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Verapamil is an L-type calcium channel blocker widely used in the treatment of cardiovascular diseases such as hypertension, angina and arrhythmias, requiring accurate therapeutic monitoring to maintain plasma, urine and saliva concentrations within a safe range. In this context, a novel analytical approach has been proposed to determine verapamil in biological samples, using bar adsorptive microextraction coated with reversed-phase polymers followed by high-performance liquid chromatography with diode array detection. Two adsorbents have been chosen, i.e. STRATA-CN and ENVI-18 polymers, showing recoveries from 56.01 ± 2.16% to 96.82 ± 0.61% under optimized experimental conditions, such as sample pH: 10.0 (STRATA-CN) and 8.0 (ENVI-18), 2 h of equilibrium time, stirring speed at 990 rpm, back-extraction solvent using methanol:acetonitrile (1 : 1 v/v), and 1 h under sonication. The analytical method showed linearity from 20 to 600 ng mL -1 ( r ≥ 0.99), as well as adequate precision (with RSD% below 15%) and accuracy (with RE% within 15% of the nominal value). Finally, the analytical method was applied to plasma, urine and saliva samples and proved to be a promising alternative for the trace analysis of verapamil in biological matrices.

A few decades ago, women diagnosed with multiple sclerosis were discouraged from becoming pregnant. However, with new knowledge about the disease and treatments, this recommendation has changed, and it is pregnancy after the diagnosis of the disease is no longer contraindicated, with family planning being essential in this process. This review aims to provide a comprehensive overview of the family planning process for people with multiple sclerosis., Competing Interests: The authors have no conflict of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)

The study aimed to evaluate the effects of Pereskia aculeata Miller (ora-pro-nobis [OPN]) flour on body and biochemical parameters, thermogenic activity, and molecular expression of markers in the muscle tissue of mice subjected to resistance training (RT). Twelve mice were randomly assigned to two groups (n=6 animals/group): G1: control (Control) fed a standard diet + RT and G2: experimental (OPN) fed a diet based on OPN flour + RT. The RT consisted of a 6-week program using a vertical ladder combined with a fixed weight attached to the animal. Several parameters were measured, including assessment of body composition, biochemical markers, thermogenic activity, and molecular (mRNA expression of interleukin (IL)-6, fibronectin type III domain-containing protein 5 (FNDC5), peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (TFAM). The OPN group exhibited a decrease in body weight and visceral adiposity, higher energy expenditure, and lipid oxidation rate. In addition, it was observed an increase in muscle volume and in mRNA expression levels of IL-6, FNDC5, PGC-1α, and TFAM. These findings suggest that OPN flour could be a nutritional option to enhance performance in RT.

The Next-Generation (NG) IEDB Tools website (https://nextgen-tools.iedb.org) provides users with a redesigned interface to many of the algorithms for epitope prediction and analysis that were originally released on the legacy IEDB Tools website. The initial release focuses on consolidation of all tools related to HLA class I epitopes (MHC binding, elution, immunogenicity, and processing), making all of these predictions accessible from a single application and allowing for their simultaneous execution with minimal user inputs. Additionally, the PEPMatch tool for identifying highly similar epitopes in a set of curated proteomes, as well as a tool for epitope clustering, are available on the site. The NG Tools site allows users to build data pipelines by sending the output of one tool as input for the next. Over the next several years, all pre-existing IEDB Tools, and any newly developed tools, will be integrated into this new site. Here we describe the philosophy behind the redesign and demonstrate the utility and productivity enhancements that are enabled by the new interface., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

