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A kinetic study of the chemiluminescent (CL) reaction mechanism of lophine-derived hydroperoxides and silylperoxides induced by a base and fluoride, respectively, provided evidence for the formation of a 1,2-dioxetane as a high-energy intermediate (HEI) of this CL transformation. This was postulated using a linear Hammett relationship, consistent with the formation of negative charge on the transition state of HEI generation (ρ > 1). The decomposition of this HEI leads to chemiexcitation with overall low singlet excited state formation quantum yield (Φ S from 1.1 to 14.5 × 10 -5 E mol -1 ); nonetheless, Φ S = 1.20 × 10 -3 E mol -1 was observed with both peroxides substituted with bromine. The use of electron-donating substituents increases chemiexcitation efficiency, while it also reduces the rate for both formation and decomposition of the HEI. Different possible pathways for HEI decomposition and chemiexcitation are discussed in light of literature data from the perspective of the substituent effect. This system could be explored in the future for analytical and labeling purposes or for biological oxidation through chemiexcitation.

Objective: to identify the implementation process of the World Health Organization Surgical Safety Checklist in Brazilian hospitals., Methods: this is a cross-sectional study with 531 participants during a Congress of Perioperative Nursing, promoted by the Brazilian Association of Operating Room Nurses, Anesthetic Recovery and Material and Sterilization Center, in 2017., Results: among the nursing professionals included, 84.27% reported the checklist implementation in the workplace. Regarding daily application in the Sign-in stage, 79.65% of professionals confirmed patient identification with two indicators; in the Time-out stage, 51.36% of surgeries started regardless of confirmation of one of the items. In the Sign-out stage, 69.34% of professionals did not count or occasionally counted the surgical instruments and suture needles, and only 36.36% reviewed concerns about postoperative recovery., Conclusion: this study identified needs for improvements in applying the checklist in the Brazilian reality, to guarantee safer surgical procedures.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm and was the first neoplastic disease associated with a well-defined genotypic anomaly - the presence of the Philadelphia chromosome. The advances in cytogenetic and molecular assays are of great importance to the diagnosis, prognosis, treatment, and monitoring of CML. The discovery of the breakpoint cluster region (BCR)-Abelson murine leukemia (ABL) 1 fusion oncogene has revolutionized the treatment of CML patients by allowing the development of targeted drugs that inhibit the tyrosine kinase activity of the BCR-ABL oncoprotein. Tyrosine kinase inhibitors (known as TKIs) are the standard therapy for CML and greatly increase the survival rates, despite adverse effects and the odds of residual disease after discontinuation of treatment. As therapeutic alternatives, the subsequent TKIs lead to faster and deeper molecular remissions; however, with the emergence of resistance to these drugs, immunotherapy appears as an alternative, which may have a cure potential in these patients. Against this background, this article aims at providing an overview on CML clinical management and a summary on the main targeted drugs available in that context., Competing Interests: Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors contributed their efforts in this manuscript., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

The need for new immunomodulatory drugs is due to the side effects associated with the prolonged use of the currently used immunomodulatory drugs. In this context, the present work aimed to investigate the immunomodulatory effect of an ethanolic concentrated extract from Physalis angulata. The cytotoxicity of samples was determined using peritoneal macrophages though the Alamar Blue assay. The immunomodulatory activity of the ethanolic extract from P. angulata on activated macrophages was determined by measurement of nitrite and cytokine production. The immunosuppressive effects of the ethanolic extract from P. angulata was evaluated on lymphocyte proliferation and cytokine production. The effects of the extract on cell cycle progression and cell death on lymphocytes were evaluated by flow cytometry. Lastly, the ethanolic extract from P. angulata was tested in vivo in toxicological tests and in models of peritonitis and delayed-type hypersensitivity response. The ethanolic extract from P. angulata decreased nitrite, interleukin-6, interleukin-12, and TNF- α production by activated macrophages without affecting the cell viability. In addition, the ethanolic extract from P. angulata inhibited lymphoproliferation and the secretion of interleukin-2, interleukin-6, and IFN- γ , and increased interleukin-4 secretion by activated splenocytes. Flow cytometry analysis in lymphocyte cultures showed that treatment with the ethanolic extract from P. angulata induces cell cycle arrest in the G1 phase followed by cell death by apoptosis. Moreover, mice treated with the extract from P. angulata at 100 or 200 mg/kg did not show signs of toxicity or alterations in serum components. Finally, the ethanolic extract from P. angulata significantly reduced neutrophil migration and reduced paw edema in bovine serum albumin-induced the delayed-type hypersensitivity response model. Our results demonstrate the potential of the ethanolic extract of P. angulata as an alternative for the treatment of immune-inflammatory diseases., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: High-intensity functional training (HIFT) has become more popular, and the number of practitioners has increased; however, it remains unclear whether perturbations in the immune parameters occur, even after one single bout. Our aim was to examine acute leucocyte, muscle damage, and stress marker responses following a single 'Cindy' workout session, and compare the results between novice and experienced participants., Material and Methods: Twenty-three HIFT practitioners (age 31.0 ± 1.0 years) completed the 'Cindy' workout. They were categorized as novice (3-8 months of experience; n = 10) and experienced (≥18 months; n = 13). White blood cell (WBC) count, plasma creatine kinase (CK) activity, blood cortisol level, and lactate concentration were measured. Blood analysis was performed before (pre-ex), immediately after (post-ex), 30 min after (post-30 min), and 24 h after (post-24 h) a single 'Cindy' workout session., Results: WBC count was higher post-ex (6.8 to 11.8x103/μL) and returned to baseline values within post-30 min (p<0.01). Neutrophil (3.3 to 4.5x103/μL) and lymphocyte levels (2.8 to 5.9x103/μL) were higher post-ex and returned to baseline values after post-24 h, yet lymphocytopoenia (2.2x103/μL) was observed at post-30 min (p<0.01). CK increased post-ex (174.9 to 226.7 U.L-1) and remained elevated post-24 h. Cortisol (14.7 to 17.0 μg/dL) and lactate (1.9 to 13.5 mmol.l-1) responses increased post-ex, but only the lactate level was reduced at post-30 min (p<0.01). The experienced participants had higher WBC, lymphocyte, and cortisol concentrations post-ex than the novice ones (p<0.01)., Conclusions: A single HIFT session elicited significant acute perturbations in WBC count, stress markers, and muscle tissue, which is like other similar regimens. Importantly, the experienced participants showed greater lymphocyte and cortisol responses than the novice ones., Competing Interests: The authors have declared that no competing interests exist.

Coumarins exhibit a wide variety of biological effects, including activities in the cardiovascular system and the aim of this study was to evaluate the vascular therapeutic potential of 7-Hydroxicoumarin (7-HC). The vascular effects induced by 7-HC (0.001 μM-300 μM), were investigated by in vitro approaches using isometric tension measurements in rat superior mesenteric arteries and by in silico assays using Ligand-based analysis. Our results suggest that the vasorelaxant effect of 7-HC seems to rely on potassium channels, notably through large conductance Ca 2+ -activated K + (BK Ca ) channels activation. In fact, 7-HC (300 μM) significantly reduced CaCl 2 -induced contraction as well as the reduction of intracellular calcium mobilization. However, the relaxation induced by 7-HC was independent of store-operated calcium entry (SOCE). Moreover, in silico analysis suggests that potassium channels have a common binding pocket, where 7-HC may bind and hint that its binding profile is more similar to quinine's than verapamil's. These results are compatible with the inhibition of Ca 2+ release from intracellular stores, which is prompted by phenylephrine and caffeine. Taken together, these results demonstrate a therapeutic potential of 7-HC on the cardiovascular system, making it a promising lead compound for the development of drugs useful in the treatment of cardiovascular diseases., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Mining, although relevant and indispensable for human socioeconomic development, is considered one of the most polluting anthropogenic activities. Water resources are the most vulnerable environmental compartment to the direct impacts of mining, especially in the semi-arid regions. In these regions, mining activity constitutes an important challenge in the management of water resources; since its impacts can be maximized by the adverse meteorological conditions. This study aimed to assess the level of contamination in water resources of three important mining areas in a semi-arid region, where approximately 70,000 people live. The concentrations of eleven heavy metals in sediment, surface and groundwater samples were determined by ICP OES. The results obtained for water samples indicated significant contamination by Cd, Pb, and U, based on the limits established by Brazilian and international regulatory legislation. In the case of sediment samples, higher concentrations of Cr, Cu, Ni, and V were observed. Pollution indices (PLI, CF and I geo ) revealed moderate to extreme contamination mainly along the Jacaré and Contas rivers. The Pearson correlation, Principal Component, and Hierarchical Cluster analyses were performed to identify patterns in the distribution of elements and common sources of pollution. The results suggested that the concentrations of Co, Cr, Cu, Fe, Mn, Ni, and V were mainly related to mining activities and, to a lesser extent, natural sources. In the case of Cd and Pb, contamination may have an important contribution from fertilizers use, whereas Zn has a mixed source of both lithogenic and anthropogenic origin. On the other hand, the high concentrations of U, specifically in groundwater samples, were associated with geogenic causes. Although the potential ecological risk values indicated a low ecological risk; other sediment quality indices (TEL, PEL, ΣTU, and PEL-Q) revealed that there is 25% of the probability that the content of heavy metals in water resources near the mining areas induces adverse toxic effects on aquatic organisms., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

