Lantana camara L. induces a multi-targeted cell death process in Leishmania amazonensis.

ETNOPHARMACOLOGICAL RELEVANCE: Lantana camara L. is a species known for its broad spectrum of bioactivities and is commonly used in folk therapy to address inflammatory, dermatological, gastrointestinal, intestinal worms and protozoan diseases. It boasts a diverse array of secondary metabolites such as terpenes, flavonoids, and saponins. However, despite its rich chemical profile, there remains a scarcity of studies investigating its antileishmanial properties. AIM OF THE STUDY: This research aims to explore the antileishmanial potential of L. camara, focusing also on its mechanism of action against Leishmania amazonensis. MATERIAL AND METHODS: The ethanolic extract of L. camara leaves (LCE) was obtained through static maceration, and its phytoconstituents were identified using UFLC-QTOF-MS. The colorimetric MTT method was conducted to determine the effect of LCE on promastigotes of L. amazonensis and murine macrophages. The anti-amastigote activity was evaluated by counting intracellular parasites in macrophages after Giemsa staining. Additionally, investigations into the mechanisms underlying its action were conducted using cellular and biochemical approaches. RESULTS: LCE exhibited significant activity against both promastigotes and intracellular amastigotes of L. amazonensis, with IC50 values of 12.20 µg/mL ± 0.12 and 7.09 µg/mL ± 1.24, respectively. These IC50 values indicate very promising antileishmanial activity, comparable to those found for the positive control miltefosine (5.10 µg/mL ± 1.79 and 8.96 µg/mL ± 0.50, respectively). Notably, LCE exhibited negligible cytotoxicity on macrophages (IC50 = 223.40 µg/mL ± 47.02), demonstrating selectivity towards host cells (SI = 31.50). The antileishmanial activity of LCE involved a multi-targeted cell death process, characterized by morphological and ultrastructural alterations observed through SEM and TEM analyses, as well as oxidative effects evidenced by the inhibition of trypanothione reductase, elevation of ROS and lipid levels, and mitochondrial dysfunction evaluated using DTNB, H2DCFDA, Nile red, and JC-1 assays. Additionally, extraction of ergosterol and double labeling with annexin V and PI revealed modifications to the organization and permeability of the treated parasite's plasma membrane. LCE was found to consist predominantly of terpenes, with lantadenes A, B, and C being among the eleven compounds identified through UFLC-QTOF-MS analysis. CONCLUSIONS: The extract of L. camara presents a diverse array of chemical constituents, prominently featuring high terpene content, which may underlie its antileishmanial properties through a combination of apoptotic and non-apoptotic mechanisms of cell death induced by LCE. This study underscores the therapeutic potential of L. camara as a candidate for antileishmanial treatment, pending further validation.

Exploring Cationic Guar Gum: Innovative Hydrogels and Films for Enhanced Wound Healing.

Background/Objectives: This study developed and characterized hydrogels (HG-CGG) and films (F-CGG) based on cationic guar gum (CGG) for application in wound healing. Methods: HG-CGG (2% w/v) was prepared by gum thickening and evaluated for pH, stability, spreadability, and viscosity. F-CGG was obtained using an aqueous dispersion of CGG (6% w/v) and the solvent casting method. F-CGG was characterized for thickness, weight uniformity, morphology, mechanical properties, hydrophilicity, and swelling potential. Both formulations were evaluated for bioadhesive potential on intact and injured porcine skin, as well as antioxidant activity. F-CGG was further studied for biocompatibility using hemolysis and cell viability assays (L929 fibroblasts), and its wound-healing potential by the scratch assay. Results: HG-CGG showed adequate viscosity and spreadability profiles for wound coverage, but its bioadhesive strength was reduced on injured skin. In contrast, F-CGG maintained consistent bioadhesive strength regardless of skin condition (6554.14 ± 540.57 dyne/cm2 on injured skin), presenting appropriate mechanical properties (flexible, transparent, thin, and resistant) and a high swelling capacity (2032 ± 211% after 6 h). F-CGG demonstrated superior antioxidant potential compared to HG-CGG (20.50 mg/mL ABTS+ radical scavenging activity), in addition to exhibiting low hemolytic potential and no cytotoxicity to fibroblasts. F-CGG promoted the proliferation of L929 cells in vitro, supporting wound healing. Conclusions: Therefore, CGG proved to be a promising material for developing formulations with properties suitable for cutaneous use. F-CGG combines bioadhesion, antioxidant activity, biocompatibility, cell proliferation, and potential wound healing, making it promising for advanced wound treatment.