The use of new materials in the field of biofuel production has been represented as a step in the development of remarkable catalysts. The use of lipases in the production of biodiesel is often seen as a cost-limiting step, as the operating expenses in recovering such catalysts can lead to unfeasible market expectations. In this study, hydroxyapatite (HAp) particles were evaluated as a support to immobilize commercial lipase, following application in ethyl ester synthesis. First, hydroxyapatite was synthesized through the co-precipitation method at constant pH and selected as a support to be used in enzyme immobilization. The characterization of the biocatalyst support materials produced was carried out using DRX, BET, FTIR, TGA, and SEM analysis. The lipase from Thermomyces lanuginosus was then immobilized in the matrices, and, subsequently, there was transesterification of the vegetable oil deodorization distillate (VODD). The biodiesel samples generated showed that they were within commercial standards, achieving ester conversion greater than 96.5%. Other properties such as density (0.87 g.cm -3 ) and viscosity (4.36 mm 2 .s -1 ) meet the specifications required by ASTM to be used as a biofuel. In the experiment planning technique, the results revealed an experimental trend and a defined behavior: a higher lipase loading in the immobilization and the use of temperatures in the range of 40-50 °C favor high conversions of ethyl esters. Thus, this confirms that the enzymatic chemical catalyst was able to form the main fatty acid esters even using a residual lipid raw material., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© King Abdulaziz City for Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Introduction: Multiple Sclerosis is a disease of young females at a reproductive age., Objective: discuss family planning in the context of providing care for women with MS., Method: patients with Multiple Sclerosis, female, aged between 18 and 45 years, from 01/Nov/2021 to 16/Jan/2022 participated, all of whom answered a questionnaire made available on the Google forms platform., Results: A total of 233 responses were validated. Most patients discuss family planning during their medical care (61.4 %), use low-efficacy contraceptive methods (68.7 %) and do not plan to become pregnant (70.1 %). There is a high rate of use of disease-modifying treatments (88.9 %). Among those who had already become pregnant, most of them became pregnant before diagnosis and were statically younger than patients who became pregnant after diagnosis., Conclusion: Family planning should be discussed early on and be actively initiated by the health care professional assisting the patient and incorporated into the routine consultation. We suggest efforts should be put into ensuring a decrease in the rate of unplanned pregnancy in this population. Also, it is crucial to guarantee effective contraception in patients who express the wish not to become pregnant and are using disease-modifying treatments., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Background: The Expanded Disability Status Scale (EDSS) is widely used and accepted by regulatory agencies for the assessment of neurological disability secondary to Multiple Sclerosis. The "Expanded Disability Status Scale (EDSS) by phone" was developed to be a patient-reported telephone-based alternative for the assessment of EDSS functional system scores when a physical examination is not possible. The scale has been validated in multiple languages; however, its reliability has not been assessed in Brazilian Portuguese., Methods: After cross-cultural translation and adaptation, 57 people with MS with a recent in-person visit (±6 months) were invited to answer the EDSS by phone scale on two occasions, 15 days apart. The agreement between scales (in-person and telephone-based) and between telephone-based assessments was evaluated using intraclass correlation coefficients (ICC) for absolute agreement and weighted Kappa coefficients., Results: An excellent reliability was obtained for the agreement between the in-person and telephone assessments (ICC: 0.95, 95 %CI 0.92-0.97, Kappa: 0.83, 95 %CI 0.78-0.89) and between telephone-based assessments (ICC: 0.99, 95 %CI 0.98-0.99, Kappa: 0.93, 95 %CI 0.88-0.97). After stratification by disability level, the agreement between scales was less pronounced for subjects with an EDSS ≤ 4.0., Conclusion: this study offers evidence that supports the validity of the EDSS by phone questionnaire translated into Brazilian Portuguese, particularly for patients with higher EDSS scores., Competing Interests: Declaration of Competing Interest The authors declare that there is no potential conflict of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2023. Published by Elsevier B.V.)

Precision medicine has revolutionized the field of neuroimmunology, with innovative approaches that characterize diseases based on their biology, deeper understanding of the factors leading to heterogeneity within the same disease, development of targeted therapies, and strategies to tailor therapies to each patient. This review explores the impact of precision medicine on various neuroimmunological conditions, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), optic neuritis, autoimmune encephalitis, and immune-mediated neuropathies. We discuss advances in disease subtyping, recognition of novel entities, promising biomarkers, and the development of more selective monoclonal antibodies and cutting-edge synthetic cell-based immunotherapies in neuroimmunological disorders. In addition, we analyze the challenges related to affordability and equity in the implementation of these emerging technologies, especially in situations with limited resources., Competing Interests: There is no conflict of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)

Introduction: Hemorrhagic shock is the main cause of death in the prehospital environment, which highlights the need to standardize measures aiming at bleeding control and volume replacement in this environment. In Brazil, the first prehospital packed red blood cell transfusion service started in September 2020, in Bragança Paulista, state of São Paulo., Objectives: Describe the trends and characteristics of patients who received prehospital transfusions prior to hospital treatment during the first year of operation., Methods: A retrospective data review was made of all patients who received transfusions from the mobile intensive care unit in Bragança Paulista over one year., Results: In this period, 19 patients were transfused. Since activation, the average response time was 20 min. The mean shock indexes before and after blood transfusion were 2.16 and 1.1, respectively. During the course of the 1st year of prehospital transfusions, no blood was wasted and there were no adverse effects., Conclusion: Introduction of the prehospital packed red blood cell transfusion service was successful, with significant improvement in hemodynamic parameters., Competing Interests: Conflicts of interest The author declares no conflicts of interest., (Copyright © 2023. Published by Elsevier España, S.L.U.)

