulating the immune response to favour the elimination of pathogenic microorganisms. In addition, new advances in diagnostic assays, such as nanobiosensors, are beneficial in that they enable precise identification of the pathogen. In this review, we provide an overview of the strategies and nanocarrier-based delivery systems for antichagasic agents, such as liposomes, micelles, nanoemulsions, polymeric and non-polymeric nanoparticles. We address recent progress, with a particular focus on the advances of nanovaccines and nanodiagnostics, exploring new perspectives on Chagas disease treatment.Keywords: delivery systems, nanobiosensors, nanodiagnostics, nanoparticle systems, nanovaccine

This project aims to develop an interactive control system for an autonomous service robot using an ROS (robot operating system). The system integrates an intuitive web interface and an interactive chatbot supported by Google Gemini to enhance the control experience and personalization for the user. The methodology includes the integration of an API (application programming interface) to access a database storing user preferences, such as speed and frequent destinations. Furthermore, the system employs facial recognition, people groups' recognition, and adaptive responses from the chatbot for autonomous navigation, ensuring a service tailored to the individual needs of each user. To validate the proposal, it was implemented on an autonomous service robot, integrated into a motorized wheelchair. Tests demonstrated that the system effectively adjusts the wheelchair's behavior to user preferences, resulting in safer and more personalized navigation. The use of facial recognition and chatbot interaction provided more intuitive and efficient control. The developed system significantly improves the autonomy and quality of life for wheelchair users, proving to be a viable and efficient solution for autonomous and personalized control. The results indicate that integrating technologies like ROS, intuitive web interfaces, and interactive chatbots can transform the user experience of autonomous wheelchairs, better meeting the specific needs of users.

Purpose: The volume of the vitreous chamber varies with the size of the eye. The space created in the vitreous cavity by a vitrectomy is called the vitrectomized space. The volume of the vitrectomized space is strongly correlated with the axial length of the eye. This study aims to present guidelines for estimating the using participants stratified by axial length, sex, and history of cataract surgery., Methods: This retrospective, observational, cross-sectional study included 144 randomly selected participants who underwent vitrectomies between 2013 and 2023. Before surgery, the axial lengths of participants' eyes were measured using optical biometrics. The axial lengths of the eyes in our sample were between 20-32 mm. In all cases, a complete vitrectomy was performed, followed by complete fluid-air exchange and injection of a balanced saline solution. The volume infused was recorded., Results: The median (interquartile range; range) volume of the vitrectomized space was 6.1 (3.8; 3.1-11.3) mL in men and 6.1 (3.3; 3.2-11.2) mL in women (p = 0.811). The median volume of the vitrectomized space was 5.9 (3.6; 3.1-11.2) mL in patients with phakic lenses and 6.25 (3.6; 3.3-11.3) mL in those with pseudophakic lenses (p=0.533). A positive correlation was found between the axial length and the volume of the vitrectomized space in this sample (r=0.968; p<0.001). In a cubic polynomial regression, the coefficient of determination was 0.948. Similar results were observed in both sexes and in both phakic and pseudophakic patients. The estimated cubic polynomial regression equation for this sample was VVS = 0.000589052857847605 × AL 3 - 0.025114926401582700 × AL 2 + 0.685961117595624000 × AL - 5.088226672620790000., Conclusion: We developed this axial length estimation of the volume of vitrectomized space as a guideline for the determination of vitrectomized space volume using axial length.

Pulse-wave velocity (PWV), flow-mediated dilation (FMD), and carotid intima-media thickness (CIMT) are established methods used in research and clinical settings to assess arterial stiffness, endothelial function, and subclinical atherogenesis. These measurements may reflect vascular disease and atherosclerotic progression, which are major causes of adverse cardiovascular events. These methods are particularly valuable in determining cardiovascular dysfunction among populations with different risk factors, such as diabetes mellitus, hypertension, and other metabolic dysfunction-related conditions. They provide a non-invasive and reliable source of information that complements clinical practice. Early detection, risk assessment, and therapeutic decisions regarding cardiovascular disease can be achieved, ultimately contributing to improved patient outcomes. Traditional tools for evaluating cardiovascular disease do not reveal whether metabolic syndrome affects early subclinical cardiovascular disease in patients with obesity. Recent research has highlighted the importance of including arterial stiffness and endothelial function in a comprehensive cardiovascular assessment. Therefore, the aim of the present study is to describe methods that provide information on early subclinical vascular aging, endothelial dysfunction, and atherogenic disease, enabling vascular-targeted risk stratification among populations with obesity and different metabolic profiles.

Chagas disease is a neglected infectious disease caused by the protozoan Trypanosoma cruzi , primarily transmitted by triatomine vectors, and it threatens approximately seventy-five million people worldwide. This parasite undergoes a complex life cycle, transitioning between hosts and shifting from extracellular to intracellular stages. To ensure its survival in these diverse environments, T. cruzi undergoes extreme morphological and molecular changes. The metacyclic trypomastigote (MT) form, which arises from the metacyclogenesis (MTG) process in the triatomine hindgut, serves as a crucial link between the insect and human hosts and can be considered the starting point of Chagas disease. This review provides an overview of the current knowledge regarding the parasite's life cycle, molecular pathways, and mechanisms involved in metabolic and morphological adaptations during MTG, enabling the MT to evade the immune system and successfully infect human cells.

Context: Obesity is a multicausal social problem and a pandemic, and it presents a public health challenge in many countries. Hence, public health interventions have been used in an endeavour to prevent and/or control increased obesity among populations., Objective: This review study aimed to provide an overview of the academic literature and to analyze the strategies involved in the main public policies focused on preventing and controlling obesity in a number of countries., Data Sources: MEDLINE/PubMed, Web of Science, and LILACS databases were searched., Data Extraction: Original studies were included for which the core objective was related to real-life public policy interventions for obesity., Data Analysis: The studies were organized according to their characteristics, and the qualitative analysis was based on the categorization proposed by the author Poulain. The review included 41 studies and identified 15 types of interventions focused on obesity; the largest proportion of actions were developed in school and city environments and were geared toward behavioral change, supported by direct or indirect government action. It was observed that many strategies focused on environmental line through regulatory and legislative measures, and health promotion geared toward the individual was based on the dissemination of information as a means for behavioral change. A smaller focus was given to individual care and treatment, and participative actions in the community., Conclusion: The design of public health strategies applicable to obesity as proposed by Poulain provides a valid model for evaluating interventions. The behavioral approach involving guidance through health education toward a healthy lifestyle prevails in public policies, indicating a movement toward accountability of individuals. However, it is necessary to deepen the debate on the social structures that determine obesity (and which limit possibilities of choice), aligned with cultural change regarding its occurrence, and to employ care strategies based on scientific evidence and which focus on the needs of the subjects., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.

