Inclusion of exogenous enzymes in feedlot cattle diets: Impacts on physiology, rumen fermentation, digestibility and fatty acid profile in rumen and meat.

The objective of this study was to evaluate if the inclusion of a blend composed of exogenous enzymes (amylase, protease, cellulase, xylanase and beta glucanase) in the individual and combined form in the feedlot steers diet has benefits on the physiology, rumen fermentation, digestibility and fatty acid profile in rumen and meat. The experiment used 24 animals, divided into 4 treatments, described as: T1-CON, T2-BLEND (0.5 g mixture of enzyme), T3-AMIL (0.5 g alpha-amylase), T4-BLEND+AMIL (0.5 g enzyme blend+ 0.5 g amylase). The concentration of mineral matter was higher in the meat of cattle of T4-BLEND+AMIL. A higher proportion of monounsaturated fatty acids was observed in the T3-AMIL group when compared to the others. The percentage of polyunsaturated fatty acids was higher in the T2-BLEND and T4-BLEND+AMIL compared to the T1-CON. The combination of exogenous enzymes in the diet positively modulate nutritional biomarkers, in addition to benefits in the lipid and oxidative profile meat.

Inibidores BTK e BCL-2 no Tratamento de Primeira Linha da Leucemia Linfocítica Crônica em Pacientes de Alto Risco: Revisão Sistemática e Meta-Análise em Rede / BTK and BCL-2 Inhibitors in the First-Line Treatment of Chronic Lymphocytic Leukemia in High-Risk Patients: Systematic Review and Network Meta-Analysis / Inhibidores de BTK Y BCL-2 en el Tratamiento de Primera Línea de la Leucemia Linfocítica Crónica en Pacientes de Alto Riesgo: Revisión Sistemática y un Metaanálisis en Red

Introdução: Pacientes com leucemia linfocítica crônica (LLC) com alto risco têm menores taxas de resposta, curso clínico mais agressivo e resistência à quimioterapia padrão, representando um desafio para o tratamento. Os inibidores da tirosina quinase de Bruton (BTK ­ ibrutinibe e acalabrutinibe) e o inibidor BCL-2 (venetoclax) podem ser utilizados nesses casos. Objetivo: Identificar e avaliar a eficácia e a segurança do uso de ibrutinibe, acalabrutinibe e venetoclax no tratamento de primeira linha em pacientes com LLC de alto risco. Método: Revisão sistemática de ensaios clínicos randomizados que avaliaram pacientes adultos com LLC, portadores de deleção 17p ou mutação TP53 e sem tratamento prévio. Foram pesquisadas as bases PubMed, EMBASE, LILACS e Cochrane Library, e realizadas avaliação do risco de viés pela ferramenta RoB 2 da Cochrane e avaliação da qualidade da evidência pelo GRADE. Resultados: Na meta-análise em rede para sobrevida livre de progressão (SLP), venetoclax + obinutuzumabe (RR: 0,62; IC 95% 0,41-0,95; p = 0,027) e acalabrutinibe + obinutuzumabe (RR: 0,74; IC 95% 0,55-0,99; p = 0,043) apresentaram menor risco de progressão ou óbito, com significância considerada limítrofe. Ibrutinibe + obinutuzumabe (RR: 0,93; IC 95% 0,86-1,00; p = 0,054) não apresentou diferença significativa na SLP para pacientes com LLC de alto risco. Conclusão: O tratamento de primeira linha com inibidores de BTK (ibrutinibe e acalabrutinibe) e o inibidor BCL-2 (venetoclax), associados a agentes monoclonais anti-CD20 ­ especialmente o obinutuzumabe ­, tem sido proposto como padrão para a maioria dos pacientes com LLC. Entretanto, pelos resultados desta revisão com meta-análise em rede, não foi possível confirmar essa recomendação.

Introduction: Patients with high-risk chronic lymphocytic leukemia (CLL) have lower response rates, a more aggressive clinical course, and resistance to standard chemotherapy, representing a treatment challenge. Bruton's tyrosine kinase inhibitors (BTK ­ ibrutinib and acalabrutinib) and the BCL-2 inhibitor (venetoclax) can be used in these cases. Objective: To identify and evaluate studies on the efficacy and safety of the use of ibrutinib, acalabrutinib and venetoclax in first-line treatment in patients with high-risk CLL. Method:Systematic review of randomized clinical trials that evaluated adult patients with CLL, carriers of 17p deletion or TP53 mutation and without prior treatment. The PubMed, EMBASE, LILACS and Cochrane Library databases were searched, and the risk of bias was assessed using the Cochrane RoB 2 tool and the quality of evidence was assessed with GRADE. Results: In the network meta-analysis for progression-free survival (PFS) venetoclax + obinutuzumab (RR: 0.62; 95%CI 0.41-0.95; p value 0.027) and acalabrutinib + obinutuzumab (RR: 0. 74; 95% CI 0.55-0.99; p value 0.043) presented a lower risk of progression or death, with significance considered borderline. Ibrutinib + obinutuzumab (RR: 0.93; 95% CI 0.86-1.00; p value 0.054) did not show a significant difference in PFS for patients with high-risk CLL. Conclusion: First-line treatment with BTK inhibitors (ibrutinib and acalabrutinib) and the BCL-2 inhibitor (venetoclax) associated with anti-CD20 monoclonal agents ­ especially obinutuzumab ­ have been proposed as the standard for most patients with CLL. However, based on the results of this review with network meta-analysis, it was not possible to confirm this recommendation.

