Therapeutic Potential of Natural Products in the Treatment of Schistosomiasis.

It is estimated that 250 million people worldwide are affected by schistosomiasis. Disease transmission is related to the poor sanitation and hygiene habits that affect residents of impoverished regions in tropical and subtropical countries. The main species responsible for causing disease in humans are Schistosoma Mansoni, S. japonicum, and S. haematobium, each with different geographic distributions. Praziquantel is the drug predominantly used to treat this disease, which offers low effectiveness against immature and juvenile parasite forms. In addition, reports of drug resistance prompt the development of novel therapeutic approaches. Natural products represent an important source of new compounds, especially those obtained from plant sources. This review compiles data from several in vitro and in vivo studies evaluating various compounds and essential oils derived from plants with cercaricidal and molluscicidal activities against both juvenile and adult forms of the parasite. Finally, this review provides an important discussion on recent advances in molecular and computational tools deemed fundamental for more rapid and effective screening of new compounds, allowing for the optimization of time and resources.

Diagnostic Performance of Three ELISAs for Detection of Antibodies against SARS-CoV-2 in Human Samples.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that causes coronavirus disease 2019 (COVID-19) is a disease with a high rate of transmission. Serological tests are important to perform surveys and to determine the immunological status of the population. Based on this, we evaluated three enzyme-linked immunoassays (ELISAs) using different antigens from SARS-CoV-2 in a cohort of 161 patients. The performance of the ELISA developed for immunoglobulin G (IgG) measurement against SARS-CoV-2 was evaluated based on sensitivity, specificity, and accuracy. We found specificities of 0.98, 0.98, and 0.99 and sensitivities of 0.99, 0.91, and 0.87 for the nucleocapsid (N) protein, spike protein, and receptor binding domain (RBD) fraction, respectively. The accuracy assessment indicated the N protein (accuracy = 0.98) as the antigen most likely to give a correct diagnosis. Overall, the antibody responses were present for all three proteins in subjects with confirmed SARS-CoV-2 infections, showing a similar pattern of antibody production for different antigens. In summary, these highly sensitive and specific ELISAs, with a more competitive price, appear to be a valid approach for the serodiagnosis of COVID-19.

Preclinical evaluation of single domain antibody efficacy in mitigating local tissue damage induced by Bothrops snake envenomation.

Camelid single-domain antibodies (VHH) represent a promising class of immunobiologicals for therapeutic applications due to their remarkable stability, specificity, and therapeutic potential. To enhance the effectiveness of antivenoms for snakebites, various methods have been explored to address limitations associated with serum therapy, particularly focusing on mitigating local damage and ensuring sustainable production. Our study aimed to characterize the pharmacological profile and neutralization capacity of anti-Phospholipase A2 (PLA2) monomeric VHH (Genbank accessions: KC329718). Using a post-envenoming mouse model, we used intravital microscopy to assess leukocyte influx, measured CK and LDH levels, and conducted a histopathology analysis to evaluate VHH KC329718's ability to neutralize myotoxic activity. Our findings demonstrated that VHH KC329718 exhibited heterogeneous distribution in muscle tissue. Treatment with VHH KC329718 reduced leukocyte influx caused by BthTX-I (a Lys-49 PLA2) by 28 %, as observed through intravital microscopy. When administered at a 1:10 ratio [venom or toxin:VHH (w/w)], VHH KC329718 significantly decreased myotoxicity, resulting in a 35-40 % reduction in CK levels from BthTX-I and BthTX-II (an Asp-49 PLA2) and a 60 % decrease in CK levels from B. jararacussu venom. LDH levels also showed reductions of 60%, 80%, and 60% induced by BthTX-I, BthTX-II, and B. jararacussu venom, respectively. Histological analysis confirmed the neutralization potential, displaying a significant reduction in tissue damage and inflammatory cell count in mice treated with VHH KC329718 post B. jararacussu venom inoculation. This study underscores the potential of monomeric anti-PLA2 VHH in mitigating myotoxic effects, suggesting a promising avenue for the development of new generation antivenoms to address current therapeutic limitations.

Wastewater surveillance for viral pathogens: A tool for public health.