Zika virus (ZIKV) infection is associated with severe neurological disorders and congenital malformation. Despite efforts to eradicate the disease, there is still neither vaccine nor approved drugs to treat ZIKV infection. The NS2B-NS3 protease is a validated drug target since it is essential to polyprotein virus maturation. In the present study, we describe an experimental screening of 2,320 compounds from the chemical library of the Muséum National d'Histoire Naturelle of Paris on ZIKV NS2B-NS3 protease. A total of 96 hits were identified with 90% or more of inhibitory activity at 10 μM. Amongst the most active compounds, five were analyzed for their inhibitory mechanisms by kinetics assays and computational approaches such as molecular docking. 2-(3-methoxyphenoxy) benzoic acid (compound 945) show characteristics of a competitive inhibition (K i  = 0.49 μM) that was corroborated by its molecular docking at the active site of the NS2B-NS3 protease. Taxifolin (compound 2292) behaves as an allosteric inhibitor whereas 3,8,9-trihydroxy-2-methyl-1H-phenalen-1-one (compound 128), harmol (compound 368) and anthrapurpurin (compound 1499) show uncompetitive inhibitions. These new NS2B-NS3 protease inhibitors are valuable hits to further hit-to-lead optimization., Competing Interests: Declaration of competing interest The authors report no conflicts of interest in this work., (Copyright © 2023 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

The growing interest in microRNAs (miRNAs) over recent years has led to their characterization in numerous organisms. However, there is currently a lack of data available on miRNAs from triatomine bugs (Reduviidae: Triatominae), which are the vectors of the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease. A comprehensive understanding of the molecular biology of vectors provides new insights into insect-host interactions and insect control approaches, which are key methods to prevent disease incidence in endemic areas. In this work, we describe the miRNome profiles from gut, hemolymph, and salivary gland tissues of the Rhodnius prolixus triatomine. Small RNA sequencing data revealed abundant expression of miRNAs, along with tRNA- and rRNA-derived fragments. Fifty-two mature miRNAs, previously reported in Ecdysozoa, were identified, including 39 ubiquitously expressed in the three tissues. Additionally, 112, 73, and 78 novel miRNAs were predicted in the gut, hemolymph, and salivary glands, respectively. In silico prediction showed that the top eight most highly expressed miRNAs from salivary glands potentially target human blood-expressed genes, suggesting that R. prolixus may modulate the host's gene expression at the bite site. This study provides the first characterization of miRNAs in a Triatominae species, shedding light on the role of these crucial regulatory molecules., (© 2023. Springer Nature Limited.)

Objective: We aimed to investigate estradiol (E2) as a therapeutic drug for spinal cord injury (SCI) and elucidate the disagreement in the field about the use of this hormone after an injury., Methods: Eleven animals underwent surgery (laminectomy at the T9-T10 levels) followed by an intravenous injection (100 μg) of an E2 bolus and the implantation of 0.5cm of Silastic tubing containing 3 mg of E2 (sham E2 + E2 bolus) immediately after the laminectomy. The SCI control animals received a moderate contusion using the Multicenter Animal SCI Study impactor device over the exposed spinal cord followed by an intravenous bolus injection of sesame oil and were implanted with empty Silastic tubing (injury SE + vehicle); treated rats received a bolus of E2 and a Silastic implant with 3 mg of E2 (injury E2 + E2 bolus). Functional locomotor recovery and fine motor coordination were assessed by the Basso, Beattie, and Bresnahan (BBB) open field test and grid-walking tests, respectively, from the acute (7 days post-injury [DPI]) to the chronic stages (35 DPI). Anatomical studies of the cord were performed using Luxol fast blue staining followed by densitometric analysis., Results: As observed in the BBB open field and the grid-walking tests, E2 post-SCI did not improve locomotor function but instead increased spared white matter tissue, in the rostral region., Conclusion: Estradiol post-SCI, at the dose and route of administration used in this study, failed to promote locomotor recovery but partially restored spared white matter tissue.

Introduction: Hansen's disease (HD) primarily infects peripheral nerves, with patients without HD being free of peripheral nerve damage. Household contacts (HHCs) of patients with HD are at a 5-10 times higher risk of HD than the general population. Neural thickening is one of the three cardinal signs that define a case of HD according to WHO guidelines, exclusively considering palpation examination that is subjective and may not detect the condition in the earliest cases even when performed by well-trained professionals. High-resolution ultrasound (HRUS) can evaluate most peripheral nerves, a validated technique with good reproducibility allowing detailed and accurate examination., Objective: This study aimed to use the peripheral nerve HRUS test according to the HD protocol as a diagnostic method for neuropathy comparing HHCs with healthy volunteers (HVs) and patients with HD., Methods: In municipalities from 14 different areas of Brazil we selected at random 83 HHC of MB-patients to be submitted to peripheral nerve ultrasound and compared to 49 HVs and 176 HD-patients., Results: Household contacts assessed by HRUS showed higher median and mean absolute peripheral nerve cross-sectional area (CSA) values and greater asymmetries (ΔCSA) compared to HVs at the same points. Median and mean absolute peripheral nerve CSA values were higher in patients with HD compared to HCCs at almost all points, while ΔCSA values were equal at all points. Mean ± SD focality (ΔTpT) values for HHCs and patients with HD, respectively, were 2.7 ± 2.2/2.6 ± 2.2 for the median nerve, 2.9 ± 2.7/3.3 ± 2.9 for the common fibular nerve ( p > 0.05), and 1.3 ± 1.3/2.2 ± 3.9 for the ulnar nerve ( p < 0.0001)., Discussion: Considering HRUS findings for HHCs, asymmetric multiple mononeuropathy signs (thickening or asymmetry) in at least 20% of the nerves evaluated could already indicates evidence of HD neuropathy. Thus, if more nerve points are assessed in HHCs (14 instead of 10), the contacts become more like patients with HD according to nerve thickening determined by HRUS, which should be a cutting-edge tool for an early diagnosis of leprosy cases., 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 © 2023 Voltan, Marques-Júnior, Santana, Lincoln Silva, Leite, De Paula, Bernardes Filho, Barreto, Da Silva, Conde, Salgado and Frade.)

Introduction: Hansen's disease (HD) is the most common cause of treatable peripheral neuropathy in the world that may or may not involve skin manifestations, and physical examination based on simplified neurologic evaluation is a subjective and inaccurate procedure. High-resolution ultrasound (HRUS) can be used to evaluate peripheral nerves and is a validated technique of good reproducibility, permitting a detailed and precise examination., Objectives: We proposed to establish objective criteria for absolute values of the measurement of the CSA of peripheral nerves and their indices of the ΔCSA and ΔTpT in the diagnosis of Hansen's disease neuropathy as compared with healthy voluntaries., Materials and Methods: In municipalities from different regions of Brazil, we randomly selected 234 volunteer Brazilian patients diagnosed with leprosy to be submitted to peripheral nerve echography and compared with 49 healthy Brazilian volunteers., Results: Hansen Disease assessed by high resolution ultrasound is a primarily neural disease that leads to multiple hypertrophic mononeuropathy characterized by CSA values exceeding normal limits (Med CT = 10.2 mm 2 ; UT = 9.8 mm 2 ; UPT = 9.3 mm 2 ; CFFH = 18.3 mm 2 ; T = 9.6 mm 2 ), and the pattern of asymmetry (ΔCSA>2.5 mm 2 with RR 13) and focality (ΔTPT > 2.5 mm 2 with RR 6.4) of this thickening has higher sensitivity (76,1%) and specificity (87,8 %) for its early diagnosis that laboratory tests. Analyzing each subject, the percentage of thickened nerves detected among the total number of nerves assessed was higher among patients with HD than among healthy individuals ( p < 0.0001). Individuals with two or more thickened nerves were at 24.1 times higher relative risk (95% CI: 6.74-88.98) of HD., 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 Voltan, Filho, Leite, De Paula, Santana, Silva, Barreto, Da Silva, Conde, Salgado and Frade.)

Background: Stroke is one of the highest complications of sickle-cell anemia (SCA). The Transcranial Doppler (TCD) has been adopted worldwide as a gold standard method for detecting alterations in the blood velocity in cerebral arteries. In this study, we investigated the association between laboratory parameters and increased cerebral blood flow velocity in Brazilian SCA pediatric patients., Methods: The study included 159 pediatric patients with SCA, submitted to TCD velocity screening, and the time-averaged maximum mean velocity (TAMMV) was determined in the middle cerebral artery (MCA), anterior cerebral artery (ACA), and distal intracranial internal carotid artery (ICA). We compared cerebral blood flow in patients stratified by the following: TCD1-defined as normal, with TAMMV inferior to 170 cm/s; TCD2-conditional, with TAMMV above 170 cm/s, but less than 199 cm/s; TCD3-altered, with TAMMV greater than or equal to 200 cm/s., Results: TAMMV was negatively correlated with age and weight ( p < 0.05). Moreover, TAMMV was associated or correlated with reductions in HbF, RBC, hemoglobin, hematocrit, HDL, and haptoglobin and, increases in MCV, MCH, RDW, reticulocytes, WBC, lymphocytes, monocytes, eosinophils, total and indirect bilirubin, LDH, AST, ALT, glucose, ferritin, and AAT ( p < 0.05)., Conclusion: The current study highlights the importance of the investigation of hemolytic and inflammatory biomarkers for monitoring the clinical outcome of SCA pediatric patients, to avoid acute or chronic stroke. Moreover, glucose and HDL-C appear useful for predicting higher TAMMV., 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 Adanho, Yahouédéhou, Santana, Vieira, Santiago, de Santana, Pitanga, Aleluia, Maffili, Leite, Zanette, Lyra and Goncalves.)