Introducción: Los pacientes con leucemia linfocítica crónica (LLC) de alto riesgo tienen tasas de respuesta más bajas, un curso clínico más agresivo y resistencia a la quimioterapia estándar, lo que representa un desafío para el tratamiento. En estos casos se pueden utilizar los inhibidores de la tirosina quinasa de Bruton (BTK - ibrutinib y acalabrutinib) y el inhibidor de BCL-2 (venetoclax). Objetivo:Identificar y evaluar estudios sobre la eficacia y seguridad del uso de ibrutinib, acalabrutinib y venetoclax en el tratamiento de primera línea en pacientes con LLC de alto riesgo. Método: Revisión sistemática de ensayos clínicos aleatorios que evaluaron pacientes adultos con LLC, portadores de deleción 17p o mutación TP53 y sin tratamiento previo. Se realizaron búsquedas en las bases de datos PubMed, EMBASE, LILACS y Cochrane Library y se evaluó el riesgo de sesgo mediante la herramienta Cochrane RoB 2 y la calidad de la evidencia se evaluó mediante GRADE. Resultados: En el metaanálisis en red para la supervivencia libre de progresión (SSP) venetoclax + obinutuzumab (RR: 0,62; IC 95% 0,41-0,95; valor de p 0,027) y acalabrutinib + obinutuzumab (RR: 0,74; IC 95%). 0,55-0,99; valor de p 0,043) presentaron un menor riesgo de progresión o muerte, con una significación considerada límite. Ibrutinib + obinutuzumab (RR: 0,93; IC del 95 %: 0,86-1,00; valor de p 0,054) no mostró una diferencia significativa en la SSP para pacientes con LLC de alto riesgo. Conclusión: El tratamiento de primera línea con inhibidores de BTK (ibrutinib y acalabrutinib) y el inhibidor de BCL-2 (venetoclax), asociados con agentes monoclonales anti-CD20, especialmente obinutuzumab, se ha propuesto como estándar para la mayoría de los pacientes con LLC. Sin embargo, según los resultados de esta revisión con metaanálisis en red, no fue posible confirmar esta recomendación

Effect of the Association of Fixed Oils from Abelmoschus esculentus (L.) Moench, Euterpe oleracea Martius, Bixa orellana Linné and Chronic SM® on Atherogenic Dyslipidemia in Wistar Rats.

Dyslipidemia presents high levels of serum cholesterol and is characterized as a risk factor for cardiovascular diseases, especially for the development of atherosclerosis. E. oleracea oil (OFEO), A. esculentus oil (OFAE), B. orellana oil (OFBO), and Chronic SM® granules (CHR) are rich in bioactive compounds with the potential to treat changes in lipid metabolism. This study investigated the effects of treatments with oils from A. esculentus, E. oleracea, B. orellana, and Chronic SM® on Cocos nucifera L. saturated-fat-induced dyslipidemia. The chromatographic profile showed the majority presence of unsaturated fatty acids in the tested oils. The quantification of tocotrienols and geranylgeraniol in OFBO and CHR was obtained. Treatments with OFEO, OFAE, OFBO, and CHR were able to significantly reduce glycemia, as well as hypertriglyceridemia, total cholesterol, and LDL-cholesterol, besides increasing HDL-cholesterol. The treatments inhibited the formation of atheromatous plaques in the vascular endothelium of the treated rats. The obtained results suggest that the OFEO, OFAE, OFBO, and CHR exhibit antidyslipidemic effects and antiatherogenic activity.

Cost-Effectiveness Analysis of Monoclonal Antibodies Associated With Chemotherapy in First-Line Treatment of Metastatic Colorectal Cancer.

OBJECTIVES: This study aimed to evaluate the cost-effectiveness of anti-epidermal growth factor receptor (cetuximab and panitumumab) or anti-vascular endothelial growth factor (bevacizumab) monoclonal antibodies associated with conventional chemotherapy (CT) (fluorouracil and leucovorin with irinotecan) as a first-line treatment for unresectable metastatic colorectal cancer. METHODS: A partitioned survival analysis model was adopted to simulate direct health costs and benefits comparing therapeutic options in a 10 years' time horizon. Model data were extracted from the literature and costs were obtained from Brazilian official government databases. The analysis considered the perspective of the Brazilian Public Health System; costs were measured in local currency (BRL) and benefits in quality-adjusted life-years (QALY). A 5% discount rate was applied to costs and benefits. Alternative willingness-to-pay scenarios, varying from 3 to 5 times the cost-effectiveness threshold established in Brazil, were estimated. The results were presented incremental cost-effectiveness ratio (ICER), and both deterministic and probabilistic sensitivity analyses were performed. RESULTS: The most cost-effective choice would be the association of CT with panitumumab, with an ICER of $58 330.15/QALY compared with isolated CT. The second-best option was CT with bevacizumab and panitumumab, with an ICER of $71 195.40/QALY compared with panitumumab alone. Although having higher costs, the second-best option was the most effective. Both strategies were cost-effective in part of the Monte Carlo iterations, considering the 3× threshold. CONCLUSIONS: The therapeutic option CT + panitumumab + bevacizumab represents the most significant effectiveness gain in our study. It is the second-lowest cost-effectiveness, and this option includes monoclonal antibodies association for patients with and without KRAS mutation.

Encapsulated pepper blend in the diet of confined Holstein bullocks: effect on ruminal volatile fatty acid profiles, growth performance, and animal health.

