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Chalcone (E)-1,3-diphenyl-prop-2-en-1-one and a series of 14 methoxylated derivatives have been synthesized via Claisen-Schmidt aldol condensation and characterized by FTIR, CG/MS/DIC, 1D (1H and 13C), 2D (COSY, HSQC, and HMBC) NMR, and EMAR techniques. All molecules were tested at 1 mM concentration for antifungal (Sclerotium sp., Macrophomina phaesolina and Colletotrichum gloeosporioides), antibacterial (Acidovorax citrulli two strains), and antiprotozoal (Phytomonas serpens) activities. Unmodified chalcone (CH0) and derivatives CH1, CH2, CH8 stood out in terms of antifungal activity. CH0 presented IC50 values of 47.3 µM (9.8 µg/mL) for the fungus C. gloeosporioides. In addition, fluorescence microscopy indicated that CH0 promoted loss of hyphal cell membrane integrity. The CH1 and CH2 derivatives promoted the inhibition of Sclerotium sp. with IC50 of 127.5 µM (32.9 µg/mL) and 110.4 µM (29.6 µg/mL), respectively. All molecules showed high activity against the phytoparasite P. serpens with IC50 values of 0.98, 2.40, 10.25, and 3.11 µM for the derivatives CH2, CH3, CH5 and CH14 respectively. The results demonstrated that derivatives methoxylated in both rings (CH2) as well as derivatives with a furan ring associated with the methoxy group in ring A, as well as unmodified chalcone can be promising agricultural fungicides for controlling the fungi studied.

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Objective: To generate data on the costs associated with the diagnosis and treatment of obstructive ypertrophic cardiomyopathy (HCM) from the perspective of the private health system in Brazil. Methods: A modified Delphi panel including seven different specialists (three clinical cardiologists with experience in obstructive HCM, two hemodynamicists with experience in septal ablation and two cardiac surgeons with expertise in myectomy), from two Brazilian states (São Paulo and Pernambuco), was conducted between August and November 2022. Two rounds of questions about the use of healthcare resources according to the functional class (NYHA I-IV) and a panel in a virtual platform were conducted to obtain the final consensus. Micro-costing defined costs and unit values were determined based on official price lists. Results: The total diagnosis cost per patient was estimated at BRL 11,486.81. The obstructive HCM management costs analysis showed average annual costs per patient of BRL 17,026.74, BRL 19,401.46, BRL 73,310.07, and BRL 94,885.75 for the functional classes NYHA I, NYHA II, NYHA III, and NYHA IV, respectively. The average costs per patient related to procedures in a year were BRL 12,698.53, BRL 13,462.30, BRL 58,841.67, and BRL 75,595.90 for the functional classes NYHA I, II, III, and IV, respectively. Conclusions: The annual costs of HCM management increased according to the functional class, highlighting the need for safe and effective strategies to improve patient's NYHA functional class while promoting a decrease in the need for invasive therapies.

Objetivo: Gerar dados acerca dos custos associados ao diagnóstico e tratamento da cardiomiopatia hipertrófica (CMH) obstrutiva, sob a perspectiva do sistema de saúde privado no Brasil. Métodos: Um painel Delphi modificado incluindo sete especialistas (três cardiologistas clínicos com experiência em CMH obstrutiva, dois hemodinamicistas com experiência em ablação de septo e dois cirurgiões cardíacos com experiência em miectomia) de dois estados brasileiros (São Paulo e Pernambuco) foi conduzido entre agosto e novembro de 2022. Foram realizadas duas rodadas de perguntas acerca da utilização de recursos de acordo com a classe funcional (NYHA I-IV) e uma reunião virtual para obtenção do consenso final. Os custos foram definidos por meio de microcusteio, e os valores unitários foram definidos com base em listas de preço oficiais. Resultados: O custo total do diagnóstico por paciente foi estimado em R$ 11.486,81. A análise de custos de manejo da CMH obstrutiva mostrou custos médios anuais por paciente de R$ 17.026,74, R$ 19.401,46, R$ 73.310,07 e R$ 94.885,75 para as classes funcionais NYHA I, NYHA II, NYHA III e NYHA IV, respectivamente. Os custos médios por paciente relacionados a procedimentos em um ano foram de R$ 12.698,53, R$ 13.462,30, R$ 58.841,67 e R$ 75.595,90 para as classes NYHA I, II, III e IV, respectivamente. Conclusões: Os custos anuais com o manejo da CMH aumentam de acordo com a classe funcional, destacando a necessidade de estratégias seguras e eficazes capazes de melhorar a classe funcional NYHA do paciente, ao mesmo tempo que promove diminuição da necessidade de terapias invasivas.