Background: People with multiple sclerosis (PwMS) show an increased risk of sexual dysfunction (SD), both in women and men., Objective: The aim of the present study was to apply the Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19) and evaluate our results by comparing them with those in in the literature, as well as to assess the ease of applying the scale and the engagement of the patients in discussing the topic of sexuality., Methods: We developed and applied a web-based Google form questionnaire that the respondents completed online, which included the MSISQ-19, for the assessment of sexual function. Baseline characteristics were reported as proportions and mean ± standard deviation (SD) or median ± interquartile range (IQR) as appropriate according to data distribution. Categorical variables were stratified by sex and compared with chi-squared tests. Statistical analyses were performed using STATA v. 16 (StataCorp., College Station, TX, USA)., Results: Of the 621 respondents, 541 were included in the analysis. Among the patients with MS, a total of 347 (64.14%) exhibited SD. When stratified by gender, the frequencies of SD were not significantly different., Conclusion: There is a high incidence of sexual dysfunction among PwMS and we need to identify the reasons for this and implement strategies to treat and counsel our patients. The MSISQ-19 can be used to help clinicians to assess sexual functioning in a quick and easy way and give patients the possibility to address this topic and receive appropriate help and support., Competing Interests: The authors have no conflict of interest to declare., (Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)

Many non-invasive prenatal testing (NIPT) platforms screen for sex chromosome aneuploidy (SCA) and SCA analysis is generally included in Australia where NIPT is available as a self-funded test. Little is known about the experience of receiving an NIPT result indicating an increased chance of SCA. This study aimed to explore the experiences of people who received this result and their perspectives on the information, care, and support they received from healthcare practitioners (HCPs). Semi-structured interviews were conducted with people who received an NIPT result indicating an increased chance of SCA and continued their pregnancy. Most participants only had contact with a genetic counselor after receiving their result. Transcribed data were analyzed using rigorous thematic analysis to identify important patterns and themes. Participants (18 women, 2 male partners) described embarking on NIPT, primarily based on advice from their HCP and without much consideration. Consequently, participants expressed feeling unprepared for the unanticipated complexity of their NIPT result and were faced with making a time-sensitive decision about a condition they had not previously considered. While more pre-test information was desired, timely access to genetic counseling post-test assisted with adjustment to the result. These findings suggest that routinization of NIPT may be compromising informed decision-making, resulting in unpreparedness for an increased chance result. Given the increasing uptake and expanding scope of NIPT, resources should be dedicated to educating HCPs offering NIPT and ensuring timely access to genetic counseling post-result. With appropriate funding, genetics services may be able to play a central role in offering information and support to both people who undertake NIPT and their HCPs ordering the testing. Implementing a publicly funded screening program in Australia could assist with standardizing prenatal screening care pathways and consequently better access to appropriate resources., (© 2022 National Society of Genetic Counselors.)

