Potential Effects of Essential Oil from Plinia cauliflora (Mart.) Kausel on Leishmania: In Vivo, In Vitro, and In Silico Approaches.

In the search for new chemotherapeutic alternatives for cutaneous leishmaniasis (CL), essential oils are promising due to their diverse biological potential. In this study, we aimed to investigate the chemical composition and leishmanicidal and anti-inflammatory potential of the essential oil isolated from the leaves of Plinia cauliflora (PCEO). The chemical composition of PCEO showed ß-cis-Caryophyllene (24.4%), epi-γ-Eudesmol (8%), 2-Naphthalenemethanol[decahydro-alpha] (8%), and trans-Calamenene (6.6%) as its major constituents. Our results showed that the PCEO has moderate cytotoxicity (CC50) of 137.4 and 143.7 µg/mL on mice peritoneal exudate cells (mPEC) and Vero cells, respectively. The PCEO was able to significantly decrease mPEC infection by Leishmania amazonensis and Leishmania braziliensis. The value of the inhibitory concentration (IC50) on amastigote forms was about 7.3 µg/mL (L. amazonensis) and 7.2 µg/mL (L. braziliensis). We showed that PCEO induced drastic ultrastructural changes in both species of Leishmania and had a high selectivity index (SI) > 18. The in silico ADMET analysis pointed out that PCEO can be used for the development of oral and/or topical formulation in the treatment of CL. In addition, we also demonstrated the in vivo anti-inflammatory effect, with a 95% reduction in paw edema and a decrease by at least 21.4% in migration immune cells in animals treated with 50 mg/kg of PCEO. Taken together, our results demonstrate that PCEO is a promising topical therapeutic agent against CL.

Comparative transcriptomics analysis of multidrug-resistant Acinetobacter baumannii in response to treatment with the terpenic compounds thymol and carvacrol.

Acinetobacter baumannii is a gram-negative opportunistic bacterium that has become a major public health concern and a substantial medical challenge due to its ability to acquire multidrug resistance (MDR), extended-drug resistance, or pan-drug resistance. In this study, we evaluated the antibacterial activity of thymol and carvacrol alone or in combination against clinical isolates of MDR A. baumannii. Additionally, we used RNA-sequency to perform a comparative transcriptomic analysis of the effects of carvacrol and thymol on the Acb35 strain under different treatment conditions. Our results demonstrated that thymol and carvacrol alone, effectively inhibited the bacterial growth of MDR A. baumannii isolates, with a minimum inhibitory concentration (MIC) lower than 500 µg/mL. Furthermore, the combination of thymol and carvacrol exhibited either synergistic (FICI ≤ 0.5) or additive effects (0.5 < FICI ≤ 4), enhancing their antibacterial activity. Importantly, these compounds were found to be non-cytotoxic to Vero cells and did not cause hemolysis in erythrocytes at concentrations that effectively inhibited bacterial growth. Transcriptomic analysis revealed the down-regulation of mRNA associated with ribosomal subunit assemblies under all experimental conditions tested. However, the up-regulation of specific genes encoding stress response proteins and transcriptional regulators varied depending on the experimental condition, particularly in response to the treatment with carvacrol and thymol in combination. Based on our findings, thymol and carvacrol demonstrate promising potential as chemotherapeutic agents for controlling MDR A. baumannii infections. These compounds exhibit strong antibacterial activity, particularly in combination and lower cytotoxicity towards mammalian cells. The observed effects on gene expression provide insights into the underlying mechanisms of action, highlighting the regulation of stress response pathways.

Reemergence of Dengue Virus Serotype 3, Brazil, 2023.

We characterized 3 autochthonous dengue virus serotype 3 cases and 1 imported case from 2 states in the North and South Regions of Brazil, 15 years after Brazil's last outbreak involving this serotype. We also identified a new Asian lineage recently introduced into the Americas, raising concerns about future outbreaks.

