ABSTRACT Introduction Haploinsufficiency of the hematopoietic transcription factor GATA2 is associated with a broad spectrum of diseases, including infection susceptibility and neoplasms. We aimed to investigate GATA2 variants in patients with non-tuberculous mycobacterial (NTM) and/or fungal infections (FI) without known immunodeficiencies. Method We performed GATA2 genotyping in patients with NTM and/or FI. Results Twenty-two patients were enrolled (seventeen FI, four NTM and one with both infections). The pathogenic variant NG_029334.1:g.16287C>T was found in one patient (4.5%) and two asymptomatic offsprings. We also found the likely-benign variant NG_029334.1:g.12080G>A (rs2335052), the benign variant NG_029334.1:g.16225C>T (rs11708606) and the variant of uncertain significance NG_029334.1:g.16201G>A (rs369850507) in 18.2%, 27.3%, and 4.5% of the cases, respectively. Malignant diseases were additionally diagnosed in six patients. Conclusion Although detected in 45.4% of the patients, most GATA2 variants were benign or likely benign. Identifying a pathogenic variant was essential for driving both the patient's treatment and familial counseling. Pathogenic variants carriers should receive genetic counseling, subsequent infection prevention measures and malignancies surveillance. Additionally, case-control genotyping should be carried out in Brazil to investigate whether the observed variants may be associated with susceptibility to opportunistic infections and/or concurrent neoplasms.

ABSTRACT. Since the composition of honey varies with the species of bee as well as flowering and geographical aspects, this study aimed to evaluate the physicochemical and bioactive properties of Apisand stingless bees’honey from the Brazilian Caatinga. Samples of different species of Apis mellifera L.Meliponini (Melipona subnitida, Frieseomellita varia, Melipona mandacaia, Plebeia sp.) and Apis mellifera L.werecollected from honey producersin the state of Rio Grande do Norte. Honey from A. mellifera and stingless bees showed physicochemical differences in some parameters, especially in moisture, free acidity, HMF, water activity, sugars and electric conductivity. There were no differences in color between honeys from A. mellifera and stingless bees. Honeys fromPlebeia sp., F. varia and A. mellifera showed higher antioxidant capacity followed by honeys fromM. mandacaia and M. subnitida. Flavonoids had little influence on the differentiation of antioxidant activities of stingless bees, while the opposite occurred with the phenolic content, where honeys with the highest levels of phenolic also showed higher antioxidant capacity. ABSTRACT aspects beeshoney Caatinga LMeliponini L Meliponini subnitida sp. sp Lwerecollected werecollected Norte A parameters moisture acidity HMF activity conductivity F fromM M content

Abstract Syzygium malaccense is popularly used to treat inflammation and pain-related ailments. The species was assessed regarding its antioxidant, antiglycant, anti-inflammatory, including anti-neuroinflammatory, and antinociceptive activities. Different models were employed to measure S. malaccense extract (ESM) antioxidant activity. The antiglycant activity was determined using the glucose-induced protein glycation model. LPS-induced neuroinflammation on murine BV-2 microglial cell line was used for anti-neuroinflammatory activity evaluation. The croton oil-induced ear edema test was accomplished to evaluate the in vivo anti-inflammatory activity. Acetic acid-induced writhing together with formalin-induced paw licking assays were performed to evaluate the antinociceptive potential. Finally, the chemical characterization was accomplished by a UHPLC-MS analysis. ESM presented relevant antioxidant and antiglycant activity. NO production by BV-2 cells was reduced, indicating the relevant neuroprotective activity. ESM significantly decreased the mice ear edema induced by croton oil and the nociceptive stimulus induced by acetic acid and formalin by central and peripheral mechanisms. The flavonoids myricitrin, myricetin and quercetin were identified and, as far as we know, the alkaloid reserpine was reported in the species for the first time. The antioxidant and antiglycant potential of ESM, may be related to the in vivo anti-inflammatory and antinociceptive effects, and to the in vitro neuroinflammation inhibition.