Mechanical circulatory support (MCS) is used in cardiogenic shock for periprocedural hemodynamic stability in high-risk patients and to support patients with symptomatic coronary artery disease. Depending on the MCS type, oxygenation and ventilation, in addition to increasing blood pressure by augmenting blood flow, can be achieved. MCS typically follows a failure of less invasive maneuvers or intolerance to them, such as significant ventricular arrhythmia burden from inotropic support. MCS options include intra-aortic balloon pump, transvalvular percutaneous left ventricular assist devices, venoarterial extracorporeal membrane oxygenation, and surgically implanted left ventricular assist devices. The number of MCS options has increased, and this has made the decision-making process complicated. MCS decision-making is complex, even in patients without valvular pathology. The presence of aortic valve (AV) abnormalities, such as aortic stenosis, aortic insufficiency, replaced AVs, or AV masses, adds even further to the challenge of selecting the appropriate support strategy. In this narrative review, a concise review of MCS options and the special considerations for various AV pathologies are presented., Competing Interests: Conflicts of Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Hansen's disease (HD) is an ancient disease, but more than 200,000 new cases were reported worldwide in 2019. Currently, there are not many satisfactory immunoassay methods for its diagnosis. We evaluated antibodies against Mce1A as a promising new serological biomarker. We collected plasma from new cases, contacts, and endemic controls in the city of Parnaíba and treated patients at Carpina, a former HD colony in Piauí state, northeastern Brazil. Receiver operating characteristic (ROC) curves were used to assess the assay thresholds, specificity and sensitivity of the IgA, IgM, and IgG antibodies against α-Mce1A by indirect ELISA and compared it with IgM anti-PGL-I and molecular diagnosis by quantitative polymerase chain reaction (qPCR). Venn diagrams were generated to represent the overlap in the antibody positivity pattern. Multivariate analysis was performed to assess the potential predictor of antibodies for the outcome of having an HD diagnosis. IgA and IgG were positive in 92.3 and 84% of patients, respectively. IgM was negative for all treated patients. IgG had a sensitivity and specificity of 94.7 and 100%, respectively. IgM-positive individuals had a 3.6 chance of being diagnosed with HD [OR = 3.6 (95% CI = 1.1-11.6); p = 0.028], while IgA-positive individuals had a 2.3 chance [OR = 2.3 (95% CI = 1.2-4.3); p = 0.005] compared to endemic controls. We found that the Mce1A antibody profile can be an excellent diagnostic method of HD. IgA is an ideal biomarker for confirming contact with the bacillus. IgM has potential in the detection of active disease. IgG antibodies confirm the performance of these serological markers in diagnosis and therapeutic follow-up., 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 Lima, Filho, Antunes, Santana, de Almeida, Toro, Bragagnollo, Manso, de Paula, Alves, Riley, Arruda and Frade.)

The present study evaluated the gut microbiota profiles of 40 women and correlated them with their nutritional, inflammatory, and hormonal profiles. Stool and blood samples were collected, and anthropometric measurements were obtained from 20 women diagnosed with obesity ("case" group) and 20 women with weight in the normal range ("control" group). Bacteria belonging to two phyla, Firmicutes and Bacteroidetes, one class, Mollicutes, and four genera were evaluated by real-time polymerase chain reaction. Levels of 18 inflammatory cytokines were measured using the Luminex assay, and ghrelin and leptin levels were measured using enzymatic immunoadsorption assay. Mollicutes proportion differed significantly between the case and control groups, and a significant positive association was detected between the presence of Mollicutes and obesity. Statistically significant differences were observed between the proportions of Firmicutes and Bacteroidetes in the two groups, with a higher proportion of Firmicutes/Bacteroidetes ratio among the gut microbiota of women in the case group compared to those of the control group. Higher counts of Escherichia coli and Clostridium spp. were observed in the control group than in the case group, whereas higher counts of Lactobacillus spp. and Bacteroides spp. were detected in the case group than in the control group. There was a positive correlation between interleukin-6 (IL-6) and interferon-γ (IFN-γ) levels and the anthropometric variables and a negative correlation between IL-10 and these variables. Leptin and ghrelin concentrations differed significantly between the two groups and showed positive and negative correlation with obesity predictors, respectively. Therefore, gut microbiota was associated with obesity in women from this study group. Moreover, this microbiota was associated with inflammatory profiles and alterations in ghrelin and leptin levels., (© 2022. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Purpose of Review: Major bleeding in cardiac surgery is commonly encountered, and, until recently, most frequently managed with fresh frozen plasma (FFP). However, a Cochrane review found this practice to be associated with a significant increase in red blood cell (RBC) transfusions and costs. These findings have led to off-label uses of prothrombin complex concentrates (PCCs) in cardiac surgery. The purpose of this review is to compare and contrast the use of FFP and PCC, review the components, limitations and risks of different types of PCCs, and discuss the latest evidence for the use of PCC versus FFP in cardiac surgery., Recent Findings: A recent review and meta-analysis suggests that PCC administration in cardiac surgery is more effective than FFP in reducing RBC transfusions and costs., Summary: The current data supports the use of 4F-PCC instead of FFP as the primary hemostatic agent in cases of major bleeding in cardiac surgery. The use of PCCs is associated with reduced rates of RBC transfusions while maintaining a favorable safety profile. Clear advantages of PCC over FFP include its smaller volume, higher concentration of coagulation factors and shorter acquisition and administration times., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Triatomines have evolved salivary glands that produce versatile molecules with various biological functions, including those leading their interactions with vertebrate hosts' hemostatic and immunological systems. Here, using high-throughput transcriptomics and proteomics, we report the first sialome study on the synanthropic triatomine Triatoma sordida . As a result, 57,645,372 reads were assembled into 26,670 coding sequences (CDS). From these, a total of 16,683 were successfully annotated. The sialotranscriptomic profile shows Lipocalin as the most abundant protein family within putative secreted transcripts. Trialysins and Kazal-type protease inhibitors have high transcript levels followed by ubiquitous protein families and enzyme classes. Interestingly, abundant trialysin and Kazal-type members are highlighted in this triatomine sialotranscriptome. Furthermore, we identified 132 proteins in T. sordida salivary gland soluble extract through LC-MS/MS spectrometry. Lipocalins, Hemiptera specific families, CRISP/Antigen-5 and Kazal-type protein inhibitors proteins were identified. Our study provides a comprehensive description of the transcript and protein compositions of the salivary glands of T. sordida . It significantly enhances the information in the Triatominae sialome databanks reported so far, improving the understanding of the vector's biology, the hematophagous behaviour, and the Triatominae subfamily's evolution., 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 Praça, Santiago, Charneau, Mandacaru, Bastos, Bentes, Silva, da Silva, da Silva, de Sousa, Soares, Ribeiro, Santana and de Araújo.)

