Trypanosoma cruzi killing and immune response boosting by novel phenoxyhydrazine-thiazole against Chagas disease.

Trypanosoma cruzi (T. cruzi) causes Chagas, which is a neglected tropical disease (NTD). WHO estimates that 6 to 7 million people are infected worldwide. Current treatment is done with benznidazole (BZN), which is very toxic and effective only in the acute phase of the disease. In this work, we designed, synthesized, and characterized thirteen new phenoxyhydrazine-thiazole compounds and applied molecular docking and in vitro methods to investigate cell cytotoxicity, trypanocide activity, nitric oxide (NO) production, cell death, and immunomodulation. We observed a higher predicted affinity of the compounds for the squalene synthase and 14-alpha demethylase enzymes of T. cruzi. Moreover, the compounds displayed a higher predicted affinity for human TLR2 and TLR4, were mildly toxic in vitro for most mammalian cell types tested, and LIZ531 (IC50 2.8 µM) was highly toxic for epimastigotes, LIZ311 (IC50 8.6 µM) for trypomastigotes, and LIZ331 (IC50 1.9 µM) for amastigotes. We observed that LIZ311 (IC50 2.5 µM), LIZ431 (IC50 4.1 µM) and LIZ531 (IC50 5 µM) induced 200 µg/mL of NO and JM14 induced NO production in three different concentrations tested. The compound LIZ331 induced the production of TNF and IL-6. LIZ311 induced the secretion of TNF, IFNγ, IL-2, IL-4, IL-10, and IL-17, cell death by apoptosis, decreased acidic compartment formation, and induced changes in the mitochondrial membrane potential. Taken together, LIZ311 is a promising anti-T. cruzi compound is not toxic to mammalian cells and has increased antiparasitic activity and immunomodulatory properties.

The Effects of Different Exercise Training Types on Body Composition and Physical Performance in Older Adults with Sarcopenic Obesity: A Systematic Review and Meta-Analysis.

OBJECTIVES: To carry out a systematic review and meta-analysis to verify the effects of different exercise training types on body composition and physical performance in older adults with sarcopenic obesity (SO). DESIGN: Systematic review and meta-analysis. SETTING AND PARTICIPANTS: Older adults (≥60 years). METHODS: Database searches were performed in MEDLINE (via PubMed), EMBASE, Cochrane Library, Web of Science, SCOPUS, and LILACS on January 10th, 2023. We included: randomized and/or controlled clinical trials; physical exercise as an intervention; analysis of body composition and/or muscle function; and sarcopenic obesity diagnosis. We used the Risk of Bias 2 tool and PEDro scale. The GRADE certainty of evidence was also performed. RESULTS: Fourteen studies were included in the systematic review and nine studies in the meta-analysis. A decrease in body fat (%) favoring the exercise group was identified (SMD: -0.34 [95% CI: -0.53 to -0.16]; p=0.0003) (GRADE: ⊕⊕⊕◯ Moderate). Only resistance training showed fat reduction (SMD: -0.27 [95% CI: -0.48 to -0.06]; p=0.01). Increases in upper (SMD: 0.41 [95% CI: 0.04 to 0.78]; p=0.03) (GRADE: ⊕⊕◯◯ Low) and lower (SMD: 0.80 [95% CI: 0.22 to 1.39]; p=0.007) (GRADE: ⊕⊕⊕⊕ High) limb strength was identified with exercise. Chair stand test showed increases with exercise (SMD: 0.73 [95% CI: 0.40 to 1.07]; p<0.0001) (GRADE: ⊕⊕⊕⊕ High), especially for resistance training (SMD: 0.62 [95% CI: 0.21 to 1.02]; p=0.003) and combined training (SMD: 0.99 [95% CI: 0.40 to 1.57]; p=0.0005). The PEDro scale for the studies in our review ranged from 3 to 8 (mean = 5.8 (1.6)), meaning fair methodological quality, and most studies were overall judged with at least low/some concerns in terms of risk of bias. CONCLUSION AND IMPLICATIONS: Overall, moderate to high certainty of evidence was found for body fat, lower limb strength, and chair stand test. On the other hand, low certainty of evidence was found for upper limb strength. Resistance, combined, and aerobic training evoked divergent results between the variables analyzed. Although promising, our results should be considered sparingly, but may guide additional exercise recommendations to improve specific health parameters in older adults with SO.