This current study presents the phytochemical analysis of Croton velutinus, describing phenylpropanoids obtained from this species. The fractionation of the roots hexane extract led to the isolation of four new phenylpropanoids derivatives, velutines A-D (1-4) and three known (5-7). Their structures were established based on spectroscopic (1D-2D NMR; HRMS and IR) analysis. Cytotoxic, trypanocidal and anti-inflammatory activities of compounds 1-7 were evaluated. Only compounds 2 and 5 showed cytotoxic activity against cancer cell lines (B16F10, HL-60, HCT116, MCF-7 and HepG2), with IC 50 values ranging from 6.8 to 18.3 μM and 11.1 to 18.3 μM, respectively. Compounds 2 and 5 also showed trypanocidal activity against bloodstream trypomastigotes with EC 50 values of 9.0 and 9.58 μM, respectively. Finally, the anti-inflammatory potential of these compounds was evaluated on cultures of activated macrophages. All compounds exhibited concentration-dependent suppressive activity on the production of nitrite and IL-1β by macrophages stimulated with LPS and IFN-γ. These results indicate phenylpropanoids esters (2 and 5) from C. velutinus as promising cytotoxic, trypanocidal and anti-inflammatory candidates that warrants further studies., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Brazil's HIV burden has greatly increased over the past decade, especially for socially marginalized and vulnerable groups such as adolescents, women, and men who have sex with men. The reasoning for worsening HIV outcomes is complex, but ongoing economic and political crises have placed extreme operational and financial burdens on both the public health system and HIV-related civil society, affecting both treatment and prevention efforts and delivery., Context: Community-based HIV-related health-promotion activities have continued in Nova Iguaçu, Rio de Janeiro, despite these setbacks. These efforts have been led by a semi-independent community advisory board and engagement group based at the Hospital Geral de Nova Iguaçu with support from researchers based at the Oswaldo Cruz Foundation., Methods: The research team supported, documented, and participated in various activities led by the community advisory board and engagement group from 2017-2018 including meetings, community workshops/lectures, production of health promotion materials, and the dissemination of research findings., Results: The research team utilized the concepts of vernacular knowledge and critical pedagogy to describe and document the ongoing, bottom-up approach, community-led efforts of the community advisory board and engagement group. In particular, we describe the process of stakeholder engagement, popularization of research results, and resource sharing spearheaded by the community advisory board in Nova Iguaçu., Conclusion: The community advisory board demonstrates how community-led efforts are essential to HIV and AIDS response efforts in light of worsening HIV burdens and global shifts towards biomedicalization. Their HIV-related activities rely on existing community networks and resources with secondary support from a research team. This illustrates a key intervention point between traditional research and an empowering community mobilization that can inform similar efforts in other low-resource settings.

This paper focuses on our research and intervention in health promotion with patients and communities affected by various infectious diseases, in the project Knowledge-Sharing Platform. This project is developed at the National Institute of Infectious Diseases Evandro Chagas in the Oswaldo Cruz Foundation, Rio de Janeiro, Brazil, and promotes the continuing involvement of health researchers and professionals in the collaborative production of knowledge on health with patients and community groups and in their training as community health promoters. The new epidemic scenario created the demand for a space of dialogue and knowledge-sharing on the prevention of COVID-19 transmission. Due to the interruption of regular activities in the Knowledge-Sharing Platform, a strategy was launched to serve as a link between science and society and help overcome the social isolation imposed by the COVID-19 pandemic. The WhatsApp group allowed project members to participate by addressing questions (audio) on COVID-19 through mediation by community group leaders. The main questions by participants related to risk factors, transmission, immunity to the novel coronavirus, care related to prevention, symptoms, and treatment; and COVID-19 and influenza vaccine. The educational material Caring in the Age of COVID-19 was produced and shared with community leaders and distributed to the respective groups and was eventually shared in their communities as a response to a demand for knowledge that responds to the concerns of people already exposed to structural vulnerability.

Mesenchymal stem/stromal cells (MSCs) are stromal-derived non-hematopoietic progenitor cells that reside in and can be expanded from various tissues sources of adult and neonatal origin, such as the bone marrow, umbilical cord, umbilical cord blood, adipose tissue, amniotic fluid, placenta, dental pulp and skin. The discovery of the immunosuppressing action of MSCs on T cells has opened new perspectives for their use as a therapeutic agent for immune-mediated disorders, including allergies. Atopic dermatitis (AD), a chronic and relapsing skin disorder that affects up to 20% of children and up to 3% of adults worldwide, is characterized by pruritic eczematous lesions, impaired cutaneous barrier function, Th2 type immune hyperactivation and, frequently, elevation of serum immunoglobulin E levels. Although, in the dermatology field, the application of MSCs as a therapeutic agent was initiated using the concept of cell replacement for skin defects and wound healing, accumulating evidence have shown that MSC-mediated immunomodulation can be applicable to the treatment of inflammatory/allergic skin disorders. Here we reviewed the pre-clinical and clinical studies and possible biological mechanisms of MSCs as a therapeutic tool for the treatment of atopic dermatitis., (Copyright © 2020 Daltro, Meira, Santos, Ribeiro dos Santos and Soares.)

Chronic Chagas disease cardiomyopathy (CCC) is the most frequent and severe form of this parasitic disease. CCC is caused by a progressive inflammation in the heart, resulting in alterations that can culminate in heart failure and death. The use of dendritic cells (DCs) appears as an option for the development of treatments due to their important role in regulating immune responses. Here, we investigated whether tolerogenic cells (tDCs) could interfere with the progression of CCC in an experimental model of Chagas disease. The tDCs were generated and characterized as CD11b + CD11c + cells, low expression of MHC-II, CD86, CD80, and CD40, and increased expression of PD-L. These cells produced low levels of IL-6 and IL-12p70 and higher levels of IL-10, compared to mature DCs (mDCs). Interestingly, tDCs inhibited lymphoproliferation and markedly increased the population of FoxP3 + Treg cells in vitro , compared to mature DCs. In a mouse model of CCC, treatment with tDCs reduced heart inflammation and fibrosis. Furthermore, tDCs treatment reduced the gene expression of pro-inflammatory cytokines ( Ifng and Il12 ) and of genes related to cardiac remodeling ( Col1a2 and Lgals3 ), while increasing the gene expression of IL-10. Finally, administration of tDCs, increased the percentage of Treg cells in the hearts and spleens of chagasic mice. Ours results show that tolerogenic dendritic cells have therapeutic potential on CCC, inhibiting disease progression., (Copyright © 2020 Santos, Aragão-França, Meira, Cerqueira, Vasconcelos, Nonaka, Pontes-de-Carvalho and Soares.)

