A novel fatty acid mimetic with pan-PPAR partial agonist activity inhibits diet-induced obesity and metabolic dysfunction-associated steatotic liver disease.

OBJECTIVE: The prevalence of metabolic diseases is increasing globally at an alarming rate; thus, it is essential that effective, accessible, low-cost therapeutics are developed. Peroxisome proliferator-activated receptors (PPARs) are transcription factors that tightly regulate glucose homeostasis and lipid metabolism and are important drug targets for the treatment of type 2 diabetes and dyslipidemia. We previously identified LDT409, a fatty acid-like compound derived from cashew nut shell liquid, as a novel pan-active PPARα/γ/δ compound. Herein, we aimed to assess the efficacy of LDT409 in vivo and investigate the molecular mechanisms governing the actions of the fatty acid mimetic LDT409 in diet-induced obese mice. METHODS: C57Bl/6 mice (6-11-month-old) were fed a chow or high fat diet (HFD) for 4 weeks; mice thereafter received once daily intraperitoneal injections of vehicle, 10 mg/kg Rosiglitazone, 40 mg/kg WY14643, or 40 mg/kg LDT409 for 18 days while continuing the HFD. During treatments, body weight, food intake, glucose and insulin tolerance, energy expenditure, and intestinal lipid absorption were measured. On day 18 of treatment, tissues and plasma were collected for histological, molecular, and biochemical analysis. RESULTS: We found that treatment with LDT409 was effective at reversing HFD-induced obesity and associated metabolic abnormalities in mice. LDT409 lowered food intake and hyperlipidemia, while improving insulin tolerance. Despite being a substrate of both PPARα and PPARγ, LDT409 was crucial for promoting hepatic fatty acid oxidation and reducing hepatic steatosis in HFD-fed mice. We also highlighted a role for LDT409 in white and brown adipocytes in vitro and in vivo where it decreased fat accumulation, increased lipolysis, induced browning of WAT, and upregulated thermogenic gene Ucp1. Remarkably, LDT409 reversed HFD-induced weight gain back to chow-fed control levels. We determined that the LDT409-induced weight-loss was associated with a combination of increased energy expenditure (detectable before weight loss was apparent), decreased food intake, increased systemic fat utilization, and increased fecal lipid excretion in HFD-fed mice. CONCLUSIONS: Collectively, LDT409 represents a fatty acid mimetic that generates a uniquely favorable metabolic response for the treatment of multiple abnormalities including obesity, dyslipidemia, metabolic dysfunction-associated steatotic liver disease, and diabetes. LDT409 is derived from a highly abundant natural product-based starting material and its development could be pursued as a therapeutic solution to the global metabolic health crisis.

Middle-Range Theory of Occupational Stress in Health Professionals.

Introduction: Occupational stress affects health professionals; however, no literature was found on the middle-range theory for this outcome in health professionals. Methods: Methodological study for the theoretical validation of a nursing diagnosis using the theoretical framework of Walker and Avant and the Betty Neuman systems models. The research was conducted in five stages: comprehension of the system model; selection and review of studies; development of the conceptual-theoretical-empirical structure; elaboration of a diagram and proposition of a nursing diagnosis; and evaluation of the empirical adequacy of the theory and validity of the system model. These steps were conducted using a scoping review and a sample of 138 articles selected in the Scopus, Web of Science, MEDLINE/PubMed, CINAHL, PsycINFO, LILACS, Science Direct, Cochrane Library, and Google Scholar databases. A data extraction instrument was developed, and study variables (attributes, antecedents, and clinical consequences) were analyzed using descriptive statistics (absolute and relative frequencies) and presented in tables. Results: The middle-range theory comprised 16 concepts, 20 propositions, and one diagram. A total of 15 related factors, 29 defining characteristics, six at-risk populations, and one associated condition were indicated to propose the nursing diagnosis for occupational stress. Conclusion: The middle-range theory supported elaborating elements to propose a nursing diagnosis for occupational stress.

Diet quality and nutritional status in children with human immunodeficiency virus.

Background: Poor diet quality in children and adolescents may contribute to decreased immunity and lead to an increased risk of opportunistic diseases. Aim: To investigate diet quality and its relationship to nutritional status in human immunodeficiency virus (HIV)-infected pediatric patients (HIV-PIHIV). Methods: We conducted a cross-sectional study with 87 patients aged between 6 and 19 years carried out in two University Hospitals. Diet quality was analyzed by an adapted Healthy Eating Index (HEI) and nutritional status. The association between HEI with body mass index-for-age (BMI-for-age) and height-for-age was performed using a linear regression model. Clinical, maternal, anthropometric, and dietary data were collected through a semi-structured questionnaire, based on nutrition service protocols. Results: Diet quality was intermediate (median IAS = 54.8 interquartile range: 47.5 to 65.9 points), due to low consumption of fruits, vegetables, and dairy products and high empty calories and sodium by the PPIHIV. The multivariate regression model indicated that HEI was not significant for explaining BMI-for-age [ß = -0.01; 95% CI = (-0.03; 0.01); p 0.40] nor height-for-age [ß = 0.01; 95% CI = (-0.02; 0.03); p 0.51]. However, it was observed that adolescents showed 1 Z-score [95% CI = (-1.6; -0.44); p 0.001] a reduction in BMI-for-age compared with children, and those black patients showed an increase in BMI-for-age Z-score of 0.57 [95% CI = (0.7; 1.1); p 0.03] compared with non-blacks. Conclusion: The diet quality of the HIV-infected children and adolescents was below desired. No association was found between diet quality and inadequate nutritional status of HIV-PIHIV.