Sirtuins: Key pieces in the host response to pathogens' puzzle.

Global warming is changing the distribution of different pathogens around the globe, and humans are more susceptible to new or re-emerging infections. The human response to microbes is complex and involves different mechanisms of the immune system. Regulation of gene expression of immunity genes and of metabolism of immune cells are essential in this process. Both mechanisms could be regulated by protein lysine acetylation that will control chromatin structure affecting gene expression or key enzyme activity involved in cellular processes. Protein acetylation is crucial for the immunity and involves two families of enzymes: lysine acetyltransferases (KATs), which will promote protein acetylation, and lysine deacetylases (KDACs) that will reduce this modification. Lysine deacetylases are divided into Zinc-dependent or HDACs and NAD+ -dependent, or Sirtuins. These enzymes are in the nucleus, cytosol, and mitochondria of mammalian cells affecting different cellular pathways, such as metabolism, gene expression, DNA repair, cell proliferation, and apoptosis, opening the opportunity to explore these proteins as drug targets in different diseases, including cancer and neurodegenerative illness. Although widely explored in chronic diseases, very little is known about the role of Sirtuins during host response against microbes' infection. In this review we aim to explore the most recent literature evidencing a role for these enzymes during host responses to viruses, bacterial and protozoan infections, pointing out how these proteins can be manipulated by these pathogens to progress in the infection. Moreover, we will uncover the potential of host KDACs as therapeutic targets to prevent infections by activating effector immune functions.

1,3-Thiazole derivatives as privileged structures for anti-Trypanosoma cruzi activity: Rational design, synthesis, in silico and in vitro studies.

Chagas disease is a deadly and centenary neglected disease that is recently surging as a potential global threat. Approximately 30% of infected individuals develop chronic Chagas cardiomyopathy and current treatment with the reference benznidazole (BZN) is ineffective for this stage. We presently report the structural planning, synthesis, characterization, molecular docking prediction, cytotoxicity, in vitro bioactivity and mechanistic studies on the anti-T. cruzi activity of a series of 16 novel 1,3-thiazoles (2-17) derived from thiosemicarbazones (1a, 1b) in a two-step and reproducible Hantzsch-based synthesis approach. The anti-T. cruzi activity was evaluated in vitro against the epimastigote, amastigote and trypomastigote forms of the parasite. In the bioactivity assays, all thiazoles were more potent than BZN against epimastigotes. We found that the compounds presented an overall increased anti-tripomastigote selectivity (Cpd 8 was 24-fold more selective) than BZN, and they mostly presented anti-amastigote activity at very low doses (from 3.65 µM, cpd 15). Mechanistic studies on cell death suggested that the series of 1,3-thiazole compounds herein reported cause parasite cell death through apoptosis, but without compromising the mitochondrial membrane potential. In silico prediction of physicochemical properties and pharmacokinetic parameters showed promising drug-like results, being all the reported compounds in compliance with Lipinski and Veber rules. In summary, our work contributes towards a more rational design of potent and selective antitripanosomal drugs, using affordable methodology to yield industrially viable drug candidates.