A focus on water quality has intensified globally, considering its critical role in sustaining life and ecosystems. Wastewater, reflecting societal development, profoundly impacts public health. Wastewater-based epidemiology (WBE) has emerged as a surveillance tool for detecting outbreaks early, monitoring infectious disease trends, and providing real-time insights, particularly in vulnerable communities. WBE aids in tracking pathogens, including viruses, in sewage, offering a comprehensive understanding of community health and lifestyle habits. With the rise in global COVID-19 cases, WBE has gained prominence, aiding in monitoring SARS-CoV-2 levels worldwide. Despite advancements in water treatment, poorly treated wastewater discharge remains a threat, amplifying the spread of water-, sanitation-, and hygiene (WaSH)-related diseases. WBE, serving as complementary surveillance, is pivotal for monitoring community-level viral infections. However, there is untapped potential for WBE to expand its role in public health surveillance. This review emphasizes the importance of WBE in understanding the link between viral surveillance in wastewater and public health, highlighting the need for its further integration into public health management.

Galectins in Protozoan Parasitic Diseases: Potential Applications in Diagnostics and Therapeutics.

Neglected tropical diseases (NTDs) constitute a group of diseases that generally develop in tropical or subtropical climatic conditions and are related to poverty. Within the spectrum of NTDs, diseases caused by protozoa such as malaria, Chagas disease, and leishmaniasis exhibit elevated mortality rates, thereby constituting a substantial public health concern. Beyond their protozoan etiology, these NTDs share other similarities, such as the challenge of control and the lack of affordable, safe, and effective drugs. In view of the above, the need to explore novel diagnostic predictors and therapeutic targets for the treatment of these parasitic diseases is evident. In this context, galectins are attractive because they are a set of lectins bound to ß-galactosides that play key roles in a variety of cellular processes, including host-parasite interaction such as adhesion and entry of parasites into the host cells, and participate in antiparasitic immunity in either a stimulatory or inhibitory manner, especially the galectins-1, -2, -3, and -9. These functions bestow upon galectins significant therapeutic prospects in the context of managing and diagnosing NTDs. Thus, the present review aims to elucidate the potential role of galectins in the diagnosis and treatment of malaria, leishmaniasis, and Chagas disease.

The Impact of the COVID-19 Pandemic on the Mental Health of Teachers and Its Possible Risk Factors: A Systematic Review.

(1) Objective: The objective was to analyze the development of psychiatric pathologies/burnout syndrome and their possible risk factors in teachers in the context of the COVID-19 pandemic. (2) Methods: A qualitative systematic review was carried out, according to the PRISMA protocol, in the PubMed, Scopus, and Web of Science databases using a combination of the following descriptors [MeSH]: "mental health", "mental disorders'', "covid-19" and "school teachers''. Articles selected were written in English, Portuguese and Spanish, published between November 2019 and December 2022. (3) Results: The most common psychiatric pathologies were generalized anxiety disorders and depression. Burnout syndrome was also quite prevalent. Of the 776 articles identified, 42 were selected after applying the eligibility criteria. Although there is variability among the analyzed studies, the risk factors most correlated with increased morbidity in teachers were: (i) being female; (ii) age below the fifth decade of life; (iii) pre-existence of chronic or psychiatric illnesses before the pandemic; (iv) difficulty in adapting to the distance education model; (v) family/work conflicts; (vi) negative symptoms caused by the pandemic. (4) Conclusions: Therefore, the COVID-19 impact on mental health appears to be more common in female teachers in their fifth decade of life and with pre-existing psychiatric comorbidities. However, prospective studies are needed to better map this situation.

Immunomodulation for the Treatment of Chronic Chagas Disease Cardiomyopathy: A New Approach to an Old Enemy.

Chagas disease is a parasitic infection caused by the intracellular protozoan Trypanosoma cruzi. Chronic Chagas cardiomyopathy (CCC) is the most severe manifestation of the disease, developed by approximately 20-40% of patients and characterized by occurrence of arrhythmias, heart failure and death. Despite having more than 100 years of discovery, Chagas disease remains without an effective treatment, especially for patients with CCC. Since the pathogenesis of CCC depends on a parasite-driven systemic inflammatory profile that leads to cardiac tissue damage, the use of immunomodulators has become a rational alternative for the treatment of CCC. In this context, different classes of drugs, cell therapies with dendritic cells or stem cells and gene therapy have shown potential to modulate systemic inflammation and myocarditis in CCC models. Based on that, the present review provides an overview of current reports regarding the use of immunomodulatory agents in treatment of CCC, bringing the challenges and future directions in this field.