Do combinations of fipronil, eugenol and carvacrol have synergistic effects against Rhipicephalus sanguineus?

The tick Rhipicephalus sanguineus is one of the main ectoparasites that affects dogs, causing direct and indirect damage to parasitized animals. Currently, infestation control is mainly carried out by using synthetic acaricidal drugs. However, a decrease in efficacy and an increase in resistance to the main therapeutic protocols against tick infestations have been increasingly reported and confirmed, a factor that has driven research into the potential acaricide activity of natural compounds, including in association with synthetic molecules. The aim of this work was to evaluate whether the combinations of fipronil (FIP) and eugenol (EUG), FIP and carvacrol (CAR), and EUG and CAR would have synergistic effects against immature and unfed adult stages of R. sanguineus through in vitro bioassays. Bioassays were carried out using the larval packet test (FAO 2004) adapted for nymphs and adults. The synergistic activity was explored by combining each solution, based on the estimated LC50, in a 1:1 ratio (FIP: EUG, FIP: CAR and EUG: CAR). CompuSyn software was used to evaluate the various pairwise combinations of FIP, EUG and CAR, checking if there was synergism or antagonism between them. FIP and EUG and FIP and CAR showed combination index (CIn) values above 1.45, indicating antagonism. The synergistic activity between EUG and CAR was verified against all unfed phases of R. sanguineus, since the CIn was below 0.70, a value that indicates synergism. The combination of fipronil with either eugenol or carvacrol presented antagonistic effects against R. sanguineus larvae. On the other hand, carvacrol and eugenol had excellent pharmacological synergism against all tick stages with mortality values in the range of 80 to 100%, including the adult stage, which is less susceptible than immature stages.

[Spatial-temporal distribution of visceral leishmaniasis in Brazil from 2007 to 2020Distribución espaciotemporal de la leishmaniasis visceral en Brasil en el período 2007-2020]. / Distribuição espaço-temporal da leishmaniose visceral no Brasil no período de 2007 a 2020.

Objective: To analyze the dynamics of the spatial and temporal distribution of visceral leishmaniasis in Brazil from 2007 to 2020. Method: This ecological study focused on the spatial pattern of visceral leishmaniasis cases in Brazil from 2007 to 2020 using data from the Information System for Notifiable Diseases (SINAN). The variables analyzed were the incidence rate of visceral leishmaniasis and the visceral leishmaniasis composite indicator (VLCI), from which triennial thematic maps were constructed. The global Moran index was calculated to assess the existence of spatial autocorrelation, and the local Moran index was used to identify areas with higher and lower risk of visceral leishmaniasis in Brazil. Results: During the study period, there were 48 705 cases of visceral leishmaniasis, with an incidence rate of 25.53 cases per 100 000 population. There was spatial autocorrelation in all triennial blocks, with municipalities in the North and Northeast regions having an incidence equal to or greater than 50 cases per 100 000 population. Regarding the VLCI there was an increase in the number of municipalities classified as low risk for transmission, and a growing presence of state capitals with a classification of very high risk. Conclusion: The incidence of visceral leishmaniasis varied over the trienniums. The border region between the states of Tocantins, Maranhão, and Pará, along with the state of Ceará, stood out in the spatial distribution of the disease incidence and risk stratification by VLCI. These areas should be a priority for surveillance and control efforts for the disease.

Objetivo: Analizar la dinámica de la distribución espaciotemporal de la leishmaniasis visceral en Brasil en el período 2007-2020. Métodos: En este estudio ecológico del patrón de distribución espacial de los casos de leishmaniasis visceral ocurridos en Brasil en el período 2007-2020 se utilizaron datos del sistema de información de enfermedades de declaración obligatoria (SINAN). Las variables analizadas fueron el coeficiente de incidencia de leishmaniasis visceral y el índice compuesto de leishmaniasis visceral, a partir de los cuales se construyeron mapas temáticos trienales. Se calcularon el índice general de Moran para verificar la existencia de autocorrelación espacial, y el índice local de Moran para delimitar las zonas de mayor y menor riesgo de leishmaniasis visceral en Brasil. Resultados: En el período estudiado, hubo 48 705 casos de leishmaniasis visceral, con una incidencia de 25,53 casos por 100 000 habitantes. En todos los bloques trienales hubo una autocorrelación espacial, en la cual varios municipios de las regiones norte y nordeste registraron una incidencia de 50 casos por 100 000 habitantes o una tasa superior. En relación con el índice compuesto de leishmaniasis visceral, se observó un aumento del número de municipios considerados de riesgo bajo de transmisión y una tendencia ascendente del número de ciudades capitales con clasificación de riesgo muy alto. Conclusión: La incidencia de leishmaniasis visceral varió a lo largo de los períodos trienales. La región fronteriza entre Tocantins, Maranhão y Pará, junto con el estado de Ceará, se destacó en términos de la distribución espacial de la incidencia de la enfermedad y la estratificación del riesgo según el índice compuesto de leishmaniasis visceral. Es preciso dar prioridad a estos lugares en lo referente a las medidas y los servicios de vigilancia y control de esta enfermedad.