Purpose: Neuropathological studies have demonstrated distinct profiles of microglia activation and myelin injury among different multiple sclerosis (MS) phenotypes and disability stages. PET imaging using specific tracers may uncover the in vivo molecular pathology and broaden the understanding of the disease heterogeneity., Methods: We used the 18-kDa translocator protein (TSPO) tracer (R)-[ 11 C]PK11195 and [ 11 C]PIB PET images acquired in a hybrid PET/MR 3 T system to characterize, respectively, the profile of innate immune cells and myelin content in 47 patients with MS compared to 18 healthy controls (HC). For the volume of interest (VOI)-based analysis of the dynamic data, (R)-[ 11 C]PK11195 distribution volume (V T ) was determined for each subject using a metabolite-corrected arterial plasma input function while [ 11 C]PIB distribution volume ratio (DVR) was estimated using a reference region extracted by a supervised clustering algorithm. A voxel-based analysis was also performed using Statistical Parametric Mapping. Functional disability was evaluated by the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Symbol Digit Modality Test (SDMT)., Results: In the VOI-based analysis, [ 11 C]PIB DVR differed between patients and HC in the corpus callosum (P = 0.019) while no differences in (R)-[ 11 C]PK11195 V T were observed in patients relative to HC. Furthermore, no correlations or associations were observed between both tracers within the VOI analyzed. In the voxel-based analysis, high (R)-[ 11 C]PK11195 uptake was observed diffusively in the white matter (WM) when comparing the progressive phenotype and HC, and lower [ 11 C]PIB uptake was observed in certain WM regions when comparing the relapsing-remitting phenotype and HC. None of the tracers were able to differentiate phenotypes at voxel or VOI level in our cohort. Linear regression models adjusted for age, sex, and phenotype demonstrated that higher EDSS was associated with an increased (R)-[ 11 C]PK11195 V T and lower [ 11 C]PIB DVR in corpus callosum (P = 0.001; P = 0.023), caudate (P = 0.015; P = 0.008), and total T 2 lesion (P = 0.007; P = 0.012), while better cognitive scores in SDMT were associated with higher [ 11 C]PIB DVR in the corpus callosum (P = 0.001), and lower (R)-[ 11 C]PK11195 V T (P = 0.013)., Conclusions: Widespread innate immune cells profile and marked loss of myelin in T 2 lesions and regions close to the ventricles may occur independently and are associated with disability, in both WM and GM structures., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are the most common autoimmune diseases of the central nervous system (CNS). They present chronic relapsing courses that demand treatment with disease-modifying drugs (DMDs) to prevent inflammatory activity. Disease-modifying drugs lead to immunomodulation or immunosuppression through diverse mechanisms (e.g., shifting lymphocyte and cytokine profile, suppressing specific lymphocyte subpopulations). Thus, patients are more prone to infectious complications and associated worsening of disease., Objective: To present feasible strategies for mitigating the infection risk of MS and NMOSD treated patients., Methods: Targeted literature review concerning the management of infection risk with an emphasis on vaccination, therapy-specific measures, and particularities of the Brazilian endemic infectious diseases' scenario., Conclusion: We propose a vaccination schedule, infectious screening routine, and prophylactic measures based on the current scientific evidence. Awareness of emergent tropical diseases is necessary due to evidence of demyelinating events and possible parainfectious cases of MS and NMOSD., Competing Interests: Samira Luisa Pereira Apóstolos, Maria Fernanda Mendes, and Dagoberto Callegaro have participated in lectures and developed written educational materials for Biogen, Roche, Merck, and Novartis., (Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Underreporting of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is a global problem and might hamper Coronavirus Disease (COVID-19) epidemiological control. Taking this into consideration, we estimated possible SARS-CoV-2 infection underreporting in Brazil among patients with severe acute respiratory syndrome (SARS). An ecological study using a descriptive analysis of the SARS report was carried out based on data supplied by the Influenza Epidemiological Surveillance Information (SIVEP)-Flu (in Brazilian Portuguese, Sistema de Vigilância Epidemiológica da Gripe) in the period between January 2015 and March 2021. The number of SARS cases and related deaths after infection by SARS-CoV-2 or Influenzae was described. The estimation of underreporting was evaluated considering the relative increase in the number of cases with undefined etiological agent comparing 2020 to 2015−2019; and descriptive analysis was carried out including data from January−March/2021. In our data, SARS-CoV-2 infection and the presence of SARS with undefined etiological agent were associated with the higher number of cases and deaths from SARS in 2020/2021. SARS upsurge was six times over that expected in 2020, according to SARS seasonality in previous years (2015−2019). The lowest possible underdiagnosis rate was observed in the age group < 2 y.o. and individuals over 30 y.o., with ~50%; while in the age groups 10−19 and 20−29 y.o., the rates were 200−250% and 100%, respectively. For the remaining age groups (2−5 and 5−9 y.o.) underreporting was over 550%, except for female individuals in the age group 2−5 y.o., in which a ~500% rate was found. Our study described that the SARS-CoV-2 infection underreporting rate in Brazil in SARS patients is alarming and presents different indices, mainly associated with the patients’ age groups. Our results, mainly the underreporting index according to sex and age, should be evaluated with caution.

Introduction: The COVID-19 pandemic has affected several neglected populations such as the Indigenous peoples, which have suffered a high impact from the pandemic., Objectives: To analyze the impact on the health and disease process according to the COVID-19 evolution in the Brazilian Indigenous population., Methods: Data was collected from press releases by the Health Ministry and a descriptive analysis of the numbers of Indigenous individuals infected with the SARS-CoV-2 in Brazil was carried out., Results: In February 2021, there were 41,855 confirmed cases of Indigenous individuals infected by the SARS-CoV-2, including 4,387 active cases, 36,809 recovered cases, and 549 deaths. The Brazilian Indigenous population is distributed in over 300 ethnic groups and, due to the high number of deaths by the COVID-19, many of these groups are endangered. The elderly are the most affected age group, and they play a fundamental role among the Indigenous population for transmitting their customs mainly orally. Indigenous populations do not have proper access to transport to specialized health centers, since many areas are inaccessible and other cases require air or river transportation, which many times results in late assistance. When managing the COVID-19, it is important to emphasize the need for social isolation to prevent the virus from spreading among the Indigenous groups, mainly due to their contact with other ethnic groups represented by missionaries, hunters, and wood explorers, among others., Conclusion: The adoption of practices that can reduce the virus transmission among the Indigenous population and provide them with better access to treatment, mainly for the elderly, must be prioritized in Brazil., (© 2021. W. Montague Cobb-NMA Health Institute.)