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Non-small cell lung cancer (NSCLC) is still diagnosed at late stages in Brazil. The availability of newer treatment options has changed patient management, however, few real-world data have been published since then. This is a population-based retrospective cohort study that aims to evaluate the characteristics of stage III/IV NSCLC patients and their journey in the Brazilian private healthcare system. Patients aged ≥18 years, residing in Brazil who had their first medical appointment between 2016 and 2018 were included in the study. The sociodemographic and clinical characteristics of the patients and time intervals of interest were described. A total of 10,394 patients were analyzed. The majority of the patients were male (58.5%) with a median age of 64.0 (IQR = 58.0 - 71.0) years. In relation to characteristics of the disease, most of the tumors were characterized as adenocarcinomas (52.3%) and diagnosed at stage IV (72.2%). Most patients arrived at the hospital with an established NSCLC diagnosis, while 45.7% were diagnosed at the first medical appointment in the hospital or later. For patients who were diagnosed at the first medical appointment or later, a median interval of 15.0 (IQR = 6.0 - 33.0) days was observed between the first medical appointment and the diagnosis. The first treatment was given after a median of 25.0 (IQR = 6.0 - 49.0) days after diagnosis for patients without a prior diagnosis, and 57.0 (IQR: 33.0 - 98.0) days for patients with a prior diagnosis. The most common treatments were chemotherapy alone (33.8%), chemotherapy combined with radiotherapy (21.5%), radiotherapy alone (13.1%), adjuvant or neoadjuvant treatment (9.3%), surgery (3.3%), and immunotherapy (0.7%; alone or combined). At the end of follow-up (September, 2020), 52.3% of the patients had died. Despite having more treatment options in the private sector, data show that there is a need to improve access to technologies.

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Croton grewioides Baill. is an aromatic species with proven bioactive properties. Considering the potential of the species, the aim of this study was to chemically characterize and evaluate the in vitro antibacterial activity of the essential oils of C. grewioides on Xanthomonas campestris pv. campestris. The essential oils of the accessions of C. grewioides were extracted by the hydrodistillation method and analyzed by gas chromatography - mass spectrometry. For determination of the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the essential oils and of the compound eugenol, the microdilution method was used at concentrations that ranged from 125 to 4000 µg.mL-1. Streptomycin sulfate was used as a positive control (12.5 to 100 µg.mL-1). Growth kinetics and the membrane permeability trial were evaluated for the concentrations 2×, 1×, 1/2×, 1/4×, and 1/8× MIC of the essential oil CGR-108. The major compounds identified in the essential oils were eugenol, methyl eugenol, and methyl chavicol. The essential oil of the accession CGR-108 had a lower MIC (> 500 and < 1000 µg.mL-1) and MBC equal to <2000 µg.mL-1. For eugenol, MIC was obtained with contractions >250 and < 500 µg.mL-1 and MBC with >500 µg.mL-1 and < 1000 µg.mL-1. A loss of cell viability of the bacteria was observed after 30 min of exposure to the essential oil of the accession CGR-108 at the concentrations of 2× and 1× MIC, which was proven by the fluorescence intensity with propidium iodide. The essential oils of Croton grewioides Baill. and the compound eugenol show antibacterial potential on Xanthomonas campestris pv. campestris.

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Phytomonas serpens is a trypanosomatid phytoparasite, found in a great variety of species, including tomato plants. It is a significant problem for agriculture, causing high economic loss. In order to reduce the vegetal infections, different strategies have been used. The biological activity of molecules obtained from natural sources has been widely investigated to treat trypanosomatids infections. Among these compounds, chalcones have been shown to have anti-parasitic and anti-inflammatory effects, being described as having a remarkable activity on trypanosomatids, especially in Leishmania species. Here, we evaluated the antiprotozoal activity of the chalcone derivative (NaF) on P. serpens promastigotes, while also assessing its mechanism of action. The results showed that treatment with the derivative NaF for 24 h promotes an important reduction in the parasite proliferation (IC50/24 h = 23.6 ± 4.6 µM). At IC50/24 h concentration, the compound induced an increase in reactive oxygen species (ROS) production and a shortening of the unique flagellum of the parasites. Electron microscopy evaluation reinforced the flagellar phenotype in treated promastigotes, and a dilated flagellar pocket was frequently observed. The treatment also promoted a prominent autophagic phenotype. An increased number of autophagosomes were detected, presenting different levels of cargo degradation, endoplasmic reticulum profiles surrounding different cellular structures, and the presence of concentric membranar structures inside the mitochondrion. Chalcone derivatives may present an opportunity to develop a treatment for the P. serpens infection, as they are easy to synthesize and are low in cost. In order to develop a new product, further studies are still necessary.

