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Introduction: MOGAD encephalitis and ADEM share several clinical features with autoimmune encephalitis (AE) associated with antineuronal antibodies (ANeA); nonetheless, treatment and prognosis differ. Anti-MOG antibodies (abs) are not routinely tested in possible AE, and epidemiological studies on MOGAD encephalitis are scarce., Objectives: To determine the frequency of anti-MOG abs in the serum and CSF in a cohort of possible AE and to compare the clinical characteristics of MOGAD patients and those with seropositive AE., Methods: 481 patients with possible AE from the Brazilian Autoimmune Encephalitis Network underwent tissue-based assay and cell-based assay (CBA) for ANeA. Anti-MOG abs were assessed in serum and CSF with in-house CBA. Clinical and laboratory characteristics of MOGAD and seropositive AE patients were compared., Results: Of the 481 patients, 87 (18 %) had ANeA, and 17 (3.5 %) had anti-MOG abs. Three AE patients with anti-MOG abs and ANeA were excluded from further analysis. Anti-MOG abs were detected in 4 (1.2 %) of the 328 adults and 10 (6.5 %) of the 153 children. Of the 14 patients with MOGAD, nine had ADEM (mostly children), and five had encephalitis (including three adults). Only one patient with ADEM had anti-MOG abs exclusively in CSF. All patients with MOGAD encephalitis were seropositive for anti-MOG abs, and three had normal brain MRI. Patients with MOGAD had fewer behavioral changes (MOGAD 21 % x AE 96 %, p ≤ 0.0001) and movement disorders (MOGAD 42 % x AE 81 %, p = 0.0017) and more demyelinating symptoms, such as myelitis and optic neuritis (MOGAD 14 % x AE 0 %, p = 0.013)., Conclusion: Approximately 3.5 % of patients with possible AE harbor anti-MOG abs, and 0.9 % of the adults had MOGAD encephalitis. Anti-MOG abs were more frequent than other ANeAs regularly tested in AE. We provide evidence that MOGAD is a differential diagnosis in possible AE, even in adult patients with normal brain MRI, and that serum anti-MOG should be considered as an add-on diagnostic tool in AE among adults and pediatric patients., Competing Interests: Declaration of competing interest RH reports the speaker's honoraria from UCB; AD and LECA were employed by Fleury Group; LAD received a grant from Laboratory Fleury without personal compensation; the remaining authors declare no conflict of interest. The research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Aim: This study aims to explore the perceptions of feedback among undergraduate students and faculty members at a Brazilian private nursing school., Background: Feedback plays a crucial role in the socioemotional development of learners, with its interpretation varying across different sociocultural contexts. Student evaluations frequently express dissatisfaction regarding both the quality and quantity of feedback received. Conversely, delivering feedback poses a challenge for faculty, requiring the establishment of an empathetic connection that fosters trust and credibility. Brazil, being a developing country characterized by social disparities and economic challenges, presents a unique backdrop for examining feedback dynamics., Design: Qualitative research, employing Inductive Content Analysis, was used to understand feedback perceptions in Brazilian nursing education. Symbolic interactionism was adopted as methodological framework and guided data interpretation., Methods: We carried out five virtual focus groups composed of a group of teachers (n=5) and four of students (n=34). Semi-structured interviews guided data collection. The recorded sessions were subsequently analyzed to identify key themes and codes. Symbolic interactionism was employed as a framework to derive meaning from qualitative data., Results: Content analysis generated two categories that reveal the perception of teachers and students in the feedback process. The first, called "Feedback in Education: Sociocultural Influences for Students and Teachers", expresses the beliefs and interpretations of students and teachers within the shared feedback environment. The second called "Challenging resonance, transformative construction: Navigating the dualities of feedback for teachers and students", which elucidated how relational dynamics shape behaviors and attitudes, promoting the development of social skills and learning. Faculty's previous feedback experiences significantly influence their self-perception and behavior with students. As a result of the resonance of these past interactions, we recognize that the teaching self also plays a crucial role in the quality and perception of feedback. Furthermore, students construct social reality with similar beliefs and values, they believe in the learning potential generated by feedback. Our findings also corroborate that perceptions of feedback are deeply influenced by the sociocultural context and the narratives corroborate previous findings indicating that, in Brazil, honest feedback can be implicitly perceived as criticism rather than an opportunity for growth., Conclusions: Faculty members often draw on their past experiences when