Central and Effector Memory Human CD4+ and CD8+ T Cells during Cutaneous Leishmaniasis and after In Vitro Stimulation with Leishmania (Viannia) braziliensis Epitopes

Cutaneous Leishmaniasis (CL) is a Neglected Tropical Disease characterized by skin ulcers caused by Leishmania spp. protozoans and there is no safe and effective vaccine to reduce its negative consequences. In a previous work by our group, we identified T cell epitopes of Leishmania (Viannia) braziliensis which stimulated patients' T cells in vitro. In the present work, the peptides were tested as two pools for their ability to rescue memory T cells during natural infection by Leishmania. We analyzed the frequency of central memory (TCM, CD45RA-CD62L+) and effector memory (TEM, CD45RA + CD62L-) cells during active CL and post-treatment. In parallel, we investigated cell proliferation levels and the cytokines produced after stimulation. Interestingly, we observed higher frequencies (%) in CD4+ TEM during CL, and CD8+ TEM and CD8+ TCM during CL and post-treatment. Cell proliferation was increased, and a significant difference in expression was observed on T-bet and RORγT. Besides that, IFN-γ, IL-2, and IL-10 were detected in patient samples. Collectively, this dataset suggests that during CL there is an increase in the frequency of TCM and TEM, especially in the CD8 compartment. These results indicate a potentially immunogenic profile of the peptide pools, which can support the development of anti-Leishmania formulations.

Chemokine receptors on human regulatory T cells during cutaneous leishmaniasis.

The aim of this work was to define the population of regulatory T cells (Tregs) which are circulating in the blood of Leishmania infected individuals clinically displaying a lesion (active disease-AD) and sub-clinical (SC) ones. We have individually collected blood samples, processed the PBMC and stained with fluorochrome-conjugated antibodies against CD3, CD4, Foxp3, CD25, CTLA-4, Ki-67, CCR4, CCR5, and CCR7. Cells were analyzed by flow cytometry. Our results suggest that CD25 and CTLA-4 are upregulated in Tregs of AD patients when compared to SC and uninfected (UN) controls. Moreover, Tregs proliferate upon infection based on Ki-67 nuclear antigen staining. Finally, we have observed that these Tregs of SC and AD patients upregulate CCR4, but not CCR5 and CCR7. There is an increase in the number of circulating Tregs in the blood of Leishmania infected individuals. These cells are potentially more suppressive based on the increased upregulation of CD25 and CTLA-4 during clinical infection (AD) when compared to SC infection. Tregs of both SC and AD cohorts are proliferating and express CCR4, which potentially guide them to the skin, but do not upregulate CCR5 and CCR7.

Políticas de permanência estudantil na educação superior: reflexões de uma revisão da literatura para o contexto brasileiro / Políticas de retención de estudiantes en educación superior: reflexiones a partir de una revisión de la literatura para el contexto brasileño / Student retention policies in higher education: reflections from a literature review for the Brazilian context

Resumo A evasão no ensino superior é uma questão de interesse global e, para reduzi-la, diversas políticas foram criadas visando ao incentivo da permanência de alunos nas universidades. Este artigo objetivou identificar padrões de avaliação de políticas de permanência estudantil na educação superior mediante uma revisão sistemática da literatura, com base em 39 documentos selecionados nas bases Scopus, Sage Journals, Web of Science, Google Acadêmico e Periódicos Capes. Em relação às formas de avaliação, os resultados indicaram a predominância de análises dos efeitos das políticas sobre a evasão, mas também havia estudos que avaliaram o desempenho e o tempo até a diplomação dos alunos. As pesquisas foram majoritariamente aplicadas em ambientes universitários de natureza pública, o que indica a escassez de produções científicas sobre instituições de ensino privadas. Quanto aos formatos das políticas de permanência, a literatura apontou quatro espécies de auxílio com naturezas distintas: financeiro, assistencial, baseado em mérito acadêmico e por critérios de necessidade/vulnerabilidade dos estudantes. Com a pesquisa, propôs-se uma avaliação das políticas de permanência em formato tríplice, considerando a permanência, o desempenho e o tempo até a diplomação. Entre as lacunas da literatura, evidenciaram-se os estudos comparativos de diferentes políticas.