Adolescência e juventude & saúde mental / Adolescence and Youth & Mental Health

Falar de Saúde Mental é tão importante quanto falar sobre a saúde física das pessoas. A Saúde Mental é o que somos e fazemos, incluindo as condições para este fazer, que se constituem a partir de um sentir e se pensar no mundo, por isso tão fundamental! Também se expressa nas várias doenças físicas, enquanto realidade psicossomática, e até na disposição para o combate a esses males, já que a divisão "físico versus psíquico" é apenas didática, uma vez que somos unos

Adolescência e juventude & saúde mental / Adolescence and youth & mental health

O foco do livro, como diz o título, é a "Saúde Mental de Adolescentes e Jovens", derivado da necessidade de ações de saúde para este público e da união de esforços para a implementação da "Linha de Cuidado para a Adolescência e Juventude para o SUS-SP", junto às apresentações e discussões sobre Saúde Mental e Adolescência e Juventude, realizadas em 2 cursos que ofertamos em 2023 com os temas "Adolescência e Saúde Mental no SUS: desafios e possibilidades para a produção de cuidados" e "A Rede Intersetorial como Perspectiva Diante das Vulnerabilidades dos Adolescentes: desafios atuais na Saúde Mental", integrando também a contribuição de outros especialistas da área.

The endoplasmic reticulum of trypanosomatids: An unrevealed road for chemotherapy.

The endoplasmic reticulum (ER) of higher eukaryotic cells forms an intricate membranous network that serves as the main processing facility for folding and assembling of secreted and membrane proteins. The ER is a highly dynamic organelle that interacts with other intracellular structures, as well as endosymbiotic pathogenic and non-pathogenic microorganisms. A strict ER quality control (ERQC) must work to ensure that proteins entering the ER are folded and processed correctly. Unfolded or misfolded proteins are usually identified, selected, and addressed to Endoplasmic Reticulum-Associated Degradation (ERAD) complex. Conversely, when there is a large demand for secreted proteins or ER imbalance, the accumulation of unfolded or misfolded proteins activates the Unfold Protein Response (UPR) to restore the ER homeostasis or, in the case of persistent ER stress, induces the cell death. Pathogenic trypanosomatids, such as Trypanosoma cruzi, Trypanosoma brucei and Leishmania spp are the etiological agents of important neglected diseases. These protozoans have a complex life cycle alternating between vertebrate and invertebrate hosts. The ER of trypanosomatids, like those found in higher eukaryotes, is also specialized for secretion, and depends on the ERAD and non-canonical UPR to deal with the ER stress. Here, we reviewed the basic aspects of ER biology, organization, and quality control in trypanosomatids. We also focused on the unusual way by which T. cruzi, T. brucei, and Leishmania spp. respond to ER stress, emphasizing how these parasites' ER-unrevealed roads might be an attractive target for chemotherapy.

Distinct mRNA and protein interactomes highlight functional differentiation of major eIF4F-like complexes from Trypanosoma brucei.

Gene expression in pathogenic protozoans of the family Trypanosomatidae has several novel features, including multiple eIF4F-like complexes involved in protein synthesis. The eukaryotic eIF4F complex, formed mainly by eIF4E and eIF4G subunits, is responsible for the canonical selection of mRNAs required for the initiation of mRNA translation. The best-known complexes implicated in translation in trypanosomatids are based on two related pairs of eIF4E and eIF4G subunits (EIF4E3/EIF4G4 and EIF4E4/EIF4G3), whose functional distinctions remain to be fully described. Here, to define interactomes associated with both complexes in Trypanosoma brucei procyclic forms, we performed parallel immunoprecipitation experiments followed by identification of proteins co-precipitated with the four tagged eIF4E and eIF4G subunits. A number of different protein partners, including RNA binding proteins and helicases, specifically co-precipitate with each complex. Highlights with the EIF4E4/EIF4G3 pair include RBP23, PABP1, EIF4AI and the CRK1 kinase. Co-precipitated partners with the EIF4E3/EIF4G4 pair are more diverse and include DRBD2, PABP2 and different zinc-finger proteins and RNA helicases. EIF4E3/EIF4G4 are essential for viability and to better define their role, we further investigated their phenotypes after knockdown. Depletion of either EIF4E3/EIF4G4 mRNAs lead to aberrant morphology with a more direct impact on events associated with cytokinesis. We also sought to identify those mRNAs differentially associated with each complex through CLIP-seq with the two eIF4E subunits. Predominant among EIF4E4-bound transcripts are those encoding ribosomal proteins, absent from those found with EIF4E3, which are generally more diverse. RNAi mediated depletion of EIF4E4, which does not affect proliferation, does not lead to changes in mRNAs or proteins associated with EIF4E3, confirming a lack of redundancy and distinct roles for the two complexes.