providing feedback, highlighting the adaptive nature of feedback interactions. Additionally, the feedback process is consistently influenced by the commitment to maintaining positive relationships with students. Students recognize the constructive dimension of feedback as a valuable tool for learning and personal growth., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A 30-year-old woman had 5 days of visual hallucinations, nystagmus, memory impairment and mutism. On examination, she was disorientated with reduced attention span, gaze-evoked nystagmus, paratonia and abnormal frontal reflexes. Cerebrospinal fluid (CSF) showed 80 cells, protein 0.41 g/L and glucose 3.2 mmol/L (plasma glucose 5.0 mmol/L). MR scan of the brain showed involvement of limbic and extra-limbic regions and brainstem. Commercial cell-based assays were negative, but tissue-based assays showed neuropil staining, and cell-based assays for anti-metabotropic glutamate receptor 5 (mGluR5) antibodies were positive in serum and CSF. Six months later, she was diagnosed with Hodgkin's lymphoma. This case emphasises the broader clinical spectrum of anti-mGluR5 encephalitis, challenging its initial characterisation as Ophelia syndrome. It underscores the significance of interpreting commercial cell-based assays and advocates for tissue-based assay testing followed by cell-based assay testing in serum and CSF for diagnosing rare autoimmune encephalitis., Competing Interests: Competing interests: RH reports speaker’s honoraria from Novartis and Biogen. LAD reports receiving funding from Fleury Laboratory for the BrAIN (Braziian Autoimmune Encephalitis Network) Project and BrAIN Registry (Brazilian National Registry on Autoimmune Encephalitis). The other authors report no disclosures relevant to the manuscript., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background:  Autoimmune encephalitis (AIE) is a group of inflammatory diseases characterized by the presence of antibodies against neuronal and glial antigens, leading to subacute psychiatric symptoms, memory complaints, and movement disorders. The patients are predominantly young, and delays in treatment are associated with worse prognosis., Objective:  With the support of the Brazilian Academy of Neurology (Academia Brasileira de Neurologia, ABN) and the Brazilian Society of Child Neurology (Sociedade Brasileira de Neurologia Infantil, SBNI), a consensus on the diagnosis and treatment of AIE in Brazil was developed using the Delphi method., Methods:  A total of 25 panelists, including adult and child neurologists, participated in the study., Results:  The panelists agreed that patients fulfilling criteria for possible AIE should be screened for antineuronal antibodies in the serum and cerebrospinal fluid (CSF) using the tissue-based assay (TBA) and cell-based assay (CBA) techniques. Children should also be screened for anti-myelin oligodendrocyte glucoprotein antibodies (anti-MOG). Treatment should be started within the first 4 weeks of symptoms. The first-line option is methylprednisolone plus intravenous immunoglobulin (IVIG) or plasmapheresis, the second-line includes rituximab and/or cyclophosphamide, while third-line treatment options are bortezomib and tocilizumab. Most seizures in AIE are symptomatic, and antiseizure medications may be weaned after the acute stage. In anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, the panelists have agreed that oral immunosuppressant agents should not be used. Patients should be evaluated at the acute and postacute stages using functional and cognitive scales, such as the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Modified Rankin Scale (mRS), and the Clinical Assessment Scale in Autoimmune Encephalitis (CASE)., Conclusion:  The present study provides tangible evidence for the effective management of AIE patients within the Brazilian healthcare system., Competing Interests: LAD reports that she has received a grant for the Brazilian Autoimmune Encephalitis Network (Rede Brasileira de Encefalites Autoimunes), from Laboratório Fleury., (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/).)

Vaccinia-related kinase 1 (VRK1) and the δ and ε isoforms of casein kinase 1 (CK1) are linked to various disease-relevant pathways. However, the lack of tool compounds for these kinases has significantly hampered our understanding of their cellular functions and therapeutic potential. Here, we describe the structure-based development of potent inhibitors of VRK1, a kinase highly expressed in various tumor types and crucial for cell proliferation and genome integrity. Kinome-wide profiling revealed that our compounds also inhibit CK1δ and CK1ε. We demonstrate that dihydropteridinones 35 and 36 mimic the cellular outcomes of VRK1 depletion. Complementary studies with existing CK1δ and CK1ε inhibitors suggest that these kinases may play overlapping roles in cell proliferation and genome instability. Together, our findings highlight the potential of VRK1 inhibition in treating p53-deficient tumors and possibly enhancing the efficacy of existing cancer therapies that target DNA stability or cell division.