Resumen La deserción en la educación superior es un tema de interés mundial y, para reducirla, se crearon varias políticas para alentar a los estudiantes a permanecer en las universidades. Este artículo tuvo como objetivo identificar patrones de evaluación de las políticas de retención de estudiantes en la educación superior a través de una revisión sistemática de la literatura, con base en 39 documentos seleccionados en Scopus, Sage Journals, Web of Science, Google Academic y periódicos CAPES. Con relación a las formas de evaluación, los resultados indicaron el predominio de análisis sobre los efectos de las políticas en la deserción, pero que también hubo estudios que evaluaron el desempeño y el tiempo de graduación de los estudiantes. Las investigaciones se aplicaron mayoritariamente en ambientes universitarios públicos, lo que indica una escasez de producción científica sobre las instituciones educativas privadas. En cuanto a los formatos de las políticas de retención, la literatura señaló cuatro tipos de ayudas con distinta naturaleza: económicas, asistenciales, basadas en el mérito académico y en criterios de necesidad/vulnerabilidad de los estudiantes. Con base en la investigación, se propuso una evaluación de las políticas de retención de formato triple, considerando la permanencia, el desempeño y el tiempo hasta la graduación. Entre las brechas en la literatura, se destacaron los estudios comparativos entre los tipos de políticas.

Abstract Dropout in higher education is a matter of global interest, and several policies were created to encourage students to stay in universities. This article aimed to identify patterns of evaluation of student retention policies in higher education through a systematic literature review, selecting 39 documents from Scopus, Sage Journals, Web of Science, Google academic, and CAPES Periodicals. Regarding evaluation forms, the results indicated the predominance of analyses on the effects of policies on dropout. However, some studies evaluated students' performance and time to graduation. Research works were mostly applied in public university environments, which indicates a scarcity of scientific production about private educational institutions. As for the formats of permanence policies, the literature pointed out four types of aid with different natures: financial, assistance, based on academic merit, and by criteria of students' need/vulnerability. Based on the research, it was proposed that the evaluation of permanence policies should be threefold, considering permanence, performance, and time until graduation. Among the gaps in the literature, comparative studies between the types of policies were highlighted.

Prevalence of Leishmania infantum in Dogs from Deforested Areas of the Amazon Biome.

Background and Objectives: Species of Leishmania genus are intracellular parasites responsible for severe zoonotic diseases worldwide, such as leishmaniasis. In Brazil, the most important species is Leishmania infantum. In the northern region, the state of Pará is notable, with a high number of cases reported in recent years. The second largest number of cases of human visceral leishmaniasis in the region in recent years has been reported in the city of Marabá (Pará state). We investigated the prevalence of L. infantum in domestic dogs from Marabá in Amazon region in Brazil. Materials and Methods: A total of 400 blood samples were tested using the dual-path platform chromatographic immunoassay (DPP® CVL-Bio-Manguinhos), and molecular diagnosis based in cathepsin L-like gene, which has better specificity and sensitivity than other similar tests. Results: The prevalence of L. infantum was 75.5% (302/400) in the serological test, and 59.25% (237/400) in molecular diagnosis, and 45.5% (182/400) in both tests. Interpretation and Conclusion: The results confirmed that the parasite L. infantum was prevalent in the dog population of the studied region and adoption of appropriate public policies are urgently needed.

Relação entre os níveis de ferritina e o prognóstico da COVID-19 / Relationship between ferritin levels and the prognosis of COVID-19

O elevado nível de ferritina sérica tem sido associado à COVID-19 grave devido à sua estimulação por citocinas relacionadas com o processo inflamatório. Embora este aumento seja esperado, esta revisão propõe analisar o quão elevado o nível de ferritina pode estar relacionado com esta severidade. Nesta linha de pensamento, a hiperferritinemia na COVID-19 poderia ser um importante fator de previsão e outra forma de compreender as complicações da COVID-19 - coagulopatia, síndrome do desconforto respiratório agudo (SDRA). Além disso, esta correlação tem sido vista como uma possível quinta síndrome entre as outras "síndromes hiperferritinêmicas", todas caracterizadas por ferritina sérica elevada; esta é uma comparação e análise pertinente em termos de tratamentos. [au]