Dairy bulls in feedlots have been a viable alternative for dairy producers to reinforce the family's income. Aspects such as balanced diets and proper management are essential for these animals to develop and allow an economic return fully. Plant extracts are performance enhancers and ruminal and intestinal health promoters. Therefore, this study aims to evaluate whether the addition of encapsulated pepper (EP) blend (Capsicum annuum, Capsicum frutescens, and Capsicum chinense - rich in capsaicin) interferes with the volatile fatty acid profile in the rumen and enhances the growth performance of Holstein bullocks in a feedlot. For the experiment, 24 whole bullocks were used, distributed into three treatments, with eight replicates per treatment (one animal as an experimental unit, kept in an individual stall): groups T0, T200, and T400, receiving 0 mg, 200 mg, and 400 mg EP/kg of concentrate, respectively. Knowing the intake of concentrate and the average body weight during the experiment, we calculated the dose in mg/kg/day of the EP; that is, the T200 animals consumed 2.45 mg EP/kg (body weight -BW)/day; and T400 consumed 4.9 mg EP/kg BW/day. The animals from T400 presented a more significant weight gain between days 15 and 45 of confinement compared to T0 (P=0.05). This same treatment (T400) had a trend of lower weight gain between days 46 and 90 (P=0.09). Likewise, the T400 group had higher feed efficiency than T0 between days 15 and 45. Furthermore, the treatments affected the white blood cell count, with the T400 bullocks showing a higher number of neutrophils and lymphocytes. Higher levels of C-reactive protein (CRP) were measured in the serum of steers from both groups that consumed pepper (P<0.01). Interaction between treatment × day was observed for the activity of glutathione enzymes (GST and GPx) and levels of lipoperoxidation (LPO) (characterized by antioxidant stimulation) associated with the reduction in serum LPO; similar antioxidant enzymes behavior was observed in the liver. In the small intestine (jejunum), the activities of antioxidant enzymes (GST and GPx) were lower in the two groups of cattle that consumed EP, and LPO was lower. The treatments affected the concentration of acetic acid in the rumen fluid, presenting lower levels in T400 compared to T200 and similar T0 (P≤0.05). There was an interaction of day vs. treatment for propionic acid, presenting a higher concentration on day 45 at T400 than T0. These results, therefore, allow us to conclude that adding 400 mg of pepper extract can be an excellent additive for weight gain at the beginning of the experiment; however, over time, this dose of additive negatively affects weight gain. Both EP doses stimulated serum and tissue antioxidant responses, reducing lipoperoxidation. However, the 400 mg EP/kg concentrate suggests a pro-inflammatory response (leukocytosis and elevated CRP), s probably related to the high dose (i.e., between 1.7 and 2.4 g/animal/day).

Intramuscular compatibility of an injectable anti-inflammatory nanodispersion from a standardized Bixa orellana oil (Chronic®): a toxicological study in Wistar rats.

Bixa orellana L. is a plant popularly known as "ucurum", "annatto", and "achiote". It is native to South America, and its seeds are an abundant source of geranylgeraniol and tocotrienols. Nanoencapsulation is a valuable technique that can decrease the drug needed to achieve an effect, decreasing potential toxicity, side effects and potentiate the anti-inflammatory effect. This study aimed to evaluate the acute toxicity of an intramuscular application of a nanodispersion containing a standardized extract from the seeds of Bixa orellana (NBO) in Wistar rats. The chemical evaluation showed δ-tocotrienol at 0.725 ± 0.062 mg/mL (72.6 ± 0.9%). The stability study showed the nanoparticles had an average size from 53.15 ± 0.64 to 59.9 ± 3.63 nm, with a polydispersity index ranging from 0.574 ± 0.032 to 0.574 ± 0.32, Zeta potential from 18.26 ± 0.59 to 19.66 ± 1.45 mV. After testing the intramuscular application of NBO with doses from 1 to 5 mg/kg in animals, it was observed that the acute treatment did not elicit any toxic effects within this range. The dose of 10 mg/kg, although not affecting hematological and biochemical parameters (CPK, LDH, myoglobin, AST, ALT, TC, TG, glucose levels, creatinine, and urea), could induce some muscle tissue changes, including leukocyte infiltration, morphological chances, and potentially necrosis. In conclusion, the results showed that the treatments devoided toxicity between 1 and 5 mg/kg.

Avaliação da satisfação de mães em relação aos serviços públicos de saúde de Montes Claros (MG) / Evaluation of mothers' satisfaction with public health services in Montes Claros (MG) / Evaluación de la satisfacción de las madres con los servicios públicos de salud en Montes Claros (MG)

Este artigo pretendeu avaliar a satisfação das mães em relação aos serviços públicos de saúde de Montes Claros (MG). Para isso, realizou-se estudo transversal de base populacional, composto por amostra representativa de crianças menores de 24 meses da cidade de Montes Claros (MG), a partir de questionário descritivo, aplicado às mães dessas crianças. A análise dos dados ocorreu por meio de estatística descritiva, concluindo-se que, em relação à última consulta realizada, 70% das mães ficaram satisfeitas quanto ao tempo de espera, ao serviço de informação, à qualidade do serviço e à estrutura da unidade. Apesar de 40,1% terem relatado que tiveram consultas marcadas duas vezes ou mais no ano, consideraram o atendimento favorável. Portanto, a satisfação das mães quanto ao serviço de saúde, ao atendimento, ao acesso à atenção primária e à estrutura da unidade influenciam positivamente no tratamento da criança.

This article aimed to evaluate mothers' satisfaction with public health services in Montes Claros (MG). To that end it carried out a population-based cross-sectional study, consisting of a representative sample of children younger than 24 months in the city of Montes Claros (MG), based on a descriptive questionnaire applied to mothers with children younger than 24 months. Data analysis was performed using descriptive statistics, concluding that 70% of the mothers, regarding the last consultation, were satisfied with the waiting time, information service, quality of service, and structure of the unit. Although 40.1% reported that they had consultations scheduled 2 times a year or less, they considered the service favorable. Thus, the mothers' satisfaction with the health service, the care, the access to primary care, and the structure of the unit positively influence the child's treatment.

