Synthesis and Anti-Trypanosoma cruzi Activity of New Pyrazole-Thiadiazole Scaffolds.

Chagas disease, a silent but widespread disease that mainly affects a socioeconomically vulnerable population, lacks innovative safe drug therapy. The available drugs, benznidazole and nifurtimox, are more than fifty years old, have limited efficacy, and carry harmful side effects, highlighting the need for new therapeutics. This study presents two new series of pyrazole-thiadiazole compounds evaluated for trypanocidal activity using cellular models predictive of efficacy. Derivatives 1c (2,4-diCl) and 2k (4-NO2) were the most active against intracellular amastigotes. Derivative 1c also showed activity against trypomastigotes, with the detachment of the flagellum from the parasite body being a predominant effect at the ultrastructural level. Analogs have favorable physicochemical parameters and are predicted to be orally available. Drug efficacy was also evaluated in 3D cardiac microtissue, an important target tissue of Trypanosoma cruzi, with derivative 2k showing potent antiparasitic activity and a significant reduction in parasite load. Although 2k potentially reduced parasite load in the washout assay, it did not prevent parasite recrudescence. Drug combination analysis revealed an additive profile, which may lead to favorable clinical outcomes. Our data demonstrate the antiparasitic activity of pyrazole-thiadiazole derivatives and support the development of these compounds using new optimization strategies.

Tuberculosis preventive treatment in newborns.

OBJECTIVE: To describe the reported cases of newborns subjected to tuberculosis preventive treatment (TPT) in the state of Paraná, Brazil, and to evaluate the safety and effectiveness in preventing the progression of TB disease in this population. METHOD: Observational, descriptive case series, with secondary data. The characteristics of the participants were analyzed from the information systems of preventive treatment of TB (of Paraná), between 2009 and 2016. To evaluate which children had developed tuberculosis later or died, we used the data from the information systems of TB (in Brazil), and mortality (in Paraná), covering the years 2009 to 2018. RESULTS: A total of 24 children underwent TPT with the age at treatment onset ranging from 0 to 87 days (median: 23 days). In 95.8 %, the exposure occurred at home, and in 33.3 % of cases, the mother was the source of the infection. A total of 20.8 % of the children tested positive for tuberculosis test at 3 months of age, 83.3 % completed treatment, and 2 experienced adverse events (gastrointestinal issues). No children developed TB or died during the minimum of a 2-year evaluation period through the official databases. CONCLUSIONS: In this case series, the adherence to the plan was high, with few adverse events and 100 % protection against infection.

Validation of the Brazilian Version of the Modified Scale for Delineating Advanced Practice Nursing Roles.

OBJECTIVES: to validate the Brazilian version of the Modified Scale for Delineating Advanced Practice Nursing Roles. METHODS: this was a methodological study for the clinical validation of an instrument, conducted with 207 nurses working in primary care. Exploratory and confirmatory factor analysis, Cronbach's alpha test, and z-test for proportion comparison were used. RESULTS: the internal reliability of the scale was 0.944, with alpha greater than 0.80 in most domains, except for Education (0.786). In the exploratory factor analysis, considering the criterion of eigenvalue greater than one, eight factors were identified, explaining 79.38% of the variance. In the comparison of proportions, the adequate responses (≥ 2) in the domain of Comprehensive Direct Care, in both analyzed groups, were statistically equal. This domain had the highest score of adequate responses, followed by Education and Systems Support. Insufficient scoring was observed in the domains of Publication and Professional Leadership. CONCLUSIONS: the instrument demonstrated stability and reliability to be used in the evaluation of advanced nursing practice.

Padrão de Atividade Física "Guerreiros de Fim de Semana": Risco ou Benefício para a Saúde? / "Weekend Warriors" Physical Activity Pattern: Health Risk or Benefit?

A vida frenética, principalmente nos grandes centros urbanos, dificulta, para algumas pessoas, a realização de atividade física de forma regular (3-5 vezes por semana). Todavia, a possibilidade de realizar essas atividades em um ou dois dias da semana pode ser uma alternativa bastante interessante, uma vez que este padrão de atividade física tem sido associado a menor mortalidade por todas as causas, cardiovasculares e câncer. Nesta breve revisão narrativa, abordaremos os principais estudos científicos sobre os "Guerreiros de Fim de Semana" e sua relação com os benefícios e riscos à saúde. Certamente, a incorporação desse padrão de atividade física nas recomendações e orientações futuras promoverá melhora das condições de saúde e auxiliará o poder público a adequar as estratégias de combate ao sedentarismo.