Surgical exclusion of the left atrial appendage (LAA) for stroke prevention in atrial fibrillation is frequently incomplete and remains to be optimized. We present a man who did not tolerate anticoagulant and failed percutaneous occlusion. Intraoperative echocardiographic contrast was used to assist surgical exclusion. Follow-up showed a persistent occlusion., Competing Interests: None

Loss of basic utilities, such as drinking water and electricity distribution, were sustained for months in the aftermath of Hurricane Maria's (HM) landfall in Puerto Rico (PR) in September 2017. The goal of this study was to assess if there was deterioration in biological quality of drinking water due to these disruptions. This study characterized the microbial composition of drinking water following HM across nine drinking water systems (DWSs) in PR and utilized an extended temporal sampling campaign to determine if changes in the drinking water microbiome were indicative of HM associated disturbance followed by recovery. In addition to monitoring water chemistry, the samples were subjected to culture independent targeted and non-targeted microbial analysis including quantitative PCR (qPCR) and genome-resolved metagenomics. The qPCR results showed that residual disinfectant was the major driver of bacterial concentrations in tap water with marked decrease in concentrations from early to late sampling timepoints. While Mycobacterium avium and Pseudomonas aeruginosa were not detected in any sampling locations and timepoints, genetic material from Leptospira and Legionella pneumophila were transiently detected in a few sampling locations. The majority of metagenome assembled genomes (MAGs) recovered from these samples were not associated with pathogens and were consistent with bacterial community members routinely detected in DWSs. Further, whole metagenome-level comparisons between drinking water samples collected in this study with samples from other full-scale DWS indicated no significant deviation from expected community membership of the drinking water microbiome. Overall, our results suggest that disruptions due to HM did not result in significant and sustained deterioration of biological quality of drinking water at our study sites., 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., (© 2021 The Author(s).)

Background: Regarding the leprosy transmission through the upper airways, overcrowded locations such as prisons can become a risk to get sick. Like the leprosy hidden endemic demonstrated in male prison population, being interesting to assess the leprosy scene also among confined women., Methods: A prospective descriptive study conducted at Female Penitentiary, Brazil. Leprosy Suspicion Questionnaire (LSQ) were applied to the participants, and submitted to specialized dermatoneurological exam, peripheral nerve ultrasonography, and anti-PGL-I serology., Findings: 404 female inmates were evaluated, 14 new cases were diagnosed (LG-leprosy group), a new case detection rate (NCDR) of 3.4%, 13 multibacillary, while another 390 constituted the Non-Leprosy group (NLG). Leprosy cases were followed up during multidrug therapy with clinical improvement. The confinement time median was 31 months in LG, similar to NLG, less than the time of leprosy incubation. Regarding LSQ, the neurological symptoms reached the highest x2 values as Q1-numbness (5.6), Q3-anesthetizes areas in the skin (7.5), Q5-Stinging sensation (5.8), and Q7-pain in the nerves (34.7), while Q4-spots on the skin was 4.94. When more than one question were marked in the LSQ means a 12.8-fold higher to have the disease than a subject who marked only one or none. The high 34% rate of anti-PGL-I seropositivity in the penitentiary, higher levels in LG than NLG. Three additional leprosy cases each were diagnosed on the second (n = 66) and third (n = 14) reevaluations 18 and 36 months after the initial one. Semmes-Weinstein monofilaments demonstrated lower limbs (32.2%) more affected than the upper limbs (25%) with improvement during the follow-up., Interpretation: The NCDR in this population showed an hidden endemic of leprosy as well as the efficacy of a search action on the part of a specialized team with the aid of the LSQ and anti-PGL-I serology as an auxiliary tracking tools., Competing Interests: The authors have declared that no competing interests exist.

Sjögren's Syndrome (SS) is an autoimmune exocrinopathy characterized by the progressive damage of salivary and lacrimal glands associated with lymphocytic infiltration. Identifying new non-invasive biomarkers for SS diagnosis remains a challenge, and alterations in saliva composition reported in patients turn this fluid into a source of potential biomarkers. Among these, proteases are promising candidates since they are involved in several key physio-pathological processes. This study evaluated differentially expressed proteases in SS individuals' saliva using synthetic fluorogenic substrates, zymography, ELISA, and proteomic approaches. Here we reported, for the first time, increased activity of the serine protease dipeptidyl peptidase-4/CD26 (DPP4/CD26) in pSS saliva, the expression level of which was corroborated by ELISA assay. Gelatin zymograms showed that metalloproteinase proteolytic band profiles differed significantly in intensity between control and SS groups. Focusing on matrix metalloproteinase-9 (MMP9) expression, an increased tendency in pSS saliva (p = 0.0527) was observed compared to the control group. Samples of control, pSS, and sSS were analyzed by mass spectrometry to reveal a general panorama of proteases in saliva. Forty-eight protein groups of proteases were identified, among which were the serine proteases cathepsin G (CTSG), neutrophil elastase (ELANE), myeloblastin (PRTN3), MMP9 and several protease inhibitors. This work paves the way for proteases to be explored in the future as biomarkers, emphasizing DPP4 by its association in several autoimmune and inflammatory diseases. Besides its proteolytic role, DPP4/CD26 acts as a cell surface receptor, signal transduction mediator, adhesion and costimulatory protein involved in T lymphocytes activation., 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 Garreto, Charneau, Mandacaru, Nóbrega, Motta, de Araújo, Tonet, Modesto, Paula, de Sousa, Santana, Acevedo and Bastos.)

Objective: to identify the information demands of families of children with Autism Spectrum Disorder., Method: this is a qualitative study conducted through semi-structured and audio-recorded interviews with 55 family members, in the states of Paraná, Ceará, and Macapá, between September 2018 and September 2019. Thematic category analysis and Qualitative Data Analysis Software resources were used for data organization., Results: it was identified that families need information regarding the characteristics of Autism Spectrum Disorder (definition, cause, possibility of cure, prognosis and the probability of having another child with Autism Spectrum Disorder); child's routine and behavior; future rights and expectations., Final Considerations: information demands are relevant to support professionals, health managers and other services in health care organization to support families of children with autism.

Purpose: To develop an equation for estimating the vitreous chamber volume in pseudophakic patients based on the axial length of the eye., Methods: A consecutive series of patients who underwent vitrectomy surgery for a macular hole or an epiretinal membrane were enrolled. The inclusion criteria were as follows: having pseudophakia, being older than 50 years, and having eyes with axial length ranging from 21 to 26 mm. Before the surgery, the axial length was measured using optical biometry. Pars plan vitrectomy was performed, and, after the fluid-air exchange, the vitreous chamber was filled with Brilliant Blue G (0.005%). The infused volume of each eye was recorded. Then, epiretinal membrane peeling or internal limiting membrane peeling and a new fluid-air exchange were performed. Main outcomes and measures were the vitreous chamber volume and axial length., Results: The sample consisted of 112 patients. The mean [standard deviation (SD), range] age was 71 years (7, 53-90). Sixty-five individuals (58%) were women. In 58 (51.8%) patients, surgery was performed on the right eye. The mean (SD; range) axial length was 23.78 mm (0.93; 21.55-25.26), and the mean (SD; range) vitreous chamber volume was 4.96 mL (0.69; 3.60-6.40). Pearson's correlation coefficient (r = 0.950; p < 0.01) was positive, and the coefficient of determination (R 2 ) was 0.902. The estimated regression equation was Y = 0.71X - 11.84, where Y was the vitreous chamber volume, X was the axial length of the eye, the linear coefficient for the straight line was - 11.83, and the angular coefficient was 0.71 (p < 0.01)., Conclusion: These data suggest that the vitreous chamber volume is significantly correlated with the axial length and the former could probably be calculated using biometry. New studies with larger samples will be required to confirm these observations and will allow the development of an algorithm (perhaps non-linear) that includes extreme axial length values and that takes into account other factors such as the status of the lens and sex.