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This study investigated the hypothesis that methionine supplementation of Japanese quail (Coturnix coturnix japonica) hens can reduce the effects of oxidative stress and improve the performance of the offspring exposed to heat stress during growth. For that, the quail hens were fed with three diets related to the methionine supplementation: methionine-deficient diet (Md); diet supplemented with the recommended methionine level (Met1); and diet supplemented with methionine above the recommended level (Met2). Their chicks were identified, weighed, and housed according to the maternal diet group from 1 to 14 d of age. On 15 d of age, chicks were weighed and divided into two groups: thermoneutral ambient (constant temperature of 23 °C) and intermittent heat stress ambient (daily exposure to 34 °C for 6 h). Methionine-supplemented (Met1 and Met2) hens had higher egg production, better feed conversion ratio, higher hatchability of total and fertile eggs, and offspring with higher body weight. Supplemented (Met1 and Met2) hens showed greater expression of glutathione synthase (GSS) and methionine sulfoxide reductase A (MSRA) genes, greater total antioxidant capacity, and lower lipid peroxidation in the liver. The offspring of hens fed the Met2 diet had lower death rate (1 to 14 d), higher weight on 15 d of age, weight gain, and better feed conversion ratio from 1 to 14 d of age. Among chicks reared under heat stress, the progeny of methionine-supplemented hens had higher weight on 35 d, weight gain, expression of GSS, MSRA, and thermal shock protein 70 (HSP70) genes, and total antioxidant capacity in the liver, as well as lower heterophil/lymphocyte ratio. Positive correlations between expression of glutathione peroxidase 7 (GPX7) and MSRA genes in hens and offspring were observed. Our results show that maternal methionine supplementation contributes to offspring development and performance in early stages and that, under conditions of heat stress during growth, chicks from methionine-supplemented hens respond better to hot environmental conditions than chicks from nonsupplemented hens. Supplementation of quail hens diets with methionine promoted activation of different metabolic pathways in offspring subjected to stress conditions.

The deficiency of nutrients such as methionine in the diet of birds is affecting fertility rate, egg production, egg weight, and progeny weight. In addition, the maternal environment influences gene expression through epigenetic mechanisms, where the conditions experienced by the parental generation during embryonic development can produce effects on the progeny. This study investigates how methionine supplementation in the diet of quail hens can reduce the effects of oxidative stress and improve the performance of progeny subjected to heat stress during growth. For that, the quail hens were fed with diets containing three different levels of methionine; and their chicks were created (15 on 35 d of age) into thermoneutral and/or intermittent heat stress ambient. It was observed that methionine supplementation in the quail hens had a positive effect on mortality during the initial phase and greater weight gain in the progeny growth phase. In addition, genetic inheritance was observed through the positive correlation between the expression of genes (maternal and progeny) related to oxidative stress. The results show that methionine supplementation in the maternal diet contributes to the development and performance of the progeny when subjected to heat stress during the growth phase.

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Acanthamoeba is a free-living amoeba (FLA) that is ubiquitous in nature and can cause serious pathologies in humans. This protozoan has been detected in several environmental sources, such as soil, water, and swimming pools. The aim of this study was to evaluate the occurrence and molecular diversity of Acanthamoeba spp. in aquatic environments of the state of Sergipe, northeastern Brazil, and to determine the pathogenic potential of the isolated samples. A total of 138 samples were collected from 69 aquatic environments and, after cell culture, 74% of the samples were positive for FLA, 47% belonging to the genus Acanthamoeba. Genotypic analysis was performed using the primers JDP1 and JDP2, confirming distinct Acanthamoeba genotypes: 18 (75%) isolates belonging to genotype T4, two (8%) to T3, and one isolate (4%) to genotype T5. Tests carried out to analyze the pathogenic potential showed that 11 isolates could grow at 0.5 M mannitol concentration and seven isolates supported hyperosmolarity. In the thermotolerance test, two isolates grew at 37°C. These results confirm the presence and the pathogenic potential of FLA of the genus Acanthamoeba in aquatic environments of the municipalities of Sergipe.

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Chalcone is a molecule with known biological activities. Based on this, a series of chalcone derivatives bearing methyl, phenyl or furanyl substituents at different positions of A and B rings were synthesised, characterised, and evaluated regarding antiprotozoal activity. Molecules were synthesised via base catalyzed Claisen-Schmidt condensation and characterised by IR and NMR spectral data. Antiprotozoal activity against Phytomonas serpens, Leishmania amazonensis and Acanthamoeba polyphaga was performed. All compounds inhibited more than 50% of the growth of P. serpens while five had this effect on L. amazonensis and all of them no more than 35% of inhibition on A. polyphaga. Remarkably interesting antiprotozoal effects were recorded with compound 5, with IC50 of 1.59 µM for P. serpens and 11.49 µM for L. amazonensis. The addition of a naphthyl group to the B ring can be postulated to be the cause of the 10 times increase observed in its trypanocidal activity.

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The objective of this study was to investigate the seasonal variance of the content and chemical composition of the essential oil from Lantana camara accessions at two harvest times, and to analyze the trypanocidal activity on Phytomonas serpens. Essential oil content ranged from 0.13 to 0.29% in the rainy season and from 0.13 to 0.33% in the dry season. The compounds E-caryophyllene, α-humulene, α-curcumene and germacrene D defined the formation of four chemical clusters in the rainy and dry seasons, classified as: Cluster 1 (E-caryophyllene + germacrene D); Cluster 2 (germacrene D + E-caryophyllene); Cluster 3 (α-humulene + E-caryophyllene); and Cluster 4 (α-curcumene + E-caryophyllene). All L. camara essential oils, representing the four chemical clusters, inhibited P. serpenswith low concentrations, considering the following IC50 values: 18.34±6.60 µg/mL (LAC-018, Cluster 1); 9.14±3.87 µg/mL (LAC-027, Cluster 2); 14.56±3.40 µg/mL (LAC-037, Cluster 3); and 14.97±2.68 µg/mL (LAC-019, Cluster 4).