Extensive low-density Plasmodium falciparum reservoir in the island of Príncipe, an isolated malaria pre-elimination setting.

OBJECTIVES: The isolated Príncipe is at the malaria pre-elimination stage. Autochthonous clinical cases have been reported sporadically on the island, signaling the possibility of a sizable subpatent (i.e., rapid diagnostic test- and microscopy-negative and polymerase chain reaction [PCR]-positive) parasite reservoir. METHODS: Asymptomatic low-density infections were detected by quantitative PCR (qPCR) targeting Plasmodium falciparum multicopy genes (pfr364 and varATS). Positivity rates were assayed for samples surveyed by active case detection (n = 112) and reactive case detection (n = 221) in 2022. RESULTS: qPCR unveiled 70% of low parasitemia carriers, reaching >90% in reactive case detection. The high P. falciparum prevalence was confirmed by the two high-sensitivity qPCR protocols. Higher positivity rates were observed in the localities where most malaria cases were reported in 2022. Most parasitemias were very low (<2 Pf /µl). CONCLUSIONS: These findings suggest that pre-elimination surveillance can benefit from the routine application of highly sensitive tools to unveil otherwise invisible but potentially relevant parasite populations.

4-Quinolinylhydrazone analogues kill Leishmania (Leishmania) amazonensis by inducing apoptosis and mitochondria-dependent pathway cell death.

Despite efforts, available alternatives for the treatment of leishmaniasis are still scarce. In this work we tested a class of 15 quinolinylhydrazone analogues and presented data that support the use of the most active compound in cutaneous leishmaniasis caused by Leishmania amazonensis. In general, the compounds showed activity at low concentrations for both parasitic forms (5.33-37.04 µM to promastigotes, and 14.31-61.98 µM to amastigotes). In addition, the best compound (MHZ15) is highly selective for the parasite. Biochemical studies indicate that the treatment of promastigotes with MHZ15 leads the loss of mitochondrial potential and increase in ROS levels as the primary effects, which triggers accumulation of lipid droplets, loss of plasma membrane integrity and apoptosis hallmarks, including DNA fragmentation and phosphatidylserine exposure. These effects were similar in the intracellular form of the parasite. However, in this parasitic form there is no change in plasma membrane integrity in the observed treatment time, which can be attributed to metabolic differences and the resilience of the amastigote. Also, ultrastructural changes such as vacuolization suggesting autophagy were observed. The in vivo effectiveness of MHZ15 in the experimental model of cutaneous leishmaniasis was carried out in mice of the BALB/c strain infected with L. amazonensis. The treatment by intralesional route showed that MHZ15 acted with great efficiency with significantly reduction in the parasite load in the injured paws and draining lymph nodes, without clinical signs of distress or compromise of animal welfare. In vivo toxicity was also evaluated and null alterations in the levels of hepatic enzymes aspartate aminotransferase, and alanine aminotransferase was observed. The data presented herein demonstrates that MHZ15 exhibits a range of favorable characteristics conducive to the development of an antileishmanial agent.

Immature Stages, Natural History and Population Biology of Opoptera syme (Hübner, 1821), (Lepidoptera: Nymphalidae: Satyrinae) from Southeastern Brazil.

The present study describes the immature stages of Opoptera syme (Hübner, [1821]) using SEM and Micro-CT to generate 2D and 3D models to study the morphology and chaetotaxy, and present information on the natural history, behavior, and population biology. In laboratory, eggs were laid singly, and the isolated larvae passed through six to seven instars. Host plant in the study site is unknown, but larvae are known to feed on bamboos; in laboratory, larvae accepted the ornamental bamboo Bambusa textilis McClure, 1940. Adults are diurnal and univoltine, flying from December to April (the austral summer). The present study adds information to the biology and natural history of Brassolini, an iconic and still poorly known tribe of Neotropical butterflies.

Ensino funcional ou acadêmico em ciências para estudantes com deficiência ou autismo? / Functional or academic education in sciences for students with disabilities or autism?

RESUMO Este ensaio teórico teve por objetivo identificar contribuições da organização do conhecimento científico na sistematização do ensino em ciências, para a constituição humana típica e atípica. Isso foi realizado a partir de ponderações entre textos da área de Ensino de Ciências e pressupostos da Teoria Histórico-Cultural. Assim, apresentamos reflexões acerca de discussões que polarizam a educação de pessoas com deficiência ou autismo no direcionamento curricular, em relação às habilidades funcionais e acadêmicas. A partir da análise de limitações, possibilidades e estratégias educacionais para aulas de ciências, concluímos que as habilidades funcionais, que envolvem conhecimentos cotidianos, não podem configurar critério de exclusão curricular de habilidades acadêmicas, do conhecimento científico, para a educação de pessoas com desenvolvimento atípico. Compreendemos que uma educação científica escolar com vias ao desenvolvimento integral é indissociável das habilidades da vida diária.