Identification of the novel HLA-DQB1*05:240 allele that differs from HLA-DQB1*05:01:09 at three positions in exon 2., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Objectives: People with multiple sclerosis (MS) are a vulnerable group for severe coronavirus disease 2019 (COVID-19), particularly those taking immunosuppressive disease-modifying therapies (DMTs). We examined the characteristics of COVID-19 severity in an international sample of people with MS., Methods: Data from 12 data sources in 28 countries were aggregated (sources could include patients from 1-12 countries). Demographic (age, sex), clinical (MS phenotype, disability), and DMT (untreated, alemtuzumab, cladribine, dimethyl fumarate, glatiramer acetate, interferon, natalizumab, ocrelizumab, rituximab, siponimod, other DMTs) covariates were queried, along with COVID-19 severity outcomes, hospitalization, intensive care unit (ICU) admission, need for artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression adjusted for age, sex, MS phenotype, and Expanded Disability Status Scale (EDSS) score., Results: Six hundred fifty-seven (28.1%) with suspected and 1,683 (61.9%) with confirmed COVID-19 were analyzed. Among suspected plus confirmed and confirmed-only COVID-19, 20.9% and 26.9% were hospitalized, 5.4% and 7.2% were admitted to ICU, 4.1% and 5.4% required artificial ventilation, and 3.2% and 3.9% died. Older age, progressive MS phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl fumarate, ocrelizumab and rituximab were associated with hospitalization (adjusted odds ratio [aOR] 1.56, 95% confidence interval [CI] 1.01-2.41; aOR 2.43, 95% CI 1.48-4.02) and ICU admission (aOR 2.30, 95% CI 0.98-5.39; aOR 3.93, 95% CI 1.56-9.89), although only rituximab was associated with higher risk of artificial ventilation (aOR 4.00, 95% CI 1.54-10.39). Compared to pooled other DMTs, ocrelizumab and rituximab were associated with hospitalization (aOR 1.75, 95% CI 1.29-2.38; aOR 2.76, 95% CI 1.87-4.07) and ICU admission (aOR 2.55, 95% CI 1.49-4.36; aOR 4.32, 95% CI 2.27-8.23), but only rituximab was associated with artificial ventilation (aOR 6.15, 95% CI 3.09-12.27). Compared to natalizumab, ocrelizumab and rituximab were associated with hospitalization (aOR 1.86, 95% CI 1.13-3.07; aOR 2.88, 95% CI 1.68-4.92) and ICU admission (aOR 2.13, 95% CI 0.85-5.35; aOR 3.23, 95% CI 1.17-8.91), but only rituximab was associated with ventilation (aOR 5.52, 95% CI 1.71-17.84). Associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death. Stratification by age, MS phenotype, and EDSS score found no indications that DMT associations with COVID-19 severity reflected differential DMT allocation by underlying COVID-19 severity., Discussion: Using the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab with increased risk of hospitalization, ICU admission, and need for artificial ventilation and of ocrelizumab with hospitalization and ICU admission. Despite the cross-sectional design of the study, the internal and external consistency of these results with prior studies suggests that rituximab/ocrelizumab use may be a risk factor for more severe COVID-19., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

The Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology (DCNI/ABN) and Brazilian Committee for Treatment and Research in Multiple Sclerosis and Neuroimmunological Diseases (BCTRIMS) provide recommendations in this document for vaccination of the population with demyelinating diseases of the central nervous system (CNS) against infections in general and against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19. We emphasize the seriousness of the current situation in view of the spread of COVID-19 in our country. Therefore, reference guides on vaccination for clinicians, patients, and public health authorities are particularly important to prevent some infectious diseases. The DCNI/ABN and BCTRIMS recommend that patients with CNS demyelinating diseases (e.g., MS and NMOSD) be continually monitored for updates to their vaccination schedule, especially at the beginning or before a change in treatment with a disease modifying drug (DMD). It is also important to note that vaccines are safe, and physicians should encourage their use in all patients. Clearly, special care should be taken when live attenuated viruses are involved. Finally, it is important for physicians to verify which DMD the patient is receiving and when the last dose was taken, as each drug may affect the induction of immune response differently.

There are 130 described species in the genus Mycodrosophila Oldenberg, 1914, distributed across all biogeographic regions. Most of these species show essential mycophagy. Currently, ten species are known from the Neotropical Region, nine of which are found in the Amazon, Atlantic Forest, Cerrado and Pampa biomes of Brazil. In this study, we describe the adult external morphology and structures of male and/or female terminalia for two new species from the Amazon Biome of Brazil. In addition, we propose a new species group, the Mycodrosophila neoprojectans group, encompassing the two new species described here, together with three previously described species from the Neotropics.