El objetivo de este estudio fue investigar la variación estacional del contenido y la composición química del aceite esencial de accesiones de Lantana camara en dos tiempos de cosecha y analizar la actividad tripanocida en Phytomonas serpens. El contenido de aceite esencial osciló entre 0,13% y 0,29% en la temporada de lluvias y entre 0,13% y 0,33% en la temporada seca. Los compuestos E-cariofileno, α-humuleno, α-curcumeno y germacreno D definieron la formación de cuatro grupos químicos en las estaciones lluviosa y seca, clasificados como: Grupo 1 (E-cariofileno + germacreno D); Grupo 2 (germacreno D + E-cariofileno); Grupo 3 (α-humuleno + E-cariofileno); y Grupo 4 (α-curcumeno + E-cariofileno). Todos los aceites esenciales de L. camara, que representan los cuatro grupos químicos, inhibieron P. serpens con bajas concentraciones, considerando los siguientes valores de CI50:18,34 ± 6,60 µg / mL (LAC-018, grupo 1); 9,14 ± 3,87 µg / ml (LAC-027, grupo 2); 14,56 ± 3,40 µg / ml (LAC-037, grupo 3); y 14,97 ± 2,68 µg / ml (LAC-019, grupo 4).

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Composites based on virgin and recycled polypropylene (PP and rPP) reinforced with 15 wt% sisal fibers, with and without alkali treatment, were prepared by compression molding in a mat composed of a three-layer sandwich structure. The sisal was characterized by Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). The composites were characterized according to physical and mechanical properties. Additionally, a factorial experimental design was used to statistically evaluate the mechanical properties of the composite. The FTIR and XRD indicated the partial removal of amorphous materials from the surface of the sisal after alkali treatment. The composites' density results varied from 0.892 to 0.927 g·cm-3, which was in the desirable range for producing lightweight automotive components. A slight decrease in the hardness of the pure rPP and rPP composites in relation to the PP was observed. The water absorption was higher in rPP composites, regardless of the chemical treatment. Moreover, the impact resistance of PP and its composites was higher than the values for rPP. Statistical analysis showed that the alkali treatment was a significant factor for the hardness of the rPP and PP composites, and that the addition of the sisal layer was relevant to improve the impact resistance of the composites.

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Objective: Understanding unmet needs related to hemophilia A management in Brazil is critical for supporting decision-making. Methods: A modified Delphi consensus panel was conducted. Hematologists with extensive experience treating hemophilia in the Brazilian Public Health System were invited to answer questions regarding indicators of severe hemophilia prophylaxis effectiveness, emicizumab treatment indications, and bypassing agents used to reduce bleeding in patients with inhibitors, immune tolerance induction (ITI) use, and adherence. The consensus was defined as ≥75% of votes in Round 1 or using a 5-point Likert-type scale (1 = strongly disagree, 2 = disagree, 3 = neither agree nor disagree, 4 = agree, and 5 = strongly agree) in Round 2, which included questions not reaching minimum cut-off in the first step. Results: Nine expert panelists with extensive experience in the Brazilian Public Health System participated. The panel reached an agreement on recommendations about prophylaxis, bleeding treatment patterns, and bleeding sites. From patients' perspectives, venous access and infusion frequency were the most significant barriers to improving patient treatment. According to most experts, emicizumab will not replace ITI or long-term factor VIII therapy. Still, emicizumab was thought to be a good therapeutic option for patients with difficult venous access, patients requiring central venous access, in the presence of inhibitors, or patients experiencing infusion-related pain. Conclusion: The information gleaned from this study may be helpful to both decision-makers and those in charge of developing healthcare economic models for the treatment of hemophilia A in Brazil.

Objetivo: É fundamental entender as necessidades não atendidas relacionadas ao manejo da hemofilia A no Brasil. Métodos: Foi conduzido um painel Delphi modificado. Foram convidados hematologistas com vasta experiência no tratamento de hemofilia no SUS para responder a perguntas sobre indicadores de eficácia da profilaxia, indicações de tratamento com emicizumabe, uso de agentes de bypass, uso de indução de tolerância imunológica (ITI) e adesão. O consenso foi definido como ≥75% dos votos na rodada 1 ou usando uma escala do tipo Likert de 5 pontos (1 = discordo totalmente, 2 = discordo, 3 = não concordo nem discordo, 4 = concordo e 5 = concordo totalmente) na segunda rodada, que incluiu questões que não atingiram o corte mínimo na primeira etapa. Resultados: Nove especialistas participaram e houve consenso sobre recomendações para profilaxia, padrões de tratamento de sangramento e locais de sangramento. O acesso venoso e a frequência da infusão foram identificados como as barreiras mais significativas para melhorar o tratamento do paciente. De acordo com a maioria, emicizumabe não substituirá a ITI ou tratamento com fator VIII de longo prazo. Emicizumabe foi considerado uma boa opção terapêutica para