Photoinactivation of Yeast and Biofilm Communities of Candida albicans Mediated by ZnTnHex-2-PyP4+ Porphyrin.

Candida albicans is the main cause of superficial candidiasis. While the antifungals available are defied by biofilm formation and resistance emergence, antimicrobial photodynamic inactivation (aPDI) arises as an alternative antifungal therapy. The tetracationic metalloporphyrin Zn(II) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin (ZnTnHex-2-PyP4+) has high photoefficiency and improved cellular interactions. We investigated the ZnTnHex-2-PyP4+ as a photosensitizer (PS) to photoinactivate yeasts and biofilms of C. albicans strains (ATCC 10231 and ATCC 90028) using a blue light-emitting diode. The photoinactivation of yeasts was evaluated by quantifying the colony forming units. The aPDI of ATCC 90028 biofilms was assessed by the MTT assay, propidium iodide (PI) labeling, and scanning electron microscopy. Mammalian cytotoxicity was investigated in Vero cells using MTT assay. The aPDI (4.3 J/cm2) promoted eradication of yeasts at 0.8 and 1.5 µM of PS for ATCC 10231 and ATCC 90028, respectively. At 0.8 µM and same light dose, aPDI-treated biofilms showed intense PI labeling, about 89% decrease in the cell viability, and structural alterations with reduced hyphae. No considerable toxicity was observed in mammalian cells. Our results introduce the ZnTnHex-2-PyP4+ as a promising PS to photoinactivate both yeasts and biofilms of C. albicans, stimulating studies with other Candida species and resistant isolates.

Activity of poly(methacrylic acid)-silver nanoparticles on fluconazole-resistant Candida albicans strains: Synergistic and cytotoxic effects.

AIMS: To synthesize and evaluate the antifungal activity of poly(methacrylic acid)-silver nanoparticles (PMAA-AgNPs) against nine Candida albicans isolated from clinical specimens. METHODS AND RESULTS: The effects of PMAA-AgNPs-fluconazole combination was analysed by checkerboard methodology. The synergistic potential of PMAA-AgNPs-fluconazole was determined by the fractional inhibitory concentration index (FICI). The inhibition of germ tube formation and the determination of PMAA-AgNPs cytotoxicity were also performed. All C. albicans strains were susceptible to PMAA-AgNPs and resistant to fluconazole. PMAA-AgNPs at subinhibitory concentrations restored the susceptibility of resistant C. albicans to fluconazole, whose FICI ranged from 0.3 to 0.5. The synergistic interaction of the combination was observed in eight of nine strains. The PMAA-AgNPs-fluconazole combination was also able to inhibit the germ tube formation. PMAA-AgNPs showed a dose-dependent decrease in viability for cells tested, with 50% cytotoxic concentration (CC50 ) values of 6.5, 4.9 and 6.8 µg ml-1 for macrophages, fibroblasts and Vero cells, respectively. CONCLUSIONS: This study demonstrated that, in general, PMAA-AgNPs acts synergistically in combination with fluconazole, inhibiting fluconazole-resistant C. albicans strains. PMAA-AgNPs-fluconazole combination was also able to inhibit germ tube formation, an important virulence factor. Inhibitory effect of PMAA-AgNPs alone or in combination was higher in C. albicans than in mammalian cells. SIGNIFICANCE AND IMPACT OF STUDY: This study shows the potential of PMAA-AgNPs combined with fluconazole to inhibit fluconazole-resistant C. albicans strains.