Tolerogenic Dendritic Cells Reduce Cardiac Inflammation and Fibrosis in Chronic Chagas Disease.

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.

Anti-inflammatory activity of SintMed65, an N-acylhydrazone derivative, in a mouse model of allergic airway inflammation.

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.

Betulinic Acid Derivative BA5, Attenuates Inflammation and Fibrosis in Experimental Chronic Chagas Disease Cardiomyopathy by Inducing IL-10 and M2 Polarization.

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-1ß, 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.

Os bebês no contexto das brincadeiras de aventura: um ensaio de análise / The babies in the context of adventure play: an analysis essay / Bebés en el contexto de los juegos de aventura: um ensayo de análisis

O objetivo do estudo é apresentar um ensaio de análise sobre as primeiras manifestações de um bebê no contexto das brincadeiras de aventura. Para tanto, analisamos narrativas de registros em vídeo sobre as primeiras brincadeiras, em contexto de aventura, de um bebê do gênero feminino, com menos de 1 ano de idade. As análises foram construídas com base em estudos de Kleppe, Melhuish e Sandseter (2017), Le Breton (2009) e Goldschmied e Jackson (2008). Concluímos que a qualidade das oportunidades para brincar oferecidas aos bebês poderá tornar as experiências em situação de risco controlado uma aventura, sendo os adultos os responsáveis por oferecer e dar segurança para o brincar em contexto de aventura na infância.

The objective of the study is to present an analysis essay on the first manifestations of a baby in the context of adventure play. To do so, we analyzed narratives of video recordings about the first games, in the context of adventure, of a female baby, under 1 year old. The analyzes were built based on studies by Kleppe, Melhuish and Sandseter (2017), Le Breton (2009) and Goldschmied and Jackson (2008). We conclude that the quality of the opportunities to play, offered to babies, may turn experiences in a controlled risk situation into an adventure, and adults are responsible for offering and providing security for opportunities to play in the context of adventure in childhood.

El objetivo del estudio es presentar un ensayo de análisis sobre las primeras manifestaciones de un bebé en el contexto de los juegos de aventura. Para ello, analizamos narraciones de grabaciones de video sobre los primeros juegos en el contexto de la aventura, de un bebé de sexo femenino menor de 1 año. Los análisis se construyeron con base en estudios de Kleppe, Melhuish y Sandseter (2017), Le Breton (2009) y Goldschmied y Jackson (2008). Concluimos que la calidad de las oportunidades del juego ofrecidas a los bebés puede convertir experiencias en una situación de riesgo controlado en una aventura, siendo los adultos los encargados de ofrecer y brindar seguridad a las oportunidades del juego en el contexto de la aventura en la infancia.

O trabalho de Enfermagem a partir da experiência de enfermeiras da linha de frente contra Covid-19: na trilha da precarização / El trabajo de enfermería a partir de la experiencia de enfermeras de la línea de frente contra la Covid-19: en el rumbo de la precarización / Analysis of nursing work seen from the experiences of frontline nurses against Covid-19: on the path of precarization

A experiência de trabalhar no enfrentamento da Covid-19, em meio a um processo tenso, contraditório e com repercussões na própria saúde, constitui o contexto desta pesquisa, que tem o objetivo de entender o trabalho de Enfermagem na experiência de enfermeira(o)s da linha de frente contra a Covid-19, em Alagoas, Brasil. Trata-se de pesquisa qualitativa, com análise de conteúdo das histórias orais temáticas de seis enfermeiras que atuaram na linha de frente das cidades de Arapiraca e Maceió, estado de Alagoas, Brasil. As categorias temáticas que se destacaram na análise foram: desvalorização; ausência de estrutura física e de recursos para o trabalho; vínculo precário de trabalho; e relação entre sobrecarga, adoecimento e desgaste. Constatou-se que essas categorias compõem o que tem sido chamado de precarização do trabalho, já estabelecida anteriormente, mas amplificada na pandemia, a exemplo da experiência das trabalhadoras de Enfermagem.(AU)