Site selection for nature-based solutions for stormwater management in urban areas: An approach combining GIS and multi-criteria analysis.

In recent years, particularly following the definition of the UN Sustainable Development Goals (SDGs) for 2030, Nature-Based Solutions (NBS) have gained considerable attention, capturing the interest of both the scientific community and policymakers committed to addressing urban environmental issues. However, the need for studies to guide decision-makers in identifying suitable locations for NBS implementation within urban stormwater management is evident. To address this gap, the present study employs a methodological approach grounded in multi-criteria analysis integrated with Geographic Information Systems (GIS) to identify areas with potential for NBS implementation. In this process, ten NBS were proposed and tested in the drainage area of a shallow tropical urban lake in Londrina, southern Brazil. Additionally, the study investigates areas hosting lower-income populations, a relevant aspect for public managers given the diverse economic subsidies required to implement NBS. Furthermore, the study incorporates a preliminary analysis that evaluates the potential ecosystem benefits to determine the most suitable NBS for a specific site. The result shows that all the ten analyzed NBS were deemed suitable for the study area. Rain barrels had the highest percentage coverage in the study area (37.1%), followed by tree pits (27.9%), and rain gardens (25.4%). Despite having the highest distribution in the basin area, rain barrels exhibited only moderate ecosystem benefits, prompting the prioritization of other NBS with more significant ecological advantages in the final integrated map. In summary, the methodology proposed showed to be a robust approach to selecting optimal solutions in densely populated urban areas.

Exploring novel pyrazole-nitroimidazole hybrids: Synthesis and antiprotozoal activity against the human pathogen trichomonas vaginalis.

Trichomoniasis, a prevalent sexually transmitted infection (STI) caused by the protozoan Trichomonas vaginalis, has gained increased significance globally. Its relevance has grown in recent years due to its association with a heightened risk of acquiring and transmitting the human immunodeficiency virus (HIV) and other STIs. In addition, many publications have revealed a potential link between trichomoniasis and certain cancers. Metronidazole (MTZ), a nitroimidazole compound developed over 50 years ago, remains the first-choice drug for treatment. However, reports of genotoxicity and side effects underscore the necessity for new compounds to address this pressing global health concern. In this study, we synthesized ten pyrazole-nitroimidazoles 1(a-j) and 4-nitro-1-(hydroxyethyl)-1H-imidazole 2, an analog of metronidazole (MTZ), and assessed their trichomonacidal and cytotoxic effects. All compounds 1(a-j) and 2 exhibited IC50 values ≤ 20 µM and ≤ 41 µM, after 24 h and 48 h, respectively. Compounds 1d (IC50 5.3 µM), 1e (IC50 4.8 µM), and 1i (IC50 5.2 µM) exhibited potencies equivalent to MTZ (IC50 4.9 µM), the reference drug, after 24 h. Notably, compound 1i showed high anti-trichomonas activity after 24 h (IC50 5.2 µM) and 48 h (IC50 2.1 µM). Additionally, all compounds demonstrated either non-cytotoxic to HeLa cells (CC50 > 100 µM) or low cytotoxicity (CC50 between 69 and 100 µM). These findings suggest that pyrazole-nitroimidazole derivatives represent a promising heterocyclic system, serving as a potential lead for further optimization in trichomoniasis chemotherapy.

Microwave extraction and molecular imprinted polymer isolation of bergenin applied to the dendrochronological chemical study of Peltophorum dubium.