Este artículo pretendió evaluar la satisfacción de las madres con los servicios públicos de salud en Montes Claros (Minas Gerais, Brasil). Para ello, se realizó un estudio transversal de base poblacional, constituido por una muestra representativa de niños menores de 24 meses de la ciudad de Montes Claros, Minas Gerais, a partir de un cuestionario descriptivo aplicado a madres con hijos menores de 24 meses. El análisis de los datos se realizó mediante estadística descriptiva, y se obtuvo que con relación a la última consulta el 70% de las madres se mostraron satisfechas con el tiempo de espera, el servicio de información, la calidad del servicio y la satisfacción con la estructura de la unidad. Aunque el 40,1% refirió tener consultas programadas menor o igual a dos veces al año, considerándose favorable el servicio. Por tanto, la satisfacción de las madres con el servicio de salud, la atención, el acceso a la atención primaria y la estructura de la unidad influyen positivamente en el tratamiento del niño.

Acute and Reproductive Toxicity Evaluation of Ormona® SI and Ormona® RC-Two New Nutraceuticals with Geranylgeraniol, Tocotrienols, Anthocyanins, and Isoflavones-In Adult Zebrafish.

The zebrafish is a popular organism to test the toxicity of compounds. Here, we evaluate the acute and reproductive toxicity of Ormona SI® (OSI) and RC® (ORC), two herbal products developed for menopausal women with tocotrienols, geranylgeraniol, isoflavones, and anthocyanins. The acute toxicity was evaluated by behavioral alterations, lethality, and tissue changes (intestine, liver, kidney) after oral treatment with high product doses (500, 1000, and 2000 mg/kg). The reproductive toxicity was evaluated after 21 days of oral treatment with OSI and ORC at 200 mg/kg. Our results show that the LD50 could not be assessed due to the low mortality rate even with the highest dose; the behavioral alterations were not different from those of the group treated only with the vehicle (2% DMSO). The tissue changes were minor in OSI and more severe in ORC at the highest (2000 mg/kg) dose, while no tissue abnormality was observed at 500 mg/kg. In the reproductive assessment, continuous treatment could decrease the maturation of the reproductive cells, which also significantly decreases the egg spawning. This effect was attributed to the estrogenic activity of the isoflavones. In conclusion, the acute toxicity analysis shows that the products did not elicit lethal or sublethal effects observed in the model when used up to 500 mg/kg. Regarding the reproductive toxicity, decreased fertility was observed, which was expected due to the presence of isoflavones (phytoestrogens). Considering that the product is intended for menopausal and postmenopausal women, the presence of isoflavones is beneficial. Further studies should be performed to corroborate these results in mammals.

Potential of the Compounds from Bixa orellana Purified Annatto Oil and Its Granules (Chronic®) against Dyslipidemia and Inflammatory Diseases: In Silico Studies with Geranylgeraniol and Tocotrienols.

Some significant compounds present in annatto are geranylgeraniol and tocotrienols. These compounds have beneficial effects against hyperlipidemia and chronic diseases, where oxidative stress and inflammation are present, but the exact mechanism of action of such activities is still a subject of research. This study aimed to evaluate possible mechanisms of action that could be underlying the activities of these molecules. For this, in silico approaches such as ligand topology (PASS and SEA servers) and molecular docking with the software GOLD were used. Additionally, we screened some pharmacokinetic and toxicological parameters using the servers PreADMET, SwissADME, and ProTox-II. The results corroborate the antidyslipidemia and anti-inflammatory activities of geranylgeraniol and tocotrienols. Notably, some new mechanisms of action were predicted to be potentially underlying the activities of these compounds, including inhibition of squalene monooxygenase, lanosterol synthase, and phospholipase A2. These results give new insight into new mechanisms of action involved in these molecules from annatto and Chronic®.

[Risk of initiation to smoking with the use of electronic cigarettes: systematic review and meta-analysis]. / Risco de iniciação ao tabagismo com o uso de cigarros eletrônicos: revisão sistemática e meta-análise.

This article aims to evaluate the association between the use of electronic cigarettes and initiation to smoking, through a systematic review with meta-analysis of longitudinal studies. A bibliographic search was performed on the MEDLINE, Embase, LILACS and PsycInfo databases. Reference selection, data extraction and risk of bias assessment of the studies were independently carried out in pairs, and the disagreements were discussed with a third researcher to reach a consensus. Meta-analysis was performed using the Mantel-Haenszel random effects model. Among the 25 studies included, 22 evaluated the outcome of conventional cigarette experimentation and nine assessed the outcome of current smoking (in the last 30 days). The meta-analysis showed that the use of electronic cigarettes increased the risk of conventional cigarette experimentation by almost three and a half times (RR=3.42; 95%CI 2.81-4.15), and by more than four times the risk of current smoking (RR=4.32; 95%CI 3.13-5.94). The risk of smoking initiation is significantly higher among electronic cigarette users. The marketing authorization of such devices may represent a threat to public health policies in Brazil.