The application of sewage sludge in soils can bring benefits to agricultural productivity, however, the risks arising from this application must be measured and carefully evaluated. Persistent organics compounds and drugs can be present in the sewage sludge and if applied to the soil, they can cause severe risks to the soil biota and contamination of groundwater. This work determined 174 persistent organic compounds and drugs in sludge samples from a wastewater treatment plant using chromatographic methods. The drugs ciprofloxacin, enrofloxacin and diclofenac were quantified, and values varied according to sampling period. For persistent organic compounds, cresols were the most abundant compounds in sewage sludge. With the analyses made of both the elutriate and the filtrate, it was possible to verify the potential for soil retention or leaching that each compound can present with the application of sewage sludge in the agriculture., Competing Interests: The authors declare no conflict of interest., (© 2021 Published by Elsevier Ltd.)

Chagas disease is a debilitating and neglected disease caused by the protozoan Trypanosoma cruzi . Soon after infection, interactions among T. cruzi and host innate immunity cells can drive/contribute to disease outcome. Dendritic cells (DCs), present in all tissues, are one of the first immune cells to interact with Trypanosoma cruzi metacyclic trypomastigotes. Elucidating the immunological events triggered immediately after parasite-human DCs encounter may aid in understanding the role of DCs in the establishment of infection and in the course of the disease. Therefore, we performed a transcriptomic analysis of a 12 h interaction between T. cruzi and MoDCs (monocyte-derived DCs) from three human donors. Enrichment analyses of the 468 differentially expressed genes (DEGs) revealed viral infection response as the most regulated pathway. Additionally, exogenous antigen processing and presentation through MHC-I, chemokine signaling, lymphocyte co-stimulation, metallothioneins, and inflammasome activation were found up-regulated. Notable, we were able to identify the increased gene expression of alternative inflammasome sensors such as AIM2, IFI16, and RIG-I for the first time in a T. cruzi infection. Both transcript and protein expression levels suggest proinflammatory cytokine production during early T. cruzi -DCs contact. Our transcriptome data unveil antiviral pathways as an unexplored process during T. cruzi -DC initial interaction, disclosing a new panorama for the study of Chagas disease outcomes., 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 Gil-Jaramillo, Rocha, Raiol, Motta, Favali, Brigido, Bastos and Santana.)

Plasmodium blood stages, responsible for human to vector transmission, termed gametocytes, are the precursor cells that develop into gametes in the mosquito. Male gametogenesis works as a bottleneck for the parasite life cycle, where, during a peculiar and rapid exflagellation, a male gametocyte produces 8 intracellular axonemes that generate by budding 8 motile gametes. Understanding the molecular mechanisms of gametogenesis is key to design strategies for controlling malaria transmission. In the rodent P. berghei, the microtubule-based motor kinesin-8B (PbKIN8B) is essential for flagellum assembly during male gametogenesis and its gene disruption impacts on completion of the parasitic life cycle. In efforts to improve our knowledge about male gametogenesis, we performed an iTRAQ-based quantitative proteomic comparison of P. berghei mutants with disrupted kinesin-8B gene (ΔPbkin8B) and wild type parasites. During the 15 min of gametogenesis, ΔPbkin8B parasites exhibited important motor protein dysregulation that suggests an essential role of PbKIN8B for the correct interaction or integration of axonemal proteins within the growing axoneme. The energy metabolism of ΔPbkin8B mutants was further affected, as well as the response to stress proteins, protein synthesis, as well as chromatin organisation and DNA processes, although endomitoses seemed to occur. SIGNIFICANCE: Malaria continues to be a global scourge, mainly in subtropical and tropical areas. The disease is caused by parasites from the Plasmodium genus. Plasmodium life cycle alternates between female Anopheles mosquitoes and vertebrate hosts through bites. Gametocytes are the parasite blood forms responsible for transmission from vertebrates to vectors. Inside the mosquito midgut, after stimulation, male and female gametocytes transform into gametes resulting in fertilization. During male gametogenesis, one gametocyte generates eight intracytoplasmic axonemes that generate, by budding, flagellated motile gametes involving a process termed exflagellation. Sexual development has a central role in ensuring malaria transmission. However, molecular data on male gametogenesis and particularly on intracytoplasmic axoneme assembly are still lacking. Since rodent malaria parasites permit the combination of in vivo and in vitro experiments and reverse genetic studies, our group investigated the molecular events in rodent P. berghei gametogenesis. The P. berghei motor ATPase kinesin-8B is proposed as an important component for male gametogenesis. We generated Pbkin8B gene-disrupted gametocytes (ΔPbkin8B) that were morphologically similar to the wild- type (WT) parasites. However, in mutants, male gametogenesis is impaired, male gametocytes are disabled in their ability to assemble axonemes and to exflagellate to release gametes, reducing fertilization drastically. Using a comparative quantitative proteomic analysis, we associated the nonfunctional axoneme of the mutants with the abnormal differential expression of proteins essential to axoneme organisation and stability. We also observed a differential dysregulation of proteins involved in protein biosynthesis and degradation, chromatin organisation and DNA processes in ΔPbkin8B parasites, although DNA condensation, mitotic spindle formation and endomitoses seem to occur. This is the first functional proteomic study of a kinesin gene-disrupted Plasmodium parasite providing new insights into Plasmodium male gametogenesis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: There is growing recognition for a reciprocal, bidirectional link between anxiety disorders and obesity. Although the mechanisms linking obesity and anxiety remain speculative, this bidirectionality suggests shared pathophysiological processes. Neuroinflammation and oxidative damage are implicated in both pathological anxiety and obesity. This study investigates the relative contribution of comorbid diet-induced obesity and stress-induced anxiety to neuroinflammation and oxidative stress., Methods: Thirty-six (36) male Lewis rats were divided into four groups based on diet type and stress exposure: 1) control diet unexposed (CDU) and 2) exposed (CDE), 3) Western-like high-saturated fat diet unexposed (WDU) and 4) exposed (WDE). Neurobehavioral tests were performed to assess anxiety-like behaviors. The catalytic concentrations of glutathione peroxidase and reductase were measured from plasma samples, and neuroinflammatory/oxidative stress biomarkers were measured from brain samples using Western blot. Correlations between behavioral phenotypes and biomarkers were assessed with Pearson's correlation procedures., Results: We found that WDE rats exhibited markedly increased levels of glial fibrillary acidic protein (185 %), catalase protein (215 %), and glutathione reductase (GSHR) enzymatic activity (418 %) relative to CDU rats. Interestingly, the brain protein levels of glutathione peroxidase (GPx) and catalase were positively associated with body weight and behavioral indices of anxiety., Conclusions: Together, our results support a role for neuroinflammation and oxidative stress in heightened emotional reactivity to obesogenic environments and psychogenic stress. Uncovering adaptive responses to obesogenic environments characterized by high access to high-saturated fat/high-sugar diets and toxic stress has the potential to strongly impact how we treat psychiatric disorders in at-risk populations., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: This study evaluates an active search strategy for leprosy diagnosis based on responses to a Leprosy Suspicion Questionnaire (LSQ), and analyzing the clinical, immunoepidemiological and follow-up aspects for individuals living in a prison population., Methods: A cross-sectional study based on a questionnaire posing 14 questions about leprosy symptoms and signs that was distributed to 1,400 prisoners. This was followed by dermatoneurological examination, anti-PGL-I serology and RLEP-PCR. Those without leprosy were placed in the Non-leprosy Group (NLG, n = 1,216) and those diagnosed with clinical symptoms of leprosy were placed in the Leprosy Group (LG, n = 34)., Findings: In total, 896 LSQ were returned (64%), and 187 (20.9%) of the responses were deemed as positive for signs/symptoms, answering 2.7 questions on average. Clinically, 1,250 (89.3%) of the prisoners were evaluated resulting in the diagnosis of 34 new cases (LG), based on well-accepted clinical signs and symptoms, a new case detection rate of 2.7% within this population, while the NLG were comprised of 1,216 individuals. The confinement time medians were 39 months in the LG while it was 36 months in the NLG (p>0.05). The 31 leprosy cases who responded to the questionnaire (LSQ+) had an average of 1.5 responses. The symptoms "anesthetized skin area" and "pain in nerves" were most commonly mentioned in the LG while "tingling, numbness in the hands/feet", "sensation of pricks and needles", "pain in nerves" and "spots on the skin" responses were found in more than 30% of questionnaires in the NLG. Clinically, 88.2% had dysesthetic macular skin lesions and 97.1% presented some peripheral nerve impairment, 71.9% with some degree of disability. All cases were multibacillary, confirming a late diagnosis. Anti-PGL-I results in the LG were higher than in the NLG (p<0.0001), while the RLEP-PCR was positive in 11.8% of the patients., Interpretation: Our findings within the penitentiary demonstrated a hidden prevalence of leprosy, although the individuals diagnosed were likely infected while living in their former communities and not as a result of exposure in the prison. The LSQ proved to be an important screening tool to help identify leprosy cases in prisons., Competing Interests: The authors have declared that no competing interests exist.