ABSTRACT This theoretical essay aimed to identify contributions from the organization of scientific knowledge in the systematization of science teaching, for the typical and atypical human constitution. This was carried out based on considerations between texts from the Science Teaching area and assumptions from the Historical-Cultural Theory. Thus, we present reflections on discussions that polarize the education of people with disabilities or autism in terms of curriculum, in relation to functional and academic skills. From the analysis of limitations, possibilities and educational strategies for science classes, we conclude that functional abilities, which involve everyday knowledge, cannot constitute a criterion for curricular exclusion of academic skills, of scientific knowledge, for the education of people with atypical development. We understand that a school scientific education with pathways to integral development is inseparable from daily life skills.

Proposition of an Energy Intake Estimating Scale through Item Response Theory.

BACKGROUND: Traditional methods for assessing individual energy consumption often involve lengthy and intricate procedures. This study aims to introduce an Energy Consumption Estimation Scale, utilizing Item Response Theory (IRT) for adolescents aged 18-19 years. METHODS: This psychometric investigation applies IRT to 93 items extracted from a validated food frequency questionnaire. The study encompasses a representative sample of 2515 adolescents from the São Luís birth cohort in Brazil. The latent trait, energy intake, is derived using IRT and subsequently validated through hierarchical multiple linear regression modeling. Significance was established at p < 0.05. RESULTS: A Samejima's model was successfully fitted (CFI and TLI > 0.9 and RMSEA < 0.08), effectively capturing variations across all energy consumption levels. Factors associated with the latent trait demonstrate consistent behavioral patterns. Adolescents with higher energy intake exhibited increased consumption of dairy products, artificially sweetened beverages, and seasonal fruits and vegetables. CONCLUSIONS: The proposed Energy Consumption Estimation Scale demonstrates a reliable measurement of energy intake and serves as a practical and concise alternative for assessing energy consumption among adolescents. These findings suggest the potential for adapting similar models for different age groups and incorporating diverse food items based on the obtained results.

Assessment of the Brazilian Version of the Epworth Sleepiness Scale Using Item Response Theory: A Psychometric Study.

There seems to be a consensus that adolescents worldwide are not getting enough sleep. This study aimed to evaluate the psychometric properties of the Epworth Sleepiness Scale (ESS) in adolescents using the item response theory. A psychometric study was conducted with 2206 adolescents aged 18 and 19 years in the city of São Luís, Maranhão, Brazil. The dimensionality of the ESS was assessed by principal component analysis. A Samejima's graded response model (SGRM) was fitted to it. The findings of this study showed a good internal consistency and the unidimensionality of the ESS. Considering the latent trait continuum, we obtained three levels, with anchor items. For the item 'Sitting still in a public place', the adolescents presented a small possibility of dozing in level 1, and a medium and great possibility in level 2. The item 'Sitting around talking to someone' presented small, medium, and great possibilities of dozing in level 3. The ESS with five items showed satisfactory psychometric properties. In addition, the results from the SGRM showed that adolescents with high levels of sleepiness are likely to nod off or sleep sitting up while talking to someone. This study allows us to understand excessive daytime sleepiness in adolescents.

Characteristics of deaths by suicide in postmortem studies in Brazil: A systematic review and meta-analysis.

INTRODUCTION: Suicide is one of the leading causes of death, with a trend for its increase in Brazil in past decades. This study aimed to review the characteristics of suicides in Brazilian postmortem studies. METHODS: Studies investigating suicide deaths in Brazil, and based on autopsy or psychological autopsy were included. Proportions were pooled across studies with the use of random and fixed effects models. RESULTS: 6777 references were retrieved from six databases (searches up to January, 2023), and 45 studies included. In autopsy studies (k = 37, n = 16,231), substance use at toxicological analysis was found in 36.42% of cases (95% CI: 30.05-43.32), previous suicide attempts in 23.92% (95% CI: 6.73-57.78). In psychological autopsy studies (k = 8, n = 139), previous suicide attempts were reported in 28.09% (95% CI: 19.74-38.28), psychiatric conditions/symptoms in 90.67% (95% CI: 67.79-97.82), family history of suicidality in 21.33% (95% CI: 13.5-32.03). Most suicide deaths were reported in males and took place at the victim's home, hanging was the most frequent suicide method. Included studies presented significant limitations in quality assessment. CONCLUSION: Future studies should present more robust methodology, including bigger samples, the use of controls, and validated methodology.