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Objetivo: Identificar as condutas terapêuticas e a variabilidade na prática clínica, assim como necessidades não atendidas e barreiras para a adequada assistência a pacientes com polineuropatia amiloidótica familiar relacionada à transtirretina (PAF-TTR), no Brasil. Métodos: Estudo transversal, por meio de questionário semiestruturado on-line enviado por e-mail. Foram incluídos médicos com experiência no manejo clínico-assistencial de pacientes com PAF-TTR no Brasil. O questionário foi composto por 30 questões envolvendo características gerais da população brasileira com PAF-TTR, características das escolhas terapêuticas e da falha, definições de progressão de doença e estadiamento, e métodos para mensuração do impacto na qualidade de vida. Resultados: Seis profissionais responderam ao inquérito. Quanto ao diagnóstico e à classificação da doença, houve consenso quanto ao uso de quadro clínico associado a testagem genética para o diagnóstico, e foram considerados adequados os critérios de Coutinho e do Ministério da Saúde, apesar de serem pouco úteis na avaliação da progressão da doença. Entre os especialistas, 83,3% entendem que a terapia atualmente disponível no Sistema Único de Saúde (SUS) atende às necessidades dos pacientes no estágio I da doença, entretanto todos os especialistas apontam necessidades assistenciais não atendidas, uma vez que esse medicamento não possui benefício definido para os estágios II e III da doença. A progressão da doença é definida como qualquer novo sintoma ou piora daqueles preexistentes, não sendo necessária modificação no estágio da doença para caracterizar tal evento. Conclusões: A condução deste estudo permitiu a identificação de aspectos importantes para auxiliar no entendimento da prática clínico-assistencial no país e das necessidades em saúde desses pacientes

Objective: To identify therapeutic approaches and variability in clinical practice, as well as unmet needs and barriers to adequate care for patients with familial transthyretin-related amyloidotic polyneuropathy (FAP) in Brazil. Methods: Cross-sectional study using an online semi-structured questionnaire sent by email. Physicians with experience in the clinical-care management of patients with FAP in Brazil were included. The questionnaire consisted of 30 questions involving general characteristics of the Brazilian population with FAP; characteristics of therapeutic choices and failure; definitions of disease progression and staging; and methods for measuring the impact on quality of life. Results: Six professionals responded to the survey. As for the diagnosis and classification of the disease, there was a consensus regarding the use of a clinical picture associated with genetic testing for the diagnosis and, as appropriate, the criteria proposed by Coutinho and the Ministry of Health, although not very useful in evaluating the progression of the disease. 83.3% of experts understand that the therapy currently available in the SUS meets the needs of patients in stage I of the disease, however, all experts point out unmet care needs, since this drug has no defined benefit for stages II and III of the disease. Disease progression is defined as any new symptom or worsening of pre-existing ones, and no change in the stage of the disease is necessary to characterize such an event. Conclusions: The conduction of this study allowed to identify important aspects to a better understanding of the clinical care practice in the country and unmet needs of these patients

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Objetivo: Avaliar o impacto orçamentário da inclusão da cladribina oral no tratamento de esclerose múltipla remitente-recorrente em alta atividade da doença (EMRR HDA) no Sistema de Saúde Suplementar (SSS). Métodos: Foi conduzida uma análise de impacto orçamentário, sob a perspectiva do SSS, com horizonte temporal de quatro anos, considerando a abordagem de coorte aberta na qual o número de pacientes elegíveis para tratamento varia em cada ano com a introdução de novos pacientes diagnosticados de EMRR HDA e a retirada de indivíduos prevalentes devido a morte ou progressão secundária. Foram considerados custos médicos diretos, incluindo a aquisição e administração de medicamentos, monitoramento, eventos adversos e surtos. Os comparadores utilizados na análise foram: alentuzumabe, fingolimode, natalizumabe e ocrelizumabe. Os custos foram apresentados em real brasileiro (BRL). Resultados: O custo incremental da inclusão da cladribina oral para o SSS foi estimado em 463.265 BRL, 739.691 BRL, -1.414.963 BRL, -3.719.007 BRL, nos anos 1, 2, 3 e 4, respectivamente. Isso resultou em um custo incremental total de -3.931.015 BRL no período analisado, representando 1,5% da redução orçamentária total no tratamento de EMRR HDA. Conclusão: A inclusão da cladribina oral para o tratamento de pacientes com diagnóstico de EMRR HDA poderia gerar uma economia substancial para o sistema brasileiro de saúde suplementar, atingindo um valor de cerca de 3,9 milhões de BRL em um período de quatro anos