Identification of 1,2,3-triazole-phthalimide derivatives as potential drugs against COVID-19: a virtual screening, docking and molecular dynamic study.

In this work we aimed to perform an in silico predictive screening, docking and molecular dynamic study to identify 1,2,3-triazole-phthalimide derivatives as drug candidates against SARS-CoV-2. The in silico prediction of pharmacokinetic and toxicological properties of hundred one 1,2,3-triazole-phtalimide derivatives, obtained from SciFinder® library, were investigated. Compounds that did not show good gastrointestinal absorption, violated the Lipinski's rules, proved to be positive for the AMES test, and showed to be hepatotoxic or immunotoxic in our ADMET analysis, were filtered out of our study. The hit compounds were further subjected to molecular docking on SARS-CoV-2 target proteins. The ADMET analysis revealed that 43 derivatives violated the Lipinski's rules and 51 other compounds showed to be positive for the toxicity test. Seven 1,2,3-triazole-phthalimide derivatives (A7, A8, B05, E35, E38, E39, and E40) were selected for molecular docking and MFCC-ab initio analysis. The results of molecular docking pointed the derivative E40 as a promising compound interacting with multiple target proteins of SARS-CoV-2. The complex E40-Mpro was found to have minimum binding energy of -10.26 kcal/mol and a general energy balance, calculated by the quantum mechanical analysis, of -8.63 eV. MD simulation and MMGBSA calculations confirmed that the derivatives E38 and E40 have high binding energies of -63.47 ± 3 and -63.31 ± 7 kcal/mol against SARS-CoV-2 main protease. In addition, the derivative E40 exhibited excellent interaction values and inhibitory potential against SAR-Cov-2 main protease and viral nucleocapsid proteins, suggesting this derivative as a potent antiviral for the treatment and/or prophylaxis of COVID-19.Communicated by Ramaswamy H. Sarma.

Leishmanicidal and cytotoxic activity of essential oil from the fruit peel of Myrciaria floribunda (H. West ex Willd.) O. Berg: Molecular docking and molecular dynamics simulations of its major constituent onto Leishmania enzyme targets.

Cutaneous Leishmaniasis (CL) is a neglected disease characterized by highest morbidity rates worldwide. The available treatment for CL has several limitations including serious side effects and resistance to the treatment. Herein we aimed to evaluate the activity of essential oil from the peel of Myrciaria floribunda fruits (MfEO) on Leishmania amazonensis. The cytotoxic potential of MfEO on host mammalian cells was evaluated by MTT. The in vitro leishmanicidal effects of MfEO were investigated on the promastigote and intracellular amastigote forms. The ultrastructural changes induced by MfEO were evaluated by Scanning Electron Microscopy (SEM). The molecular docking of the major compounds δ-Cadinene, γ-Cadinene, γ-Muurolene, α-Selinene, α-Muurolene and (E)-Caryophyllene onto the enzymes trypanothione reductase (TreR) and sterol 14-alpha demethylase (C14DM) were performed. Our results showed that MfEO presented moderate cytotoxicity for Vero cells and macrophages. The MfEO inhibited the growth of promastigote and the survival of intracellular amastigotes, in a dose- and time- dependent way. The MfEO presented high selectivity towards amastigote forms, being 44.1 times more toxic for this form than to macrophages. Molecular docking analysis showed that the major compounds of MfEO interact with Leishmania enzymes and that δ-Cadinene (δ-CAD) presented favorable affinity energy values over TreR and C14DM enzymes, when compared with the other major constituents. Molecular dynamics (MD) simulation studies revealed a stable binding of δ-CAD with lowest binding free energy values in MMGBSA assay. Our results suggested that δ-CAD may be a potent inhibitor of TreR and C14DM enzymes. Communicated by Ramaswamy H. Sarma.