Cardiovascular diseases (CVD) are the leading cause of death worldwide. Growth factor therapy has emerged as novel therapeutic strategy under investigation for CVD. In this sense, adrenomedullin-2 (ADM-2) has been recently identified as a new angiogenic factor able to regulate the regional blood flow and cardiovascular function. However, the therapeutic value of ADM-2 is limited by its short biological half-life and low plasma stability. Poly (lactic-co-glycolic acid) (PLGA) micro- and nanoparticles have been investigated as growth factor delivery systems for cardiac repair. In this study, we aimed to develop PLGA nanoparticles containing ADM-2 intended for therapeutic angiogenesis. PLGA nanoparticles containing ADM-2 were prepared by a double emulsion modified method, resulting in 300 nm-sized stable particles with zeta potential around - 30 mV. Electron microscopy analysis by SEM and TEM revealed spherical particles with a smooth surface. High encapsulation efficiency was reached (ca.70%), as quantified by ELISA. ADM-2 associated to polymer nanoparticles was also determined by EDS elemental composition analysis, SDS-PAGE and LC-MS/MS for peptide identification. In vitro release assays showed the sustained release of ADM-2 from polymer nanoparticles for 21 days. Cell viability experiments were performed in J774 macrophages and H9c2 cardiomyocyte cells, about which PLGA nanoparticles loaded with ADM-2 did not cause toxicity in the range 0.01-1 mg/ml. Of note, encapsulated ADM-2 significantly induced cell proliferation in EA.hy926 endothelial cells, indicating the ADM-2 bioactivity was preserved after the encapsulation process. Collectively, these results demonstrate the feasibility of using PLGA nanoparticles as delivery systems for the angiogenic peptide ADM-2, which could represent a novel approach for therapeutic angiogenesis in CVD using growth factor therapy., 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 © 2019 Elsevier B.V. All rights reserved.)

Purpose: To describe and characterize a finding, i.e., delayed posterior leakage of food residue during swallowing, according to age, gender and food consistency, which occurred in the event., Methods: Data were collected through the analysis of each functional videonasoendoscopy test of swallowing previously recorded in a specialist outpatient clinic. The study population included 200 patients, both males and females, aged between 46 and 87 years, with and without an underlying pathology for dysphagia. The images were studied individually by the researcher and analyzed by judges in order to identify and select images that would confirm the presence or absence of the study event., Results: Delayed escape was found in 45 out of the 200 analyzed tests. The tests selected for the study showed delayed posterior bolus leakage in at least one consistency. The highest frequency of delayed posterior leakage occurred with fluids. The analysis showed the significance of the study event with the population related to older ages in the sample analyzed., Conclusion: Delayed posterior leakage occurs predominantly in the liquid consistency in older populations with no gender predominance.

The Scanning Bipolar Electrochemical Microscope (SBECM) allows precise positioning of an electrochemical micro-probe serving as bipolar electrode that can be wirelessly interrogated by coupling the electrochemical detection reaction with an electrochemiluminescent reporting process. As a result, the spatially heterogeneous concentrations of an analyte of interest can be converted in real time into a map of sample reactivity. However, this can only be achieved upon optimization of the analytical performance ensuring adequate sensitivity. Here, we present the evaluation and optimized operation of the SBECM for the detection of small changes in local O 2 concentrations. Parameters for achieving an improved sensitivity as well as possibilities for improving the signal-to-noise ratio in the optical signal readout are evaluated. The capability of the SBECM for O 2 detection is shown at controlled conditions by recording the topography of a patterned sample and monitoring O 2 evolution from a photoelectrocatalyst material., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Chagas disease is an illness caused by the protozoan parasite Trypanosoma cruzi. The current chemotherapy is based on benznidazole, and, in some countries, Nifurtimox, which is effective in the acute phase of the disease, but its efficacy in the chronic phase remains controversial. It can also cause serious side effects that lead sufferers to abandon treatment. In the present work, is reported the synthesis and trypanocidal activity of new 2-(phenylthio)ethylidene thiosemicarbazones (4-15) and 1,3-thiazoles (16-26). The cyclization of thiosemicarbazones into 1,3-thiazoles presents an improvement in the cytotoxic profile for T. cruzi parasite, denoting selective compounds. Compound 18 was identified as the most promising of all compounds tested, showing an IC 50 of 2.6 μM for the trypomastigote form and a non-cytotoxic effect on mouse spleen cells, reaching a selective index of 95.1. Among the 22 compounds tested, six compounds present a better trypanocidal activity, and five compounds have an equipotent activity compared to benznidazole. Flow cytometry and ultrastructural analysis were performed and indicate that compound 18 causes parasite cell death through apoptosis and acts via an autophagic pathway., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Asthma is a chronic, complex and heterogeneous inflammatory illness, characterized by obstruction of the lower airways. About 334 million people worldwide suffer from asthma, and these estimates, as well as the severity of the disease, have increased in the last decades. Glucocorticoids are currently the most widely used drugs in the treatment and control of asthma symptoms, but their prolonged use can cause serious adverse effects. N-acylhydrazone derivatives have been tested in pre-clinical studies in models of inflammatory diseases. Here we tested SintMed65 (N'-[(1E)-3-(4-nitrophenylhydrazono)]-(2E)-propan-2-ylidene-3,5-dinitrobenzohydrazide), a compound belonging to a novel class of immunosuppressive drugs, in a mouse model of allergic airway inflammation. BALB/c mice were sensitized previously and challenged with ovalbumin for five consecutive days and SintMed65 treatment was performed orally 1 h prior to challenge with ovalbumin. Administration of SintMed65, as well as the reference drug dexamethasone, reduced cellularity and the number of eosinophils in the bronchoalveolar fluid (BALF). SintMed65 also reduced the production of Th2 cytokines IL-4, IL-5 and IL-13 in the BALF, and IL-4, IL-10 and CCL8 gene expression in lung, compared to vehicle-treated mice. Importantly, a reduction in the number of leukocytes and in the mucus production in lungs of SintMed65-treated mice was found, compared to the vehicle-treated group. In contrast, IgE production was not significantly altered after treatment with SintMed65. Our results demonstrate that compound SintMed65 possesses anti-inflammatory characteristics, suggesting its therapeutic potential for the treatment of allergic diseases., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aim: To gather information regarding endodontic treatment protocols and continuing education attendance of dentists in some cities located in Northeastern Brazil (Sergipe and Bahia States), a region that comprises a very-low-income population., Methods: A questionnaire containing different questions (e.g., routine treatment protocols, the use of new technologies, time required to conclude the treatment, and attendance in an endodontic continuing education) was distributed to 250 dentists. The collected data were analyzed through descriptive statistics and Poisson regression ( p < 0.05)., Results: A total of 199 dentists practicing endodontic treatment in the cities of Aracaju ( n  = 58), Salvador ( n  = 83), and towns of Estância ( n  = 8), Itabaiana ( n  = 16), Itabaianinha ( n  = 5), Lagarto ( n  = 10), Ribeirópolis ( n  = 3), Simão Dias ( n  = 6), and Tobias Barreto ( n  = 10) participated in this research. Most of the respondents have concluded their graduation in Dentistry in less than 10 years (62.3%), with nearly 75.4% of the sample having attended postgraduation education in the field. Regarding treatment protocols, the frequency for using rotary/reciprocating systems and for always using rubber dam isolation during root canal treatment (RCT) was 78% and 62%, respectively, which was also more prevalent among dentists who attended a continuous education program ( p < 0.05). Lastly, the professionals who attended ( p < 0.05) to a continuous education program in Endodontics were more frequently associated to performing incisors and molars RCT in one clinical appointment ( p < 0.05)., Conclusions: The results of this survey indicated that even in an area where most of the population has low-income conditions, the professionals are seeking for knowledge by attending to postgraduation programs, following the new tendencies in Endodontics with most of the professionals having employed technological resources., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2019 Maria Tereza Pedrosa Albuquerque et al.)