Antifungal activity of selective serotonin reuptake inhibitors against Cryptococcus spp. and their possible mechanism of action.

Fungal infections caused by Cryptococcus spp. pose a threat to health, especially in immunocompromised individuals. The available arsenal of drugs against cryptococcosis is limited, due to their toxicity and/or lack of accessibility in low-income countries, requiring more therapeutic alternatives. Selective serotonin reuptake inhibitors (SSRIs), through drug repositioning, are a promising alternative to broaden the range of new antifungals against Cryptococcus spp. This study evaluates the antifungal activity of three SSRIs, sertraline, paroxetine, and fluoxetine, against Cryptococcus spp. strains, as well as assesses their possible mechanism of action. Seven strains of Cryptococcus spp. were used. Sensitivity to SSRIs, fluconazole, and itraconazole was evaluated using the broth microdilution assay. The interactions resulting from combinations of SSRIs and azoles were investigated using the checkerboard assay. The possible action mechanism of SSRIs against Cryptococcus spp. was evaluated through flow cytometry assays. The SSRIs exhibited in vitro antifungal activity against Cryptococcus spp. strains, with minimum inhibitory concentrations ranging from 2 to 32 µg/mL, and had synergistic and additive interactions with azoles. The mechanism of action of SSRIs against Cryptococcus spp. involved damage to the mitochondrial membrane and increasing the production of reactive oxygen species, resulting in loss of cellular viability and apoptotic cell death. Fluoxetine also was able to cause significant damage to yeast DNA. These findings demonstrate the in vitro antifungal potential of SSRIs against Cryptococcus spp. strains.

Antibacterial activity of menadione alone and in combination with oxacillin against methicillin-resistant Staphylococcus aureus and its impact on biofilms.

Introduction. Antibiotic resistance is a major threat to public health, particularly with methicillin-resistant Staphylococcus aureus (MRSA) being a leading cause of antimicrobial resistance. To combat this problem, drug repurposing offers a promising solution for the discovery of new antibacterial agents.Hypothesis. Menadione exhibits antibacterial activity against methicillin-sensitive and methicillin-resistant S. aureus strains, both alone and in combination with oxacillin. Its primary mechanism of action involves inducing oxidative stress.Methodology. Sensitivity assays were performed using broth microdilution. The interaction between menadione, oxacillin, and antioxidants was assessed using checkerboard technique. Mechanism of action was evaluated using flow cytometry, fluorescence microscopy, and in silico analysis.Aim. The aim of this study was to evaluate the in vitro antibacterial potential of menadione against planktonic and biofilm forms of methicillin-sensitive and resistant S. aureus strains. It also examined its role as a modulator of oxacillin activity and investigated the mechanism of action involved in its activity.Results. Menadione showed antibacterial activity against planktonic cells at concentrations ranging from 2 to 32 µg ml-1, with bacteriostatic action. When combined with oxacillin, it exhibited an additive and synergistic effect against the tested strains. Menadione also demonstrated antibiofilm activity at subinhibitory concentrations and effectively combated biofilms with reduced sensitivity to oxacillin alone. Its mechanism of action involves the production of reactive oxygen species (ROS) and DNA damage. It also showed interactions with important targets, such as DNA gyrase and dehydroesqualene synthase. The presence of ascorbic acid reversed its effects.Conclusion. Menadione exhibited antibacterial and antibiofilm activity against MRSA strains, suggesting its potential as an adjunct in the treatment of S. aureus infections. The main mechanism of action involves the production of ROS, which subsequently leads to DNA damage. Additionally, the activity of menadione can be complemented by its interaction with important virulence targets.

Distribuição espaço-temporal da leishmaniose visceral no Brasil no período de 2007 a 2020 / Spatial-temporal distribution of visceral leishmaniasis in Brazil from 2007 to 2020 / Distribución espaciotemporal de la leishmaniasis visceral en Brasil en el período 2007-2020

RESUMO Objetivo. Analisar a dinâmica da distribuição espacial e temporal da leishmaniose visceral no Brasil no período de 2007 a 2020. Métodos. Este estudo ecológico do padrão espacial dos casos de leishmaniose visceral ocorridos no Brasil de 2007 a 2020 utilizou dados do Sistema de Informação de Agravos e Notificação (SINAN). As variáveis analisadas foram o coeficiente de incidência da leishmaniose visceral e o índice composto da leishmaniose visceral (ICLV), a partir das quais foram construídos mapas temáticos trienais. Foi calculado o índice de Moran global, para verificar a existência de autocorrelação espacial, e o índice de Moran local, para delimitar áreas de maior e menor risco para adoecimento por leishmaniose visceral no Brasil. Resultados. No período estudado, ocorreram 48 705 casos de leishmaniose visceral, com incidência de 25,53 casos/100 000 habitantes. Em todos os blocos trienais, houve autocorrelação espacial, havendo municípios das regiões Norte e Nordeste com incidência igual ou superior a 50 casos/100 000 habitantes. Com relação ao ICLV, houve aumento do número de municípios considerados de baixo risco de transmissão e presença crescente do número de capitais com classificação de risco muito intenso. Conclusão. A incidência de leishmaniose visceral variou ao longo dos triênios. A região de fronteira entre Tocantins, Maranhão e Pará, juntamente com o estado do Ceará, destacou-se na distribuição espacial da incidência da doença e na estratificação de risco pelo ICLV. Tais localidades devem ser prioritárias para ações e serviços voltados à vigilância e ao controle da doença.