Situação atual da oferta de serviços de atenção à saúde da população LGBTI no estado de São Paulo / Current situation of the offer of health care services to the LGBTI population in the state of Sao Paulo

Neste artigo damos um panorama geral dos problemas e serviços já disponíveis para a população LGBT em todo o estado de São Paulo, destacando mais detalhadamente os localizados na capital.

Questões LGBTI+ e garantia dos direitos sexuais de crianças e adolescentes / LGBTI+ issues and guaranteeing the sexual rights of children and adolescents

0 artigo faz uma análise nas mudanças legais envolvendo os direitos de crianças e adolescentes no Brasil, além das iniciativas que envolver direitos sexuais e reprodutivos, procurando atualizar a importância desses na promoção da saúde dessas populações, considerando as especificidades das questões de género e sexualidade agrupadas nos grupos LGBT. Discorre sobre a importância da atenção, atualização e da promoção do não preconceito contra crianças que apresentem diversidade de gênero em serviços de saúde, escolas e famílias, e da promoção em saúde geral antevendo as mudanças da puberdade trans e LGBT, incluindo o direito a assistência à promoção da prevenção em saúde sexual e reprodutiva para este público e a importância da garantia da autonomia e sigilo nesta promoção.

Relatório de atividades de pesquisa da especialização em saúde coletiva: planejamento de ações estratégicas de saúde baseadas em evidências científicas no município de Franco da Rocha / Report of research activities of the specialization in public health: planning of strategic health actions based on scientific evidence in the municipality of Franco da Rocha

Em janeiro de 2020 a Organização Mundial de Saúde declarou Emergência de Saúde Pública de Importância Internacional devido à doença denominada COVID-19, causada pelo coronavírus SARS-CoV-2. Em 11 de março foi declarada a pandemia da COVID-19 que apresenta desafios sem precedentes para políticas e sistemas de saúde de todo o mundo. O Brasil já registrou mais de meio milhão de mortes desde o início da pandemia, segundo boletim do Conselho Nacional de Secretários de Saúde (Conass) do dia 21 de junho de 2021

The Deposition of a Lectin from Oreochromis niloticus on the Surface of Titanium Dioxide Nanotubes Improved the Cell Adhesion, Proliferation, and Osteogenic Activity of Osteoblast-like Cells.

Titanium and its alloys are used as biomaterials for medical and dental applications, due to their mechanical and physical properties. Surface modifications of titanium with bioactive molecules can increase the osseointegration by improving the interface between the bone and implant. In this work, titanium dioxide nanotubes (TiO2NTs) were functionalized with a lectin from the plasma of the fish Oreochromis niloticus aiming to favor the adhesion and proliferation of osteoblast-like cells, improving its biocompatibility. The TiO2NTs were obtained by anodization of titanium and annealed at 400 °C for 3 h. The resulting TiO2NTs were characterized by high-resolution scanning electron microscopy. The successful incorporation of OniL on the surface of TiO2NTs, by spin coating, was demonstrated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIE), and attenuated total reflection-Fourier transform infrared spectrum (ATR-FTIR). Our results showed that TiO2NTs were successfully synthesized in a regular and well-distributed way. The modification of TiO2NTs with OniL favored adhesion, proliferation, and the osteogenic activity of osteoblast-like cells, suggesting its use to improve the quality and biocompatibility of titanium-based biomaterials.

Physiological, metabolic, and stomatal adjustments in response to salt stress in Jatropha curcas.