RESUMO O acesso à informação e as abordagens interculturais no setor da saúde são essenciais para eliminar as desigualdades no acesso aos serviços de saúde. Os modelos interculturais, como as medicinas tradicionais, complementares e integrativas (MTCI), são uma parte importante da atenção à saúde na maioria dos países e frequentemente contribuem para ampliar o acesso à atenção primária. Apesar do reconhecimento legal e da existência de políticas para a integração das MTCI nos sistemas de saúde, a sua contribuição para a saúde, o bem-estar e a atenção centrada nas pessoas para alcançar a saúde universal ainda é subestimada. Este artigo apresenta o progresso (de 2017 a 2020) alcançado pela Biblioteca Virtual em Saúde especializada em MTCI (BVS MTCI Américas), uma iniciativa criada como ferramenta para reduzir as disparidades na produção e no acesso a informações validadas sobre as MTCI. Realizando um trabalho colaborativo em rede, a BVS MTCI Américas contribui para a democratização da saúde, o acesso a dados científicos verificados, a visibilidade dos conhecimentos não convencionais, o fortalecimento das capacidades de pesquisa e a troca de experiências para a tomada de decisões bem informada.

ABSTRACT Access to information and intercultural approaches in the field of health are essential for the elimination of inequities in health access and care. Intercultural models such as traditional, complementary, and integrative medicine (TCIM) are an important part of health care in most countries and often contribute to expanding access to primary health care. Despite legal recognition and policies to integrate TCIM into health systems, their contribution to health, well-being, and people-centered care to achieve universal health is still underestimated. This article presents the progress (2017-2020) achieved by the Virtual Health Library specialized in the TCIM (VHL TCIM Americas), an initiative created as a tool to reduce the gaps in the production and access to validated information on TCIM. Through collaborative network work, VHL TCIM Americas contributes to the democratization of health, access to verified scientific data, visibility of non-conventional knowledge, strengthening of research capacities, and exchange of experiences for informed decision-making.

RESUMEN El acceso a la información y los abordajes interculturales en el ámbito de la salud son esenciales para la eliminación de inequidades en el acceso a los servicios de salud y la atención sanitaria. Los modelos interculturales, como las medicinas tradicionales, complementarias e integrativas (MTCI) son una parte importante del cuidado de la salud en la mayoría de los países y frecuentemente contribuyen a ampliar el acceso a la atención primaria de salud. A pesar del reconocimiento legal y de la existencia de políticas para la integración de las MTCI en los sistemas de salud, aún se subestima su contribución a la salud, el bienestar y la atención de la salud centrada en las personas para alcanzar la salud universal. En este artículo se presentan los avances (2017-2020) alcanzados por la Biblioteca Virtual en Salud especializada en las MTCI (BVS MTCI Américas), iniciativa creada como herramienta para disminuir las brechas en la producción y el acceso a la información validada sobre las MTCI. Mediante el trabajo colaborativo en red, la BVS MTCI Américas contribuye a la democratización de la salud, el acceso a datos científicos verificados disponibles, la visibilización de conocimientos no convencionales, el fortalecimiento de capacidades de investigación y el intercambio de experiencias para la toma informada de decisiones.

RESUMO: O objetivo deste estudo foi avaliar a maturidade pulmonar de cordeiros prematuros e a termo por meio da análise do líquido amniótico utilizando os seguintes métodos: teste de Clements, teste de citologia do azul do Nilo, coloração de hematoxilina-Shorr, contagem de corpos lamelares e testes radiográficos. Um desses métodos tem por objetivo identificar recém-nascidos de alto risco e fornecer intervenção clínica imediata após o nascimento. Ao todo, 56 animais (24 ovelhas e 32 cordeiros) foram incluídos no estudo e divididos em 3 grupos. O grupo I foi composto por 8 ovelhas com aproximadamente 145 dias de gestação; este grupo deu à luz 10 cordeiros naturalmente. O Grupo II foi composto por 8 ovelhas com 138 dias de gestação; este grupo deu à luz 11 cordeiros por cesariana. Grupo III consistiu de 8 ovelhas com 138 dias de gestação; este grupo recebeu dexametasona intramuscular (16 mg / animal) 36 horas antes de uma cesariana. O Grupo III entregou 11 cordeiros. Os testes citológicos foram realizados em microscópio com aumento máximo de 1000x, enquanto o teste de Clements foi observado visualmente por um dos pesquisadores. A contagem de corpos lamelares de líquido amniótico foi medida usando microscopia eletrônica de transmissão. Dentre os métodos de coloração, o hematoxilina-Shorr foi confiável, sendo que o Grupo III apresentou maior número de células orangeofílicas quando comparado ao grupo II, provavelmente devido à administração de corticóide. O teste de Clements mostrou maturidade pulmonar em aproximadamente 20% dos cordeiros do Grupo I e o Grupo II apresentou 9,1% de bolhas; entretanto, o Grupo III apresentou o maior percentual de maturidade pulmonar (36,4%). Os corpos lamelares foram medidos e todos os grupos apresentaram tamanhos entre 0,019 e 0,590μm. A avaliação radiográfica revelou que a maioria dos cordeiros apresentava algum grau de radiodensidade pulmonar, indicando padrão acinar ao nascimento. Esses resultados estão alinhados com as expectativas de cada grupo. Verificamos que o grupo normal apresentou maior maturidade pulmonar, enquanto o Grupo II apresentou imaturidade pulmonar, o que é esperado por se tratar de cordeiros nascidos prematuramente e o Grupo III apresentou maturidade pulmonar quase comparável ao grupo de parto normal (Grupo I). Isso se deve ao fato de que, embora esses animais sejam prematuros, o uso da dexametasona auxiliou na maturação pulmonar. Portanto, esses testes de maturidade pulmonar são considerados eficazes quando mais de uma técnica são utilizadas e podem ser usadas rotineiramente no cuidado de uma ovelha gestante em trabalho de parto, onde uma simples coleta de líquido amniótico pode prever uma gravidez de alto risco e alertar o veterinário se o recém-nascido precisa de tratamento de suporte intensivo.