ABSTRACT Objective. To analyze the dynamics of the spatial and temporal distribution of visceral leishmaniasis in Brazil from 2007 to 2020. Method. This ecological study focused on the spatial pattern of visceral leishmaniasis cases in Brazil from 2007 to 2020 using data from the Information System for Notifiable Diseases (SINAN). The variables analyzed were the incidence rate of visceral leishmaniasis and the visceral leishmaniasis composite indicator (VLCI), from which triennial thematic maps were constructed. The global Moran index was calculated to assess the existence of spatial autocorrelation, and the local Moran index was used to identify areas with higher and lower risk of visceral leishmaniasis in Brazil. Results. During the study period, there were 48 705 cases of visceral leishmaniasis, with an incidence rate of 25.53 cases per 100 000 population. There was spatial autocorrelation in all triennial blocks, with municipalities in the North and Northeast regions having an incidence equal to or greater than 50 cases per 100 000 population. Regarding the VLCI there was an increase in the number of municipalities classified as low risk for transmission, and a growing presence of state capitals with a classification of very high risk. Conclusion. The incidence of visceral leishmaniasis varied over the trienniums. The border region between the states of Tocantins, Maranhão, and Pará, along with the state of Ceará, stood out in the spatial distribution of the disease incidence and risk stratification by VLCI. These areas should be a priority for surveillance and control efforts for the disease.

RESUMEN Objetivo. Analizar la dinámica de la distribución espaciotemporal de la leishmaniasis visceral en Brasil en el período 2007-2020. Métodos. En este estudio ecológico del patrón de distribución espacial de los casos de leishmaniasis visceral ocurridos en Brasil en el período 2007-2020 se utilizaron datos del sistema de información de enfermedades de declaración obligatoria (SINAN). Las variables analizadas fueron el coeficiente de incidencia de leishmaniasis visceral y el índice compuesto de leishmaniasis visceral, a partir de los cuales se construyeron mapas temáticos trienales. Se calcularon el índice general de Moran para verificar la existencia de autocorrelación espacial, y el índice local de Moran para delimitar las zonas de mayor y menor riesgo de leishmaniasis visceral en Brasil. Resultados. En el período estudiado, hubo 48 705 casos de leishmaniasis visceral, con una incidencia de 25,53 casos por 100 000 habitantes. En todos los bloques trienales hubo una autocorrelación espacial, en la cual varios municipios de las regiones norte y nordeste registraron una incidencia de 50 casos por 100 000 habitantes o una tasa superior. En relación con el índice compuesto de leishmaniasis visceral, se observó un aumento del número de municipios considerados de riesgo bajo de transmisión y una tendencia ascendente del número de ciudades capitales con clasificación de riesgo muy alto. Conclusión. La incidencia de leishmaniasis visceral varió a lo largo de los períodos trienales. La región fronteriza entre Tocantins, Maranhão y Pará, junto con el estado de Ceará, se destacó en términos de la distribución espacial de la incidencia de la enfermedad y la estratificación del riesgo según el índice compuesto de leishmaniasis visceral. Es preciso dar prioridad a estos lugares en lo referente a las medidas y los servicios de vigilancia y control de esta enfermedad.

Considerações da percepção dos cuidadores diante do cuidado com pacientes com esclerose lateral amiotrófica / Considerations of the caregivers' perception regarding the care of patients with amyotrophic lateral sclerosis / Consideraciones de percepción profesional antes de cuidar a pacientes con esclerosis amiotrófica lateral

Objetivo: Analisar as considerações dos cuidadores de pacientes diagnosticados com esclerose lateral amiotrófica para obtenção de melhor compreensão quanto sua saúde mental. Método: Trata-se de uma revisão integrativa da literatura de caráter narrativo, realizada através das bases BVS Brasil, BVSalud, Lilacs, Pepsic e site da ABRELA, entre abril e maio de 2020. Foram incluídos artigos no idioma português onde considera-se cuidadores, saúde mental relacionados a pacientes diagnosticados com esclerose lateral amiotrófica. Resultados: Desde os primeiros sintomas de esclerose lateral amiotrófica até o momento da morte, o paciente e seu cuidador, passam por perturbações emocionais e sociais significativas, das quais contribuem negativamente na qualidade de vida de ambos. Os cuidadores, em sua maioria mulheres e parentes, apresentaram níveis de sobrecarga percebida e atenção negligenciada a si mesmos. Conclusão: Conclui-se que os cuidadores necessitam de maiores ferramentas que possibilitem a manutenção de seus aspectos psicológicos, gerando maior qualidade de vida (AU).