Exploring Anthocyanin and Free and Bound Phenolic Compounds from Two Morphotypes of Araçá (Psidium cattleianum Sabine) by LC-ESI-QqQ-MS/MS.

Araçá is a Brazilian native fruit belonging to the Myrtaceae family. Although some studies already prove its health benefits, it is still necessary to explore the phenolic compounds in all its parts separately. This study aimed to investigate the free, esterified, glycosylated, and insoluble phenolics in two morphotypes of araçá, red and yellow, evaluating peel, pulp, and seed separately, using liquid chromatography coupled to mass spectrometry (LC-ESI-QqQ-MS/MS). Fourteen phenolics and five anthocyanins were quantified in both morphotypes. The peels presented the highest contents, followed by the pulp and seeds. Red araçá stood out over the yellow one only in the phenolic fractions resulting from the peel, with the yellow araçá being superior in the phenolic fractions of the pulp and seed. The highest antioxidant capacities were detected for the pulp-esterified phenolics (498.3 µmol g-1) and peel-free phenolics (446.7 µmol g-1) of yellow araçá. Principal component analysis (PCA) indicated specific markers to differentiate the samples. All parts of the araçá proved to be a rich source of phenolic compounds, in different fractions, mainly in the peel. This information will be beneficial to stimulate the consumption of native fruits and their possible use in the development of new products.

Compreensão dos usuários sobre os níveis de atenção à saúde com enfoque na atenção primária à saúde / Users' understanding of health care levels with a focus on primary health care

Objetivo: analisar a compreensão dos usuários sobre os níveis de atenção à saúde com enfoque na atenção primária à saúde. Método: estudo de quantitativo, com delineamento transversal, exploratório e descritivo realizado no Hospital Municipal e Unidade Básica de Saúde localizados no município de Arandu/SP, no período de 15 a 31 de outubro de 2021. Resultados: idade média foi de 31 a 59 anos com 54,71%, sexo feminino com representatividade de 92,45%, 39,62% possuíam o ensino médio e 71,69% religião católica. A ocupação prevalente foi do lar e aposentado com 13,20%. 60,37% não apresentam morbidades, 81,13% procuram o hospital para atendimento, 81% destacou a escuta qualificada das demandas pelo hospital e 83% afirmaram que o agendamento no Centro de Saúde é difícil de conseguir. Conclusão: a construção de políticas públicas e ampliação dos serviços de assistência primária à saúde são a melhor estratégia para garantir a sustentabilidade dos sistemas de saúde.(AU)

Objective: to analyze users' understanding of health care levels with a focus on primary health care. Method: a basic, exploratory and descriptive study carried out at the Municipal Hospital and Health Unit carried out in the municipality of Arandu/SP1, from 15 to 31 of 2020. Results: mean age was 31 to 59 years with54.71%, female sex, representing 92.45%, 39.62% had high school and 71.69% were Catholic. The predominant occupation was housewives and retired with 13.20%. 60.37% do not have morbidities 81.13% and demand 8 the hospital for care, 1% highlighted to respect the demands by the hospital 83% said scheduling at the Health Center is difficult to achieve. Conclusion: the construction of public policies and health care services guaranteed to the best health strategy to guarantee the maintenance of health systems.(AU)

Objetivo: analizar la comprensión de los usuarios sobre los niveles de atención de salud con enfoque en la atención primaria de salud. Método: estudio cuantitativo, transversal, exploratorio y descriptivo realizado en el Hospital Municipal y Unidad Básica de Salud localizados en el municipio de Arandu/SP, del 15 al 31 de octubre de 2021. Resultados: la edad media fue de 31 a 59 años con 54,71%, sexo femenino con una representatividad de 92,45%, 39,62% tenían enseñanza media y 71,69% religión católica. La ocupación prevalente fue doméstica y jubilado con 13,20%. El 60,37% no tenían morbilidades, el 81,13% buscaban el hospital para ser atendidos, el 81% destacaron la escucha calificada de las demandas por el hospital y el 83% afirmaron que la programación en el Centro de Salud es difícil de conseguir. Conclusión: la construcción de políticas públicas y la ampliación de los servicios de atención primaria son la mejor estrategia para garantizar la sostenibilidad de los sistemas de salud.(AU)

Brazilian National Food and Nutritional Security System: what are the similarities in the decentralization process?