Abstract: The aim of this study was to evaluate the lung maturity of premature and full-term lambs by analyzing amniotic fluid using the following methods: Clements test, Nile blue cytology test, hematoxylin-Shorr stain, lamellar body count, and radiographic tests. The use of these methods is intended to identify high-risk newborns and provide immediate clinical intervention after birth. Altogether, 56 animals (24 ewes and 32 lambs) were included in the study and divided into 3 groups. Group I consisted of 8 ewes that were at approximately 145 days of gestation; this group delivered 10 lambs naturally. Group II consisted of 8 ewes that were at 138 days’ gestation; this group delivered 11 lambs by cesarean section. Group III consisted of 8 ewes at 138 days’ gestation; this group was administered intramuscular dexamethasone (16mg/animal) 36 hours prior to a cesarean section. Group III delivered11 lambs. Cytological tests were performed using a microscope with a maximum magnification of 1000x, while the Clements test was visually observed by one of the researchers. Amnioticfluid lamellar body counts were measured using transmission electron microscopy. Among the staining methods, hematoxylin-Shorr was reliable, and Group III had a greater number of orangeophilic cells when compared to Group II, probably due to corticoid administration. The Clements test showed pulmonary maturity in approximately 20% of Group I lambs and Group II showed 9.1% of bubbles; however, Group III had the highest pulmonary maturity percentage (36.4%). The lamellar bodies were measured, and all groups had sizes between 0.019 and 0.590μm. Radiographic evaluation revealed that the majority of lambs presented some level of pulmonary radiodensity, indicating an acinar pattern at birth. These results are in line with the expectations of each group. We found that the normal group showed greater pulmonary maturity, whereas Group II presented pulmonary immaturity, which is expected because this group comprised lambs born prematurely and Group III showed pulmonary maturity almost comparable to the normal delivery group (Group I). This is due to the fact that although these animals are premature, the use of dexamethasone helped in pulmonary maturation. Therefore, these pulmonary maturity tests are considered effective when more than one technique is used and can be used routinely in the care of a pregnant ewe in labor, where a simple collection of amniotic fluid can predict a high-risk pregnancy and alert the veterinarian if the newborn needs intensive supportive treatment.

ABSTRACT Objective: Assess adherence to school food offered by the School Food Program (Programa Nacional de Alimentação Escolar - PNAE) and the associated factors among Brazilian adolescents. Methods: Cross-sectional study with data from the Study of Cardiovascular Risks in Adolescents conducted in 2013-2014, with 58,707 adolescents aged 12 to 17 years-old who attended public schools. Logistic regression models were stratified by sex and the significance level of 5% was adopted for all analyses. Results: There was low adherence to school meals (17.2%). The chance of regular consumption of school meals was higher among male adolescents belonging to the medium (p<0.05) and the low (p<0.05) socioeconomic score categories. For females, the chance of regular consumption of food offered at school was higher among black-skinned, brown-skinned, indigenous-skinned or yellow-skinned adolescents (p<0.05), aged 16 and 17 (p<0.05), who worked (p<0.001) and belonged to the medium (p<0.05) and low (p<0.05) socioeconomic score categories. The regular purchase of food in school cafeterias reduced the chance of regular consumption of school meals for males (p<0.001) and females (p<0.001). Conclusions: Adherence to the food offered by the PNAE is far from ideal, and it is important to create public policies that encourage the consumption of school meals and improve adherence. In addition, the strengthening and drafting of regulations aimed at the sale of food in the interior and surrounding schools' areas is necessary.