Chronic Chagas disease cardiomyopathy (CCC) is a major cause of heart disease in Latin America and treatment for this condition is unsatisfactory. Here we investigated the effects of BA5, an amide semi-synthetic derivative betulinic acid, in a model of CCC. Mice chronically infected with T. cruzi were treated orally with BA5 (10 or 1 mg/Kg), three times per week, for 2 months. BA5 treatment decreased inflammation and fibrosis in heart sections but did not improve exercise capacity or ameliorate cardiac electric disturbances in infected mice. Serum concentrations of TNF-α, IFN-γ, and IL-1β, as well as cardiac gene expression of pro-inflammatory mediators, were reduced after BA5 treatment. In contrast, a significant increase in the anti-inflammatory cytokine IL-10 concentration was observed in BA5-treated mice in both tested doses compared to vehicle-treated mice. Moreover, polarization to anti-inflammatory/M2 macrophage phenotype was evidenced by a decrease in the expression of NOS2 and proinflammatory cytokines and the increase in M2 markers, such as Arg1 and CHI3 in mice treated with BA5. In conclusion, BA5 had a potent anti-inflammatory activity on a model of parasite-driven heart disease related to IL-10 production and a switch from M1 to M2 subset of macrophages.

The fungal metabolite 3-hydroxyanthranilic acid (3-HAA) was used as a redox mediatorwith the aim of increasing dye degradation by Fenton oxidative processes (Fe 2+ /H 2 O 2 , Fe 3+ /H 2 O 2 ). ItsFe 3+ -reducing activity can enhance the generation of reactive oxygen species as HO ● radicals.Initially, the influence of 3-HAA on decolorization kinetics of five dyes (methylene blue,chromotrope 2R, methyl orange, phenol red, and safranin T) was investigated using decolorizationdata from a previous work conducted by the present research group. Fe 3+ -containing reaction datawere well fitted with first-order and mainly second-order kinetic models, whereas the BMG(Behnajady, Modirshahla and Ghanbary) model obtained optimal fit to Fe 2+ . Improvements inkinetic parameters (i.e., apparent rate constants and maximum oxidation capacity) were observedwith the addition of 3-HAA. In another set of experiments, a decrease in apparent activation energywas observed due to introducing 3-HAA into reactions containing either Fe 2+ or Fe 3+ in order todecolorize phenol red at different temperatures. This indicates that the redox mediator decreasesthe energy barrier so as to allow reactions to occur. Thus, based on recent experiments and thereaction kinetics models evaluated herein, pro-oxidant properties have been observed for 3-HAAin Fenton processes., Competing Interests: The authors declare no conflict of interest.

Objective: To systematically review the published studies that compare lower limb muscle strength in patients with low back pain to matched healthy controls., Methods: We searched Medline, SciELO, Cumulative Index to Nursing and Allied Health (CINAHL), and Scopus up until December 2017. Studies comparing lower limb muscle strength in people diagnosed with low back pain to healthy control participants were included in the systematic review., Results: 14 studies, which included 951 healthy controls and 919 patients with low back pain, fulfilled the inclusion criteria. Meta-analysis revealed a lower muscle strength of hip abductor/extensors and knee extensors in patients with low back pain in comparison to healthy controls. The average strength of hip abductors (Five studies, SMD=0.7 95% CI: 0.49 to 0.9) and hip extensors (Two studies, SMD=0.93, 95% CI: 0.62 to 1.23) was significantly lower in patients with low back pain compared to that of healthy controls. Knee extensor muscle strength was significantly lower in patients with low back pain compared to healthy controls (Three studies, WMD=0.31 Nm/kg, 95% CI: 0.1 to 0.5). The meta-analysis indicated a no significant difference in knee flexor muscle strength in patients with low back pain compared to healthy controls., Conclusions: Lower limb muscle is impaired in patients with low back pain.

Objective: To adapt data collection of the Information System software with the nursing process in Intensive Therapy for use in medical and surgical clinic units., Methods: A descriptive study developed in three stages. The first consisted of team training; in the second, the software was applied in clinical practice with 100 patients; and in the third, we analyzed the modifications to be done., Results: There was inter-observer agreement of 91%, followed by application of the software in 100 patients. In the "patient registration" module, it was suggested the exclusion of one item, inclusion of six and modification of four of them. In the anamnesis screens, no items were flagged to be deleted; 26 inclusions and 7 changes were proposed. In the physical examination screens, it was suggested the exclusion of 31 items, inclusion of 26 and modification of 27., Conclusion: Modifying information systems and going through stages methodologically constructed and implemented was important.