Objective: To evaluate the budget impact of adopting cladribine tablets as a treatment strategy for relapsing remitting multiple sclerosis with high disease activity (RRMS HDA), from the Brazilian private healthcare system perspective. Methods: A budget impact analysis, under private healthcare system perspective, with a 4-years time horizon was conducted, considering the open cohort approach in which the number of patients eligible for treatment varies each year with the introduction of newly diagnosed RRMS HDA patients and the drop out of prevalent individuals due to death or secondary progression. Direct medical costs, including acquisition, drug administration, monitoring, adverse events and relapses were considered. Comparators used in the analysis were: alentuzumab, fingolimod, natalizumab and ocrelizumab. Costs were presented in Brazilian real (BRL). Results: The incremental cost of incorporating cladribine tablets into the private healthcare system was estimated at 463,265BRL, 739,961BRL, -1,414,963 BRL, -3,716,007 BRL, in years 1, 2, 3 and 4, respectively. This resulted in a total incremental cost of -3,931,015 BRL over the period analyzed, representing 1.5% of the total budget reduction in the treatment of RRMS HDA. Conclusion: Incorporation of cladribine tablets for the management of RRMS HDA could generate substantial savings for the private healthcare system, reaching a value of approximately 3.9 million BRL in a 4-years period

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Objetivo: Definir um limiar de custo para o sistema intrauterino liberador de levonorgestrel 52 mg (SIU-LNG 52 mg) para o tratamento do sangramento uterino anormal (SUA) sob a perspectiva do Sistema de Saúde Suplementar brasileiro. Métodos: Foi elaborado um modelo de custo-efetividade para definir o limiar de custo de inserção de SIU-LNG 52 mg em mulheres com SUA em comparação à histerectomia. Um modelo de Markov foi estruturado com ciclos anuais para reproduzir o tratamento do SUA em um e cinco anos, considerando custos médicos diretos e o percentual de histerectomias evitadas como desfecho. O custo da histerectomia foi variado até o valor de 10.000 reais brasileiros (BRL) com incrementos de 500 BRL a cada nova simulação para avaliar o limiar de custo do SIU-LNG 52 mg para igualar o custo total de tratamento de ambas as estratégias analisadas. Resultados: O SIU-LNG 52 mg demonstrou ser uma opção de tratamento dominante quando comparada à histerectomia, levando à redução da frequência de realização do procedimento cirúrgico em 59,62% das mulheres e redução de 2.557,91 BRL no custo total de tratamento em cinco anos. Ao considerar a histerectomia a 6.000 BRL, o custo do procedimento com SIU-LNG 52 mg poderia ser de até 6.150,35 BRL e 3.994,60 BRL para igualar o custo total de tratamento, em horizontes temporais de um e cinco anos, respectivamente. Conclusão: SIU-LNG 52 mg demonstrou ser uma opção dominante para o manejo do SUA, sendo capaz de atrelar economia para o sistema de saúde a benefícios para a mulher perante a cirurgia.

Objective: To define a cost threshold for the use of levonorgestrel-releasing intrauterine system 52 mg (LNG-IUS 52 mg) for the treatment of heavy menstrual bleeding (HMB) in the Brazilian Supplementary Health System perspective. Methods: A cost-effectiveness model was built to define the cost threshold for insertion of LNG-IUS 52 mg considering women with diagnosis of HMB as the target population and hysterectomy as the comparator. A Markov model was structured with annual cycles to reproduce HMB treatment in 1 and 5 years, considering direct medical costs and the percentage of avoided hysterectomies as the outcome. Hysterectomy cost was varied up to 10,000 Brazilian real (BRL) with increments of 500 BRL at each new simulation to define LNG-IUS 52 mg cost threshold, to provide equal total treatment costs for both strategies. Results: LNG-IUS 52 mg proved to be a cost-saving option when compared to hysterectomy, leading to a reduction in the frequency of the surgical procedure by 59.62% and a total treatment cost reduction of 2,557.91 BRL in 5 years. When considering hysterectomy at 6,000 BRL, the cost of the procedure with LNG-IUS 52 mg could be up to 6,150.35 BRL and 3,994.60 BRL to provide equal total treatment cost in 1 and 5 years time horizon, respectively. Conclusion: LNG-IUS 52 mg has proven to be a cost-saving option for the health system in the management of HMB, in addition to the known benefits for women against surgery.

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Leishmaniasis is a neglected disease caused by Leishmania. Chemotherapy remains the mainstay for leishmaniasis control; however, available drugs fail to provide a parasitological cure, and are associated with high toxicity. Natural products are promising leads for the development of novel chemotherapeutics against leishmaniasis. This work investigated the leishmanicidal properties of ethanolic extract of Croton blanchetianus (EECb) on Leishmania infantum and Leishmania amazonensis, and found that EECb, rich in terpenic compounds, was active against promastigote and amastigote forms of both Leishmania species. Leishmania infantum promastigotes and amastigotes presented IC50 values of 208.6 and 8.8 µg/mL, respectively, whereas Leishmania amazonensis promastigotes and amastigotes presented IC50 values of 73.6 and 3.1 µg/mL, respectively. Promastigotes exposed to EECb (100 µg/mL) had their body cellular volume reduced and altered to a round shape, and the flagellum was duplicated, suggesting that EECb may interfere with the process of cytokinesis, which could be the cause of the decline in the parasite multiplication rate. Regarding possible EECb targets, a marked depolarization of the mitochondrial membrane potential was observed. No cytotoxic effects of EECb were observed in murine macrophages at concentrations below 60 µg/mL, and the CC50 obtained was 83.8 µg/mL. Thus, the present results indicated that EECb had effective and selective effects against Leishmania infantum and Leishmania amazonensis, and that these effects appeared to be mediated by mitochondrial dysfunction.