RESUMEN Objetivo: Evaluar la adherencia a la comida escolar ofrecida por el Programa Nacional de Alimentación Escolar y los factores asociados entre los adolescentes brasileños. Métodos: Estudio transversal con datos del Estudio de Riesgos Cardiovasculares en Adolescentes realizado en 2013-2014, con 58.707 adolescentes de 12 a 17 años que asistieron a escuelas públicas. Los modelos de regresión logística se realizaron estratificados por sexo, y se aplicó el nivel de significancia del 5% para todos los análisis. Resultados: Hubo baja adherencia a las comidas escolares (17,2%). La posibilidad de consumo regular de comidas escolares fue mayor entre los adolescentes varones pertenecientes a las categorías de puntaje socioeconómico medio (p<0,05) y bajo (p<0,05). Para las mujeres, la probabilidad de consumo regular de alimentos ofrecidos en la escuela fue mayor entre las adolescentes de piel negra, marrón, indígena o amarilla (p<0,05), de 16 y 17 años (p<0,05), quién trabaja (p<0,001) y pertenece a las categorías de puntaje socioeconómico medio (p<0,05) y bajo (p<0,05). La compra regular de alimentos en las cafeterías escolares redujo la posibilidad de consumo regular de comidas escolares para hombres (p<0,001) y mujeres (p<0,001). Conclusiones: La adhesión a los alimentos ofrecidos por el PNAE está lejos de ser ideal, y es importante crear políticas públicas que fomenten el consumo de comidas escolares, mejoren su adherencia, además de ayudar en el fortalecimiento y la redacción de regulaciones dirigidas a la venta de alimentos en el interior y las áreas de las escuelas circundantes.

Abstract Leigh syndrome is an early onset progressive disorder caused by defects in mitochondrial oxidative phosphorylation. Pathogenic variants in nuclear and mitochondrial genes are associated with the syndrome. Homozygous pathogenic variants in the C12orf65 gene impair the mitochondrial oxidative phosphorylation system. We describe a new case of Leigh syndrome caused by a novel pathogenic variant of the C12orf65 gene resulting in the lack of the Gly-Gly-Gln (GGQ) domain in the predicted protein, and review clinical and molecular data from previously reported patients. Our study supports that the phenotype caused by C12orf65 gene variants is heterogeneous and varies from spastic paraparesis to Leigh syndrome. Loss-of-function variants are more likely to cause the disease, and variants affecting the GGQ domain tend to be associated with more severe phenotypes, reinforcing a possible genotype-phenotype correlation.

RESUMO Enxaqueca piora o sofrimento do paciente que tem esclerose múltipla (EM). ID-migraine é uma ferramenta útil para seleção de pacientes com enxaqueca e Migraine Disability Assessment (MIDAS) é um questionário que avalia o impacto da doença. O objetivo do presente estudo foi avaliar a presença e impacto de enxaqueca em pacientes com EM. Métodos: Pacientes diagnosticados com EM e tratados em clínicas especializadas foram convidados a responder um questionário online se também apresentassem cefaleia. Resultados: O estudo incluiu 746 participantes com cefaleia e EM que preencheram completamente as respostas. Foram 625 mulheres e 121 homens, sendo 69% dos pacientes com idade entre 20 e 40 anos. Enxaqueca foi identificada em 404 pacientes (54,1%) e moderado a grave impacto da doença foi observado em 68,3% dos casos. Conclusão: Enxaqueca é uma cefaleia primária frequente e incapacitante relatada por pacientes com EM.

ABSTRACT Migraine adds to the burden of patients suffering from multiple sclerosis (MS). The ID-migraine is a useful tool for screening migraine, and the Migraine Disability Assessment questionnaire can evaluate disease burden. The aim of the present study was to assess the presence and burden of migraine in patients with MS. Methods: Patients diagnosed with MS attending specialized MS units were invited to answer an online survey if they also experienced headache. Results: The study included 746 complete responses from patients with MS and headache. There were 625 women and 121 men, and 69% of all the patients were aged between 20 and 40 years. Migraine was identified in 404 patients (54.1%) and a moderate-to-high burden of disease was observed in 68.3% of the patients. Conclusion: Migraine is a frequent and disabling type of primary headache reported by patients with MS.