Preclinical imaging studies of posttraumatic epileptogenesis (PTE) have largely been proof-of-concept studies with limited animal numbers, and thus lack the statistical power for biomarker discovery. Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) is a pioneering multicenter trial investigating preclinical imaging biomarkers of PTE. EpiBios4Rx faced the issue of harmonizing the magnetic resonance imaging (MRI) procedures and imaging data metrics prior to its execution. We present here the harmonization process between three preclinical MRI facilities at the University of Eastern Finland (UEF), the University of Melbourne (Melbourne), and the University of California, Los Angeles (UCLA), and evaluate the uniformity of the obtained MRI data. Adult, male rats underwent a lateral fluid percussion injury (FPI) and were followed by MRI 2 days, 9 days, 1 month, and 5 months post-injury. Ex vivo scans of fixed brains were conducted 7 months post-injury as an end point follow-up. Four MRI modalities were used: T2-weighted imaging, multi-gradient-echo imaging, diffusion-weighted imaging, and magnetization transfer imaging, and acquisition parameters for each modality were tailored to account for the different field strengths (4.7 T and 7 T) and different MR hardwares used at the three participating centers. Pilot data collection resulted in comparable image quality across sites. In interim analysis (of data obtained by April 30, 2018), the within-site variation of the quantified signal properties was low, while some differences between sites remained. In T2-weighted images the signal-to-noise ratios were high at each site, being 35 at UEF, 48 at Melbourne, and 32 at UCLA (p < 0.05). The contrast-to-noise ratios were similar between the sites (9, 10, and 8, respectively). Magnetization transfer ratio maps had identical white matter/ gray matter contrast between the sites, with white matter showing 15% higher MTR than gray matter despite different absolute MTR values (MTR both in white and gray matter was 3% lower in Melbourne than at UEF, p < 0.05). Diffusion-weighting yielded different degrees of signal attenuation across sites, being 83% at UEF, 76% in Melbourne, and 80% at UCLA (p < 0.05). Fractional anisotropy values differed as well, being 0.81 at UEF, 0.73 in Melbourne, and 0.84 at UCLA (p < 0.05). The obtained values in sham animals showed low variation within each site and no change over time, suggesting high repeatability of the measurements. Quality control scans with phantoms demonstrated stable hardware performance over time. Timing of post-TBI scans was designed to target specific phases of the dynamic pathology, and the execution at different centers was highly accurate. Besides a few outliers, the 2-day scans were done within an hour from the target time point. At day 9, most animals were scanned within an hour from the target time point, and all but 2 outliers within 24 h from the target. The 1-month post-TBI scans were done within 31 ± 3 days. MRI procedures and animal physiology during scans were similar between the sites. Taken together, the 10% inter-site difference in FA and 3% difference in MTR values should be included into analysis as a covariate or balanced out in post-processing in order to detect disease-related effects on brain structure at the same scale. However, for a MRI biomarker for post-traumatic epileptogenesis to have realistic chance of being successfully translated to validation in clinical trials, it would need to be a robust TBI-induced structural change which tolerates the inter-site methodological variability described here., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) is a National Institutes for Neurological Diseases and Stoke funded Centers-Without-Walls international multidisciplinary study aimed at preventing epileptogenesis. The preclinical biomarker discovery in EpiBios4Rx applies a multicenter study design to allow the number of animals that are required for adequate statistical power for the analysis to be studied in an efficient manner. Further, the use of multiple centers mimics the clinical trial situation, and therefore potentially the chance of successful clinical translation of the outcomes of the study. Its successful implementation requires harmonization of procedures and data analyses between the three contributing centers in Finland, Australia, and USA. The objective of the present analysis was to develop metrics for analysis of the success of harmonization of procedures to guide further data analyses and plan the future multicenter preclinical studies. The interim analysis of data is based on the analysis of data from 212 rats with lateral fluid-percussion injury or sham-operation included in the biomarker discovery by April 30, 2018. The details of protocols, including production of injury, post-injury follow-up, blood sampling, electroencephalogram recording, and magnetic resonance imaging have been presented in the accompanying manuscripts in this Supplement. Implementation of protocols in EpiBios4Rx project participant centers was visualized in 2D using t-distributed stochastic neighborhood embedding (t-SNE). The protocols applied to each rat were presented as feature vectors of procedure related variables (e.g., impact pressure, anesthesia time). The total number of protocol features linked to each rat was 112. The missing data was accounted in visualization by utilizing imputation and adding the number of missing values as a third dimension to 2D t-SNE plot, resulting in a 3D overview of protocol data. Intraclass correlation coefficient (ICC) using Euclidean distances and area under receiver operating characteristic curve (AUC) of k-nearest neighbor classifier (KNN) were utilized to quantify the degree of clustering by center. Both subsets of data with incomplete protocol vectors omitted and missing protocol data imputed were assessed. Our data show that a visible clustering by center was observed in all t-SNE plots, except for day 7 neuroscores. Both ICC and AUC indicated clustering by center in all protocol variable subsets, excluding unimputed day 7 neuroscores (ICC 0.04 and AUC 0.6). ICC for imputed set of all protocol related variables was 0.1 and KNN AUC 0.92. In conclusion, both ICC and AUC indicated differences in protocol between EpiBios4Rx participating centers, which needs to be taken into account in data analysis. Importantly, the majority of observed differences are recoverable as they relate to insufficient updates in record keeping. While AUC score of KNN is a more sensitive measure for protocol harmonization than ICC for data that displays complex splintered clustering, ICC and AUC provide complementary measures to assess the degree of procedural harmonization. This experience should be helpful for other groups planning such multicenter post-traumatic epileptogenesis studies in the future., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In the last decades, the demand for lithium-ion batteries (LIBs) has been growing fast to attend the markets of electric and hybrid vehicles and of electric portable devices. As scarce metals like cobalt and lithium are employed in their manufacturing the recycling of spent LIBs is a strategic solution for the sustainability of these minerals and also the maintenance of the LIBs production. Therefore, efforts should be driven to produce low cost, environment-friendly and industrially scalable recycling processes. In this study, a closed-loop process with these characteristics was developed to recover cobalt and lithium compounds from LiCoO 2 cathodes of spent cell phone lithium-ion batteries. The process employs citric acid as green leaching agent to recover cobalt as CoC 2 O 4 .2H 2 O and Co 3 O 4 and lithium as Li 2 CO 3 . Lithium compound was recovered from a proposed new and original method based on simple chemical procedures as evaporation-calcination and water dissolution. The developed process also allows the resynthesis of LiCoO 2 as a stoichiometric, well crystallized and structurally ordered compound from the recovered Co and Li compounds, in a closed-loop recycling process. The obtained results indicate that the developed process has great potential to be scaled up to a recycling industrial plant of spent lithium-ion batteries., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Immunosuppressive drugs are widely used for the treatment of immune-mediated diseases and inflammation, but the toxicity and side effects of the available immunosuppressors make the search of new agents of great relevance. Here, we evaluated the immunomodulatory activity of an N-acylhydrazone derivative, (E)-N'-(3,4-dimethoxybenzylidene)-4-methoxybenzohydrazide (LASSBio-1386), a phosphodiesterase-4 (PDE-4) inhibitor. LASSBio-1386 inhibited lymphocyte activation in a concentration-dependent fashion, decreasing lymphoproliferation and IFN-γ and IL-2 production stimulated by anti-CD3/CD28 mAbs or concanavalin A (Con A) and inducing cell-cycle arrest in the G0/G1 phase. These effects were not blocked by RU486, a glucocorticoid receptor (GR) antagonist, indicating an effect independent of glucocorticoid receptor activation. Combination index-isobologram analysis indicates a synergistic effect between LASSBio-1386 and dexamethasone in lymphoproliferation inhibition. LASSBio-1386 presented immunomodulatory action in macrophage cultures, as observed by a significant and concentration-dependent decrease in NO and TNF-α production, an effect achieved by reducing IĸB expression and NF-κB activation. In the mouse model of endotoxic shock, LASSBio-1386 at 50 and 100 mg/kg protected 50 and 85% of mice against LPS-induced lethality, respectively. In agreement to its in vitro action, treatment with 100 mg/kg of LASSBio-1386 reduced TNF-α and IL-1β serum levels, while increased IL-6 and IL-10. Finally, LASSBio-1386 reduced the paw edema in a BSA-induced delayed-type hypersensitivity model. These findings demonstrate the immunomodulatory and immunosuppressant effects of LASSBio-1386 and indicate this molecule is a promising pharmacologic agent for immune-mediated diseases., (Copyright © 2018 Elsevier B.V. All rights reserved.)

This corrects the article on p. 406 in vol. 10, PMID: 29949837., (Copyright © 2018 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Purpose: The use of tolerogenic dendritic cells (TolDCs) to control exacerbated immune responses may be a prophylactic and therapeutic option for application in autoimmune and allergic conditions. The objective of this work was to evaluate the effects of TolDC administration in a mouse model of allergic airway inflammation caused by mite extract., Methods: Mouse bone marrow-derived TolDCs were induced by incubation with granulocyte-macrophage colony-stimulating factor (GM-CSF) and dexamethasone, and then characterized by flow cytometry and cytokine production by enzyme-linked immunosorbent assay (ELISA). For the in vivo model of Blomia tropicalis-induced allergy, mice transplanted with antigen-pulsed TolDCs were sensitized intraperitoneally with B. tropicalis mite extract (BtE) adsorbed to aluminium hydroxide. After challenge by nasal administration of BtE, bronchoalveolar lavage fluid (BALF), lungs, spleen and serum were collected for analysis., Results: Induction of TolDCs was efficiently achieved as shown by low expression of major histocompatibility complex (MHC) II, programmed death-ligand (PD-L) 2 and pro-inflammatory cytokine production, and up-regulation of interleukin (IL)-10, upon LPS stimulation in vitro. Transplantation of 1 or 2 doses of BtE-pulsed TolDCs reduced the number of inflammatory cells in BALF and lungs as well as mucus deposition. Moreover, compared to saline-injected controls, TolDC-treated mice showed lower serum levels of anti-BtE immunoglobulin E (IgE) antibodies as well as reduced Gata3 and IL-4 gene expression in the lungs and decreased IFN-γ levels in the supernatant of splenocyte cultures Transplantation of TolDCs increased the percentage of the regulatory T cells in the spleen and the lungs., Conclusions: Preventive treatment with TolDCs protects against dust mite-induced allergy in a mouse model, reinforcing the use of tolerogenic dendritic cells for the management of allergic conditions., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2018 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease.)

The scope of this article is to assess the oral health conditions and self-perceived chewing ability among the elderly seniors (≥ 80 years). Data from the FIBRA multicentric study were used. The sample consisted of 2,341 individuals with no cognitive impairment, aged ≥ 65 years, between 2008 and 2009, where the elderly were subjected to data collection. Regarding the outcome, age was dichotomized into 65-79 and 80 and over. The association between longevity and the socio-demographic and behavioral variables, general and oral health and self-perceived chewing ability was assessed by Poisson regression. Complete data are now available for 2,126 seniors. The mean age was 70.91 (SD =± 4.11) years among the young elderly and 82.70 (SD =± 2.61) among the elderly seniors. The sample of individuals aged ≥ 80 years was 11.7%. Low education, single marital status and lack of work were associated with longevity, as well as self-reporting of having no natural teeth and difficulty or pain when chewing hard foods. The results suggest an association between longevity with sociodemographic characteristics and oral health.

The first zoeal-stage larva of a possibly new species of mud shrimp Naushonia (Decapoda: Gebiidea: Laomediidae) was described from plankton samples taken off the Fernando de Noronha Archipelago, being the first occurrence at the oceanic islands of the Equatorial Atlantic. Five zoea I larvae were obtained and dissected for observation of mouthparts. This zoea I of Naushonia sp. is well distinguished from the first larvae of N. portoricensis (Rathbun 1901) from the Caribbean and N. cangronoides (Kingsley 1897) from the Northwest Atlantic in terms of development and setation of appendages, and possibly belongs to a new, undescribed species. The present study widens the knowledge on tropical oceanic decapod larvae and provides detailed drawings and new photographic illustrations with extended depth of field of these organisms.