Background: Anti-IgLON5 disease is a rare chronic autoimmune disorder characterized by IgLON5 autoantibodies predominantly of the IgG4 subclass. Distinct pathogenic effects were described for anti-IgLON5 IgG1 and IgG4, however, with uncertain clinical relevance., Methods: IgLON5-specific IgG1-4 levels were measured in 46 sera and 20 cerebrospinal fluid (CSF) samples from 13 HLA-subtyped anti-IgLON5 disease patients (six females, seven males) using flow cytometry. Intervals between two consecutive serum or CSF samplings (31 and 10 intervals, respectively) were categorized with regard to the immunomodulatory treatment active at the end of the interval, changes of anti-IgLON5 IgG1 and IgG4 levels, and disease severity. Intrathecal anti-IgLON5 IgG4 synthesis (IS) was assessed using a quantitative method., Results: The median age at onset was 66 years (range: 54-75), disease duration 10 years (range: 15-156 months), and follow-up 25 months (range: 0-83). IgLON5-specific IgG4 predominance was observed in 38 of 46 (83%) serum and 11 of 20 (55%) CSF samples. Anti-IgLON5 IgG4 levels prior clinical improvement in CSF but not serum were significantly lower than in those prior stable/progressive disease. Compared to IgLON5 IgG4 levels in serum, CSF levels in HLA-DRB1*10:01 carriers were significantly higher than in non-carriers. Indeed, IgLON5-specific IgG4 IS was demonstrated not only in four of five HLA-DRB1*10:01 carriers but also in one non-carrier. Immunotherapy was associated with decreased anti-IgGLON5 IgG serum levels. In CSF, lower anti-IgLON5 IgG was associated with immunosuppressive treatments used in combination, that is, corticosteroids and/or azathioprine plus intravenous immunoglobulins or rituximab., Conclusion: Our findings might indicate that CSF IgLON5-specific IgG4 is frequently produced intrathecally, especially in HLA-DRB1*10:01 carriers. Intrathecally produced IgG4 may be clinically relevant. While many immunotherapies reduce serum IgLON5 IgG levels, more intense immunotherapies induce clinical improvement and may be able to target intrathecally produced anti-IgLON5 IgG. Further studies need to confirm whether anti-IgLON5 IgG4 IS is a suitable prognostic and predictive biomarker in anti-IgLON5 disease., Competing Interests: TS-H reports travel grants and speaker honoraria from Roche. MBr has received honoraria for speaking from Sanofi. No conflict of interest with respect to the present study. AH reports speaker honoraria for UCB, Bioprojet, Servier, Medice, Jazz Pharmaceuticals BH reports speaker honoraria Jazz and Abbvie and advisor feed from Lundbeck. MS reports personal fees and grants from Merck Healthcare Deutschland and Bayer Vital GmbH and grant support from the University of Greifswald Gerhard-Domagk fellowship. HT reports speaker honoraria from Jansen, UCB and Zambon. TB has participated in meetings sponsored by and received honoraria lectures, advisory boards, consultations from pharmaceutical companies marketing treatments for MS: Allergan, Biogen, Biologix, Bionorica, BMS/Celgene, Eisei, Janssen-Cilag, MedDay, Merck, Novartis, Roche, Sandoz, Sanofi-Genzyme, Teva, UCB. His institution has received financial support in the past 12 months by unrestricted research grants Bayer, Biogen, BMS/Celgene, Merck, Novartis, Roche, Sanofi-Genzyme, Teva and for participation in clinical trials in multiple sclerosis sponsored by Alexion, Bayer, Biogen, BMS/Celgene, Merck, Novartis, Roche, Sanofi-Aventis, Teva. JL reports travel honoraria and speakers fees from the Cure Huntington’s Disease Initiative CHDI, the Movement Disorders Society as the German Society for Cerebrospinal Fluid Diagnostic and Clinical Neurochemistry DGLN. His institution received financial compensation for clinical trials with JL as principal investigator from CHDI. He is member of the executive board of the DGLN. He received research funding from the German Federal Ministry of Education and Research BMBF. RH reports speaker honoraria from UCB and Biogen. The Medical University of Vienna Austria; employer of RH receives payment for antibody assays and for antibody validation experiments organized by Euroimmun Lübeck, Germany. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Koneczny, Macher, Hutterer, Seifert-Held, Berger-Sieczkowski, Blaabjerg, Breu, Dreyhaupt, Dutra, Erdler, Fae, Fischer, Frommlet, Heidbreder, Högl, Klose, Klotz, Liendl, Nissen, Rahimi, Reinecke, Ricken, Stefani, Süße, Teive, Weis, Berger, Sabater, Gaig, Lewerenz and Höftberger.)