Objective: To analyze the caregivers' considerations regarding patients diagnosed with amyotrophic lateral sclerosis to obtain a better understanding of their mental health. Method: This is an integrative review of the literature of a narrative character, carried out through the VHL Brazil, BVSalud, Lilacs, Pepsic databases and ABRELA, between April and May 2020. Articles in Portuguese were included, including caregivers, mental health related to patients diagnosed with amyotrophic lateral sclerosis. Results: From the first symptoms of amyotrophic lateral sclerosis to the moment of death, the patient and his caregiver undergo significant emotional and social disturbances, which contribute negatively to the quality of life of both. Caregivers, mostly women and relatives, had levels of perceived overload and neglected attention to themselves. Conclusion: It is concluded that caregivers need greater tools that enable the maintenance of their psychological aspects, generating greater quality of life (AU).

Objetivo: Analizar las consideraciones de los cuidadores de pacientes diagnosticados de esclerosis lateral amiotrófica para conocer mejor su salud mental. Método: Se trata de una revisión integradora de la literatura de carácter narrativo, realizada a través de las bases de datos BVS Brasil, BVSalud, Lilacs, Pepsic y sitio web ABRELA, entre abril y mayo de 2020. Se incluyeron artículos en portugués, incluyendo cuidadores, salud mental relacionados con pacientes diagnosticados con esclerosis lateral amiotrófica. Resultados: Desde los primeros síntomas de la esclerosis lateral amiotrófica hasta el momento de la muerte, el paciente y su cuidador sufren importantes trastornos emocionales y sociales, que contribuyen negativamente a la calidad de vida de ambos. Los cuidadores, en su mayoría mujeres y familiares, tenían niveles de sobrecarga percibida y descuidaban la atención hacia ellos mismos. Conclusión: Se concluye que los cuidadores necesitan mayores herramientas que permitan el mantenimiento de sus aspectos psicológicos, generando mayor calidad de vida (AU).

Problemáticas na aprendizagem na pandemia COVID-19: Diretrizes e ferramentas educacionais / Learning issues in the COVID-19 pandemic: Educational guidelines and tools

Aprimoramento no processo educacional tem sido enfoque de profissionais distintos a fim de proporcionar benefícios ao aluno no processo de aprendizagem ou no seu desenvolvimento psicológico, físico e social. Entretanto, em decorrência da pandemia de COVID-19, fez-se necessário a adaptação para um novo contexto e, em específico, que atendesse às demandas da educação básica transpassando as atividades, até então presenciais, para o modelo digital. Mediante a esse cenário, este estudo perpassa as diretrizes que orientam os profissionais da educação, as problemáticas oriundas do ensino remoto e as ferramentas tecnológicas para a prática do ensino no período citado. Com base no arcabouço teórico disponível, o presente estudo pautou-se em uma revisão narrativa da literatura científica. Os achados indicam a importância das diretrizes enquanto políticas públicas para a unificação do processo educacional e estratégias para a adaptação na utilização de ferramentas digitais. Porém, o contexto de ensino remoto, seja por meio de aulas síncronas ou assíncronas, também enfatiza a desigualdade social persistente no Brasil e outros prejuízos ao aluno, sejam eles desenvolvimentais ou relacionados à aprendizagem. Com isso, são evidenciados prejuízos para alunos que apresentam uma condição socioeconômica inferior, que tendem a não possuir acesso a estas diferentes tecnologias e, independentemente desse fator, os prejuízos educacionais presentes no processo da aprendizagem e nas dinâmicas não realizadas no ambiente escolar devido ao distanciamento social.

Improvement in the educational process has been the focus of different professionals in order to provide benefits to the student in the learning process or in their psychological, physical and social development. However, as a result of the COVID-19 pandemic, it was necessary to adapt to a new context and, in particular, to meet the demands of basic education, transferring the activities, until then face-to-face, to the digital model. Given this scenario, this study permeates the guidelines that guide education professionals, the problems arising from remote teaching and the technological tools for the practice of teaching in the aforementioned period. Based on the available theoretical framework, the present study was based on a narrative review of the scientific literature. The findings indicate the importance of guidelines as public policies for the unification of the educational process and strategies for adapting to the use of digital tools. However, the context of remote teaching, whether through synchronous or asynchronous classes, also emphasizes persistent social inequality in Brazil and other damages to the student, whether developmental or related to learning. As a result, losses are evident for students who have a lower socioeconomic condition, who tend not to have access to these different technologies and, regardless of this factor, the educational losses present in the learning process and in the dynamics not carried out in the school environment due to the social distance.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in the diagnosis of microorganisms.

Microbiology culture is the gold standard method for identifying microorganisms. This identification protocol takes several days to complete. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a technique that can identify different microorganisms quickly and accurately. The objective of this work was to evaluate the use of MALDI-TOF MS in the routine of clinical laboratories to identify microorganisms and to identify their resistance to antimicrobials. This study evaluated the relevance of the MALDI-TOF MS technique for microbiological diagnosis through a literature review. The authors found that MALDI-TOF MS can identify bacteria, fungi, viruses and parasites, even in blood cultures, and also serves to assess antimicrobial resistance. Thus, MALDI-TOF MS can become an indispensable tool in laboratory diagnosis.

Ocimum gratissimum essential oil and eugenol against Ctenocephalides felis felis and Rhipicephalus sanguineus: In vitro activity and residual efficacy of a eugenol-based spray formulation.