Background and Objectives: To describe the clinical features and disease outcomes of coronavirus disease 2019 (COVID-19) in patients with neuromyelitis optica spectrum disorder (NMOSD)., Methods: The Neuroimmunology Brazilian Study Group has set up the report of severe acute respiratory syndrome (SARS-CoV2) cases in patients with NMOSD (pwNMOSD) using a designed web-based case report form. All neuroimmunology outpatient centers and individual neurologists were invited to register their patients across the country. Data collected between March 19 and July 25, 2020, were uploaded at the REDONE.br platform. Inclusion criteria were as follows: (1) NMOSD diagnosis according to the 2015 International Panel Criteria and (2) confirmed SARS-CoV2 infection (reverse transcription-polymerase chain reaction or serology) or clinical suspicion of COVID-19, diagnosed according to Center for Disease Control / Council of State and Territorial Epidemiologists (CDC/CSTE) case definition. Demographic and NMOSD-related clinical data, comorbidities, disease-modifying therapy (DMT), COVID-19 clinical features, and severity were described., Results: Among the 2,061 pwNMOSD followed up by Brazilian neurologists involved on the registry of COVID-19 in pwNMOSD at the REDONE.br platform, 34 patients (29 women) aged 37 years (range 8-77), with disease onset at 31 years (range 4-69) and disease duration of 6 years (range 0.2-20.5), developed COVID-19 (18 confirmed and 16 probable cases). Most patients exhibited mild disease, being treated at home (77%); 4 patients required admission at intensive care units (severe cases); and 1 patient died. Five of 34 (15%) presented neurologic manifestations (relapse or pseudoexacerbation) during or after SARS-CoV2 infection., Discussion: Most NMOSD patients with COVID-19 presented mild disease forms. However, pwNMOSD had much higher odds of hospitalization and intensive care unit admission comparing with the general Brazilian population. The frequency of death was not clearly different. NMOSD disability, DMT type, and comorbidities were not associated with COVID-19 outcome. SARS-CoV2 infection was demonstrated as a risk factor for NMOSD relapses. Collaborative studies using shared NMOSD data are needed to suitably define factors related to COVID-19 severity and neurologic manifestations., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Recent changes to the diagnostic criteria for multiple sclerosis (MS) and new medications have had a major impact on the way in which specialists manage the disease., Objective: To investigate factors considered by Brazilian neurologists in managing MS, and to identify how these contribute to diagnosis and treatment., Methods: Potential participants were selected by a steering committee (MS experts who developed this survey). Only MS specialists were included in the study (neurologists who had completed a neuroimmunology fellowship or who were treating more than 30 MS patients). Links to the online questionnaire were distributed between March 2019 and January 2020. This questionnaire was composed of sections with hypothetical MS scenarios., Results: Neurologists from 13 Brazilian states responded to the survey (n = 94). In the clinically isolated syndrome (CIS) scenario, the respondents agreed to treat patients with a high risk of MS diagnosis, whereas in the radiologically isolated syndrome (RIS) half of the respondents opted not to treat, even among high-risk patients. In cases of low-activity relapsing-remitting MS (RRMS), the choice of treatment was distributed among interferon beta, glatiramer acetate and teriflunomide, which were changed to fingolimod and natalizumab, as RRMS severity increased. The topics in which disagreement was found included practices regarding use of disease-modifying therapy (DMT) for pregnant patients and the washout period required for some DMTs., Conclusions: This study enabled identification of areas of agreement and disagreement about MS treatment among Brazilian neurologists, which can be used to update future protocols and improve patient management.

Background: Basic steps in the management of patients with Multiple Sclerosis (MS), such as good patient understanding of the disease and active participation in its management are extremely important, as they directly influence treatment adherence and success. Therefore, this study aimed to evaluate the perception of MS patients and neurologists pertaining to the most common disease symptoms, disabilities that impact on quality of life, and patient concerns and difficulties during medical visits, as information that can be used to improve the doctor-patient relationship., Methods: A cross-sectional study involving two groups: the first composed of neurologists and the second of patients. Participants of the first group were selected by a Steering Committee (15 predetermined neurologists representing each region of Brazil and specialized in MS and neuroimmunological disorders, who also assumed the role of creating the survey and questionnaire). Participants of the second group were selected following dissemination of a questionnaire on the AME's social networks (Amigos Múltiplos pela Esclerose, a non-governmental organization to support patients with MS). Questions about sociodemographic data, disease impact on quality of life, symptoms perception, and concerns and issues regarding disease care were put to both groups., Results: A total of 317 patients and 182 neurologists answered the questionnaires. Significant divergences were found between the perceptions of patients and neurologists in relation to orientation and information given during medical appointments, and also regarding patient participation in treatment and therapy choice. Considering the topic assessing impact on quality of life, more than 70% of neurologists perceived that autonomy to work and travel, and future planning were aspects that most affected patient lives, however, almost 50% of patients reported that disease monitoring did not affect their life in any way. Analysis of data regarding MS symptoms revealed neurologists to consider physical symptoms, such as ambulation issues, imbalance, falls and urinary incontinence, to be those most interfering with patient quality of life, whereas patients considered non-physical symptoms, such as fatigue, pain, cognitive and memory problems to be more significant. Patients with primary progressive MS complained more about ambulation issues, imbalance and falls (p<0.05), when compared to patients with other disease phenotypes., Conclusion: Significant differences in disease perception were found in this study. While neurologists tended to overestimate the consequences and symptoms of the disease, for most patients, the disease impact on activities did not appear to be as significant, with more complaints regarding non-physical symptoms. Although neurologists described involving patients in treatment decisions and providing them with appropriate orientation during medical appointments, the opposite was reported by patients. These results may help to improve treatment adherence and disease outcomes by redefining the doctor-patient relationship., (Copyright © 2021. Published by Elsevier B.V.)