The high level of serum ferritin has been associated with severe COVID-19 due to its stimulation by cytokines related to the inflammatory process. Although this increase is expected, this review proposes to analyze how high ferritin can be related to this severeness. According to this premise, the hyperferritinemia on COVID-19 could be an important factor of prediction and another way to understand the complications of COVID-19 -coagulopathy, acute respiratory distress syndrome (ARDS). Furthermore, this correlation has been seen as a possible fifth syndrome among the other "hyperferritinemic syndromes", which are all characterized by high serum ferritin; this is an pertinent comparison and analyzation in terms of treatments. [au]

Prevalence of Leishmania infantum in dogs from deforested areas of the Amazon biome

Background and Objectives: Species of Leishmania genus are intracellular parasites responsible for severe zoonotic diseases worldwide, such as leishmaniasis. In Brazil, the most important species is Leishmania infantum. In the northern region, the state of Pará is notable, with a high number of cases reported in recent years. The second largest number of cases of human visceral leishmaniasis in the region in recent years has been reported in the city of Marabá (Pará state). We investigated the prevalence of L. infantum in domestic dogs from Marabá in Amazon region in Brazil. Materials and Methods: A total of 400 blood samples were tested using the dual-path platform chromatographic immunoassay (DPP® CVL—Bio-Manguinhos), and molecular diagnosis based in cathepsin L-like gene, which has better specificity and sensitivity than other similar tests. Results: The prevalence of L. infantum was 75.5% (302/400) in the serological test, and 59.25% (237/400) in molecular diagnosis, and 45.5% (182/400) in both tests. Interpretation and Conclusion: The results confirmed that the parasite L. infantum was prevalent in the dog population of the studied region and adoption of appropriate public policies are urgently needed.

Unraveling the Role of Immune Checkpoints in Leishmaniasis.

Leishmaniasis are Neglected Tropical Diseases affecting millions of people every year in at least 98 countries and is one of the major unsolved world health issues. Leishmania is a parasitic protozoa which are transmitted by infected sandflies and in the host they mainly infect macrophages. Immunity elicited against those parasites is complex and immune checkpoints play a key role regulating its function. T cell receptors and their respective ligands, such as PD-1, CTLA-4, CD200, CD40, OX40, HVEM, LIGHT, 2B4 and TIM-3 have been characterized for their role in regulating adaptive immunity against different pathogens. However, the exact role those receptors perform during Leishmania infections remains to be better determined. This article addresses the key role immune checkpoints play during Leishmania infections, the limiting factors and translational implications.

Carriers based on poly-3-hydroxyalkanoates containing nanomagnetite to trigger hormone release.

Poly-3-hydroxybutyrate (P(3HB)) and poly-3-hydroxybutyrate-co-3-hydroxyhexanoate (P(3HB-co-3HHx)) are biocompatible and bioabsorbable biopolymers produced by different bacteria with potential for drug delivery in thermo-responsive magnetic microcarriers. Microparticles of P(3HB) and P(3HB-co-3HHx), with 5.85% mol of 3HHx, produced by Burkholderia sacchari, containing nanomagnetite (nM) and lipophilic hormone were prepared by simple emulsion (oil/water) technique leading to progesterone (Pg) encapsulation efficiency higher than 70% and magnetite loads of 3.1 and 2.3% (w/w) for P(3HB)/nM/Pg and P(3HB-co-3HHx)/nM/Pg, respectively. These formulations were characterized by Infrared spectroscopy, X-ray diffraction, Thermal gravimetric analysis and Electron microscopy (TEM, SEM) techniques. The P(3HB)/nM/Pg and P(3HB-co-3HHx)/nM/Pg microparticles presented spherical geometry with wrinkled surfaces and average size between 2 and 40 µm for 90% of the microparticles. The release profiles of the P(3HB)/nM/Pg and P(3HB-co-3HHx)/nM/Pg formulations showed a hormone release trigger (6.9 and 11.1%, respectively) effect induced by oscillating external magnetic field (0.2 T), after 72 h. Progesterone release in non-magnetic tests with P(3HB-co-3HHx)/nM/Pg revealed a slight increment (5.6%) in relation to P(3HB)/nM/Pg. The experimental release of the P(3HB)/nM/Pg and P(3HB-co-3HHx)/nM/Pg samples presented a good agreement with Higuchi model. The 3HHx comonomer content improves the hormone release of the P(3HB-co-3HHx)/nM/Pg formulation with potential for application to synchronize the estrous cycle.