Fleas and ticks are among the main ectoparasites that affect pets. The indiscriminate and incorrect use of chemical antiparasitics may be related to increased insect resistance and environmental contamination, requiring prospection for active ingredients that are less harmful to animals, humans and the environment. The use of essential oils and their isolated compounds has been reported as a potential alternative to synthetic antiparasitics, but there is a lack of studies involving the design and development of stable and safe natural products-based formulations. Therefore, the aim of this study was to establish LC50 and LC90 of Ocimum gratissimum essential oil and eugenol on immature stages and adults of Ctenocephalides felis felis and Rhipicephalus sanguineus; and to design and to determine the in vitro efficacy and residual effect of a natural product-based spray formulation for flea and tick control in pets. Bioassays were carried out according to the filter paper impregnation technique for fleas and through the larval packet test for ticks. O. gratissimum essential oil and eugenol presented pulicidal and acaricidal activity in vitro against immature stages and adults of C. felis felis and immature stages of R. sanguineus. The greater potency of eugenol against fleas and ticks led to the choice of eugenol as the active ingredient in the pharmaceutical form developed. The developed eugenol-based sprays presented adequate physical and chemical characteristics and stability, had pulicidal and acaricidal efficacy after 24 h and residual effect against fleas for up to 48 days.

Fluazuron orally administered to guinea pigs: pharmacokinetic and efficacy against Amblyomma sculptum.

BACKGROUND: Brazilian spotted fever (BSF), the most lethal tick-borne disease in the Western Hemisphere, is caused by the bacterium Rickettsia rickettsii and transmitted by the bite of Amblyomma sculptum. Capybaras are considered primary hosts of this tick and amplifier hosts of R. rickettsii, generating new infected lineages of A. sculptum in BSF-endemic areas. To define a possible treatment regimen for controlling the tick A. sculptum in capybaras, the aim of this study was to establish an effective fluazuron (FLU) dose to control A. sculptum larvae in artificially infested guinea pigs. METHODS: In Study I (pharmacokinetic and pharmacodynamic analysis), 24 guinea pigs were divided into four equal groups: control group (CG; untreated) and treated groups receiving FLU administered by gavage in three doses: G1-1 mg/kg, G2-5 mg/kg and G3-10 mg/kg, once a day for 15 days (d0 to d + 14). Blood samples were collected from the animals of the treated groups before and at d + 1, + 2, + 4, + 7, + 15 and + 21. The guinea pigs were artificially infested at d + 7 with A. sculptum larvae, and specimens were recovered at d + 11 to d + 14 and kept in a climatized chamber for 14 days. In Study II (evaluation of pharmacokinetic parameters), one group of eight animals received FLU administered by gavage in a single dose of 10 mg/kg, and blood samples were collected before and on day 0 (8 h after treatment), + 1, + 4, + 7, + 15, + 21 and + 28 after single FLU administration. FLU was analyzed in plasma samples by high-performance liquid chromatography with ultraviolet detection. RESULTS: FLU plasma concentrations increased quickly, indicating rapid absorption, and decreased slowly. Some larvae from all treated groups exhibited morphological and behavioral changes. FLU interfered in molting, and the efficacy obtained was 100% for all treated groups. CONCLUSIONS: The results offer promising perspectives for the development of a palatable feed cube containing FLU for free-living capybaras to control A. sculptum and also to prevent BSF in areas where capybaras have been shown to play a primary role.

Rapid scale-up of COVID-19 training for frontline health workers in 11 African countries.

BACKGROUND: The global spread of the SARS-CoV-2 virus highlights both the importance of frontline healthcare workers (HCW) in pandemic response and their heightened vulnerability during infectious disease outbreaks. Adequate preparation, including the development of human resources for health (HRH) is essential to an effective response. ICAP at Columbia University (ICAP) partnered with Resolve to Save Lives and MOHs to design an emergency training initiative for frontline HCW in 11 African countries, using a competency-based backward-design approach and tailoring training delivery and health facility selection based on country context, location and known COVID-19 community transmission. METHODS: Pre- and post-test assessments were conducted on participants completing the COVID-19 training. Parametric and non-parametric methods were used to examine average individual-level changes from pre- to post-test, and compare performance between countries, cadres, sex and facility types. A post-evaluation online training survey using Qualtrics was distributed to assess participants' satisfaction and explore training relevance and impact on their ability to address COVID-19 in their facilities and communities. RESULTS: A total of 8797 HCW at 945 health facilities were trained between June 2020 and October 2020. Training duration ranged from 1 to 8 days (median: 3 days) and consisted of in person, virtual or self guided training. Of the 8105 (92%) HCW working at health facilities, the majority (62%) worked at secondary level facilities as these were the HF targeted for COVID-19 patients. Paired pre- and post-test results were available for 2370 (25%) trainees, and 1768 (18%) participants completed the post-evaluation training survey. On average, participants increased their pre- to post-test scores by 15 percentage points (95% CI 0.14, 0.15). While confidence in their ability to manage COVID-19 was high following the training, respondents reported that lack of access to testing kits (55%) and PPE (50%), limited space in the facility to isolate patients (45%), and understaffing (39%) were major barriers. CONCLUSION: Ongoing investment in health systems and focused attention to health workforce capacity building is critical to outbreak response. Successful implementation of an emergency response training such as this short-term IPC training initiative in response to the COVID-19 pandemic, requires speed, rigor and flexibility of its design and delivery while building on pre-existing systems, resources, and partnerships.