La experiencia de trabajar en el enfrentamiento de la Covid-19, en el medio de un proceso tenso, contradictorio, con repercusiones sobre la propia salud, constituye el contexto de esta investigación, con el objetivo de entender el trabajo de enfermería en la experiencia de enfermeros(as) de la línea de frente contra la Covid-19, en Alagoas, Brasil. Se trata de una investigación cualitativa con análisis del contenido de las historias orales temáticas de 6 enfermeras que actuaron en la línea de frente en las ciudades de Arapiraca y Maceió, estado de Alagoas, Brasil. Las categorías temáticas que se destacaron en el análisis fueron: desvalorización, ausencia de estructura física y recursos para el trabajo, vínculo precario de trabajo y relación entre sobrecarga, ponerse enfermo y desgaste. Se constató que esas categorías componen lo que se ha denominado de precarización del trabajo, ya establecida anteriormente, pero amplificada en la pandemia, a ejemplo de la experiencia de las trabajadoras de enfermería.(AU)

The experience of working in the confrontation of Covid-19, amid tension, contradictions and impacts in the workers' health constitutes the context of this research, with the objective of understanding the nursing work in the experience of frontline nurses against Covid-19, in Alagoas, Brazil. This is a qualitative research, using content analysis of the thematic oral histories of 6 nurses, who worked on the frontline in the cities of Arapiraca and Maceió, state of Alagoas, Brazil. The thematic categories emerging from the analysis were: devaluation; lack of physical structure and resources for work; precarious work bond; and the relationship between overload, illness, and wear and tear. It was found that these categories are encompassed by the term work precarization, previously established, but amplified in the pandemic, following the experience of nursing workers.(AU)

Erratum: Tolerogenic Dendritic Cells Reduce Airway Inflammation in a Model of Dust Mite Triggered Allergic Inflammation.

This corrects the article on p. 406 in vol. 10, PMID: 29949837.

Tolerogenic Dendritic Cells Reduce Airway Inflammation in a Model of Dust Mite Triggered Allergic Inflammation.

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.

Repercussions of circulatory electrical stimulation on quality of life, lubrication and pelvic floor muscles: a pilot study / Repercussões da eletroestimulação circulatória na qualidade de vida, lubrificação e musculatura pélvica: um estudo piloto

Abstract Introduction: The climacteric is one of the transition periods in the life cycle of women between the reproductive and non-reproductive phase, and it is characterized by various metabolic, psychological and social changes, either by psychic disorders or sexual dysfunctions promoting changes in quality of life. Objective: To analyze the repercussions of electrical stimulation on quality of life, lubrication and myoelectric activity of pelvic floor muscles in postmenopausal women. Methods: This was a pilot study in which the sample consisted of ten menopausal volunteers aged 48-60 years. We used the Female Sexual Function Index questionnaire to determine the improvement in lubrication and the WHOQOL-BREF questionnaire to assess quality of life. The pelvic floor muscles were evaluated by electromyography with an intracavitary electrode. The protocol used was: phasic contraction evaluated by three contractions of two seconds and six of rest; three tonic contractions for ten seconds with ten-second rest; and endurance for thirty seconds. The intervention was performed by another researcher, through circulatory stimulation with the Dualpex 961 Quark®. Results: Electromyography after circulatory stimulation showed statistically significant results with an increase in Fast Fourier Transform in tonic and phasic contractions, obtaining a positive effect on the perception and awareness of contractions due to increased blood flow. Also, there was improvement in lubrication and quality of life in all areas. Conclusion: Circulatory stimulation had repercussions on pelvic floor muscles in menopausal women in both muscle physiology and lubrication, with an influence on the quality of life of volunteers.