Molecular Diagnosis and Prevalence of Trypanosoma vivax (Trypanosomatida: Trypanosomatidae) in Buffaloes and Ectoparasites in the Brazilian Amazon Region.

Trypanosoma vivax Ziemann is a parasite that affects both wild and domestic ungulates and is transmitted mechanically via tabanids and other blood-sucking insects in the Americas. A total of 621 blood samples from water buffaloes (Bubalus bubalis (Linnaeus) (Artiodactyla: Bovidae), and 184 ectoparasite samples (Amblyomma cajennense (Fabricius) sensu stricto and Rhipicephalus (Boophilus) microplus (Canestrini) (Acari: Ixodidae), and Haematopinus tuberculatus (Burmeister) (Phthiraptera: Haematopinidae)) were obtained from 60 farms in the State of Pará, Brazilian Amazon. Twelve buffalo blood samples (1.89%) and 11 ectoparasites (6%) were positive for T. vivax based on the cathepsin L-like gene. All sequences were 99% similar to T. vivax from northeastern Brazil (EU753788) in amplified PCR assays on each of the hosts tested.

Competências dos médicos no atendimento a idosos em situação de violência: revisão de escopo / Doctors' competences in caring for older people in situations of violence: scope review

Resumo Objetivo descrever, por meio das evidências da literatura, as competências dos médicos de serviços hospitalares diante de situações de violência contra a pessoa idosa (VCPI). Método revisão de escopo com busca em bases de dados/plataformas/buscadores e literatura cinzenta abrangendo Medline; BVS; Embase; CINAHL; Web of Science; BDTD, OpenGrey, OpenThesis, RCAAP, Portal de Teses e Dissertações da CAPES, DART-Europe E-theses Portal e Theses Canada Portal (catálogos Aurora e Voilà). Os descritores e palavras-chave utilizados, combinados com os operadores booleanos OR, AND e NOT, foram: "Physicians", "Médicos", "Atitude", "Attitude", "Conhecimento", "Knowledge", "Behavior", "Atendimento Médico", "Cuidados Médicos", "Medical Care", "Serviços Hospitalares", "Hospital Services", "Hospital", "Hospitalists", "Médicos Hospitalares", "Maus-Tratos ao Idoso", "Elder Abuse", "Physical Abuse", "Elder Neglect", "Aged Abuse", "Elder Mistreatment". Resultados seis trabalhos foram selecionados. Evidenciou-se falta de conhecimento sobre o tema e a abordagem, e de treinamento específico. Quanto às habilidades, os achados que mais levaram os médicos a suspeitarem de abuso foram achados físicos ligados à aparência, higiene e lesões - problemas de comunicação e relacionamento foram pouco apontados. Na atitude houve pesquisa de abusos em apenas 44% das suspeitas e percentuais baixos ou nulos de denúncia de casos. Apenas um estudo explorou a atitude frente às negligências, onde 24,8% relataram aos serviços sociais e 21,3% informaram à polícia. Conclusão a maioria dos casos de VCPI continua não percebida e, consequentemente, não reportada ou manejada. Há múltiplos problemas quanto às competências dos médicos hospitalares ao abordarem tais situações, cenário que expõe a demanda por medidas de sensibilização, capacitação e incentivo ao adequado enfrentamento da VCPI.