Evaluation of the antifungal effect of chlorogenic acid against strains of Candida spp. resistant to fluconazole: apoptosis induction and in silico analysis of the possible mechanisms of action.

Introduction. Candida spp. are commensal fungal pathogens of humans, but when there is an imbalance in the microbiota, or weak host immunity, these yeasts can become pathogenic, generating high medical costs.Gap Statement. With the increase in resistance to conventional antifungals, the development of new therapeutic strategies is necessary. This study evaluated the in vitro antifungal activity of chlorogenic acid against fluconazole-resistant strains of Candida spp. Mechanism of action through flow cytometry and in silico analyses, as well as molecular docking assays with ALS3 and SAP5, important proteins in the pathogenesis of Candida albicans associated with the adhesion process and biofilm formation.Results. The chlorogenic acid showed in vitro antifungal activity against the strains tested, causing reduced cell viability, increased potential for mitochondrial depolarization and production of reactive oxygen species, DNA fragmentation and phosphatidylserine externalization, indicating an apoptotic process. Concerning the analysis through docking, the complexes formed between chlorogenic acid and the targets Thymidylate Kinase, CYP51, 1Yeast Cytochrome BC1 Complex e Exo-B-(1,3)-glucanase demonstrated more favourable binding energy. In addition, chlorogenic acid presented significant interactions with the ALS3 active site residues of C. albicans, important in the adhesion process and resistance to fluconazole. Regarding molecular docking with SAP5, no significant interactions were found between chlorogenic acid and the active site of the enzyme.Conclusion. We concluded that chlorogenic acid has potential use as an adjuvant in antifungal therapies, due to its anti-Candida activity and ability to interact with important drug targets.

Protease-activated receptor 2 enhances innate and inflammatory mechanisms induced by lipopolysaccharide in macrophages from C57BL/6 mice.

OBJECTIVE: This study was conducted to investigate the effects of the synthetic PAR2 agonist peptide (PAR2-AP) SLIGRL-NH2 on LPS-induced inflammatory mechanisms in peritoneal macrophages. METHODS: Peritoneal macrophages obtained from C57BL/6 mice were incubated with PAR2-AP and/or LPS, and the phagocytosis of zymosan fluorescein isothiocyanate (FITC) particles; nitric oxide (NO), reactive oxygen species (ROS), and cytokine production; and inducible NO synthase (iNOS) expression in macrophages co-cultured with PAR-2-AP/LPS were evaluated. RESULTS: Co-incubation of macrophages with PAR2AP (30 µM)/LPS (100 ng/mL) enhanced LPS-induced phagocytosis; production of NO, ROS, and the pro-inflammatory cytokines interleukin (IL)-1ß, tumour necrosis factor (TNF)-α, IL-6, and C-C motif chemokine ligand (CCL)2; and iNOS expression and impaired the release of the anti-inflammatory cytokine IL-10 after 4 h of co-stimulation. In addition, PAR2AP increased the LPS-induced translocation of the p65 subunit of the pro-inflammatory transcription factor nuclear factor kappa B (NF-κB) and reduced the expression of inhibitor of NF-κB. CONCLUSION: This study provides evidence of a role for PAR2 in macrophage response triggered by LPS enhancing the phagocytic activity and NO, ROS, and cytokine production, resulting in the initial and adequate macrophage response required for their innate response mechanisms.

[Abandonment of tuberculosis treatment in Brazil, 2012-2018: trend and spatiotemporal distribution]. / Abandono do tratamento da tuberculose no Brasil, 2012-2018: tendência e distribuição espaço-temporal.

Ecological study that analyzes the trend and the spatiotemporal distribution of new cases of tuberculosis (TB) that abandoned treatment in Brazil, notified in the Notifiable Diseases Information System, in the period from 2012 to 2018. For the study of the trend used the Prais-Winsten generalized linear regression model was used and the Moran Global and Local indices for spatial analysis. The mean and median proportion of TB treatment dropout in Brazil was 10.4%. The highest averages of the indicator were concentrated in the Southeast (10.78 ± 1.38), South (10.70 ± 2.94) and North (10.35 ± 1.13), and; in the states of Rondônia (14.35 ± 2.34), Rio Grande do Sul (13.60 ± 4.23) and Rio de Janeiro (12.64 ± 1.73), only Acre and Piauí showed this indicator below 5%. In Brazil, there was a tendency towards stability in the proportion of abandonment of TB treatment, a decrease in the North, Northeast and South regions and only in the Federal District there was growth. There was a heterogeneous and non-random distribution, with five capitals comprising the High-Risk cluster. We conclude that the proportion of TB treatment abandonment in Brazil is above what is acceptable and that the identification of high-risk areas can contribute to the elaboration and strengthening of more specific control actions.