This study describes methodologies for extracting and isolating bergenin, a C-glucoside of 4-O-methylgallic acid found in some plants and it presents various in vitro and in vivo biological activities. Bergenin was previously obtained from the Pelthophorum dubim (Fabaceae) roots with a good yield. Conventional chromatographic procedures of the CHCl3 soluble fraction of the MeOH extract gave 3.62% of this glucoside. An HPLC/DAD method was also developed and validated for bergenin and its precursor, gallic acid quantifications. Microwave extractions with different solvents were tested to optimize the extraction of bergenin, varying the temperature and time. MAE (Microwave Assisted Extraction) was more efficient than conventional extraction procedures, giving a higher yield of bergenin per root mass (0.45% vs. 0.0839%). Molecularly imprinted polymer (MIP) and non-imprinted polymer (NIP) based on bergenin as the template molecule, methacrylic acid, and ethylene glycol dimethacrylate were synthesized and characterized by FTIR and SEM (Scanning Electron Microscopy). Bergenin adsorption experiments using MIP and NIP followed by molecular imprinted solid phase extraction (MISPE) showed that MIP had a higher selectivity for bergenin than NIP. A dendrochronological study using the proposed method for detection and quantification of gallic acid and bergenin in five P. dubium growth rings of a 31-year-old heartwood and in the phelloderm and barks indicated that bergenin was more abundant in the 11-14th growth rings of the heartwood and decreased from the heartwood to the barks.

A Review of the Synthesis of Oxazoline Derivatives.

Oxazolines are important heterocyclic systems due to their biological activities, such as antibacterial, antimalarial, anticancer, antiviral, anti-inflammatory, antifungal, antipyretic, and antileishmanial. They have been widely applied as chiral auxiliaries, polymers, catalysts, protecting groups, building blocks, and ligands in asymmetric synthesis. Due to their importance, many synthetic routes to prepare oxazoline moieties have been investigated and developed by researchers around the world. In this review, we summarized several synthetic methodologies published in the literature. The main substrates are nitriles, carboxylic acids, and acid derivatives, which react with a variety of reactants under conventional heating, microwave irradiation or ultrasound irradiation conditions. Syntheses via intramolecular cyclisation from amides have also been reported. Many publications have highlighted procedures based on solvent-free conditions using eco-friendly, reusable, and easy-availability catalysts.

Ecological modeling, biogeography, and phenotypic analyses setting the tiger cats' hyperdimensional niches reveal a new species.

Recently, the tiger-cat species complex was split into Leopardus tigrinus and Leopardus guttulus, along with other proposed schemes. We performed a detailed analysis integrating ecological modeling, biogeography, and phenotype of the four originally recognized subspecies-tigrinus, oncilla, pardinoides, guttulus-and presented a new multidimensional niche depiction of the species. Species distribution models used > 1400 records from museums and photographs, all checked for species accuracy. Morphological data were obtained from institutional/personal archives. Spotting patterns were established by integrating museum and photographic/camera-trap records. Principal component analysis showed three clearly distinct groups, with the Central American specimens (oncilla) clustering entirely within those of the Andes, namely the pardinoides group of the cloud forests of the southern Central-American and Andean mountain chains (clouded tiger-cat); the tigrinus group of the savannas of the Guiana Shield and central/northeastern Brazil (savanna tiger-cat); and the guttulus group in the lowland forests of the Atlantic Forest domain (Atlantic Forest tiger-cat). This scheme is supported by recent genetic analyses. All species displayed different spotting patterns, with some significant differences in body measurements/proportions. The new distribution presented alarming reductions from the historic range of - 50.4% to - 68.2%. This multidimensional approach revealed a new species of the elusive and threatened tiger-cat complex.

Validation of the Brazilian Version of the Modified Scale for Delineating Advanced Practice Nursing Roles / Validación de la Versión Brasileña de la Escala Modificada de Delimitación de la Función del Enfermero de Prácticas Avanzadas / Validação da Versão Brasileira da Escala Modificada de Delineamento da Função de Enfermeiro de Práticas Avançadas

ABSTRACT Objectives: to validate the Brazilian version of the Modified Scale for Delineating Advanced Practice Nursing Roles. Methods: this was a methodological study for the clinical validation of an instrument, conducted with 207 nurses working in primary care. Exploratory and confirmatory factor analysis, Cronbach's alpha test, and z-test for proportion comparison were used. Results: the internal reliability of the scale was 0.944, with alpha greater than 0.80 in most domains, except for Education (0.786). In the exploratory factor analysis, considering the criterion of eigenvalue greater than one, eight factors were identified, explaining 79.38% of the variance. In the comparison of proportions, the adequate responses (≥ 2) in the domain of Comprehensive Direct Care, in both analyzed groups, were statistically equal. This domain had the highest score of adequate responses, followed by Education and Systems Support. Insufficient scoring was observed in the domains of Publication and Professional Leadership. Conclusions: the instrument demonstrated stability and reliability to be used in the evaluation of advanced nursing practice.