Resumo Introdução: O climatério constitui um dos períodos de transição no ciclo vital da mulher entre a fase reprodutiva e a não reprodutiva, caracterizado por várias alterações metabólicas e psicológicas, seja por distúrbios psíquicos ou disfunções sexuais, promovendo alterações na qualidade de vida. Objetivo: Analisar as repercussões da eletroestimulação na qualidade de vida, lubrificação e atividade mioelétrica dos músculos do assoalho pélvico em mulheres menopausadas. Métodos: Trata-se de um estudo piloto no qual a amostra foi composta por dez voluntárias em menopausa com idade entre 48 e 60 anos. Para avaliar a melhora da lubrificação foi utilizado o questionário Female Sexual Function Index. Quanto à qualidade de vida, utilizou-se o questionário WHOQOL-bref. Já para a avaliação dos músculos do assoalho pélvico, utilizou-se a eletromiografia com eletrodo intracavitário. O protocolo utilizado foi: contração fásica avaliada por três contrações de dois segundos e seis de repouso; três contrações tônicas sustentadas por dez segundos com repouso de dez segundos; endurance durante trinta segundos. A intervenção foi realizada por outra pesquisadora, através de estimulação circulatória com o aparelho Dualpex 961 Quark®. Resultados: A eletromiografia pós-estimulação circulatória obteve resultados significativos, com aumento na Fast Fourier Transform nas contrações tônicas e fásicas, obtendo efeito positivo na percepção e conscientização das contrações devido ao aumento do fluxo sanguíneo. Houve, também, melhora na lubrificação e na qualidade de vida em todos os domínios. Conclusão: A estimulação circulatória apresentou repercussões nos músculos do assoalho pélvico em mulheres menopausadas tanto na fisiologia muscular quanto na lubrificação, influenciando a qualidade de vida das voluntárias.

Structural design, synthesis and pharmacological evaluation of thiazoles against Trypanosoma cruzi.

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, IC50trypo = 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 IC50 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.

Protective effects of mito-TEMPO against doxorubicin cardiotoxicity in mice.

PURPOSE: Doxorubicin (DOX) is a chemotherapeutic that is widely used for the treatment of many human tumors. However, the development of cardiotoxicity has limited its use. The aim of the present study was to evaluate the possible efficacy of mito-TEMPO (mito-T) as a protective agent against DOX-induced cardiotoxicity in mice. METHODS: C57BL/6 mice were treated twice with mito-T at low (5 mg/kg body weight) or high (20 mg/kg body weight) dose and once with DOX (24 mg/kg body weight) or saline (0.1 mL/20 g body weight) by means of intraperitoneal injections. The levels of malondialdehyde (MLDA), a marker of lipid peroxidation, and serum levels of creatine kinase were evaluated 48 h after the injection of DOX. RESULTS: DOX induced lipid peroxidation in heart mitochondria (p < 0.001), and DOX-treated mice receiving mito-T at low dose had levels of MLDA significantly lower than the mice that received only DOX (p < 0.01). Furthermore, administration of mito-T alone did not cause any significant changes from control values. Additionally, DOX-treated mice treated with mito-T at high dose showed decrease in serum levels of total CK compared to mice treated with DOX alone (p < 0.05). CONCLUSION: Our results indicate that mito-T protects mice against DOX-induced cardiotoxicity.

Predictors of low perceptual-motor skills in children at 4-5 years of age / Preditores da baixa habilidade percepto-motora em crianças de 4-5 anos de idade

Abstract Objectives: the purpose of this study was to evaluate the predictors of low perceptual-motor skills in children at preschool age. Methods: this is a cross-sectional study nested in a birth cohort involving mother-child pairs. The children's perceptual-motor skills were assessed individually in their homes when they were 4-5 years old using the Pre-Literacy Skills and Knowledge Test (THCP®), a vali-dated Brazilian instrument. Logistic regression analysis was used to estimate the association between cognitive perceptual-motor skills and potential maternal and child risk factors. Results: of the 199 children included in the study, 53.8% were boys, 90.8% attended school, and 91.1% were enrolled in a public school. Among the children, 114 (57.3%), 41 (20.6%) and 44 (22.1%) had low, moderate and high perceptual-motor skills, respectively. Multivariate logistic regression analysis revealed greater odds of children at preschool age having low perceptual motor skills for boys (OR=2.10; CI95%= 1.14-3.88), children who did not attend school (OR=4.61; CI95%= 1.21-17.49), and those with a household income <5 minimum wages (MW) (OR=4.28; CI95%= 1.49-12.26). Conclusions: our study showed that male gender, not attending school and a monthly household income <5 MW were predictors of low perceptual-motor skills in children at 4-5 years of age.