Chagas is a neglected tropical disease caused by Trypanosoma cruzi , and affects about 25 million people worldwide. N , N '-Squaramide 17 (S) is a trypanocidal compound with relevant in vivo effectiveness. Here, we produced, characterized, and evaluated cytotoxic and trypanocidal effects of macrophage-mimetic liposomes from lipids extracted of RAW 264.7 cells to release S. As results, the average hydrodynamic diameter and Zeta potential of mimetic lipid membranes containing S (MLS) was 196.5 ± 11 nm and -61.43 ± 2.3 mV, respectively. Drug entrapment efficiency was 73.35% ± 2.05%. After a 72 h treatment, MLS was observed to be active against epimastigotes in vitro (IC 50 = 15.85 ± 4.82 μM) and intracellular amastigotes (IC 50 = 24.92 ± 4.80 μM). Also, it induced low cytotoxicity with CC 50 of 1199.50 ± 1.22 μM towards VERO cells and of 1973.97 ± 5.98 μM in RAW 264.7. MLS also induced fissures in parasite membrane with a diameter of approximately 200 nm in epimastigotes. MLS showed low cytotoxicity in mammalian cells and high trypanocidal activity revealing this nanostructure a promising candidate for the development of Chagas disease treatment.

Triatomines are hematophagous insects that transmit Trypanosoma cruzi , the etiological agent of Chagas disease. This neglected tropical disease represents a global health issue as it is spreading worldwide. The saliva of Triatominae contains miscellaneous proteins crucial for blood feeding acquisition, counteracting host's hemostasis while performing vasodilatory, anti-platelet and anti-coagulant activities, besides modulating inflammation and immune responses. Since a set of biological processes are mediated by protein complexes, here, the sialocomplexomes (salivary protein complexes) of five species of Triatominae were studied to explore the protein-protein interaction networks. Salivary multiprotein complexes from Triatoma infestans, Triatoma dimidiata, Dipetalogaster maxima, Rhodnius prolixus , and Rhodnius neglectus were investigated by Blue-Native- polyacrylamide gel electrophoresis coupled with liquid chromatography tandem mass spectrometry. More than 70 protein groups, uncovering the landscape of the Triatominae salivary interactome, were revealed. Triabin, actin, thioredoxin peroxidase and an uncharacterized protein were identified in sialocomplexes of the five species, while hexamerin, heat shock protein and histone were identified in sialocomplexes of four species. Salivary proteins related to triatomine immunity as well as those required during blood feeding process such as apyrases, antigen 5, procalins, and nitrophorins compose different complexes. Furthermore, unique proteins for each triatomine species were revealed. This study represents the first Triatominae sialocomplexome reference to date and shows that the approach used is a reliable tool for the analysis of Triatominae salivary proteins assembled into complexes., (Copyright © 2020 Santiago, Charneau, Mandacaru, Bentes, Bastos, de Sousa, Ricart, de Araújo and Santana.)

The excessive release of heme during hemolysis contributes to the severity of sickle cell anemia (SCA) by exacerbating hemoglobin S (HbS) autoxidation, inflammation and systemic tissue damage. The present study investigated the effect of hydroxyurea (HU) on free radical neutralization and its stimulation of antioxidant genes in human peripheral blood mononuclear cells (PBMC) and human umbilical vein endothelial cells (HUVEC) in the presence or absence of hemin. HU (100 and 200 μM) significantly reduced the production of intracellular reactive oxygen species (ROS) induced by hemin at 70 μM in HUVEC. HUVECs treated with HU+hemin presented significant increases in nitric oxide (NO) production in culture supernatants. HU alone or in combination with hemin promoted the induction of superoxide dismutase-1 ( SOD1 ) and glutathione disulfide-reductase ( GSR ) in HUVECs and PBMCs, and glutathione peroxidase ( GPX1 ) in PBMCs. Microarray analysis performed in HUVECs indicated that HU induces increased expression of genes involved in the antioxidant response system: SOD2, GSR , microsomal glutathione S-transferase ( MGST1 ), glutathione S-transferase mu 2 ( GSTM2 ), carbonyl reductase 1 ( CBR1 ) and klotho B ( KLB ). Significant increases in expression were observed in genes with kinase activity: protein kinase C beta ( PRKCB ), zeta ( PRKCZ ) and phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 beta ( PIK3C2B ). HU also induced a significant increase in expression of the gene p62/sequestosome ( p62/SQSTM1 ) and a significant decrease in the expression of the transcriptional factor BACH1 in HUVECs. Upstream analysis predicted the activation of Jun, miR-155-5p and mir-141-3p. These results suggest that HU directly scavenges free radicals and induces the expression of antioxidant genes via induction of the Nrf2 signaling pathway., (Copyright © 2020 Santana, Pitanga, de Santana, Zanette, Vieira, Yahouédéhou, Adanho, Viana, Luz, Borges and Goncalves.)

Leishmania infantum is a flagellated protozoan and one of the main causative agents of visceral leishmaniasis. This disease usually affects the human reticuloendothelial system, can cause death and available therapies may lead to serious side effects. Since it is a neglected tropical disease, the incentives for the development of new drugs are insufficient. It is important to know Leishmania virulence factors that contribute most to the disease in order to develop drugs. In the present work, we have produced L. infantum prolyl oligopeptidase (rPOPLi) in Escherichia coli , and investigated its biochemical properties as well as the effect of POP inhibitors on its enzymatic activity and on the inhibition of the macrophage infection by L. infantum . The optimal activity occurred at pH 7.5 and 37°C in the presence of DTT, the latter increased rPOPLi catalytic efficiency 5-fold on the substrate N- Suc-Gly-Pro-Leu-Gly-Pro-AMC. The enzyme was inhibited by TPCK, TLCK and by two POP specific inhibitors, Z-Pro-prolinal (ZPP, IC 50 4.2 nM) and S17092 (IC 50 3.5 nM). Besides being a cytoplasmic enzyme, POPLi is also found in punctuate structures within the parasite cytoplasm or associated with the parasite plasma membrane in amastigotes and promastigotes, respectively. Interestingly, S17092 and ZPP prevented parasite invasion in murine macrophages, supporting the involvement of POPLi in the invasive process of L. infantum. These data suggest POPLi as a virulence factor that offers potential as a target for designing new antileishmanial drugs., (Copyright © 2020 Lasse, Azevedo, de Araújo, Motta, Andrade, Rocha, Sampaio, Charneau, Gèze, Grellier, Santana and Bastos.)