RESUMEN Objetivos: validar la Escala Modificada de Delimitación de la Función del Enfermero de Prácticas Avanzadas, versión brasileña. Métodos: estudio metodológico de validación clínica de un instrumento, realizado con 207 enfermeros activos en la atención primaria. Se utilizaron análisis factorial exploratorio y confirmatorio, prueba alfa de Cronbach y prueba z para la comparación de proporciones. Resultados: la fiabilidad interna de la escala fue de 0,944, y el alfa fue mayor que 0,80 en la mayoría de los dominios, excepto en Educación (0,786). En el análisis factorial exploratorio, considerando el criterio de autovalor mayor que uno, se identificaron ocho factores, explicando el 79,38% de la varianza. En la comparación de proporciones, las respuestas suficientes (≥ 2) en el dominio de Cuidados Integrales Directos, en ambos grupos analizados, fueron estadísticamente iguales. Este dominio tuvo la mayor puntuación de respuestas suficientes, seguido por Educación y Apoyo de Sistemas. Se observó una puntuación insuficiente en los dominios de Publicación y Liderazgo Profesional. Conclusiones: el instrumento demostró estabilidad y fiabilidad para ser utilizado en la evaluación de la práctica avanzada de enfermería.

RESUMO Objetivos: validar a Escala Modificada de Delineamento da Função do Enfermeiro de Práticas Avançadas, versão brasileira. Métodos: estudo metodológico de validação clínica de instrumento, realizado com 207 enfermeiros atuantes na atenção primária. Utilizaram-se análise fatorial exploratória e confirmatória, teste alfa de Cronbach e teste z para comparação de proporções. Resultados: a confiabilidade interna da escala foi de 0,944, e o alfa maior que 0,80 na maioria dos domínios, exceto Educação (0,786). Na análise fatorial exploratória, considerando o critério do autovalor maior que um, identificaram-se oito fatores, explicando 79,38% da variância. Na comparação de proporções, as respostas suficientes (≥ 2) no domínio Cuidados Abrangentes Diretos, em ambos os grupos analisados, foram estatisticamente iguais. Esse domínio teve a maior pontuação de respostas suficientes, seguido por Educação e Suporte de Sistemas. Pontuação insuficiente foi observada nos domínios Publicação e Liderança Profissional. Conclusões: o instrumento demonstrou estabilidade e confiabilidade para ser utilizado na avaliação da prática avançada de enfermagem.

Exploring Streptococcus pneumoniae capsular typing through MALDI-TOF mass spectrometry and machine-learning algorithms in Argentina: Identifying prevalent NON PCV13 serotypes alongside PCV13 serotypes.

Introduction: Laboratory surveillance of Streptococcus pneumoniae serotypes plays a crucial role in effectively implementing vaccines to prevent invasive pneumococcal diseases. The conventional method of serotyping, known as the Quellung reaction, is both time-consuming and expensive. However, the emergence of MALDI-TOF MS technology has revolutionized microbiology laboratories by enabling rapid and cost-effective serotyping based on protein profiles. Objectives: In this study, we aimed to investigate the viability of utilizing MALDI-TOF MS technology as an adjunctive and screening method for capsular typing of Streptococcus pneumoniae. Our approach involved developing classification models based on MALDI-TOF MS to discern between Streptococcus pneumoniae strains originating from PCV13 (13-valent pneumococcal conjugate vaccine) and NON PCV13 isolates. Methods: Firstly, we established a comprehensive spectral database comprising isolates of serotypes present in the PCV13 vaccine, along with the top 10 most prevalent NON PCV13 serotypes based on local epidemiological data. This database served as a foundation for developing unsupervised models utilizing MALDI-TOF MS spectra, which enabled us to identify inherent patterns and relationships within the data. Our analysis involved a dataset comprising 215 new isolates collected from nationwide surveillance in Argentina. Our approach involved developing classification models based on MALDI-TOF MS to discern between Streptococcus pneumoniae strains originating from PCV13 (13-valent pneumococcal conjugate vaccine) and NON PCV13 isolates. Results: Although our findings revealed suboptimal performance in serotype classification, they provide valuable insights into the potential of machine learning algorithms in this context. The sensitivity of the models ranged from 0.41 to 0.46, indicating their ability to detect certain serotypes. The observed specificity consistently remained at 0.60, suggesting a moderate level of accuracy in identifying non-vaccine serotypes. These results highlight the need for further refinement and optimization of the algorithms to enhance their discriminative power and predictive accuracy in serotype identification.By addressing the limitations identified in this study, such as exploring alternative feature selection techniques or optimizing algorithm parameters, we can unlock the full potential of machine learning in robust and reliable serotype classification of S. pneumoniae. Our work not only provides a comprehensive evaluation of multiple machine learning models but also emphasizes the importance of considering their strengths and limitations. Conclusion: Overall, our study contributes to the growing body of research on utilizing MALDI-TOF MS and machine learning algorithms for serotype identification purposes.