O objetivo deste artigo é avaliar a associação entre uso de cigarros eletrônicos e iniciação ao tabagismo, por meio de uma revisão sistemática com meta-análise de estudos longitudinais. Busca bibliográfica foi realizada nas bases MEDLINE, Embase, LILACS e PsycInfo. As etapas de seleção de referências, extração dos dados e avaliação do risco de viés dos estudos foi realizada em dupla, de forma independente e as divergências discutidas com um terceiro pesquisador para obtenção de consenso. Meta-análise foi realizada por meio do modelo Mantel-Haenszel de efeitos aleatórios. Dentre os 25 estudos incluídos, 22 avaliaram o desfecho de experimentação de cigarro convencional e nove avaliaram o desfecho de tabagismo atual (nos últimos 30 dias). A meta-análise demonstrou que o uso de cigarro eletrônico aumentou em quase três vezes e meia o risco de experimentação de cigarro convencional (RR=3,42; IC95% 2,81-4,15) e em mais de quatro vezes o risco de tabagismo atual (RR=4,32; IC95% 3,13-5,94). O risco de iniciação ao tabagismo é significativamente maior entre usuários de cigarro eletrônico. A liberação da comercialização desses dispositivos pode representar uma ameaça para as políticas de saúde pública no Brasil.

Risco de iniciação ao tabagismo com o uso de cigarros eletrônicos: revisão sistemática e meta-análise / Risk of initiation to smoking with the use of electronic cigarettes: systematic review and meta-analysis

Resumo O objetivo deste artigo é avaliar a associação entre uso de cigarros eletrônicos e iniciação ao tabagismo, por meio de uma revisão sistemática com meta-análise de estudos longitudinais. Busca bibliográfica foi realizada nas bases MEDLINE, Embase, LILACS e PsycInfo. As etapas de seleção de referências, extração dos dados e avaliação do risco de viés dos estudos foi realizada em dupla, de forma independente e as divergências discutidas com um terceiro pesquisador para obtenção de consenso. Meta-análise foi realizada por meio do modelo Mantel-Haenszel de efeitos aleatórios. Dentre os 25 estudos incluídos, 22 avaliaram o desfecho de experimentação de cigarro convencional e nove avaliaram o desfecho de tabagismo atual (nos últimos 30 dias). A meta-análise demonstrou que o uso de cigarro eletrônico aumentou em quase três vezes e meia o risco de experimentação de cigarro convencional (RR=3,42; IC95% 2,81-4,15) e em mais de quatro vezes o risco de tabagismo atual (RR=4,32; IC95% 3,13-5,94). O risco de iniciação ao tabagismo é significativamente maior entre usuários de cigarro eletrônico. A liberação da comercialização desses dispositivos pode representar uma ameaça para as políticas de saúde pública no Brasil.

Abstract This article aims to evaluate the association between the use of electronic cigarettes and initiation to smoking, through a systematic review with meta-analysis of longitudinal studies. A bibliographic search was performed on the MEDLINE, Embase, LILACS and PsycInfo databases. Reference selection, data extraction and risk of bias assessment of the studies were independently carried out in pairs, and the disagreements were discussed with a third researcher to reach a consensus. Meta-analysis was performed using the Mantel-Haenszel random effects model. Among the 25 studies included, 22 evaluated the outcome of conventional cigarette experimentation and nine assessed the outcome of current smoking (in the last 30 days). The meta-analysis showed that the use of electronic cigarettes increased the risk of conventional cigarette experimentation by almost three and a half times (RR=3.42; 95%CI 2.81-4.15), and by more than four times the risk of current smoking (RR=4.32; 95%CI 3.13-5.94). The risk of smoking initiation is significantly higher among electronic cigarette users. The marketing authorization of such devices may represent a threat to public health policies in Brazil.

West Nile Virus in the State of Ceará, Northeast Brazil.

In June 2019, a horse with neurological disorder was diagnosed with West Nile virus (WNV) in Boa Viagem, a municipality in the state of Ceará, northeast Brazil. A multi-institutional task force coordinated by the Brazilian Ministry of Health was deployed to the area for case investigation. A total of 513 biological samples from 78 humans, 157 domestic animals and 278 free-ranging wild birds, as well as 853 adult mosquitoes of 22 species were tested for WNV by highly specific serological and/or molecular tests. No active circulation of WNV was detected in vertebrates or mosquitoes by molecular methods. Previous exposure to WNV was confirmed by seroconversion in domestic birds and by the detection of specific neutralizing antibodies in 44% (11/25) of equids, 20.9% (14/67) of domestic birds, 4.7% (13/278) of free-ranging wild birds, 2.6% (2/78) of humans, and 1.5% (1/65) of small ruminants. Results indicate that not only equines but also humans and different species of domestic animals and wild birds were locally exposed to WNV. The detection of neutralizing antibodies for WNV in free-ranging individuals of abundant passerine species suggests that birds commonly found in the region may have been involved as amplifying hosts in local transmission cycles of WNV.

Risk of smoking relapse with the use of electronic cigarettes: A systematic review with meta-analysis of longitudinal studies.

INTRODUCTION: The use of e-cigarettes has been the subject of a public health debate on their possibility of undermining efforts for tobacco control. The aim of this study was to synthesize the risk of smoking relapse with the use of e-cigarettes by former smokers. METHODS: MEDLINE, EMBASE, PsycInfo and LILACS were searched without restriction to language or date of publication. Longitudinal observational studies evaluating the association between e-cigarette use and smoking relapse were selected by two independent reviewers, and disagreements solved by discussion with a third researcher. Data extraction and risk of bias assessment were also carried out by two independent reviewers. The meta-analysis was performed using the random effect Mantel-Haenszel model. RESULTS: From 632 retrieved records, six studies were eligible and described, while three were included in the quantitative synthesis. The studies were conducted in the USA, UK and France, with final sample size varying from 374 to 4094 former smokers. Risk of relapse was 2.03 (95% CI: 1.39-2.96) among former smoker users than non-users of e-cigarettes, and 1.38 (95% CI: 1.11-1.65) when pooling the adjusted association measures. Long-term former smokers were the main contributors for the higher relapse risk, while the impact of frequency of exposure to e-cigarettes (past, non-daily, daily) was uncertain. CONCLUSIONS: Considering the growing popularity of e-cigarettes among former smokers, our results point to the great potential for an increase in the frequency of relapse to conventional smoking and vaping for those who move to regular use of e-cigarettes.