This study aimed to analyze the multiple characteristics of the decentralization of the Brazilian National Food and Nutritional Security System (SISAN) in a period before the institutional dismantling. Data from the 26 Brazilian states were collected in two public information systems, referring to the years 2017/2018. An exploratory and descriptive study was performed using a hierarchical cluster analysis, based on an analysis model with multiple characteristics of the system decentralization. The results indicated the formation of three clusters, showing the similarity among states with greater intersectoral and participatory character, better relationship with municipalities, and allocation of resources. On the other hand, states with less intersectoral and participatory character, linked to the low allocation of resources, execution of food security actions, and municipal support were clustered. These clusters composed mainly of North and Northeastern states, with a lower Gross Domestic Product, average Human Development Index, and a higher occurrence of food insecurity, expressed characteristics that may be related to greater obstacles in the system decentralization process. This information can help in the decision-making about the SISAN in a more equitable manner, supporting the actors involved in its maintenance and defense, at a time when the country presents an austere political and economic situation, marked by the progressive worsening of food insecurity.

Brazilian National Food and Nutritional Security System: what are the similarities in the decentralization process? / Sistema Nacional de Segurança Alimentar e Nutricional: quais são as semelhanças no processo de descentralização? / Sistema Nacional de Seguridad Alimentaria y Nutricional: ¿cuáles son las similitudes en el proceso de descentralización?

This study aimed to analyze the multiple characteristics of the decentralization of the Brazilian National Food and Nutritional Security System (SISAN) in a period before the institutional dismantling. Data from the 26 Brazilian states were collected in two public information systems, referring to the years 2017/2018. An exploratory and descriptive study was performed using a hierarchical cluster analysis, based on an analysis model with multiple characteristics of the system decentralization. The results indicated the formation of three clusters, showing the similarity among states with greater intersectoral and participatory character, better relationship with municipalities, and allocation of resources. On the other hand, states with less intersectoral and participatory character, linked to the low allocation of resources, execution of food security actions, and municipal support were clustered. These clusters composed mainly of North and Northeastern states, with a lower Gross Domestic Product, average Human Development Index, and a higher occurrence of food insecurity, expressed characteristics that may be related to greater obstacles in the system decentralization process. This information can help in the decision-making about the SISAN in a more equitable manner, supporting the actors involved in its maintenance and defense, at a time when the country presents an austere political and economic situation, marked by the progressive worsening of food insecurity.

Este estudo teve como objetivo analisar as múltiplas características da descentralização do Sistema Nacional de Segurança Alimentar e Nutricional (SISAN) em um período anterior ao desmonte institucional. Dados dos 26 estados brasileiros foram coletados em dois sistemas públicos de informação, referentes aos anos de 2017/2018. Um estudo exploratório e descritivo foi realizado por meio de uma análise de cluster hierárquica baseada em um modelo de análise com múltiplas características de um sistema descentralizado. Os resultados indicaram a formação de três clusters, mostrando a semelhança entre os estados com maior caráter intersetorial e participativo, assim como melhor relação com municípios e alocação de recursos. De forma oposta, os estados com menor caráter intersetorial e participativo foram agrupados, ligados à baixa alocação de recursos, execução de ações de segurança alimentar e de apoio municipal fracos. Os clusters compostos principalmente por estados do Norte e Nordeste, com menor Produto Interno Bruto, Índice de Desenvolvimento Humano médio e maior ocorrência de insegurança alimentar, expressaram características que podem estar relacionadas a maiores obstáculos na descentralização. Essas informações podem auxiliar na tomada de decisão do SISAN de forma mais equitativa, servindo de apoio aos atores envolvidos em sua manutenção e defesa, em um momento em que o país apresenta uma situação política e econômica de austeridade, marcada pela piora progressiva da situação de insegurança alimentar.

Este estudio tuvo como objetivo analizar las múltiples características de la descentralización del Sistema Nacional de Seguridad Alimentaria y Nutricional (SISAN) en el periodo anterior al desmantelamiento institucional. Los datos de los 26 estados brasileños se recolectaron de dos sistemas de información pública referentes al periodo 2017/2018. Se realizó un estudio exploratorio y descriptivo mediante análisis de clúster jerárquico basado en un modelo de análisis con múltiples características de un sistema descentralizado. Los resultados indicaron la formación de tres clústeres, mostrando la similitud entre los estados de mayor intersectorialidad y participación, así como una mejor relación con los municipios y asignación de recursos. Por otro lado, se agruparon los estados de menor carácter intersectorial y participativo, vinculados a la baja asignación de recursos, ejecución de acciones de seguridad alimentaria y débil apoyo municipal. Los clústeres compuestos principalmente por los estados del Norte y Nordeste de Brasil, con menor Producto Interno Bruto, Índice de Desarrollo Humano medio y mayor ocurrencia de inseguridad alimentaria tuvieron características expresadas que pueden estar relacionadas con mayores obstáculos en la descentralización. Estos datos pueden ayudar al SISAN en la toma de decisiones de manera más equitativa y servir de apoyo a los actores involucrados en su mantenimiento y defensa, en momentos en que el país se enfrenta a una situación política y económica de austeridad, marcada por el progresivo empeoramiento de la inseguridad alimentaria.