The benzophenones are synthetic and natural compounds presenting a variety of activities, including photoprotective, cytotoxic and antiviral. It is herein described the preparation of a series of twenty-seven benzophenone derivatives bearing 1,2,3-triazole functionalities and the evaluation of their photoprotective, cytotoxic and antiviral on Zika Virus (ZIKV) activities. The compounds were prepared in three steps, namely reduction of benzophenone, alkylation of diphenylmethanol and CuAAC reactions. The in vitro evaluation of the photoprotective activity revealed that the most active derivative 4-((benzhydryloxy)methyl)-1-(4-nitrobenzyl)-1H-1,2,3-triazole (4k) displayed UVB sun protection factor equal to 6,9±0,53, which make this compound a possible candidate to be used in formulations for photoprotective applications. In terms of cytotoxicity, the compounds were evaluated against MDA-MB-231 and B16F10 cell lines. It was observed that the compounds were more active against MDA-MB-231 cells and three of them were capable of reducing cell viability by approximately 55% at 100 µmol L-1. In the antiviral screening against ZIKV, compound 4-(3-benzhydryloxy)propyl)-1-(3-methylbenzyl)-1H-1,2,3-triazole (5j) was the most effective in mantaining Vero cell viability.

RESUMO: Uma das formas de se estudar a laminite bovina é sua indução experimental por meio do fornecimento de grande quantidade de carboidrato de alta fermentação. O protocolo mais eficaz até o momento foi o uso de oligofrutose. Objetivou-se avaliar aspectos clínicos e histológicos dos dígitos de bovinos na indução experimental de acidose ruminal e laminite usando oligofrutose. Utilizaram-se seis bezerros mestiços (Bos taurus x Bos indicus) de um ano, divididos em Grupo I (GI) e Grupo II (GII). Os animais em GI e GII receberam oligofrutose por via intrarruminal nas doses de 13 e 17g/kg respectivamente. Os bovinos foram avaliados clinicamente por 28 horas e fragmentos de coroa e muralha abaxial dos dígitos foram colhidos para histologia 30 horas após a indução. Foram identificados sinais de acidose ruminal e metabólica como distensão ruminal com líquido, diarreia e baixo pH ruminal. Os resultados de hemogasometria indicaram baixos pH e nível plasmático de bicarbonato. Os animais não apresentaram claudicação, entretanto, observaram-se apatia e marcha mais lenta, atribuídas à acidose metabólica. Histologicamente foram observadas lesões indicativas de laminite como alterações circulatórias e infiltrado inflamatório na derme, irregularidades e áreas de destacamento da membrana basal e alterações morfológicas de células da epiderme basal. O protocolo induziu, nas primeiras 30 horas, sinais de acidose ruminal e metabólica e lesões histológicas de baixa intensidade nos dígitos. Não foi observada claudicação ou sensibilidade nos dígitos, caracterizando a fase prodrômica da enfermidade.

ABSTRACT: One of the ways to study cattle laminitis is its experimental induction by supplying a large amount of high fermentation carbohydrate. The most effective protocol until now has been the use of oligofructose. The objective of this study was to evaluate clinical and histological aspects of the hoof in experimental induction of ruminal acidosis and laminitis in calves using oligofructose. Six crossbred (Bos taurus x Bos indicus) yearling calves divided into Group I (GI) and Group II (GII) were used. Animals in GI and GII received intraruminal oligofructose in doses of 13 and 17g/kg, respectively. During 28 hours the calves were clinically evaluated and 30 hours after induction, samples were taken from coronary and abaxial wall of the hoof for histologic evaluation. Were noticed signs of ruminal and metabolic acidosis like rumen distension with fluid, diarrhea, ruminal pH reduction and, at blood gas analysis, pH and bicarbonate below reference range. Lameness was not observed however, some animals had a slower gait and apathy, possibly due to metabolic acidosis, though. Histologically, typical lesions of laminitis like circulatory changes and inflammatory infiltrate in the dermis, irregularities and areas of detachment at basement membrane and morphologic changes in cells from basal epidermis were found. The protocol induced, in the first 30 hours, clinical signs of ruminal and metabolic acidosis and low grade histologic lesions in the digits. Lameness and digit pain were not observed, characterizing the prodromic phase of the disease.