Bactericidal killing of meningococcal W strains isolated in Argentina by the sera of adolescents and infants immunized with 4-component meningococcal serogroup B vaccine (4CMenB).

Invasive meningococcal disease (IMD) is a life-threatening disease caused by meningococcal serogroups A, B, C, W, X, and Y, of which B and W are most common in Argentina. The 4-component meningococcal serogroup B (4CMenB) vaccine contains three purified recombinant protein antigens (Neisseria adhesin A [NadA], factor H binding protein [fHbp], and Neisserial Heparin Binding Antigen [NHBA]) and outer membrane vesicles (OMV), which is derived from the New Zealand epidemic strain and contains Porin A 1.4. These antigens are present and conserved in strains that belong to other serogroups. In this study, we show that 10/11 (91%) meningococcal serogroup W (MenW) strains selected to be representative of MenW isolates that caused IMD in Argentina during 2010-2011 were killed in bactericidal assays by the sera of adolescents and infants who had been immunized with the 4CMenB vaccine. We also show that MenW strains that caused IMD in Argentina during 2018-2021 were genetically similar to the earlier strains, indicating that the 4CMenB vaccine would likely still provide protection against current MenW strains. These data highlight the potential of 4CMenB vaccination to protect adolescents and infants against MenW strains that are endemic in Argentina.

Novas tendências na promoção da atividade física para a população / New trends in promoting physical activity for the population

As recomendações de atividade física para a população foram avançando desde os tempos em que somente a atividade intensa e contínua de pelo menos uma hora de duração eram as indicadas, passando para moderadas de pelo menos 30 minutos, diminuição do tempo sentado, até as evidências de que "Todo Passo ou Movimento Conta". Chegamos agora às propostas de atividade intensa, mas de curta ou curtíssima duração; que facilitariam a incorporação ao estilo de vida. As primeiras evidências são cercadas de grande entusiasmo, podendo se tornar em uma nova tendência de prescrição, mas requerem novos estudos para passarem a fazer parte do rol oficial das recomendações.

Laboratory surveillance of invasive Haemophilus influenzae disease in Argentina, 2011-2019

Abstract The incorporation of Haemophilus influenzae type b (Hib) vaccine into the Argentine National Immunization Program in 1998 resulted in a dramatic decrease in the incidence of invasive disease due to this serotype. We assessed 1405 H. influenzae (Hi) isolates causing invasive infections referred to the National Reference Laboratory between 2011 and 2019. Non-encapsulated Hi were the most common strains (44.5%), followed by types b (41.1%) and a (10.0%). Significant increase in the proportion of type b was observed, from 31.2% in 2011, to 50% in 2015, correlating with the peak incidence rate, later decreasing to 33.6% by 2019. We compared the genetic relationship between clones circulating during the period of increased Hib incidence (2011-2015) and those of the prevaccination-transition period (1997-1998). Four pulsotypes predominated in both periods, G, M, P and K, G being the most common. Multilocus sequence typing revealed that the 4 pulsotypes belonged to ST6, or one of its simple or double locus variants. Isolates from fully vaccinated individuals did not differ from those of the rest of the population studied. After ruling out aspects associated with emergence of specific clones, we concluded that factors such as low booster coverage rates, delayed vaccination schedules and use of different vaccines may have contributed to the reemergence of Hib infections.