Resumo Objetivos: avaliar os preditores da baixa habilidade percepto-motora em crianças em idade pré-escolar. Métodos: trata-se de um estudo transversal aninhado a uma coorte de nascimentos envol-vendo pares de mães-crianças. A habilidade percepto-motora das crianças foi avaliada indi-vidualmente em suas residências quando completaram 4-5 anos de idade, utilizando-se o Teste de Habilidades e Conhecimento Pré-Alfabetização (THCP®), um instrumento brasileiro validado. Análise de regressão logística foi utilizada para estimar a associação entre a baixa habilidade percepto-motora das crianças e potenciais fatores de risco materno-infantil. Resultados: das 199 crianças incluídas no estudo, 53,8% eram meninos, 90,8% frequen-tavam a escola, e 91,1% estudavam em escola pública. Entre as crianças, 114 (57,3%), 41 (20,6%) e 44 (22,1%) revelaram baixa, moderada e elevada habilidade percepto-motora, respectivamente. A análise de regressão logística ajustada revelou maior chance de crianças em idade pré-escolar apresentar baixa habilidade percepto-motora quando em meninos (OR=2,10; IC95%=1,14-3,88), crianças que não frequentavam a escola (OR=4,61; IC95%=1,21-17,49), e possuíam renda familiar <5 salários mínimos (SM) (OR=4,28; IC95%=1,49-12,26). Conclusões: nosso estudo revelou que sexo masculino, renda familiar <5 SM, e não frequentar a escola foram preditores significativos da baixa habilidade percepto-motora em crianças de 4-5 anos de idade.

O Araruna como um fenômeno de lazer: sentidos lúdicos nas expressões dos corpos brincantes / The Araruna as a leisure phenomenon: lucidy senses in the expressions of the players bodies

Buscamos refletir como o Araruna se revela como um fenômeno de lazer, identificando os sentidos lúdicos existentes nas expressões culturais dos corpos brincantes. Identificamos que os sentidos lúdicos estão presentes nas danças e também nas outras práticas corporais, como a festa junina, o carnaval, o cinema, dentre outras atividades que o Grupo realizou ao longo de sua existência. As danças e demais práticas corporais da cultura de movimento do Araruna, quando contrastadas com a esfera do lazer, trazem vários fatores que a fazem relacionar-se a esse aspecto importante do viver e isso pode ser observado a partir das expressividades dos brincantes. Tais sentidos lúdicos do Araruna dialogam com as diferentes facetas do lazer, possibilitando novas ideias para o universo da dança.

We seek to reflect how the Araruna reveals itself as a leisure phenomenon, identifying the playful senses that exist in the cultural expressions of the players bodies. We identified that the playful senses are present in dances and also in other bodily practices, such as the June party, carnival, cinema, among other activities that the Group has carried out throughout its existence. The dances and other corporal practices of Araruna's movement culture, when contrasted with the sphere of leisure, bring several factors that make it relate to this important aspect of living and this can be observed from the expressiveness of the players. Such playful senses of Araruna dialogue with the different facets of leisure, enabling new ideas for the dance universe.

Qualidade microbiológica de preparações ofertadas a idosos institucionalizados residentes / Microbiological quality of preparations offered to elderly institutionalized residents

A avaliação microbiológica de alimentos é justificada sob o aspecto da saúde pública, devido ao alimento ser considerado um veículo de transmissão de doença e/ou proliferação de microrganismos patógenos. Esse estudo objetivou analisar a qualidade microbiológica de preparações ofertadas a idosos residentes numa Instituição de Longa Permanência, na cidade de Feira de Santana-BA. Constatou-se elevada concentração de agentes biológicos com forma característica de Bacilos Gram-Negativos. Os resultados podem ser atribuídos a inadequada qualidade higiênico sanitária na manipulação dos alimentos envolvidos. Sugere-se adoção de medidas corretivas, visando reduzir os riscos de contaminação, que possam comprometer a qualidade final das preparações e a saúde dos idosos, bem como, a continuidade do estudo com novas análises para quantificação e identificação dos agentes.