Abstract Objective describing by means of the evidence in the literature, the competences of doctors in hospital services in situations of violence against older people (VAOP). Method scope review with search in databases/platforms/searchers and grey literature covering Medline; VHL; Embase; CINAHL; Web of Science; BDTD, OpenGrey, OpenThesis, RCAAP, Portal de Teses e Dissertações da CAPES, DART-Europe E-theses Portal and Theses Canada Portal (Aurora and Voilà catalogs). The descriptors and keywords used, combined with the Boolean operators OR, AND, NOT were: "Physicians", "Doctors", "Attitude", "Attitude", "Knowledge", "Knowledge", "Behavior", "Medical Care", "Medical Care", "Medical Care", "Hospital Services", "Hospital Services", "Hospital", "Hospitalists", "Hospital Doctors", "Older People Abuse", "Older People Abuse", "Physical Abuse", "Older People Neglect ", "Aged Abuse", "Older People Mistreatment". Results six papers were selected. There was a lack of knowledge on the topic and the approach, and of specific training. As for skills, the findings that most led doctors to suspect abuse were physical findings linked to appearance, hygiene and injuries - communication and relationship problems were little mentioned. In the attitude, there was a research of abuse in only 44% of the suspicions and low or null percentages on case reporting. Only one study explored the attitude towards negligence, where 24.8% reported to social services and 21.3% informed the police. Conclusion most cases of VAOP remain unnoticed and therefore unreported or unhandled. There are multiple problems regarding the competences of hospital doctors when dealing with such situations, a scenario that exposes the demand for measures to raise awareness, training, and encouragement to adequately deal with VAOP.

Programmed Cell Death Ligand (PD-L)-1 Contributes to the Regulation of CD4+ T Effector and Regulatory T Cells in Cutaneous Leishmaniasis.

Cutaneous Leishmaniasis (CL) affects up to one million people every year and treatments are costly and toxic. The regulation of the host immune response is complex and the knowledge of how CD4+ T cells are activated and maintained during Leishmania infection is still limited. Current therapies aim to target programmed cell death (PD)-1 and programmed cell death ligand (PD-L)-1 in order to boost T cell activity. However, the role of the PD-1/PD-L1 axis during Leishmania infection is still unclear. In this study, we found that patients with active and post-treatment CL displayed different subsets of CD4+PD-1+ T cells. Accordingly, L. major-infected mice upregulated PD-1 on activated CD4+ T effector cells and PD-L1 on resident macrophages and infiltrating monocytes at the site of infection. L. major-infected Pdl1-/- mice expressed lower levels of MHCII and higher levels of CD206 on macrophages and monocytes and, more importantly, the lack of PD-L1 contributed to a reduced frequency of CD4+Ly6Chi T effector cells and an increase of CD4+Foxp3+ regulatory T cells at the site of infection and in draining lymph nodes. Additionally, the lack of PD-L1 was associated with lower production of IL-27 by infiltrating monocytes and lower levels of the Th1 cytokines IFN-γ and TNF-α produced by CD4+ T effector cells. Pdl1-/- mice initially exhibited larger lesions despite having a similar parasite load. Our results describe for the first time how the interruption of the PD-1/PD-L1 axis influences the immune response against CL and suggests that this axis regulates the balance between CD4+Ly6Chi T effector cells and CD4+Foxp3+ regulatory T cells.

A contribuição da Educação permanente para o enfrentamento da violência de gênero / The contribution of continuing education to addressing gender violence

O presente manuscrito tem como objetivo relatar a experiência enquanto participantes do curso "Para elas: atenção integral à saúde da mulher em situação de violência" em ambiente virtual de aprendizagem pela plataforma UNASUS em parceria com a Universidade Federal de Minas Gerais (UFMG). O curso em questão tinha como objetivo discutir o aumento da violência contra as mulheres e sua interface com a saúde bem como apresentar a importância dos profissionais da Atenção Básica fortalecer as ações com vistas a garantia de direitos. Os temas abordados enfatizaram a contribuição das políticas públicas e a atuação da rede de proteção no enfrentamento à violência contra as mulheres.