Peroxiredoxins (Prx) are important proteins involved in hydroperoxide degradation and are related to virulence in several pathogens, including Aspergillus fumigatus. In this work, in vivo studies on the degradation of hydrogen peroxide (H 2 O 2 ) in the microenvironment of A. fumigatus fungus were performed by using an integrated Pt microelectrode. Three A. fumigatus strains were used to confirm the role of the cytosolic protein Prx1 in the defense mechanism of this microorganism: a wild-type strain, capable to expressing the protein Prx1; a Δprx strain, whose gene prx1 was removed; and a genetically complemented Δprx1::prx1 + strain generated from the Δprx1 and in which the gene prx1 was reintroduced. The fabricated microelectrode was shown to be a reliable inert probe tip for in situ and real-time measurements of H 2 O 2 in such microenvironments, with potential applications in investigations involving the mechanism of oxidative stress.

Current treatment for combatting Chagas disease, a life-threatening illness caused by the kinetoplastid protozoan parasite Trypanosoma cruzi is inadequate, and thus the discovery of new antiparasitic compounds is of prime importance. Previous studies identified the indirubins, a class of ATP kinase inhibitors, as potent growth inhibitors of the related kinetoplastid Leishmania. Herein, we evaluated the inhibitory activity of a series of 69 indirubin analogues screened against T. cruzi trypomastigotes and intracellular amastigotes. Seven indirubins were identified as potent T. cruzi inhibitors (low μΜ, nM range). Cell death analysis of specific compounds [3'oxime-6-bromoindirubin(6-BIO) analogues 10, 11 and 17, bearing a bulky extension on the oxime moiety and one 7 substituted analogue 32], as evaluated by electron microscopy and flow cytometry, showed a different mode of action between compound 32 compared to the three 6-BIO oxime- substituted indirubins, suggesting that indirubins may kill the parasite by different mechanisms dependent on their substitution. Moreover, the efficacy of four compounds that show the most potent anti-parasitic effect in both trypomastigotes and intracellular amastigotes (10, 11, 17, 32), was evaluated in a mouse model of T. cruzi infection. Compound 11 (3'piperazine-6-BIO) displayed the best in vivo efficacy (1/6 mortality, 94.5% blood parasitaemia reduction, 12 dpi) at a dose five times reduced over the reference drug benznidazole (20 mg/kg vs100 mg/kg). We propose 3'piperazine-6-BIO as a potential lead for the development of new treatments of Chagas disease.

Objective: To construct and validate a nursing care protocol in anesthesia., Method: methodological study of face and content validation, judging clarity, relevance, pertinence and comprehensiveness of a care protocol, elaborated from the integrative review of previous literature and based on the conceptual model of assistance perioperative nursing of Castellanos and Jouclas. The protocol was evaluated by five anesthesiologists and nurses from the surgical center. The results were analyzed through the content validity index., Results: among the 119 items assessed by experts, 11 (9.2%) instrument items presented content validity index of <80% and were changed. The items with disagreement were related to the selection and availability of materials and equipment, especially before anesthetic induction. The content validity index, obtained for the different items, proposed after the amendments mentioned, ranged from 80 to 100%, in the three periods of anesthesia, indicating the proper validity of the proposed content., Conclusion: the nursing care protocol in anesthesia was considered valid.

Chagas disease is one of the most significant health problems in the American continent. benznidazole (BDZ) and nifurtimox (NFX) are the only drugs approved for treatment and exhibit strong side effects and ineffectiveness in the chronic stage, besides different susceptibility among T. cruzi DTUs (Discrete Typing Units). Therefore, new drugs to treat this disease are necessary. Thiazole compounds have been described as potent trypanocidal agents. Here we report the structural planning, synthesis and anti-T. cruzi evaluation of a new series of 1,3-thiazoles (7-28), which were designed by placing this heterocycle instead of thiazolidin-4-one ring. The synthesis was conducted in an ultrasonic bath with 2-propanol as solvent at room temperature. By varying substituents attached to the phenyl and thiazole rings, substituents were observed to retain, enhance or greatly increase their anti-T. cruzi activity. In some cases, methyl at position 5 of the thiazole (compounds 9, 12 and 23) increased trypanocidal property. The exchange of phenyl for pyridinyl heterocycle resulted in increased activity, giving rise to the most potent compound against the trypomasigote form (14, IC 50trypo  = 0.37 μM). Importantly, these new thiazoles were toxic for trypomastigotes without affecting macrophages and cardiomyoblast viability. The compounds were also evaluated against cruzain, and five of the most active compounds against trypomastigotes (7, 9, 12, 16 and 23) inhibited more than 70% of enzymatic activity at 10 μM, among which compound 7 had an IC 50 in the submicromolar range, suggesting a possible mechanism of action. In addition, examination of T. cruzi cell death showed that compound 14 induces apoptosis. We also examined the activity against intracellular parasites, revealing that compound 14 inhibited T. cruzi infection with potency similar to benznidazole. The antiparasitic effect of 14 and benznidazole in combination was also investigated against trypomastigotes and revealed that they have synergistic effects, showing a promising profile for drug combination. Finally, in mice acutely-infected with T. cruzi,14 treatment significanty reduced the blood parasitaemia and had a protective effect on mortality. In conclusion, we report the identification of compounds (7), (12), (15), (23) and (26) with similar trypanocidal activity of benznidazole; compounds (9) and (21) as trypanocidal agents equipotent with BDZ, and compound 14 with potency 28 times better than the reference drug without affecting macrophages and cardiomyoblast viability. Mechanistically, the compounds inhibit cruzain, and 14 induces T. cruzi cell death by an apoptotic process, being considered a good starting point for the development of new anti-Chagas drug candidates., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Betulinic acid (BA) is a naturally occurring triterpenoid with several biological properties already described, including immunomodulatory activity. Here we investigated the immunomodulatory activity of eight semi-synthetic amide derivatives of betulinic acid. Screening of derivatives BA1-BA8 led to the identification of compounds with superior immunomodulatory activity than BA on activated macrophages and lymphocytes. BA5, the most potent derivative, inhibited nitric oxide and TNFα production in a concentration-dependent manner, and decreased NF-κB activation in Raw 264.7 cells. Additionally, BA5 inhibited the proliferation of activated lymphocytes and the secretion of IL-2, IL-4 IL-6, IL-10, IL-17A and IFNɣ, in a concentration-dependent manner. Flow cytometry analysis in lymphocyte cultures showed that treatment with BA5 induces cell cycle arrest in pre-G1 phase followed by cell death by apoptosis. Moreover, BA5 also inhibited the activity of calcineurin, an enzyme that plays a critical role in the progression of cell cycle and T lymphocyte activation. BA5 has a synergistic inhibitory effect with dexamethasone on lymphoproliferation, showing a promising profile for drug combination. Finally, we observed immunosuppressive effects of BA5 in vivo in mouse models of lethal endotoxemia and delayed type hypersensitivity. Our results reinforce the potential use of betulinic acid and its derivatives in the search for potent immunomodulatory drugs., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Rivers as barriers to dispersal and past forest refugia are two of the hypotheses proposed to explain the patterns of biodiversity in the Atlantic Forest. It has recently been shown that possible past refugia correspond to bioclimatically different regions, so we tested whether patterns of shared distribution of bird taxa in the Atlantic Forest are 1) limited by the Doce and São Francisco rivers or 2) associated with the bioclimatically different southern and northeastern regions. We catalogued lists of forest birds from 45 locations, 36 in the Atlantic forest and nine in Amazon, and used parsimony analysis of endemicity to identify groups of shared taxa. We also compared differences between these groups by permutational multivariate analysis of variance and identified the species that best supported the resulting groups. The results showed that the distribution of forest birds is divided into two main regions in the Atlantic Forest, the first with more southern localities and the second with northeastern localities. This distributional pattern is not delimited by riverbanks, but it may be associated with bioclimatic units, surrogated by altitude, that maintain current environmental differences between two main regions on Atlantic Forest and may be related to phylogenetic histories of taxa supporting the two groups.