Effects of a Serine Protease Inhibitor N-p-Tosyl-L-phenylalanine Chloromethyl Ketone (TPCK) on Leishmania amazonensis and Leishmania infantum.

Studies have previously demonstrated the importance of serine proteases in Leishmania. A well-known serine protease inhibitor, TPCK, was used in the present study to evaluate its in vitro and in vivo antileishmanial effects and determine its mechanism of action. Despite slight toxicity against mammalian cells (CC50 = 138.8 µM), TPCK was selective for the parasite due to significant activity against L. amazonensis and L. infantum promastigote forms (IC50 = 14.6 and 31.7 µM for L. amazonensis PH8 and Josefa strains, respectively, and 11.3 µM for L. infantum) and intracellular amastigotes (IC50 values = 14.2 and 16.6 µM for PH8 and Josefa strains, respectively, and 21.7 µM for L. infantum). Leishmania parasites treated with TPCK presented mitochondrial alterations, oxidative stress, modifications in lipid content, flagellar alterations, and cytoplasmic vacuoles, all of which are factors that could be considered as contributing to the death of the parasites. Furthermore, BALB/c mice infected with L. amazonensis and treated with TPCK had a reduction in lesion size and parasite loads in the footpad and spleen. In BALB/c mice infected with L. infantum, TPCK also caused a reduction in the parasite loads in the liver and spleen. Therefore, we highlight the antileishmanial effect of the assessed serine protease inhibitor, proposing a potential therapeutic target in Leishmania as well as a possible new alternative treatment for leishmaniasis.

Subtilisin of Leishmania amazonensis as Potential Druggable Target: Subcellular Localization, In Vitro Leishmanicidal Activity and Molecular Docking of PF-429242, a Subtilisin Inhibitor.

Subtilisin proteases, found in all organisms, are enzymes important in the post-translational steps of protein processing. In Leishmania major and L. donovani, this enzyme has been described as essential to their survival; however, few compounds that target subtilisin have been investigated for their potential as an antileishmanial drug. In this study, we first show, by electron microscopy and flow cytometry, that subtilisin has broad localization throughout the cytoplasm and membrane of the parasite in the promastigote form with foci in the flagellar pocket. Through in silico analysis, the similarity between subtilisin of different Leishmania species and that of humans were determined, and based on molecular docking, we evaluated the interaction capacity of a serine protease inhibitor against both life cycle forms of Leishmania. The selected inhibitor, known as PF-429242, has already been used against the dengue virus, arenaviruses, and the hepatitis C virus. Moreover, it proved to have antilipogenic activity in a mouse model and caused hypolipidemia in human cells in vitro. Here, PF-429242 significantly inhibited the growth of L. amazonensis promastigotes of four different strains (IC50 values = 3.07 ± 0.20; 0.83 ± 0.12; 2.02 ± 0.27 and 5.83 ± 1.2 µM against LTB0016, PH8, Josefa and LV78 strains) whilst having low toxicity in the host macrophages (CC50 = 170.30 µM). We detected by flow cytometry that there is a greater expression of subtilisin in the amastigote form; however, PF-429242 had a low effect against this intracellular form with an IC50 of >100 µM for intracellular amastigotes, as well as against axenic amastigotes (94.12 ± 2.8 µM for the LV78 strain). In conclusion, even though PF-429242 does not affect the intracellular forms, this drug will serve as a tool to explore pharmacological and potentially leishmanicidal targets.

[Supply of best childbirth practices in maternity units of Rede Cegonha according to Item Response Theory]. / Oferta das boas práticas do parto em maternidades da Rede Cegonha segundo a Teoria de Resposta ao Item.