Application of the MCDA method for assessing new technologies for familial hypercholesterolaemia treatment / Aplicação do método MCDA para avaliar novas tecnologias para o tratamento da hipercolesterolemia familiar

Objective: Familial hypercholesterolaemia is a hereditary disease characterized by very high levels of low-density lipoprotein cholesterol and an elevated risk of early-onset cardiovascular disorders. New drugs provide alternatives for the treatment of patients with homozygous familial hypercholesterolaemia. The study aims to explore a practical application of multiple-criteria decision analysis on prioritization of new and emerging technologies for familial hypercholesterolaemia. Methods: The decision model was constructed using the MACBETH method. There were three stages: structuring the problem, measuring the performance of alternatives, and building the model. The weights for alternatives and levels were obtained by indirect comparisons, which evaluated the attractiveness of the performance levels of the criteria using the swing weights technique. Results: The drugs lomitapide, ezetimibe, evolocumab, and mipomersen were selected as alternatives for decision-making. "Cardiovascular Death", "Stroke" and "Acute Myocardial Infarction" had the three most significant weights. The criteria with the lowest weights were "Comfort" and "LDL-C Reduction". The top-ranked technology was evolocumab, with an overall score of 59.87, followed by ezetimibe, with a score of 37.21. Conclusion: How to apply the result of a higher score in the actual decisionmaking process still requires further studies. The case in question showed that evolocumab has more performance benefits than other drugs but with a cost approximately 50 times higher

Objetivo: A hipercolesterolemia familiar é uma doença hereditária caracterizada por níveis muito elevados de lipoproteína de baixa densidade (LDL-colesterol) e um risco elevado de doenças cardiovasculares de início precoce. Novos medicamentos oferecem alternativas para o tratamento de pacientes com hipercolesterolemia familiar homozigótica. Esse estudo tem como objetivo explorar uma aplicação prática da análise de decisão multicritério na priorização de tecnologias novas e emergentes para hipercolesterolemia familiar. Métodos: O modelo de decisão foi construído usando o método MACBETH. Três etapas foram criadas: estruturação do problema, mensuração do desempenho das alternativas e construção do modelo. Os pesos para alternativas e níveis foram obtidos por comparações indiretas, que avaliaram a atratividade dos níveis de desempenho dos critérios usando a técnica de pesos de balanço. Resultados: Os medicamentos lomitapida, ezetimiba, evolocumabe e mipomersen foram selecionados como alternativas para a tomada de decisão. "Morte Cardiovascular", "Acidente vascular cerebral" e "Infarto Agudo do Miocárdio" tiveram os três pesos mais significativos. Os critérios com os menores pesos foram "Conforto" e "Redução do LDL-C". A tecnologia mais bem avaliada foi o evolocumabe, com pontuação geral de 59,87, seguido da ezetimiba, com pontuação de 37,21. Conclusão: Ainda são necessários estudos para determinar como aplicar o resultado de uma pontuação mais alta no processo de tomada de decisão. O caso em questão demonstrou que o evolocumabe tem benefícios mais significativos em relação aos outros medicamentos, mas com um custo cerca de 50 vezes maior

Evaluation of a Training Program for Credit Union Counselors / Avaliação de um Programa de Treinamento para Gestores de Cooperativas de Crédito / Evaluación del Programa de Capacitación para Consejeros de Cooperativas de Crédito

Abstract Training, Development, and Education assessments have intensified in recent decades, and empirical evidence proves their effectiveness in organizational outcomes. However, the literature shows little research on the results of training in cooperative organizations. This study aimed to evaluate a training program for credit union counselors based on Training, Development, and Education evaluation models associated with logical models. This is an empirical study with a qualitative design. Data collection was performed through an analysis of 229 documents, three semi-structured individual interviews, and a focus group. The results of the research corroborate findings related to the usefulness of the integrated use of systemic evaluation approaches and indicate that these models apply to the context of cooperative training. This study fills a methodological gap in the field of instructional psychology in third sector organizations.

Resumo As avaliações de Treinamento, Desenvolvimento e Educação têm se intensificado nas últimas décadas, e evidências empíricas comprovam a eficácia delas nos resultados organizacionais. No entanto, a literatura evidencia poucas pesquisas sobre os resultados de treinamentos em organizações cooperativas. Este estudo teve por objetivo avaliar um programa de treinamento para conselheiros de cooperativas de crédito a partir de modelos de avaliação em Treinamento, Desenvolvimento e Educação associados a modelos lógicos. Trata-se de um estudo empírico com delineamento qualitativo. A coleta de dados foi realizada por meio de análise de 229 documentos, três entrevistas individuais semiestruturadas e grupo focal. Os resultados da pesquisa corroboram achados relacionados à utilidade do uso integrado de abordagens sistêmicas de avaliação e indicam que esses modelos são aplicáveis ao contexto de treinamentos de cooperativas. Uma das contribuições deste estudo foi suprir uma lacuna metodológica no campo da psicologia instrucional em organizações do terceiro setor.