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Objetivo: Determinar o impacto da adesão ao tratamento antirretroviral sobre a utilização de recursos e custos relacionados ao manejo do HIV/AIDS no Brasil. Métodos: Uma revisão sistemática da literatura foi conduzida em dezembro/2019. Foram incluídos estudos com pacientes adultos, brasileiros, com diagnóstico de HIV/AIDS, que apresentassem dados de adesão terapêutica, utilização de recursos e custos associados ao tratamento. Resultados: Foram localizadas 964 referências, três delas elegíveis para inclusão. O custo total foi estimado em 227.362,00 BRL em seis meses (N = 100 ­ custos diretos e indiretos) e em 579.264,80 BRL por ano (N = 157 ­ custos diretos) em indivíduos aderentes ao tratamento. Já em 40 pacientes não aderentes, o custo total estimado, considerando apenas os custos diretos, foi de 136.023,25 BRL por ano. Ao padronizar essas estimativas pelo período de análise e tamanho amostral, pacientes não aderentes demonstram um menor custo total quando comparados àqueles aderentes ao tratamento [170.029,06 BRL (custos diretos) versus 184.479,24 BRL (custos diretos) e 227.362,00 BRL (custos diretos e indiretos)]. No entanto, o grupo de pacientes não aderentes ao tratamento demonstrou maior custo, com diferença estatisticamente significativa para consultas e necessidade de internação hospitalar. A razão de custo-efetividade incremental para indivíduos aderentes à terapia antirretroviral (7.622 BRL por resposta clínica) foi menor quando comparada ao grupo de indivíduos não aderentes (9.716 BRL por resposta clínica). Conclusões: Apesar da escassez de estudos que avaliem a relação entre a adesão ao tratamento e os custos com o manejo do HIV/AIDS no Brasil, os achados corroboram a hipótese de que a não adesão ao tratamento pode gerar um maior custo.

Objective: To determine the impact of adherence to antiretroviral treatment on resource utilization and costs in the management of HIV/AIDS patients in Brazil. Methods: A systematic review was conducted in December 2019. Eligibility criteria considered Brazilian adults with HIV/AIDS, presenting data on treatment adherence, resource utilization, and treatment-associated costs. Results: The search retrieved 964 references and three were eligible for inclusion. Total cost was estimated at 227,362.00 BRL in six months (N = 100 ­ direct and indirect costs) and 579,264.80 BRL per year (N = 157 ­ direct costs) in individuals adhering to the treatment. In 40 non-adherent patients, estimated total cost, considering only direct costs, was 136,023.25 BRL per year. When estimates were standardized by the analysis period and sample size, non-adherent patients demonstrate a lower total cost when compared to those adhering to the treatment [170,029.06 BRL (direct costs) versus 184,479.24 BRL (direct costs) and 227,362.00 BRL (direct and indirect costs)]. However, the group of patients who did not adhere to the treatment showed a higher cost, with a statistically significant difference, for consultations and the need for hospitalization. Incremental cost-effectiveness ratio for adherent (7,622 BRL per clinical response) was smaller when compared to non-adherent group (9,716 BRL per clinical response). Conclusions: Despite the scarcity of studies evaluating the relationship between adherence to treatment and costs with the management of HIV/AIDS in Brazil, data found corroborates the hypothesis that non-adherence to treatment may be associated with higher costs.

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Xylanases have gained increasing importance due to their diverse applications in the food, paper, and pharmaceutical industries, however, the production of these enzymes currently uses expensive substrates. It has already been estimated that more than 30% of the enzyme production cost originates from the substrate. The present study aimed to optimize the production of extracellular xylanases by the Bacillus sp. TC-DT 13 using solid-state fermentation with agro-industrial residues, with a view at reducing the production cost of these enzymes. All the agro-industrial residues were tested in submerged fermentation to select the best inductor to produce xylanase. Among these residues, wheat bran was selected as the best inducer of xylanase production with 1500 U/mL. Regarding solid-state fermentation, the use of wheat bran as the only fermentation substrate was used and a ratio of 1:4 moisture over a time of 144 hours induced higher amount of xylanase reaching 2943 U/g. The use of carbon and nitrogen sources did not result in the increase in production of xylanolitic enzymes. The use of agro-industrial residues in the solid-state fermentation, besides increasing the production of xylanase, reduces the cost of production and is an environmentally friendly alternative.