This manuscript aims to report the experience as participants of the course " For them: comprehensive health care for women in situations of violence" in a virtual learning environment through the UNASUS platform in partnership with the Federal University of Minas Gerais (UFMG). The course in question aimed to discuss the increase in violence against women and their interface with health, as well as to present the importance of Primary Care professionals to strengthen actions with a view to guaranteeing rights. The topics covered emphasized the contribution of public policies and the role of the safety net in tackling violence against women

Canine Visceral Leishmaniasis in São Paulo, Brazil, the Most Populous City of South America: Isolation, Molecular Diagnosis, and Phylogenetic Inferences.

Background and Objectives: Canine visceral leishmaniasis affects dogs, the main urban reservoirs, which favor the transmission and expansion of this zoonotic disease in areas with high anthropization process and human density. We investigated the occurence of Leishmania infatum based in molecular diagnosis, and phylogenetic analysis of isolates obtained from dogs in metropolitan region of São Paulo. Methods: A total of 201 dogs were tested by parasitological and molecular diagnosis. Phylogenetic analysis based sequences from SSUrDNA and gGAPDH genes were performed. Results: The parasitological diagnosis revealed 5% (10/201) of positivity, and the sequences obtained from seven isolates were clustered with L. infantum in phylogentic analysis based on SSUrDNA and gGAPDH genes. A total of 24.9% (50/201) of dogs were positive in molecular diagnosis based on cathepsin L-like marker. Interpretation and Conclusion: According to this study, it is necessary to implement a surveillance policy of visceral leishmaniasis, intensifying the actions of diagnosis, prevention, and control of this zoonosis.

Survey of protozoan vector-borne diseases in dogs from Atlantic Rainforest fragment around Billings Dam, São Paulo, Brazil / Levantamento de protozoários transmitidos por vetores em cães de um fragmento de Mata Atlântica nos arredores da Barragem Billings, São Paulo, Brasil

ABSTRACT: Vector-borne diseases are currently one of the biggest public health concerns worldwide. Dogs, being the closest companion animals to humans, are considered the main reservoir of some of these diseases in the urban environment. Therefore, the study of the disease behavior in dogs can help to understand the disease affecting human health. Serological and molecular diagnoses of Babesia vogeli, Rangelia vitalli, Leishmania infantum, and other trypanosomatids, were performed by immunochromatographic and PCR assays, respectively, on dogs in a dog shelter located in an Atlantic Forest fragment near the Billings Dam, São Bernardo do Campo, São Paulo-Brazil. Our molecular diagnostic results showed a high prevalence of Babesia vogeli, at 20.9% (17/81). No other protozoan was detected in any of the tests. Determining the prevalence of major vector-borne diseases is essential to establish preventive and control measures for zoonotic diseases in animals kept in shelters, in order to minimize the impact of vector-borne diseases on animal health.

RESUMO: As doenças transmitidas por vetores são atualmente um dos maiores problemas de saúde pública. Os cães, sendo os animais de companhia mais próximos dos seres humanos, são considerados os principais reservatórios de algumas dessas doenças no ambiente urbano, e o estudo de seu comportamento em cães ajuda a entender a doença como um todo na saúde humana. Diagnósticos sorológicos e moleculares de Babesia vogeli, Rangelia vitalli, Leishmania infantum e outros tripanossomatídeos, em um abrigo para cães localizado em um fragmento da Mata Atlântica próximo à Barragem Billings, São Bernardo do Campo, São Paulo, Brasil. Foram realizadas sorologias e diagnósticos moleculares, no ensaio de PCR foram utilizados marcadores moleculares de oligonucleotídeos específicos para alguns protozoários de importância na saúde animal, como Babesia vogeli, Rangelia vitalli, Leishmania infantum e outros tripanossomatídeos. Nossos resultados de diagnóstico molecular mostraram uma alta prevalência de 20,9% (17/81) de Babesia vogeli. Nenhum outro protozoário foi detectado em nenhum dos testes. A determinação da prevalência das principais doenças transmitidas por vetores é essencial para estabelecer medidas preventivas e de controle de doenças zoonóticas em animais mantidos em abrigos. Essas medidas devem ser propostas para minimizar o impacto de doenças transmitidas por vetores na saúde animal.