Resumen La introducción de la vacuna contra Haemophilus influenzae tipo b (Hib) en el Programa Nacional de Inmunización de Argentina en 1998 produjo una drástica disminución de la incidencia de enfermedad invasiva causada por este serotipo. En el Laboratorio Nacional de Referencia se estudiaron 1405 aislamientos de H. influenzae causantes de enfermedad invasiva recibidos en el período 2011-2019. H. influenzae no capsulado fue el más frecuente (44,5%), seguido por los tipos b (41,1%) y a (10,0%). Se observó un aumento significativo de la proporción del tipo b, de 31,2% en 2011 a 50% en 2015, que se correlacionó con un pico de incidencia en ese mismo año. Hacia 2019, descendió a 33,6%. Con el objetivo de evaluar los clones circulantes durante el incremento de la proporción de Hib y comparar con el período prevacunal-transición, se determinó la relación genética de una selección de aislamientos de los períodos 1997-1998 y 2011-2015. El análisis por PFGE mostró 4 pulsotipos predominantes en los 2 períodos, G, M, P y K, y el pulsotipo G fue mayoritario en ambos períodos. Por MLST se demostró que los 4 pulsotipos pertenecieron al ST6 o sus variantes (simple o doble locus). Entre los aislamientos de pacientes con vacunación completa no se hallaron clones diferentes respecto del resto de la población. Se postula que las coberturas de vacunación no satisfactorias en las dosis de refuerzo, los esquemas atrasados y el uso de diferentes vacunas pudieron haber contribuido a la reemergencia de Hib.

Temporal pattern of humoral immune response in mild cases of COVID-19.

BACKGROUND: Understanding the humoral response pattern of coronavirus disease 2019 (COVID-19) is one of the essential factors to better characterize the immune memory of patients, which allows understanding the temporality of reinfection, provides answers about the efficacy and durability of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and consequently helps in global public health and vaccination strategy. Among the patients who became infected with SARS-CoV-2, the majority who did not progress to death were those who developed the mild COVID-19, so understanding the pattern and temporality of the antibody response of these patients is certainly relevant. AIM: To investigate the temporal pattern of humoral response of specific immunoglobulin G (IgG) in mild cases of COVID-19. METHODS: Blood samples from 191 COVID-19 real-time reverse transcriptase-polymerase chain reaction (RT-qPCR)-positive volunteers from the municipality of Toledo/ Paraná/Brazil, underwent two distinct serological tests, enzyme-linked immunosorbent assay, and detection of anti-nucleocapsid IgG. Blood samples and clinicoepidemiological data of the volunteers were collected between November 2020 and February 2021. All assays were performed in duplicate and the manufacturers' recommendations were strictly followed. The data were statistically analyzed using multiple logistic regression; the variables were selected by applying the P < 0.05 criterion. RESULTS: Serological tests to detect specific IgG were performed on serum samples from volunteers who were diagnosed as being positive by RT-qPCR for COVID-19 or had disease onset in the time interval from less than 1 mo to 7 mo. The time periods when the highest number of participants with detectable IgG was observed were 1, 2 and 3 mo. It was observed that 9.42% of participants no longer had detectable IgG antibodies 1 mo only after being infected with SARS-CoV-2 and 1.57% were also IgG negative at less than 1 mo. At 5 mo, 3.14% of volunteers were IgG negative, and at 6 or 7 mo, 1 volunteer (0.52%) had no detectable IgG. During the period between diagnosis by RT-qPCR/symptoms onset and the date of collection for the study, no statistical significance was observed for any association analyzed. Moreover, considering the age category between 31 and 59 years as the exposed group, the P value was 0.11 for the category 31 to 59 years and 0.32 for the category 60 years or older, showing that in both age categories there was no association between the pair of variables analyzed. Regarding chronic disease, the exposure group consisted of the participants without any comorbidity, so the P value of 0.07 for the category of those with at least one chronic disease showed no association between the two variables. CONCLUSION: A temporal pattern of IgG response was not observed, but it is suggested that immunological memory is weak and there is no association between IgG production and age or chronic disease in mild COVID-19.

Tuberculosis preventive treatment in children and adolescents: an observational study of secondary data.