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The increased use of pesticides applied to treat diseases caused by bacteria has caused serious environmental problems. There are few fungicides/bactericides for the treatment of plant diseases caused by Xanthomonas campestris pv. campestris (Xcc), and only two natural products with general bactericidal/fungicidal use are available on the market. Thus, this study evaluated the antimicrobial activity of essential oils (EOs), and their combinations, from five distinct genotypes of Cordia curassavica (Jacq.) Roem. & Schult (Syn. Varronia curassavica Jacq.) (CCUR) against Xcc. GC/MS chemical analysis revealed α-pinene, sabinene, (E)-caryophyllene, ar-curcumene, ß-sesquiphellandrene, 7-cyclodecen-1-one, and ar-Turmerone as the major compounds of the five EOs of CCUR. All EOs showed growth inhibition of Xcc with minimum inhibitory concentration between 500 and 1000 µg mL-1. The associations between two EOs from different CCUR genotypes showed that 70% of the total combinations had an additive effect. However, the combinations between CCUR-002 × (-302, -202) and CCUR-302 × (-601) showed a synergistic effect, with mean fractional inhibitory concentration FIC50 values of 0.28, 0.42, and 0.40, respectively. This study demonstrates that combinations of C. curassavica EOs have antimicrobial activity and a potential to be used in the control of black rot. Graphical abstract.

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Xanthomonas campestris pv.campestris (Xcc) is the causative agent of black rot, a disease that causes serious damage to plants from Brassicaceae family. However, there are no chemicals or biological agent commercially registered for the control of this disease. Thus, this study aimed to evaluate the antimicrobial activity and chemical composition of Lippia gracilis essential oils (EOs) on Xcc aiming its use as effective biological control. We also investigated the effect of EOs on the integrity of the bacterial cytoplasmic membrane. Chemical analysis by GC/MS showed that the major compounds of the seven EOs of L. gracilis are thymol or carvacrol. The seven genotypes showed inhibition of bacterial growth with MIC from 700 µg.ml-1 to 1000 µg.ml-1, with the genotype LGRA-106 (rich in Thymol) with higher antimicrobial activity. The MIC for thymol and carvacrol were 250 µg.ml-1. After exposure to LGRA-106 EO (2×, 1×, 1/2×, 1/4×, and 1/8 x MIC for 5 min, it was observed a decreased cell viability and increased pI fluorescence, which indicates damage to the cytoplasmic cell membrane. This study demonstrates that L. gracilis EOs have antimicrobial activity and have a potential to be used in the control of black rot. Furthermore this antimicrobial activity is due, at least in part, to bacterial cytoplasmic membrane damage.

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Foi atendido um paciente canino, fêmea, apresentando endocardite da válvula mitral, doença periodontal severa e diabetes mellitus. A endocardite infecciosa é uma doença com baixa taxa de morbidade, porém, com alta taxa de mortalidade. É uma infecção do endocárdio que surge como consequência de uma bacteremia transitória ou permanente. A doença periodontal tem sido incriminada como responsável por bacteremia e fator de risco para a endocardite e resistência à insulina. O estado diabético é considerado um fator agravante para a endocardite e para a doença periodontal pelo comprometimento de várias funções do organismo, inclusive a resposta imune e integridade vascular. O diagnóstico da endocardite geralmente é realizado na necropsia e quando feito na clínica médica, o tratamento é bastante agressivo, prolongado e muitas vezes frustrante. O objetivo do presente trabalho é de relatar o diagnóstico e o sucesso do tratamento de um paciente com endocardite de mitral.(AU)

A canine female patient was treated with mitral valve endocarditis, severe periodontal disease and diabetes mellitus. Infective endocarditis is a disease with a low morbidity rate, but with a high mortality rate. It is an endocardial infection that arises as a consequence of transient or permanent bacteremia. Periodontal disease has been incriminated as responsible for bacteremia and risk factor for endocarditis and insulin resistance. The diabetic state is considered an aggravating factor for endocarditis and periodontal disease due to the impairment of various functions of the organism, including immune response and vascular integrity. The diagnosis of endocarditis is usually performed at necropsy and when done at the medical clinic, the treatment is quite aggressive, prolonged and often frustrating. The aim of this study is to report the diagnosis and success of the treatment of a patient with mitral endocarditis.(AU)

Se atendió a un paciente canino, hembra, presentando endocarditis de la válvula mitral, enfermedad periodontal varias y diabetes mellitus. La endocarditis infecciosa es una enfermedad con baja tasa de morbilidad, pero con alta tasa de mortalidad. Es una infección del endocardio que surge como consecuencia de una bacteriemia transitoria o permanente. La enfermedad periodontal ha sido incriminada como fuese por bacteremia y factor de riesgo para la endocarditis y resistencia a la insulina. El estado diabético se considera un factor agravante para la endocarditis y para la enfermedad periodontal por el compromiso de varias funciones del organismo, incluyendo la respuesta inmune e integridad vascular. El diagnóstico de la endocarditis generalmente se realiza en la necropsia y cuando se hace en la clínica médica, el tratamiento es bastante agresivo, prolongado y muchas veces frustrante. El objetivo del presente trabajo es relatar el diagnóstico y el éxito del tratamiento de un paciente con endocarditis de mitral.(AU)

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