Triatomines are blood-feeding insects that prey on vertebrate hosts. Their saliva is largely responsible for their feeding success. The triatomine salivary content has been studied over the past decades, revealing multifunctional bioactive proteins targeting the host´s hemostasis and immune system. Recently, sequencing of salivary-gland mRNA libraries revealed increasingly complex and complete transcript databases that have been used to validate the expression of deduced proteins through proteomics. This review provides an insight into the journey of discovery and characterization of novel molecules in triatomine saliva., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The study of international collaborations can help in understanding the benefits of such relationships and aid in developing national financing policies. In this paper, the international collaboration of Brazilian scientists was studied using SciVal ® and Incites ® database, looking at its effect on the universities, financing agencies and different areas of knowledge and research topic clusters. Cluster and principal component analyses of scientometric data were carried out. While the results confirmed known knowledge that international collaboration increases impact, this study shows that Brazilian researchers are contributing to prominent research topics worldwide, in all areas of knowledge. This finding is contrary to several points of view that identify Brazil as a regional and not an international partner in science. Important also to note the impact of Brazilian authors in international collaboration that is well above the world mean. The collaboration of Brazil with foreign partners brings benefits for both sides, creating the opportunity of Brazilian research access to financing from international agencies. Increases in measures of impact are also seen for both sides. Foreign partners likewise benefit from higher impact factors in the same topic cluster, when collaborating with Brazilian partners. Publishing open access in high impact journals is fundamental for maintaining Brazilian science at the forefront., (© Akadémiai Kiadó, Budapest, Hungary 2020.)

Oligopeptidases B (OPB) belong to the S9 prolyl oligopeptidase family and are expressed in prokaryotes, some eukaryotes and in some higher plants. OPB is not found in any of the mammalian genomes available to date. Evidences indicate that OPB participates in the infections caused by trypanosomatids Trypanosoma cruzi, Leishmania spp. and Trypanosoma brucei spp and therefore it is considered an important virulence factor. Trypanosomatids from the genera Leishmania and Trypanosoma also present other OPB, named OPB2. A more accurate investigation of trypanosomatid OPB sequences brought attention to what could be a third OPB sequence (OPB3). This review aims to discuss biochemical, structural, phylogenetic and functional properties of OPB and its potential as target for the development of drugs against Chagas disease, leishmaniasis and African trypanosomiasis., (Copyright © 2019 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Chagas disease is caused by the protozoan Trypanosoma cruzi, affecting around 8 million people worldwide. After host cell invasion, the infective trypomastigote form remains 2-4 hours inside acidic phagolysosomes to differentiate into replicative amastigote form. In vitro acidic-pH-induced axenic amastigogenesis was used here to study this step of the parasite life cycle. After three hours of trypomastigote incubation in amastigogenesis promoting acidic medium (pH 5.0) or control physiological pH (7.4) medium samples were subjected to three rounds of centrifugation followed by ultrafiltration of the supernatants. The resulting exoproteome samples were trypsin digested and analysed by nano flow liquid chromatography coupled to tandem mass spectrometry. Computational protein identification searches yielded 271 and 483 protein groups in the exoproteome at pH 7.4 and pH 5.0, respectively, with 180 common proteins between both conditions. The total amount and diversity of proteins released by parasites almost doubled upon acidic incubation compared to control. Overall, 76.5% of proteins were predicted to be secreted by classical or non-classical pathways and 35.1% of these proteins have predicted transmembrane domains. Classical secretory pathway analysis showed an increased number of mucins and mucin-associated surface proteins after acidic incubation. However, the number of released trans-sialidases and surface GP63 peptidases was higher at pH 7.4. Trans-sialidases and mucins are anchored to the membrane and exhibit an enzyme-substrate relationship. In general, mucins are glycoproteins with immunomodulatory functions in Chagas disease, present mainly in the epimastigote and trypomastigote surfaces and could be enzymatically cleaved and released in the phagolysosome during amastigogenesis. Moreover, evidence for flagella discard during amastigogenesis are addressed. This study provides the first comparative analysis of the exoproteome during amastigogenesis, and the presented data evidence the dynamism of its profile in response to acidic pH-induced differentiation., Competing Interests: The authors have declared that no competing interests exist.

The objective was to investigate the effects of functional (FT) and traditional (TT) training on trunk muscles maximal isometric strength, rate of force development and endurance with trained elderly women. Forty-five elderly women were directed into three groups: FT (n =1 6), TT (n = 14) and Control (n = 15). The FT (multi-planar, and multi-articular movements) and TT (primarily machine-based resistance exercises) performed mobility, muscle strength and power exercises. Both training groups also performed intermittent cardiometabolic activities. The maximum strength and endurance of the trunk muscles were verified, both at baseline and after 12 weeks of training (3xweek for 50 min each). Data were analyzed using a 2-way ANCOVA with contrast of adjusted mean values. FT significantly increased all variables: maximum trunk flexor strength (p = 0.002, 22%); rate of flexor force development (p = 0.001, 84%); trunk extensors maximal strength (p = 0.003, 17%); trunk extensor rate of force development (p = 0.05, 16%); trunk flexors (p = 0.001, 19%) and extensors (p = 0.017, 13%) endurance compared to baseline. TT showed an increase only in RFD of trunk extensors (p = 0.003, 53%), and flexors (p = 0.033, 42%), and trunk flexors endurance (p = 0.008, 11%). However, there was no statistically significant difference between groups. FT promoted improvement in all variables; strength, endurance and rate of force development of the trunk flexors and extensors of the elderly. On the other hand, TT improved only the rate of force development of trunk flexors and extensors and endurance of the trunk flexors. FT is recommended for elderly women as it improves a broader array of physiological parameters., (© Journal of Sports Science and Medicine.)

Background: While traditional resistance exercises have been widely used to promote muscle strength and hypertrophy in the elderly, few studies have reported the use of a functional approach in which common patterns for daily activities are considered the primary stimulus., Objective: Investigate whether functional training has similar effects the traditional on body composition and muscle strength components in physically active older women., Methods: Forty-seven older women completed a randomized and crossover clinical trial, distributed in three groups: Functional or Traditional Training (FUNCT/TRAD: n = 32; 65.28 ± 4.96 years) and Stretching Group (STRETCH: n = 15; 64.40 ± 3.68 years). Maximal dynamic strength was verified with the 1 repetition maximum (RM) test in the leg press and rowing machines. Muscular power was analyzed using 50% of the maximum load, speed was determined using a linear encoder, and isometric strength was analyzed with hand and lumbar dynamometers. ANOVA for repeated measures was applied for comparisons., Results: The FUNCT showed a significant decrease in fat percentage (p = 0.015, 3.51%) and the TRAD a significant increase in lean mass (p = 0.008, 2.92%). Both FUNCT and TRAD generated significant increases in all components of muscle strength compared to baseline whereas STRETCH showed declines in these variables. No statistically significant differences were observed between the experimental groups in body composition., Conclusion: Functional and traditional training are equally efficient in improving strength components in physically active older women and, therefore, they may be complementary to combat some of the deleterious effects of senescence. This trial was registered at Brazilian Registry of Clinical Trials (RBR-9Y8KJQ)., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In this work, we evaluated the ovicidal activity and the deleterious effects of cashew (Anacardium occidentale) nut shell oil and its fractions on the development of Musca domestica and Chrysomya megacephala, important vectors of several diseases. The insecticidal effects of this plant were also measured on the first and second instar larvae of Anticarsia gemmatalis and Spodoptera frugiperda, soy and maize pests, respectively. The fly eggs and the crop pest insect larvae were exposed to the cashew (Anacardium occidentale) nut shell liquid (CNSL) and its fractions: technical CNSL, anacardic acid, cardanol and cardol. The results show that the cardol fraction, for both species of flies, presented the lowest lethal concentration with LC 50 of 80.4 mg/L for M. domestica and 90.2 mg/L for C. megacephala. For the mortality of the larvae of A. gemmatalis and S. frugiperda, the most effective fraction was anacardic acid with LC 50 of 295.1 mg/L and 318.4 mg/L, respectively. In all species, the mortality rate of the commercial compounds (cypermethrin 600 mg/L and temephos 2 mg/L) was higher than that of the evaluated compounds. Despite this, the results obtained suggest their potential in field trials, once the fractions of A. occidentale presented high mortality at low lethal concentrations in laboratory conditions, with the possibility of integrated use in the control of disease vectors and agricultural pests, employing ecofriendly compounds., (© 2019 Wiley-VHCA AG, Zurich, Switzerland.)