We developed a highly sensitive oxygen consumption scanning microscopy system using platinized platinum disc microelectrodes. The system is capable of reliably detecting single-cell respiration, responding to classical regulators of mitochondrial oxygen consumption activity as expected. Comparisons with commercial multi-cell oxygen detection systems show that the system has comparable errors (if not smaller), with the advantage of being able to monitor inter and intra-cell heterogeneity in oxygen consumption characteristics. Our results uncover heterogeneous oxygen consumption characteristics between cells and within the same cell´s microenvironments. Single Cell Oxygen Mapping (SCOM) is thus capable of reliably studying mitochondrial oxygen consumption characteristics and heterogeneity at a single-cell level.

An epidemiological, multicenter, noninterventional, observational case-control study was conducted to describe the performance of serum beta-d-glucan (BDG) and Candida PCR in blood, serum, and sterile samples for the diagnosis of invasive candidiasis (IC) in very-low-birth-weight (VLBW) preterm neonates and to compare these techniques with culture of samples from blood and other sterile sites. Seventeen centers participated in the study, and the number of episodes analyzed was 159. A total of 9 episodes of IC from 9 patients (7 confirmed and 2 probable) and 150 episodes of suspected sepsis from 117 controls were identified. The prevalence of IC was 5.7% (95% confidence interval [95% CI], 2.1 to 9.3). The mortality was significantly higher in episodes of IC (44.4%) than in the non-IC episodes (11.1%, P < 0.01). The sensitivity and specificity of the PCR performed on blood/serum samples were 87.5% and 81.6%, respectively. The sensitivity and specificity of the BDG results were lower (75.0% and 64.6%). For cases with negative culture results, the PCR and the BDG results were positive in 27 (17.4%) and 52 (33.5%) episodes, respectively. The presence of multiorgan failure, improvement with empirical antifungal therapy, thrombocytopenia, and Candida colonization were significantly associated ( P < 0.01) with PCR or BDG positivity regardless of the results of the cultures. Serum BDG analysis and Candida PCR could be used as complementary diagnostic techniques to detect IC in VLBW neonates., (Copyright © 2017 Ramos et al.)

Chagas disease cardiomyopathy is a parasite-driven inflammatory disease to which there are no effective treatments. Here we evaluated the therapeutic potential of N,N-dimethylsphingosine(DMS), which blocks the production of sphingosine-1-phosphate(S1P), a mediator of cellular events during inflammatory responses, in a model of chronic Chagas disease cardiomyopathy. DMS-treated, Trypanosoma cruzi-infected mice had a marked reduction of cardiac inflammation, fibrosis and galectin-3 expression when compared to controls. Serum concentrations of galectin-3, IFNγ and TNFα, as well as cardiac gene expression of inflammatory mediators were reduced after DMS treatment. The gene expression of M1 marker, iNOS, was decreased, while the M2 marker, arginase1, was increased. DMS-treated mice showed an improvement in exercise capacity. Moreover, DMS caused a reduction in parasite load in vivo. DMS inhibited the activation of lymphocytes, and reduced cytokines and NO production in activated macrophage cultures in vitro, while increasing IL-1β production. Analysis by qRT-PCR array showed that DMS treatment modulated inflammasome activation induced by T. cruzi on macrophages. Altogether, our results demonstrate that DMS, through anti-parasitic and immunomodulatory actions, can be beneficial in the treatment of chronic phase of T. cruzi infection and suggest that S1P-activated processes as possible therapeutic targets for the treatment of Chagas disease cardiomyopathy.

Braylin belongs to the group of natural coumarins, a group of compounds with a wide range of pharmacological properties. Here we characterized the pharmacological properties of braylin in vitro, in silico and in vivo in models of inflammatory/immune responses. In in vitro assays, braylin exhibited concentration-dependent suppressive activity on activated macrophages. Braylin (10-40 μM) reduced the production of nitrite, IL-1β, TNF-α and IL-6 by J774 cells or peritoneal exudate macrophages stimulated with LPS and IFN-γ. Molecular docking calculations suggested that braylin present an interaction pose to act as a glucocorticoid receptor ligand. Corroborating this idea, the inhibitory effect of braylin on macrophages was prevented by RU486, a glucocorticoid receptor antagonist. Furthermore, treatment with braylin strongly reduced the NF-κB-dependent transcriptional activity on RAW 264.7 cells. Using the complete Freund's adjuvant (CFA)-induced paw inflammation model in mice, the pharmacological properties of braylin were demonstrated in vivo. Braylin (12.5-100 mg/kg) produced dose-related antinociceptive and antiedematogenic effects on CFA model. Braylin did not produce antinociception on the tail flick and hot plate tests in mice, suggesting that braylin-induced antinociception is not a centrally-mediated action. Braylin exhibited immunomodulatory properties on the CFA model, inhibiting the production of pro-inflammatory cytokines IL-1β, TNF-α and IL-6, while increased the anti-inflammatory cytokine TGF-β. Our results show, for the first time, anti-inflammatory, antinociceptive and immunomodulatory effects of braylin, which possibly act through the glucocorticoid receptor activation and by inhibition of the transcriptional activity of NF-κB. Because braylin is a phosphodiesterase-4 inhibitor, this coumarin could represent an ideal prototype of glucocorticoid receptor ligand, able to induce synergic immunomodulatory effects.

Chronic Chagas disease cardiomyopathy, caused by Trypanosoma cruzi infection, is a major cause of heart failure in Latin America. Galectin-3 (Gal-3) has been linked to cardiac remodeling and poor prognosis in heart failure of different etiologies. Herein, we investigated the involvement of Gal-3 in the disease pathogenesis and its role as a target for disease intervention. Gal-3 expression in mouse hearts was evaluated during T. cruzi infection by confocal microscopy and flow cytometry analysis, showing a high expression in macrophages, T cells, and fibroblasts. In vitro studies using Gal-3 knockdown in cardiac fibroblasts demonstrated that Gal-3 regulates cell survival, proliferation, and type I collagen synthesis. In vivo blockade of Gal-3 with N-acetyl-d-lactosamine in T. cruzi-infected mice led to a significant reduction of cardiac fibrosis and inflammation in the heart. Moreover, a modulation in the expression of proinflammatory genes in the heart was observed. Finally, histological analysis in human heart samples obtained from subjects with Chagas disease who underwent heart transplantation showed the expression of Gal-3 in areas of inflammation, similar to the mouse model. Our results indicate that Gal-3 plays a role in the pathogenesis of experimental chronic Chagas disease, favoring inflammation and fibrogenesis. Moreover, by demonstrating Gal-3 expression in human hearts, our finding reinforces that this protein could be a novel target for drug development for Chagas cardiomyopathy., (Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the effects of FIFA 11 training on injury prevention and performance in football players., Design and Methods: Systematic review and meta-analysis. We conducted a systematic search using four databases (CINAHL, Cochrane Library, EMBASE, and PubMed) to find controlled trials evaluating the effects of FIFA 11 on injury prevention and performance among football players. Weighted mean differences, standard mean differences, risk ratios, and 95% confidence intervals were calculated, and heterogeneity was assessed using the I 2 test., Results: We analyzed 11 trials, including 4700 participants. FIFA 11 resulted in a significant reduction in injury risk (risk ratio = 0.69; 95% confidence interval, 0.49-0.98; P = 0.02) and improvements in dynamic balance (weighted mean difference = 2.68; 95% confidence interval, 0.44-4.92; P = 0.02) and agility (standard mean difference = -0.36; 95% confidence interval, 0.70-0.02; P = 0.04). The meta-analysis indicated a non-significant improvement in jump height (standard mean difference = 0.25; 95% confidence interval, 0.08-0.59; P = 0.14) and running sprint (standard mean difference = -0.24; 95% confidence interval, 0.58-0.10; P = 0.17) in the FIFA 11 group., Conclusions: FIFA 11 can be considered as a tool to reduce the risk of injury. It may improve dynamic balance and agility and can be considered for inclusion in the training of football players.