This study aimed to develop an intelligible scale to measure the level of supply of best practices in labor, childbirth and delivery in maternity units in the Rede Cegonha (RC) based on the workers' perception. The scale consisted of seventeen items related to best practices, based on the instrument used in the "Evaluation of care during delivery and birth in maternity hospitals in the RC" research The three-parameter logistic model of Item Response Theory was used to create the scale and analyze the items. The scale consisted of three levels. In the first level, there are maternity hospitals that adequately offered strategies for welcoming and encouraging the pregnant woman to circulate during labor. The second level maternity wards also included the adequate offer of the right to a companion of choice, massage, ball and different birth positions. Finally, the third level maternity hospitals also offered an adequate delivery stool, as well as the items already mentioned. The findings of this study showed the contribution of each item in measuring the level of supply of best practices in care for labor, childbirth and delivery and the construction of an intelligible scale to assess RC maternity hospitals.

Este estudo objetivou elaborar uma escala interpretável para mensurar o nível de oferta das boas práticas no trabalho de parto e parto em maternidades da Rede Cegonha (RC) a partir da percepção dos trabalhadores. A escala foi composta por dezessete itens relacionados às boas práticas, obtidos a partir do instrumento utilizado na pesquisa "Avaliação da atenção ao parto e nascimento em maternidades da RC". O modelo logístico de três parâmetros da Teoria de Resposta ao Item foi utilizado para criação da escala e análise dos itens. A escala foi composta por três níveis âncoras. No primeiro nível âncora, tem-se maternidades que ofertavam adequadamente estratégias para o acolhimento e estimulando a gestante a deambular no trabalho de parto. As maternidades do segundo nível incluíram também a oferta adequada do direito a acompanhante de livre escolha da mulher, massagem, bola e diferentes posições de parto. Por fim, têm-se as maternidades do terceiro nível ofereciam também adequadamente banqueta de parto, bem como os itens já citados. Os achados deste estudo mostraram a contribuição de cada item na mensuração do nível de oferta das boas práticas de atenção ao trabalho de parto e parto e a construção de uma escala interpretativa para avaliação das maternidades da RC.

Oferta das boas práticas do parto em maternidades da Rede Cegonha segundo a Teoria de Resposta ao Item / Supply of best childbirth practices in maternity units of Rede Cegonha according to Item Response Theory

Resumo Este estudo objetivou elaborar uma escala interpretável para mensurar o nível de oferta das boas práticas no trabalho de parto e parto em maternidades da Rede Cegonha (RC) a partir da percepção dos trabalhadores. A escala foi composta por dezessete itens relacionados às boas práticas, obtidos a partir do instrumento utilizado na pesquisa "Avaliação da atenção ao parto e nascimento em maternidades da RC". O modelo logístico de três parâmetros da Teoria de Resposta ao Item foi utilizado para criação da escala e análise dos itens. A escala foi composta por três níveis âncoras. No primeiro nível âncora, tem-se maternidades que ofertavam adequadamente estratégias para o acolhimento e estimulando a gestante a deambular no trabalho de parto. As maternidades do segundo nível incluíram também a oferta adequada do direito a acompanhante de livre escolha da mulher, massagem, bola e diferentes posições de parto. Por fim, têm-se as maternidades do terceiro nível ofereciam também adequadamente banqueta de parto, bem como os itens já citados. Os achados deste estudo mostraram a contribuição de cada item na mensuração do nível de oferta das boas práticas de atenção ao trabalho de parto e parto e a construção de uma escala interpretativa para avaliação das maternidades da RC.

Abstract This study aimed to develop an intelligible scale to measure the level of supply of best practices in labor, childbirth and delivery in maternity units in the Rede Cegonha (RC) based on the workers' perception. The scale consisted of seventeen items related to best practices, based on the instrument used in the "Evaluation of care during delivery and birth in maternity hospitals in the RC" research The three-parameter logistic model of Item Response Theory was used to create the scale and analyze the items. The scale consisted of three levels. In the first level, there are maternity hospitals that adequately offered strategies for welcoming and encouraging the pregnant woman to circulate during labor. The second level maternity wards also included the adequate offer of the right to a companion of choice, massage, ball and different birth positions. Finally, the third level maternity hospitals also offered an adequate delivery stool, as well as the items already mentioned. The findings of this study showed the contribution of each item in measuring the level of supply of best practices in care for labor, childbirth and delivery and the construction of an intelligible scale to assess RC maternity hospitals.

Analysis of the AUDIT factor structure in adolescents between 18 and 19 years.