Objective- Arteriovenous fistulae (AVF) are the most common access created for hemodialysis; however, many AVF fail to mature and require repeated intervention, suggesting a need to improve AVF maturation. Eph-B4 (ephrin type-B receptor 4) is the embryonic venous determinant that is functional in adult veins and can regulate AVF maturation. Cav-1 (caveolin-1) is the major scaffolding protein of caveolae-a distinct microdomain that serves as a mechanosensor at the endothelial cell membrane. We hypothesized that Cav-1 function is critical for Eph-B4-mediated AVF maturation. Approach and Results- In a mouse aortocaval fistula model, both Cav-1 mRNA and protein were increased in the AVF compared with control veins. Cav-1 KO (knockout) mice showed increased fistula wall thickening ( P=0.0005) and outward remodeling ( P<0.0001), with increased eNOS (endothelial NO synthase) activity compared with WT (wild type) mice. Ephrin-B2/Fc inhibited AVF outward remodeling in WT mice but not in Cav-1 KO mice and was maintained in Cav-1 RC (Cav-1 endothelial reconstituted) mice (WT, P=0.0001; Cav-1 KO, P=0.7552; Cav-1 RC, P=0.0002). Cavtratin-a Cav-1 scaffolding domain peptide-decreased AVF wall thickness in WT mice and in Eph-B4 het mice compared with vehicle alone (WT, P=0.0235; Eph-B4 het, P=0.0431); cavtratin also increased AVF patency (day 42) in WT mice ( P=0.0275). Conclusions- Endothelial Cav-1 mediates Eph-B4-mediated AVF maturation. The Eph-B4-Cav-1 axis regulates adaptive remodeling during venous adaptation to the fistula environment. Manipulation of Cav-1 function may be a translational strategy to enhance AVF patency.

Aedes aegypti and Culex quinquefasciatus are vectors of diseases that constitute public health problems. The discovery of products capable of inhibiting their development which are less harmful to the environment would have a huge impact on vector control. Here, natural cashew nut shell liquid (CNSL), technical CNSL, anacardic acid, cardanol, and cardol were isolated from Anacardium occidentale and evaluated for larvicidal and pupicidal activity against Ae. aegypti and Cx. quinquefasciatus under laboratory and field conditions. The activities of phenol, resorcinol, salicylic acid, and pentadecane, commercial chemicals similar in structure to nut shell derivatives, were also evaluated. All of the fractions extracted from A. occidentale oil exerted larvicidal effects against both mosquito species (LC 50 5.4-22.6 mg/L), and two of the aforementioned were effective against pupae (LC 50 90.8-109.7 mg/L). Of all the fractions tested, cardol demonstrated the strongest larvicidal and pupicidal effects and presented the most prolonged residual activity against the larvae and pupae of Ae. aegypti and Cx. quinquefasciatus under field conditions. This study suggests that A. occidentale nut shell derivatives are sustainable and promising candidates for the development of novel insecticides to overcome the problem of harmful chemical insecticides.

Triatominae bugs are the vectors of Chagas disease, a major concern to public health especially in Latin America, where vector-borne Chagas disease has undergone resurgence due mainly to diminished triatomine control in many endemic municipalities. Although the majority of Triatominae species occurs in the Americas, species belonging to the genus Linshcosteus occur in India, and species belonging to the Triatoma rubrofasciata complex have been also identified in Africa, the Middle East, South-East Asia, and in the Western Pacific. Not all of Triatominae species have been found to be infected with Trypanosoma cruzi , but the possibility of establishing vector transmission to areas where Chagas disease was previously non-endemic has increased with global population mobility. Additionally, the worldwide distribution of triatomines is concerning, as they are able to enter in contact and harbor other pathogens, leading us to wonder if they would have competence and capacity to transmit them to humans during the bite or after successful blood feeding, spreading other infectious diseases. In this review, we searched the literature for infectious agents transmitted to humans by Triatominae. There are reports suggesting that triatomines may be competent vectors for pathogens such as Serratia marcescens, Bartonella , and Mycobacterium leprae , and that triatomine infection with other microrganisms may interfere with triatomine- T. cruzi interactions, altering their competence and possibly their capacity to transmit Chagas disease.

C ircadian l ocomotor o utput c ycles k aput (CLOCK) is a transcription factor that activates transcription of clock-controlled genes by heterodimerizing with BMAL1 and binding to E-box elements on DNA. Although several phosphorylation sites on CLOCK have already been identified, this study characterizes a novel phosphorylation site at serine 845 (Ser-836 in humans). Here, we show that CLOCK is a novel AKT substrate in vitro and in cells, and this phosphorylation site is a negative regulator of CLOCK nuclear localization by acting as a binding site for 14-3-3 proteins. To examine the role of CLOCK phosphorylation in vivo , Clock S845A knockin mice were generated using CRISPR/Cas9 technology. Clock S845A mice are essentially normal with normal central circadian rhythms and hemodynamics. However, examination of core circadian gene expression from peripheral tissues demonstrated that Clock S845A mice have diminished expression of Per2, Reverba, Dbp, and Npas2 in skeletal muscle and Per2, Reverba, Dbp, Per1 , Rora, and Npas2 in the liver during the circadian cycle. The reduction in Dbp levels is associated with reduced H3K9ac at E-boxes where CLOCK binds despite no change in total CLOCK levels. Thus, CLOCK phosphorylation by AKT on Ser-845 regulates its nuclear translocation and the expression levels of certain core circadian genes in insulin-sensitive tissues.

High-density lipoprotein (HDL) is cardioprotective because of its anti-atherogenic properties. Nevertheless, our goal to optimize HDL cholesterol (HDL-C) levels have had little effects on the atherothrombotic burden and suggests a closer look be taken at HDL function and dysfunction. HDL is a group of complex macromolecules composed of a lipid- and proteome that work in synergy to execute its anti-inflammatory, anti-atherogenic, and anti-thrombotic effects. However, throughout its life-span in circulation, HDL undergoes significant modification. Carbamylation, a non-enzymatic and irreversible post-translational modification of protein, is one effector of HDL which has growing evidence that it plays a crucial role in the development and progression of atherosclerotic cardiovascular disease (ASCVD), particularly in chronic kidney disease (CKD). We summarize HDL's function, susceptibility to modification, and discuss HDL carbamylation and its effect in cardiovascular disease.

Background: Post-traumatic stress disorder (PTSD) and obesity are highly prevalent in adolescents. Emerging findings from our laboratory and others are consistent with the novel hypothesis that obese individuals may be predisposed to developing PTSD. Given that aberrant fear responses are pivotal in the pathogenesis of PTSD, the objective of this study was to determine the impact of an obesogenic Western-like high-fat diet (WD) on neural substrates associated with fear., Methods: Adolescent Lewis rats (n = 72) were fed with either the experimental WD (41.4% kcal from fat) or the control diet. The fear-potentiated startle paradigm was used to determine sustained and phasic fear responses. Diffusion tensor imaging metrics and T2 relaxation times were used to determine the structural integrity of the fear circuitry including the medial prefrontal cortex (mPFC) and the basolateral complex of the amygdala (BLA)., Results: The rats that consumed the WD exhibited attenuated fear learning and fear extinction. These behavioral impairments were associated with oversaturation of the fear circuitry and astrogliosis. The BLA T2 relaxation times were significantly decreased in the WD rats relative to the controls. We found elevated fractional anisotropy in the mPFC of the rats that consumed the WD. We show that consumption of a WD may lead to long-lasting damage to components of the fear circuitry., Conclusions: Our findings demonstrate that consumption of an obesogenic diet during adolescence has a profound impact in the maturation of the fear neurocircuitry. The implications of this research are significant as they identify potential biomarkers of risk for psychopathology in the growing obese population., (Copyright © 2018 Elsevier Inc. All rights reserved.)