Resumen Durante las últimas décadas, las evaluaciones de capacitación, desarrollo y educación se han intensificado, y la evidencia empírica demuestra su eficacia en los resultados de la organización. Sin embargo, la literatura muestra poca investigación sobre los resultados de la capacitación en cooperativas. Este estudio tuvo como objetivo evaluar un programa de capacitación para consejeros de cooperativas de crédito con base en modelos de evaluación asociados a modelos lógicos. Se trata de un estudio empírico cualitativo. La recopilación de datos se realizó mediante el análisis de 229 documentos, tres entrevistas semiestructuradas y un grupo focal. Los resultados de la investigación corroboran los hallazgos relacionados con la utilidad del uso integrado de enfoques de evaluación sistémica e indican que estos modelos son aplicables al contexto de cooperativa. Una de las contribuciones de este estudio ha sido la de llenar la laguna metodológica en el campo de la psicología instructiva en organizaciones del tercer sector.

Manifestações clínicas apresentadas por crianças infectadas pela COVID-19: revisão integrativa / Clinical manifestations presented by children infected with COVID-19: an integrative review

Objetivo: Analisar as evidências científicas sobre as manifestações clínicas apresentadas por crianças infectadas pela COVID-19. Método: Revisão integrativa conduzida nas bases de dados PubMed, CINAHL, LILACS, Web of Science, SCOPUS E SCIENCE DIRECT. Foram selecionados 20 artigos. Resultados: Emergiram duas categorias temáticas: "Características clínicas leves ou moderadas" e "Síndrome inflamatória multissistêmica associada à COVID-19". A maioria das crianças foi infectada pelos pais ou parentes próximos. A sintomatologia apresentada pelo público infantil foi predominantemente leve ou moderada e de recuperação rápida. As principais manifestações clínicas apresentadas pelas crianças infectadas pelo SARS-CoV-2 foram febre, sinais gastrointestinais, sinais respiratórios, e mais recente, sintomas semelhantes a Doença de Kawasaki, sendo denominada como síndrome inflamatória multissistêmica associada à COVID-19. Conclusão: Frente a isso, os profissionais da saúde devem estar alertas para o reconhecimento desses casos para possibilitar o manejo adequado e oportuno durante a assistência à saúde.

Objective: The objective was to analyze the scientific evidence on the clinical manifestations presented by children infected with COVID-19. Method: Integrative review conducted in PubMed, CINAHL, LILACS, Web of Science, SCOPUS and SCIENCE DIRECT databases from December 2019 to June 2020. Twenty articles were selected. Results: Two thematic categories emerged: "Mild or moderate clinical features" and "COVID-19 associated multisystem inflammatory syndrome". Most children were infected by their parents or close relatives. The symptoms presented by children were predominantly mild or moderate and with quick recovery. The main clinical manifestations presented by children infected with SARS-CoV-2 were fever, gastrointestinal signs, respiratory signs, and more recently, symptoms similar to those of Kawasaki Disease, which was called COVID-19 associated multisystem inflammatory syndrome. Conclusion: Faced with this, health professionals must be alert to recognize these cases in order to offer appropriate and timely management during health care.

Licochalcone a Exhibits Leishmanicidal Activity in vitro and in Experimental Model of Leishmania (Leishmania) Infantum.

The efficacy of Licochalcone A (LicoA) and its two analogs were reported against Leishmania (Leishmania) amazonensis and Leishmania (Leishmania) infantum in vitro, and in experimental model of L. (L.) infantum in vitro. Initially, LicoA and its analogs were screened against promastigote forms of L. (L.) amazonensis. LicoA was the most active compound, with IC50 values of 20.26 and 3.88 µM at 24 and 48 h, respectively. Against amastigote forms, the IC50 value of LicoA was 36.84 µM at 48 h. In the next step, the effectivity of LicoA was evaluated in vitro against promastigote and amastigote forms of L. (L.) infantum. Results demonstrated that LicoA exhibited leishmanicidal activity in vitro against promastigote forms with IC50 values of 41.10 and 12.47 µM at 24 and 48 h, respectively; against amastigote forms the IC50 value was 29.58 µM at 48 h. Assessment of cytotoxicity demonstrated that LicoA exhibited moderate mammalian cytotoxicity against peritoneal murine macrophages; the CC50 value was 123.21 µM at 48 h and showed about 30% of hemolytic activity at concentration of 400 µM. L. (L.) infantum-infected hamsters and treated with LicoA at 50 mg/kg for eight consecutive days was able to significantly reduce the parasite burden in both liver and spleen in 43.67 and 39.81%, respectively, when compared with negative control group. These findings suggest that chalcone-type flavonoids can be a promising class of natural products to be considered in the search of new, safe, and effective compounds capable to treat canine visceral leishmaniosis (CVL).

Prevenção e controle da tuberculose no retratamento: uma revisão integrativa / Tuberculosis prevention and control in retreatment: an integrative review / Prevención y control de la tuberculosis en el retratamiento: una revisión integrativa

O objetivo deste artigo é avaliar as produções científicas disponíveis na literatura nacional e internacional para identificar as ações de prevenção e controle com pacientes com tuberculose em retratamento. Foi utilizado o método da revisão integrativa. Realizou-se uma pesquisa nas bases de dados BVS e PubMed, abrangendo o período de 2005 a 2016. No processo de busca, utilizou-se a associação dos termos tuberculose, retratamento, prevenção e controle. Foram identificados 11 estudos, dos quais, cinco foram coortes, três retrospectivos, dois transversais e um ecológico. Identificaram-se como ações de prevenção e controle: a estratégia do tratamento diretamente observado, educação e saúde para os pacientes/famílias, a formação continuada para a equipe multiprofissional e a otimização dos resultados dos testes de sensibilidade aos fármacos. Observou-se, portanto, que para a prevenção e o controle do retratamento da tuberculose, pode-se utilizar estratégias simples, como vínculo, acolhimento e educação em saúde, desde que essas atividades contem com o apoio de gestores, profissionais e especialmente dos usuários, que devem atuar como corresponsáveis no processo de retratamento.