Salinity is a major issue affecting photosynthesis and crop production worldwide. High salinity induces both osmotic and ionic stress in plant tissues as a result of complex interactions among morphological, physiological, and biochemical processes. Salinity, in turn, can provoke inactivation of some enzymes in the Calvin-Benson cycle and therefore affect the fine adjustment of electron transport in photosystem I and carbon related reactions. Here, we used three contrasting Jatropha curcas genotypes namely CNPAE183 (considered tolerant to salinity), CNPAE218 (sensible), and JCAL171 (intermediate) to understand salinity responses. By performing a long-term (12 months) experiment in land conditions, we investigated distinct mechanisms used by J. curcas to cope with threatening salinity effects by analyzing gas exchange, mineral nutrition and metabolic responses. First, our results highlighted the plasticity of stomatal development and density in J. curcas under salt stress. It also demonstrated that the CNPAE183 presented higher salt-tolerance whereas CNPAE218 displayed a more sensitive salt-tolerance response. Our results also revealed that both tolerance and sensitivity to salinity were connected with an extensive metabolite reprogramming in the Calvin-Benson cycle and Tricarboxylic Acid cycle intermediates with significant changes in amino acids and organic acids. Collectively, these results indicate that the CNPAE183 and CNPAE218 genotypes demonstrated certain characteristics of salt-tolerant-like and salt-sensitive-like genotypes, respectively. Overall, our results highlight the significance of metabolites associated with salt responses and further provide a useful selection criterion in during screening for salt tolerance in J. curcas in breeding programmes.

[Emergency contraceptive use among women attending Primary Health Care services in three Brazilian capital cities]. / Uso da anticoncepção de emergência entre mulheres usuárias de Unidades Básicas de Saúde em três capitais brasileiras.

Little is known regarding the use of emergency contraception among women from different regions of Brazil. The use of emergency contraception as well as contraceptive methods before and after coitus was analyzed. This cross-sectional study assessed the use of emergency contraception by interviewing 2,051 women aged between 18 and 49 attending 76 basic health units in three capitals: São Paulo-SP, Aracaju-SE and Cuiabá-MT. Aspects associated with the use of emergency contraception were analyzed by means of multiple logistic regression. Over half of the women reported the use of emergency contraception (56.7%). Having a high level of education, being from a more privileged socioeconomic group, having a paid job and having had four or more sexual partners were associated with the use of emergency contraception. Being 35 years of age or older and being in a stable relationship was negatively associated. The last time they used emergency contraception, 53.2% used another method, with the male condom and oral pill being the most frequent. Of those who did not use the method, half adopted the regular method after using it (51.7%). The conclusion drawn is that emergency contraception is widely used and does not appear to affect the use of the regular contraceptive method.

Pouco se sabe sobre o uso da anticoncepção de emergência entre mulheres de diferentes regiões do país. Este estudo analisou o uso da anticoncepção de emergência e os aspectos associados, bem como o uso de métodos contraceptivos antes e após. Trata-se de estudo transversal, conduzido com 2.051 mulheres de 18-49 anos, usuárias de 76 Unidades Básicas de Saúde de São Paulo-SP, Aracaju-SE e Cuiabá-MT. Os aspectos associados ao uso da anticoncepção de emergência foram analisados por meio de regressão logística múltipla. Mais da metade das mulheres relatou já ter usado a anticoncepção de emergência (56,7%). Ter alta escolaridade, ser de grupo socioeconômico mais favorecido, ter trabalho remunerado e ter tido quatro ou mais parceiros sexuais associou-se com uso de anticoncepção de emergência. Ter 35 anos de idade ou mais e estar em união estável associou-se negativamente. Da última vez que usaram a anticoncepção de emergência, 53,2% usavam outro método, sendo preservativo masculino e pílula oral os mais frequentes. Das que não usavam método, metade adotou método regular após o uso (51,7%). Conclui-se que a anticoncepção de emergência é amplamente utilizada e parece não contribuir para interrupção do método contraceptivo de uso regular.

A new biocompatible silver/polypyrrole composite with in vitro antitumor activity.