OBJECTIVE: To analyze the effectiveness, safety, outcomes, and associated factors of tuberculosis preventive treatment (TPT) in children and adolescents in Paraná, southern Brazil. METHOD: This was an observational cohort study with a retrospective collection of secondary data from the TPT information systems of the state of Paraná from 2009 to 2016, and tuberculosis in Brazil from 2009 to 2018. RESULTS: In total, 1,397 people were included. In 95.4% of the individuals, the indication for TPT was a history of patient-index contact with pulmonary tuberculosis. Isoniazid was used in 99.9% of the cases with TPT, and 87.7% completed the treatment. The TPT protection was 98.7%. Among the 18 people who had TB, 14 (77.8%) became ill after the second year of treatment, and four (22.2%) in the first two years (p < 0.001). Adverse events were reported in 3.3% of cases, most of them were gastrointestinal and medication was discontinued in only 2 (0.1%) patients. No risk factors associated with the illness were observed. CONCLUSIONS: The authors observed a low rate of illness in pragmatics routine conditions in TPT for children and adolescents, especially within the first two years after the end of treatment, with good tolerability and a good percentage of adherence to the treatment. TPT should be encouraged to achieve the goals of the End TB Strategy of the World Health Organization as an essential strategy to reduce the incidence rate of the disease, but studies with new schemes must continue to be carried out in real-life scenarios.

Synthesis by Microwave Irradiation, Molecular Structural Analysis and Trypanocidal Activity of Novel Pyrazole-tetrahydropyrimidine Derivatives.

BACKGROUND: A series of new eight 2-(1-aryl-3-methyl-1H-pyrazol-4-yl)-1,4,5,6-tetrahydropyrimidines 1(a-h) were synthesized by microwave irradiation technique. In vitro phenotypic screening was performed to evaluate the effect of these compounds on intracellular amastigotes forms of Trypanosoma cruzi, the etiological agent of Chagas disease. METHODS: Compounds 1(a-h) were synthesized from pyrazole-carbonitriles 2(a-h) employing microwave irradiation (50W) for 10-20 minutes. Physicochemical properties were calculated using OSIRIS DataWarrior. The toxic effect on mammalian cells (Vero Cells) and the trypanocidal activity against Trypanosoma cruzi (Dm28c-Luc) were also evaluated. RESULTS: Compounds 1(a-h) were obtained in 24-94% yields. They were completely characterized by Fourier Transform Infrared (FT-IR), Nuclear Magnetic Resonance (NMR) and High-Resolution Mass Spectrometry (HRMS) analyses. The derivatives showed low trypanocidal activity, with IC50 ranging from 47.16 to > 100 µM, with lower activity than benznidazole (1.93 µM) used as reference drug. CONCLUSION: The attractive features of this synthetic methodology are mild conditions, short reaction time, and low power. All derivatives showed low toxicity in mammalian cells, good oral bioavailability, and did not violate Lipinski´s rule of 5.

Genotoxic risk assessment of solar UV radiation in tadpoles from Brazilian wetlands.

Solar ultraviolet (UV) radiation is an environmental genotoxic factor linked to amphibian decline. Here we assessed the genotoxic risk of UVB and UVA exposure for tadpoles from open ponds in southern Brazil, a mid-latitude region influenced by stratospheric ozone depletion. Daily UV doses were measured on the surface of a pond in Taim Ecological Station (TAIM; 32°49'24''S; 52°38'31''W) on a cloudless summer day to predict the worst-case scenario for UV-induced DNA damage. Pond descriptors were related to the use of microhabitats by Boana pulchella tadpoles in two ponds over the climate seasons of 2013 and 2014. Our results indicate that shaded microhabitats were more frequent than unshaded ones in autumn, winter, and spring but not in summer. Hence, the penetration of UV radiation into the water of unshaded microhabitats was evaluated through laboratory experiments with artificial UV sources and pond water samples. Physical and biological sensors were applied in the experiments to measure the incident UV radiation and its genotoxic action. By integrating field and laboratory data, we demonstrate that low doses of biologically effective UV radiation reached the tadpoles in autumn, winter, spring, and early summer due to a high proportion of shaded microhabitats and a high concentration of solids in unshaded microhabitats. However, the relative reduction of shaded microhabitats jointly with a declining water level in late summer may have exposed tadpoles to high UV doses. Our experiments also indicate that solar UVB radiation, but not UVA, is primarily responsible for the induction of DNA pyrimidine dimers in organisms living under the surface of aquatic ecosystems. The present work highlights the determinant role of wetland descriptors for minimizing the genotoxic potential of UV radiation and its consequences for amphibians.