The present investigation describes the synthesis of a series of novel triazole derivatives from 4,4'-dihydroxybenzophenone along with their elastase inhibitory activity. The 1,2,3-triazoles were obtained via the copper(I)-catalyzed azide-alkyne cycloaddition reaction (CuAAC), also known as click reaction, between bis(4-(prop-2-yn-1-yloxy))benzophenone and several benzyl azides. It was found that five derivatives exhibited significant inhibitory effects, presenting half maximal inhibitory concentration (IC50) values in the range of 16.6 to 72.1 µM. The most active compound, namely bis(4-(1-(4-iodobenzyl)-1H-1,2,3-triazol-4-yl)methoxy)benzophenone (IC50 = 16.6 ± 1.9 µM), was found to bind to elastase with the inhibition constant (Ki) of 11.12 µM, thereby illustrating competitive inhibitory behavior. Further, docking investigations provided insights on the possible binding mode of the most active compound with the elastase.

OBJECTIVES: This is a randomized controlled trial that aims to evaluate the impact of pharmacist-led discharge counseling on reducing pharmacotherapy problems in the 30-day postdischarge period of cardiology patients from a tertiary hospital in Brazil. METHODS: At discharge, two cardiovascular pharmacy residents performed a medication counseling session with the intervention group, and the follow-up was performed by telephone (3 and 15 days after discharge). The number of pharmacotherapy problems was evaluated during a pharmacist-led ambulatory consultation 30 days after discharge. RESULTS: A total of 66 and 67 patients were randomized to the intervention and control groups, respectively, but only 51 patients were analyzed in each group, all with similar baseline characteristics. The intervention group had significantly fewer pharmacotherapy problems compared to the control (p<0.001), and 100% of the patients had at least one problem. We observed five problems significantly more frequently in the control group: “incorrect time of taking” (p=0.003), “use higher dose of medication” (p=0.007), “use lower dose of medication” (p=0.014), “restart discontinued medication” (p=0.011), and “underdosing prescription” (p=0.009). Simvastatin, enalapril, carvedilol, and atorvastatin were the medications more associated with pharmacotherapy problems. CONCLUSIONS: We concluded that pharmacist-led discharge counseling should be an indispensable service, as patients exhibited less pharmacotherapy problems in the 30-day postdischarge period, especially related to drug administration and adherence.

OBJECTIVES: This study aimed to evaluate the impact of pharmacist-provided discharge counseling on mortality rate, hospital readmissions, emergency department visits, and medication adherence at 30 days post discharge. METHODS: This randomized controlled trial was approved by the local ethics committee and included patients aged 18 years or older admitted to the cardiology ward of a Brazilian tertiary hospital. The intervention group received a pharmacist-led medication counseling session at discharge and a telephone follow-up three and 15 days after discharge. The outcomes included the number of deaths, hospital readmissions, emergency department visits, and medication adherence. All outcomes were evaluated during a pharmacist-led ambulatory consultation performed 30 days after discharge. RESULTS: Of 133 patients, 104 were included in the analysis (51 and 53 in the intervention and control groups, respectively). The intervention group had a lower overall readmission rate, number of emergency department visits, and mortality rate, but the differences were not statistically significant (p>0.05). However, the intervention group had a significantly lower readmission rate related to heart disease (0% vs. 11.3%, p=0.027), despite the small sample size. Furthermore, medication counseling contributed significantly to improved medication adherence according to three different tools (p<0.05). CONCLUSIONS: Pharmacist-provided discharge medication counseling resulted in better medication adherence scores and a lower incidence of cardiovascular-associated hospital readmissions, thus representing a useful service for cardiology patients.

RESUMO A esclerose múltipla vem se tornando um desafio crescente para os neurologistas. Com o lançamento de novos medicamentos no mercado, os neurologistas brasileiros se encontram divididos entre, apesar da evolução dos seus pacientes, seguir as regras restritas estabelecidas pelo Ministério da Saúde para distribuição de medicamentos, ou ao contrário, considerar a progressão e piora da doença, em concordância com as evidências da literatura. Devido a este impasse foi realizada uma revisão sistemática sobre as principais orientações de tratamento publicadas e foi proposto um escalonamento terapêutico para orientar o tratamento dos pacientes com esclerose múltipla no Brasil.

ABSTRACT Multiple sclerosis has become an ever-increasing challenge to neurologists. With the release of the latest medications on the market, Brazilian neurologists feel divided between following their patients’ evolution in accordance with the strict rules established by the Brazilian Ministry of Health regarding drug distribution, or following disease progression and worsening in accordance with the evidence in the literature. Therefore, a systematic review of the main published treatment guidelines was conducted and an escalating therapy proposed for guiding multiple sclerosis patient treatment in Brazil.