We used an in situ chemical oxidation method to prepare a new composite of silver nanoparticles (AgNPs) with polypyrrole (PPy), whose properties were optimized through a 23-factorial design of the synthesis conditions. The successful formation of the AgNPs/PPy composite was confirmed by UV-Visible and FTIR spectroscopies. Transmission electron microscopy revealed the presence of AgNPs smaller than 100 nm, dispersed into the PPy matrix. This hybrid composite exhibits a blue fluorescence emission after excitation in the ultraviolet region. In MTT assays, the AgNPs/PPy composite exhibited low cytotoxicity toward non-tumoral cell lines (fibroblast, Vero, and macrophages) and selectively inhibited the viability of HeLa cells. The AgNPs/PPy composite induces ultrastructural changes in HeLa cells that are consistent with the noticeable selectivity exhibited toward them when compared to its action against non-tumoral cell lineages. Also, the AgNPs/PPy exhibited a hemolytic activity below 14% for all blood groups tested, at concentrations up to 125 µg/mL. These results suggest that the AgNPs/PPy composite has a promising potential for use as an antitumoral agent.

Efficient photodynamic inactivation of Leishmania parasites mediated by lipophilic water-soluble Zn(II) porphyrin ZnTnHex-2-PyP4.

BACKGROUND: Photodynamic inactivation (PDI) is emerging as a promising alternative for cutaneous leishmaniasis (CL). The chemotherapy currently used presents adverse effects and cases of drug resistance have been reported. ZnTnHex-2-PyP4+ is a porphyrin with a high potential as a photosensitizer (PS) for PDI, due to its photophysical properties, structural stability, and cationic/amphiphilic character that can enhance interaction with cells. This study aimed to investigate the photodynamic effects mediated by ZnTnHex-2-PyP4+ on Leishmania parasites. METHODS: ZnTnHex-2-PyP4+ stability was evaluated using accelerated solvolysis conditions. The photodynamic action on promastigotes was assessed by (i) viability assays, (ii) mitochondrial membrane potential evaluation, and (iii) morphological analysis. The PS-promastigote interaction was studied. PDI on amastigotes and the cytotoxicity on macrophages were also analyzed. RESULTS: ZnTnHex-2-PyP4+, under submicromolar concentration, led to immediate inactivation of more than 95% of promastigotes. PDI promoted intense mitochondrial depolarization, loss of the fusiform shape, and plasma membrane wrinkling in promastigotes. Fluorescence microscopy revealed a punctate PS labeling in the parasite cytoplasm. PDI also led to reductions of ca. 64% in the number of amastigotes/macrophage and 70% in the infection index after a single treatment session. No noteworthy toxicity was observed on mammalian cells. CONCLUSIONS: ZnTnHex-2-PyP4+ is stable against demetallation and more efficient as PS than the ethyl analogue ZnTE-2-PyP4+, indicating readiness for evaluation in in vivo studies as an alternative approach to CL. GENERAL SIGNIFICANCE: This report highlighted promising photodynamic effects mediated by ZnTnHex-2-PyP4+ on Leishmania parasites, opening up perspectives for applications in CL pre-clinical assays and PDI of other microorganisms.

Mayaro virus detection in the western region of Pará state, Brazil.

INTRODUCTION: Mayaro virus (MAYV) was found in Pará state, Brazil, in 1955. Since then, sporadic outbreaks have occurred in different regions of the country. METHODS: Serum sample were collected from 49 individuals in 2016 and were initially tested for dengue virus (DENV) by real-time (RT) polymerase chain reaction (PCR). DENV-negative samples were tested for MAYV and Oropouche virus (OROV) by multiplexed RT quantitative PCR. RESULTS: All samples were negative for DENV and OROV, but MAYV was detected in four samples. CONCLUSIONS: Differential diagnoses of acute febrile syndrome are required, especially in regions where several arboviruses with similar clinical manifestations are endemic.