Identification of the novel HLA-B*15:554 allele that differs from HLA-B*15:01:01 at one position in exon 3., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Identification of the novel HLA-A*01:01:01:53 allele that differs from HLA-A*01:01:01:01 at four positions in intron 1., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Identification of the novel HLA-B*15:555 allele that differs from HLA-B*15:17:01 at one position in exon 2., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Identification of the novel HLA-C*07:93:02 allele that differs from HLA-C*07:93:01 at one position in exon 5., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Identification of the novel HLA-C*15:02:43 allele that differs from HLA-C*15:02:01 at one position in exon 4., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Identification of the novel HLA-B*42:02:02 allele that differs from HLA-B*42:02:01 at one position in exon 4., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The novel coronavirus disease 2019 (COVID-19) pandemic poses a potential threat to patients with autoimmune disorders, including multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Such patients are usually treated with immunomodulatory or immunosuppressive agents, which may tamper with the organism's normal response to infections. Currently, no consensus has been reached on how to manage MS and NMOSD patients during the pandemic., Objective: To discuss strategies to manage those patients., Methods: We focus on how to 1) reduce COVID-19 infection risk, such as social distancing, telemedicine, and wider interval between laboratory testing/imaging; 2) manage relapses, such as avoiding treatment of mild relapse and using oral steroids; 3) manage disease-modifying therapies, such as preference for drugs associated with lower infection risk (interferons, glatiramer, teriflunomide, and natalizumab) and extended-interval dosing of natalizumab, when safe; 4) individualize the chosen MS induction-therapy (anti-CD20 monoclonal antibodies, alemtuzumab, and cladribine); 5) manage NMOSD preventive therapies, including initial therapy selection and current treatment maintenance; 6) manage MS/NMOSD patients infected with COVID-19., Conclusions: In the future, real-world case series of MS/NMOSD patients infected with COVID-19 will help us define the best management strategies. For the time being, we rely on expert experience and guidance.

Identification of the novel HLA-A*02:839 allele that differs from HLA-A*02:01:01 in exon 4., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Identification of the novel HLA-A*03:351 allele that differs from HLA-A*03:01:01:01 in exon 1., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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.

Crotamine is a single-chain polypeptide with cell-penetrating properties, which is considered a promising molecule for clinical use. Nevertheless, its biosafety data are still scarce. Herein, we assessed the in vivo proinflammatory properties of crotamine, including its local effect and systemic serum parameters. Sixty male Wistar rats were intradermically injected with 200, 400 and 800 µg crotamine and analyzed after 1, 3 and 7 days. Local effect of crotamine was assessed by determination of MPO and NAG activities, NO levels and angiogenesis. Systemic inflammatory response was assessed by determination of IL-10, TNF-α, CRP, NO, TBARS and SH groups. Crotamine induced macrophages and neutrophils chemotaxis as evidenced by the upregulation of both NAG (0.5⁻0.6 OD/mg) and MPO (0.1⁻0.2 OD/mg) activities, on the first and third day of analysis, respectively. High levels of NO were observed for all concentrations and time-points. Moreover, 800 μg crotamine resulted in serum NO (64.7 μM) and local tissue NO (58.5 μM) levels higher or equivalent to those recorded for their respective histamine controls (55.7 μM and 59.0 μM). Crotamine also induced a significant angiogenic response compared to histamine. Systemically, crotamine induced a progressive increase in serum CRP levels up to the third day of analysis (22.4⁻45.8 mg/mL), which was significantly greater than control values. Crotamine (400 μg) also caused an increase in serum TNF-α, in the first day of analysis (1095.4 pg/mL), however a significant increase in IL-10 (122.2 pg/mL) was also recorded for the same time-point, suggesting the induction of an anti-inflammatory effect. Finally, crotamine changed the systemic redox state by inducing gradual increase in serum levels of TBARS (1.0⁻1.8 μM/mL) and decrease in SH levels (124.7⁻19.5 μM/mL) throughout the experimental period of analysis. In summary, rats intradermally injected with crotamine presented local and systemic acute inflammatory responses similarly to histamine, which limits crotamine therapeutic use on its original form.