Estudo ecológico que analisa a tendência e a distribuição espaço-temporal dos casos novos de tuberculose (TB) que abandonaram o tratamento no Brasil, notificados no Sistema de Informação de Agravos de Notificação no período de 2012 a 2018. Para o estudo da tendência, utilizou-se o modelo de regressão linear generalizada de Prais-Winsten, e para a análise espacial os índices global e local de Moran. A média e a mediana da proporção de abandono do tratamento da TB no Brasil foram de 10,4%. As maiores médias do indicador se concentraram nas regiões Sudeste (10,78 ± 1,38), Sul (10,70 ± 2,94) e Norte (10,35 ± 1,13), e nos estados de Rondônia (14,35 ± 2,34), Rio Grande do Sul (13,60 ± 4,23) e Rio de Janeiro (12,64 ± 1,73). Apenas Acre e Piauí apresentaram esse indicador abaixo de 5%. No Brasil, houve tendência de estabilidade na proporção do abandono do tratamento da TB, decréscimo nas regiões Norte, Nordeste e Sul, e somente no Distrito Federal houve crescimento. Verificou-se distribuição heterogênea e não aleatória, com cinco capitais compondo o cluster de alto-risco. Concluímos que a proporção de abandono do tratamento da TB no Brasil encontra-se acima do aceitável e que a identificação de áreas de alto risco pode contribuir para a elaboração e fortalecimento de ações de controle mais específicas.

Abandono do tratamento da tuberculose no Brasil, 2012-2018: tendência e distribuição espaço-temporal / Abandonment of tuberculosis treatment in Brazil, 2012-2018: trend and spatiotemporal distribution

Resumo Estudo ecológico que analisa a tendência e a distribuição espaço-temporal dos casos novos de tuberculose (TB) que abandonaram o tratamento no Brasil, notificados no Sistema de Informação de Agravos de Notificação no período de 2012 a 2018. Para o estudo da tendência, utilizou-se o modelo de regressão linear generalizada de Prais-Winsten, e para a análise espacial os índices global e local de Moran. A média e a mediana da proporção de abandono do tratamento da TB no Brasil foram de 10,4%. As maiores médias do indicador se concentraram nas regiões Sudeste (10,78 ± 1,38), Sul (10,70 ± 2,94) e Norte (10,35 ± 1,13), e nos estados de Rondônia (14,35 ± 2,34), Rio Grande do Sul (13,60 ± 4,23) e Rio de Janeiro (12,64 ± 1,73). Apenas Acre e Piauí apresentaram esse indicador abaixo de 5%. No Brasil, houve tendência de estabilidade na proporção do abandono do tratamento da TB, decréscimo nas regiões Norte, Nordeste e Sul, e somente no Distrito Federal houve crescimento. Verificou-se distribuição heterogênea e não aleatória, com cinco capitais compondo o cluster de alto-risco. Concluímos que a proporção de abandono do tratamento da TB no Brasil encontra-se acima do aceitável e que a identificação de áreas de alto risco pode contribuir para a elaboração e fortalecimento de ações de controle mais específicas.

Abstract Ecological study that analyzes the trend and the spatiotemporal distribution of new cases of tuberculosis (TB) that abandoned treatment in Brazil, notified in the Notifiable Diseases Information System, in the period from 2012 to 2018. For the study of the trend used the Prais-Winsten generalized linear regression model was used and the Moran Global and Local indices for spatial analysis. The mean and median proportion of TB treatment dropout in Brazil was 10.4%. The highest averages of the indicator were concentrated in the Southeast (10.78 ± 1.38), South (10.70 ± 2.94) and North (10.35 ± 1.13), and; in the states of Rondônia (14.35 ± 2.34), Rio Grande do Sul (13.60 ± 4.23) and Rio de Janeiro (12.64 ± 1.73), only Acre and Piauí showed this indicator below 5%. In Brazil, there was a tendency towards stability in the proportion of abandonment of TB treatment, a decrease in the North, Northeast and South regions and only in the Federal District there was growth. There was a heterogeneous and non-random distribution, with five capitals comprising the High-Risk cluster. We conclude that the proportion of TB treatment abandonment in Brazil is above what is acceptable and that the identification of high-risk areas can contribute to the elaboration and strengthening of more specific control actions.

Phenolic Lipids Derived from Cashew Nut Shell Liquid to Treat Metabolic Diseases.

Metabolic diseases are increasing at staggering rates globally. The peroxisome proliferator-activated receptors (PPARα/γ/δ) are fatty acid sensors that help mitigate imbalances between energy uptake and utilization. Herein, we report compounds derived from phenolic lipids present in cashew nut shell liquid (CNSL), an abundant waste byproduct, in an effort to create effective, accessible, and sustainable drugs. Derivatives of anacardic acid and cardanol were tested for PPAR activity in HEK293 cell co-transfection assays, primary hepatocytes, and 3T3-L1 adipocytes. In vivo studies using PPAR-expressing zebrafish embryos identified CNSL derivatives with varying tissue-specific activities. LDT409 (23) is an analogue of cardanol with partial agonist activity for PPARα and PPARγ. Pharmacokinetic profiling showed that 23 is orally bioavailable with a half-life of 4 h in mice. CNSL derivatives represent a sustainable source of selective PPAR modulators with balanced intermediate affinities (EC50 ∼ 100 nM to 10 µM) that provide distinct and favorable gene activation profiles for the treatment of diabetes and obesity.