The current biogeographic and taxonomic knowledge on decapod larvae in tropical oceans is still very incomplete, in spite of their huge ecological and socio-economic importance. The present study reports two new records for decapod larval forms in pelagic environments off oceanic islands in the western tropical Atlantic, and provides detailed diagnoses and images of these larvae. Samples were taken from July 2010 to November 2014 using neuston, bongo and WP-2 nets at three localities: St. Peter and St. Paul's Archipelago (SPSP), Rocas Atoll (RA) and Fernando de Noronha Archipelago (FN). The larval forms Cerataspis monstrosa (Gray, 1828) and Amphionides reynaudii (H. Milne Edwards, 1832) were recorded around these areas, constituting the first record for these oceanic islands. Out of 121 samples analyzed, one specimen of C. monstrosa (Mysis II) was found off FN, and 20 specimens of A. reynaudii in nine distinct stages (Mysis II, IV, VI, VII, VIII, IX, X, XI, XII) were found off SPSP, RA and FN.

Sorghum is a source of several minerals whose content may vary depending on the genotype and the production environment. The objective of this study was to screen sorghum genotypes for mineral content and to investigate the effect of water stress on it. A large variability was observed in the mineral content of 100 sorghum genotypes grown in environments without (WoWS) and with water stress (WthWS). The water stress decreased Mn, P, Mg and S contents in 100, 96, 93 and 56% of genotypes, respectively. The genotypes and other factors seemed to have more impact than water stress on K, Ca, Cu, Fe and Zn levels. In 100 sorghum genotypes, 2 were classified as excellent sources of Fe and 25 of Zn, in both environments. The best two genotypes to Fe content were SC21 and SC655 and to Zn were SC320 and SHAN-QUI-RED which showed great potential for use in biofortification., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Betulinic acid is a pentacyclic triterpenoid with several biological properties already described, including antiparasitic activity. Here, the anti-Trypanosoma cruzi activity of betulinic acid and its semi-synthetic amide derivatives (BA1-BA8) was investigated. The anti-Trypanosoma cruzi activity and selectivity were enhanced in semi-synthetic derivatives, specially on derivatives BA5, BA6 and BA8. To understand the mechanism of action underlying betulinic acid anti-T. cruzi activity, we investigated ultrastructural changes by electron microscopy. Ultrastructural studies showed that trypomastigotes incubated with BA5 had membrane blebling, flagella retraction, atypical cytoplasmic vacuoles and Golgi cisternae dilatation. Flow cytometry analysis showed that parasite death is mainly caused by necrosis. Treatment with derivatives BA5, BA6 or BA8 reduced the invasion process, as well as intracellular parasite development in host cells, with a potency and selectivity similar to that observed in benznidazole-treated cells. More importantly, the combination of BA5 and benznidazole revealed synergistic effects on trypomastigote and amastigote forms of T. cruzi. In conclusion, we demonstrated that BA5 compound is an effective and selective anti-T. cruzi agent., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Chagas disease is an infection caused by protozoan Trypanosoma cruzi, which affects approximately 8-10million people worldwide. Benznidazole is the only drug approved for treatment during the acute and asymptomatic chronic phases of Chagas disease; however, it has poor efficacy during the symptomatic chronic phase. Therefore, the development of new pharmaceuticals is needed. Here, we employed the bioisosterism to modify a potent antiparasitic and cruzain-inhibitor aryl thiosemicarbazone (4) into 4-thiazolidinones (7-21). Compounds (7-21) were prepared by using a straightforward synthesis and enabled good to excellent yields. As a chemical elucidation tool, X-ray diffraction of compound (10) revealed the geometry and conformation of this class compounds. The screening against cruzain showed that 4-thiazolidinones were less active than thiosemicarbazone (4). However, the antiparasitic activity in Y strain trypomastigotes and host cell cytotoxicity in J774 macrophages revealed that compounds (10 and 18-21) are stronger and more selective antiparasitic agents than thiosemicarbazone (4). Specifically, compounds (18-20), which carry a phenyl at position N3 of heterocyclic ring, were the most active ones, suggesting that this is a structural determinant for activity. In infected macrophages, compounds (18-20) reduced intracellular amastigotes, whereas Benznidazole did not. In T. cruzi-infected mice treated orally with 100mg/kg of compound (20), a decreased of parasitemia was observed. In conclusion, we demonstrated that the conversation of thiosemicarbazones into 4-thiazolidinones retains pharmacological property while enhances selectivity., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Anemia is the most common hematological problem encountered in the elderly population. A cross-sectional, population-based survey was conducted to evaluate the prevalence and factors associated with anemia in the elderly in Viçosa (State of Minas Gerais). Data were collected by means of a household survey and conducting biochemical tests on 349 elderly between June and December 2009. The prevalence of anemia was 11.7% (95% CI 8.3% -15.1%) and was found to be higher among men (15.4%) among those aged 80 years and older (30%) and those who practiced polypharmacy (16.8%). The results obtained indicate anemia determinants similar to those observed in developed countries. The real need of polypharmacy should be evaluated in health care for the elderly, in order to prevent iatrogenic complications, of which anemia is one such complication.

Background: The current treatment of Chagas disease, endemic in Latin America and emerging in several countries, is limited by the frequent side effects and variable efficacy of benznidazole. Natural products are an important source for the search for new drugs., Aim/hypothesis: Considering the great potential of natural products as antiparasitic agents, we investigated the anti-Trypanosoma cruzi activity of a concentrated ethanolic extract of Physalis angulata (EEPA)., Methods: Cytotoxicity to mammalian cells was determined using mouse peritoneal macrophages. The antiparasitic activity was evaluated against axenic epimastigote and bloodstream trypomastigote forms of T. cruzi, and against amastigote forms using T. cruzi-infected macrophages. Cell death mechanism was determined in trypomastigotes by flow cytometry analysis after annexin V and propidium iodide staining. The efficacy of EEPA was examined in vivo in an acute model of infection by monitoring blood parasitaemia and survival rate 30 days after treatment. The effect against trypomastigotes of EEPA and benznidazole acting in combination was evaluated., Results: EEPA effectively inhibits the epimastigote growth (IC50 2.9 ± 0.1 µM) and reduces bloodstream trypomastigote viability (EC50 1.7 ± 0.5 µM). It causes parasite cell death by necrosis. EEPA impairs parasite infectivity as well as amastigote development in concentrations noncytotoxic to mammalian cells. In mice acutely-infected with T. cruzi, EEPA reduced the blood parasitaemia in 72.7%. When combined with benznidazole, EEPA showed a synergistic anti-T. cruzi activity, displaying CI values of 0.8 ± 0.07 at EC50 and 0.83 ± 0.1 at EC90., Conclusion: EEPA has antiparasitic activity against T. cruzi, causing cell death by necrosis and showing synergistic activity with benznidazole. These findings were reinforced by the observed efficacy of EEPA in reducing parasite load in T. cruzi-mice. Therefore, this represents an important source of antiparasitic natural products., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

The aim of the present study was to conduct a systematic review of the literature to compare soft tissue aspects of immediate and delayed implant placement in esthetic areas. This review of literature was conducted in the following databases: MEDLINE (PubMed), Lilacs, Scielo, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL). For those studies that met the inclusion/exclusion criteria, the results were analyzed and summarized according to the treatment protocol used for implant placement. The primary parameters taken into consideration were papilla level (PL) and marginal mucosa level (MML) around implants. Four randomized controlled trials (RCT) were selected for analysis, but all were deemed as being of poor quality according to quality assessment. No studies reported any statistically significant differences concerning the soft tissue esthetic parameters analyzed around immediate or delayed implants at any follow-up periods reported. However, PL results seemed to be more reliable than were MML results, due to the PL standardization of the method of analysis, which showed a tendency for poorer results around immediately placed implants. In conclusion, although the results are based on only a few poor quality RCTs, both treatment options for implant placement demonstrated similar outcomes in the esthetic area, especially when PL was considered.