Treatment options for multiple sclerosis (MS) have changed over the last few years, bringing about a new category of drugs with more efficient profiles. However, these drugs have come with a whole new profile of potential adverse events that neurologists have to learn well and quickly. One of the most feared complications of these MS treatments is progressive multifocal leukoencephalopathy caused by the reactivation of the John Cunningham virus (JCV)., Objective: To identify the serologic profile of JCV in patients with MS., Methods: Data on serum antibodies for JCV were obtained using the enzyme-linked immunosorbent assay provided by the STRATIFY-JCV program., Results: A total of 1,501 blood tests were obtained from 1,102 patients with MS. There were 633 patients (57.1%) who were positive for antibodies for JCV and 469 patients who were negative (42.9%). Twenty-three patients became positive after initially having negative JCV antibody status. The rate of seroconversion was 18.5% over 22 months., Conclusion: The JCV serologic profile and seroconversion in Brazilian patients were similar to those described in other countries.

The expanding therapeutic arsenal in multiple sclerosis (MS) has allowed for more effective and personalized treatment, but the choice and management of disease-modifying therapies (DMTs) is becoming increasingly complex. In this context, experts from the Brazilian Committee on Treatment and Research in Multiple Sclerosis and the Neuroimmunology Scientific Department of the Brazilian Academy of Neurology have convened to establish this Brazilian Consensus for the Treatment of MS, based on their understanding that neurologists should be able to prescribe MS DMTs according to what is better for each patient, based on up-to-date evidence and practice. We herein propose practical recommendations for the treatment of MS, with the main focus on the choice and management of DMTs, as well as present a review of the scientific rationale supporting therapeutic strategies in MS.

Background: Low-education attainment is associated with worse cognitive performance in multiple sclerosis (MS) patients, and possibly with a lower cognitive reserve and/or increased inflammatory activity. Cognitive reserve refers to the capability of a source of intellectual enrichment in attenuating a negative effect of a disease-related factor; while the inflammatory activity is often related to T2-lesion load (T2-LL) increase., Objective: To disentangle the effects of cognitive reserve and an increased T2-LL in MS-patients with low-education levels., Methods: The study included 136 MS patients and 65 healthy-controls, divided in low-education (12 years or less of school education without obtaining any technical superior degree) and high-education (more than 12 years of school education with technical or superior degree) groups. An extensive battery of neuropsychological tests was applied examining intelligence quotient and six cognitive domains. Test results were z-scored and subjects with z-scores ≤ -1.5 in two or more domains were considered cognitively impaired. To test the factors associated with worse cognitive performance, regression models were applied using average cognition as target; education level, Expanded Disability Status Scale (EDSS), T2-LL, disease duration, age of disease onset, age and gender as predictors. We also tested the correlation between T2-LL and cognition in the groups. To investigate the role of education level as a source of intellectual enrichment/cognitive reserve in different stages of MS, we sub-divided the MS patients in three groups according to the disease duration (less than 5 years, between 5 and 10 years and more than 10 years)., Results: Worse average cognition was associated with low-education level, higher T2-LL and male gender. A higher frequency of cognitively impaired patients was observed in MS patients with low-education level, in all stages of the disease. In patients with a disease duration shorter than five years, there was a lower correlation between worse average cognition and T2-LL in the high-education level group, compared to the patients with low-education level; in MS patients with longer disease duration, we observed a stronger correlation between lesion burden and cognitive impairment in both groups., Conclusion: Education attainment is a source of intellectual enrichment and can enhance the cognitive reserve in MS patients. The protective effect of a high-education level was stronger in patients with less than five years of disease, suggesting a stronger role of cognitive reserve in short-term disease. In long-term disease we observed a greater impact of increased inflammatory activity on cognition., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: For young people in families with Huntington's disease (HD) the challenge of having an affected family member (AFM) compounds challenges related to being at risk of HD themselves., Objective: This study aimed to quantitatively examine the experiences of young people in families with HD, adding to existing qualitative studies regarding teenagers and young adults in families with HD., Methods: The experiences of young people with living in a family with HD were captured by an online anonymous questionnaire, available worldwide through the Huntington's Disease Youth Organization. The questionnaire contained mostly forced choice questions., Results: Most participants (n = 84/101, 83.2%) provide assistance to an AFM and 46.4% (n = 39/84) wish they didn't have to look after their AFM. Many participants (n = 64/78, 82.1%) reported feeling anxious about being at risk; 64.9% (n = 50/77) agreed it is a barrier in their life. Over one third (n = 29/76, 38.2%) of participants disagreed that they have support in relation to being at risk, despite 85.5% (n = 65/76) agreeing it is important to have support and ongoing follow up., Conclusions: Young people in families with HD endure considerable emotional, social and practical burden secondary to having an AFM and being at risk themselves. Without increased support and services, the effects of being a young caregiver and living at risk are likely to have long term impacts on the well-being of these young people.