This integrative review evaluates the national and international literature available on tuberculosis prevention and control actions in retreatment. A search was carried out in the BVS and PubMed databases between 2005 and 2016, using the terms tuberculosis, retreatment, prevention, and control. Eleven studies were identified, of which: five were cohort, three retrospective, two transversal and one ecological. The following were identified as prevention and control actions: directly observed treatment; education and health for patients/families; continuing education for the multidisciplinary team, and optimization of the drug sensitivity test results. In conclusion, simple strategies such as bonding, user embracement, and health education can be used for tuberculosis prevention and control in retreatment as long as such activities have the support of managers, professionals, and especially the users, who must act as co-responsible agents in the retreatment process.

Resumen Este artículo tiene por objetivo evaluar las producciones científicas disponibles en la literatura nacional e internacional para identificar las acciones de prevención y control con pacientes con tuberculosis en retratamiento. Se utilizó el método de revisión integrativa, a partir de búsquedas en las bases de datos BVS y PubMed en el período de 2005 a 2016. En esta búsqueda se usó los términos tuberculosis, retratamiento, prevención y control asociados. De los once estudios encontrados, cinco son cohortes, tres retrospectivos, dos transversales y uno ecológico. Las acciones de prevención y control identificadas fueron: la estrategia del tratamiento directamente observado, la educación y salud para los pacientes/familias, la formación continua para el equipo multiprofesional y la optimización de los resultados de las pruebas de sensibilidades a los fármacos. Se identificó que para la prevención y el control del retratamiento de la tuberculosis se puede utilizar estrategias simples como vínculo, acogida y educación en salud desde que estas actividades cuenten con el apoyo de gestores, profesionales y, especialmente, de los usuarios, que deben actuar como corresponsables en el proceso de retratamiento.

Discordant Zika Virus Findings in Twin Pregnancies Complicated by Antenatal Zika Virus Exposure: A Prospective Cohort.

BACKGROUND: There are limited data on the natural history of antenatal Zika virus (ZIKV) exposure in twin pregnancies, especially regarding intertwin concordance of prenatal, placental, and infant outcomes. METHODS: This prospective cohort study included twin pregnancies referred to a single institution from September 2015 to June 2016 with maternal ZIKV. Polymerase chain reaction (PCR) testing of maternal, placental, and neonatal samples was performed. Prenatal ultrasounds were completed for each twin, and histomorphologic analysis was performed for each placenta. Abnormal neonatal outcome was defined as abnormal exam and/or abnormal imaging. Two- to three-year follow-up of infants included physical exams, neuroimaging, and Bayley-III developmental assessment. RESULTS: Among 244 pregnancies, 4 twin gestations without coinfection were identified. Zika virus infection occurred at 16-33 weeks gestation. Zika virus PCR testing revealed discordance between dichorionic twins, between placentas in a dichorionic pair, between portions of a monochorionic placenta, and between a neonate and its associated placenta. Of the 8 infants, 3 (38%) had an abnormal neonatal outcome. Of 6 infants with long-term follow-up, 3 (50%) have demonstrated ZIKV-related abnormalities. CONCLUSIONS: Neonatal PCR testing, placental findings, and infant outcomes can be discordant between co-twins with antenatal ZIKV exposure. These findings demonstrate that each twin should be evaluated independently for vertical transmission.

Comparative analysis of the reproductive activity of Leporinus piau (Characiformes: Anostomidae) in lentic and lotic environments

In this study, we determined the main reproductive parameters of piau gordura, Leporinus piau, in two sections of the São Francisco River basin. Between May 2015 and April 2016, a total of 573 specimens were captured from a lentic environment (section 1), the Três Marias Reservoir (TMR), and a lotic environment (section 2), downstream of the TMR at the confluence of the São Francisco River (SFR) with the Abaeté River. Analysis of reproductive activity showed that L. piau from both sections reproduced, but females and males from section 1 exhibited higher total length, body weight, Fulton condition factor, and gonadosomatic index values, as compared to section 2. Sexual dimorphism was evident in the species, with females being larger than males. Moreover, males reached first gonadal maturation at a smaller size than females. The peak maturation/mature stage was observed in November/April for females and males in section 1 and in November/December in section 2, coinciding with high temperatures and precipitation in the region. In both sections of the river, L. piau exhibited the typical characteristics of partial spawning, with a prolonged spawning period, and preferential reproduction in lentic environments.(AU)

Neste estudo, determinamos os principais parâmetros reprodutivos do piau gordura, Leporinus piau, em duas seções da bacia do rio São Francisco. Entre maio de 2015 e abril de 2016, um total de 573 espécimes foram capturados de um ambiente lêntico (seção 1), o reservatório de Três Marias (RTM), e um ambiente lótico (seção 2), à jusante da RTM na confluência do rio São Francisco (RSF) com o rio Abaeté. A análise da atividade reprodutiva mostrou que L. piau se reproduz nas duas seções, mas fêmeas e machos da seção 1 apresentaram maiores valores de comprimento total, peso corporal, fator de condição de Fulton e índice gonadossomático em comparação com a seção 2. O dimorfismo sexual foi evidente na espécie com as fêmeas sendo maiores do que os machos. Além disso, os machos atingiram a primeira maturação gonadal em tamanho menor do que as fêmeas. O pico do estágio de maturação/maduro foi observado em novembro/abril para fêmeas e machos na seção 1 e em novembro/dezembro na seção 2, coincidindo com altas temperaturas e precipitação na região. Em ambas as seções do rio, L. piau apresentou características típicas de desova parcelada com período de desova prolongada e reproduz preferencialmente em ambientes lênticos.(AU)