OBJECTIVE: To determine the factor structure of the instrument Alcohol Use Disorders Identification Test (AUDIT) in a representative sample of adolescents aged 18 to 19 years. METHODS: Cross-sectional study performed with adolescents born in São Luís (MA). The internal consistency of the instrument was determined by the Cronbach's alpha coefficient, and the validity of the construct was assessed by Confirmatory Factor Analysis (CFA). The Kaiser-Meyer-Olkin (KMO) was estimated to analyze the adequacy of the sample. The fit quality of the factor model was analyzed according to the indexes of the Chi-square adjustment test, comparative fit index (CFI), Tucker-Lewis index (TLI) and root mean square error of approximation (RMSEA). RESULTS: The sample of the study was composed of 1,002 adolescents aged from 18 to 19 years, being 56.8% girls, 68.5% with 18 years, 63.3% brown, 48.6% belonging to class C, 15.4% did not work or did not study, and 52.1% had divorced parents. The sample was suitable for confirmatory factor analysis (KMO = 0.79); Cronbach's alpha coefficient was 0.70, demonstrating satisfactory internal consistency with factor loads above 0.5, except for item 9, "was injured or someone else was injured due to drinking." Confirmatory factor analysis revealed the validity of the three-factor model for the studied sample based on the indices of psychometric adjustments. CONCLUSION: The three-factor AUDIT factor structure was confirmed for the population of adolescents between 18 and 19 years old living in São Luís, ratifying the original conceptual domains proposed by the World Health Organization. AUDIT proved to be a reliable instrument to identify the consumption of alcohol.

Structure and work process for food and nutrition actions in Primary Health Care in Brazil, 2014. / Estrutura e processo de trabalho para as ações de alimentação e nutrição na Atenção Primária à Saúde no Brasil, 2014.

OBJECTIVE: To evaluate the conditions of structure and work process for food and nutrition actions in Primary Health Care in Brazil. METHODS: This was a cross-sectional study with secondary data from the Program for Primary Health Care Access and Quality Improvement. The proportions of Primary Health Care Center (PHCC) and health team adequacy were described according to organizational variables, using prevalence ratios and Poisson regression. RESULTS: 19,793 PHCCs and 24,549 teams were analyzed; 35.0% (n=6,928) of PHCCs were considered adequate in relation to structure and 7.9% (n=1,934) of the teams had adequate work process. Standing out in the analyses of association are PHCCs in the Southern region (44.7%) and teams in the Southeastern region (10.9%), in addition to municipalities with more than 300,000 inhabitants. CONCLUSION: The PHCCs and teams analyzed presented a low proportion of adequacy for structure and work process for food and nutrition actions.

PF-429242, a Subtilisin Inhibitor, Is Effective in vitro Against Leishmania infantum.

PF-429242 is an inhibitor of subtilisin, an important protease found in Leishmania. However, studies regarding the effect of PF-429242 on Leishmania are scarce. In this work we evaluated the antileishmanial effect of PF-429242 against Leishmania infantum and the mechanism involved in the death of the parasite. PF-429242 had low toxicity against mammalian cells (peritoneal macrophages) (CC50 = 189.07 µM) and presented activity against L. infantum promastigotes (IC50 = 2.78 µM) and intracellular amastigotes (IC50 = 14.07 µM), indicating selectivity toward the parasite. Transmission electron microscopy (TEM), as well as staining of L. infantum promastigotes with MitoTracker® Red, rhodamine 123 and MitoSOX, revealed that the mitochondria was a potential target of PF-429242. In addition, PF-429242 caused an accumulation of neutral lipids in promastigotes, which was demonstrated by Nile Red staining and TEM, and induced oxidative stress (H2DCFDA staining). Furthermore the formation of autophagic vacuoles in L. infantum promastigotes was observed by MDC staining and TEM. However, the killing induced by PF-429242 in L. infantum promastigotes appeared to be unrelated to apoptosis and/or necrosis as there was no phosphatidylserine externalization, DNA fragmentation or alterations in the permeability of the parasite plasma membrane, as assessed by annexin V-FITC, TUNEL and propidium iodide staining, respectively. The morphological and ultrastructural evaluation of the promastigotes by optical microscopy, scanning electron microscopy (SEM) and TEM, revealed the presence of parasites with flagellar defects. TEM analysis of the intracellular amastigotes indicated that mitochondrial damage and autophagy could also be involved in the death of these forms after treatment with PF-429242. In addition, PF-429242 treatment stimulated NO production from infected macrophage, but only at a high concentration (100 µM), as well as an increase of TNF levels after treatment with 10 µM of PF-429242. The compound did not stimulate ROS or IL-10 production. Together, these data highlight the antileishmanial potential of PF-429242, inducing several cellular alterations in the parasite, such as mitochondrial damage, neutral lipids accumulation, oxidative stress and autophagy which culminate in the death of L. infantum, as well as modulating host cellular responses that favor the development of an immune response against the parasite.