Objective: Transcranial Doppler (TCD) and brain MRI may be useful in evaluating patients with APS, helping to stratify the risk of cerebrovascular ischaemic events in this population. This study aimed to assess the frequency of brain MRI abnormalities in patients with primary antiphospholipid syndrome, secondary antiphospholipid syndrome and SLE and correlate to TCD findings., Methods: The study, conducted over four years at two autoimmune disease referral centres, included 22 primary antiphospholipid syndrome patients, 24 secondary antiphospholipid syndrome patients, 27 SLE patients without APS and 21 healthy controls. All participants underwent TCD to assess cerebral haemodynamics, detect microembolic signals and evaluate right-to-left shunts, followed by brain MRI and magnetic resonance angiography. MRI scans were reviewed for acute microembolism, localized cortical infarctions, border infarctions, lacunar infarctions, ischaemic lesions, white matter hyperintensity, micro and macro haemorrhages and arterial stenosis ≥50% of the cervical carotid artery, by two neuroradiologists blinded to the clinical data., Results: Brain MRI findings were similar between the groups, except for lacunar infarction, more frequent in patients with secondary antiphospholipid syndrome ( P  = 0.022). Patients with intracranial stenosis detected by TCD had a higher frequency of territorial infarction (40% vs 7.5%, P  = 0.02), lacunar (40% vs 11.3%, P  = 0.075) and border zone infarcts (20% vs 1.9%, P  = 0.034)., Conclusions: Patients with intracranial stenosis presented a higher frequency of territorial, lacunar and border zone infarcts, suggesting that evaluating the intracranial vasculature should not be neglected in patients with APS and stroke., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Competing Interests: Dr. Dutra received a grant from Laboratório Fleury for the Brazilian Autoimmune Encephalitis Network and for the Brain Registry study (Brazilian Registry on Autoimmune Encephalitis).

Hydrocephalus is a neurological condition with altered cerebrospinal fluid flow (CSF). The treatment is surgical and the most commonly used procedure is ventricle-peritoneal shunt. However, not all patients can undergo immediate surgery or achieve complete lesion reversal. Neuroprotective measures are valuable in such cases. It was evaluated whether the use of celecoxib, a selective inhibitor of COX-2, associated or not with ventricular-subcutaneous derivation, could offer benefits to the brain structures affected by experimental hydrocephalus. Seven-day-old male Wistar Hannover rats induced by intracisternal injection of kaolin 15% were used, divided into five groups with ten animals each: intact control (C), untreated hydrocephalus (H), hydrocephalus treated with celecoxib 20 mg/kg intraperitoneal (HTC), hydrocephalus treated with shunt (HTS) and hydrocephalus treated with shunt and celecoxib 20 mg/kg intraperitoneal (HTCS). Celecoxib was administered for 21 consecutive days, starting the day after hydrocephalus induction and continuing until the end of the experimental period. The surgery was performed seven days after inducing hydrocephalus. Multiple assessment methods were used, such as behavioral tests (water maze and open field), histological analysis (hematoxylin and eosin), immunohistochemistry (caspase-3, COX-2, and GFAP), and ELISA analysis of GFAP. The results of the behavioral and memory tests indicated that celecoxib improves the neurobehavioral response. The improvement can be attributed to the reduced neuroinflammation (p < 0.05), and astrogliosis (p < 0.05) in different brain regions. In conclusion, the results suggest that celecoxib holds great potential as an adjuvant neuroprotective drug for the treatment of experimental hydrocephalus., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aim: To evaluate the quality of podcasts produced by lecturers as pre-class learning material; to verify lecturers' buy-in, after a specific workshop, regarding the practice of producing and using podcasts., Background: The teaching-learning process has undergone significant changes in recent years with the proposal of the flipped classroom strategy, which places the student at the center of the learning process and uses technology that requires adaptation of lecturers, both inside and outside the classroom. Pre-class learning material is one of the features of the flipped classroom model. It provides basic concepts for problem solving in small group discussion in classroom. Podcasts for this educational purpose are a recent technology and their innovative characteristics require deeper understanding in terms of their influence and usability., Design: Prospective, descriptive and quantitative study., Setting and Population: A workshop on the production of educational podcasts was offered to 23 lecturers on the Nursing course., Methods: Data were collected in the second semester of 2021 and the quality analysis was based on criteria available in the literature., Results: Eighteen professors (78 %) participated in the study and 46 podcasts were produced. Most professors being nurses (61 %), followed by biologists (28 %). Most have a doctorate degree (72 %). These podcasts were available for a mean of five days before the classes and their mean access rate by students was 58 %. There was no correlation between the access rate and the period of availability before the relative class. Most podcasts were informative (100 %) and monologues (98 %). The average duration was 6.2 min, which is within the ideal duration recommended in the literature. All of the podcasts included a description of the learning objectives at the beginning and most of them also included a closing message at the end., Conclusion: The nursing lecturers were able to produce their podcasts, which met quality criteria and reached the standards suggested by experts in the field., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To describe the personal protective equipment training strategies during the beginning of the pandemic and to investigate the association between training and COVID-19 infection among healthcare workers., Methods: This cross-sectional study conducted between March and May 2020 included 7,142 healthcare professionals who were eligible for both online and face-to-face simulation-based training on personal protective equipment use. Simulation training attendance was assessed by reviewing the attendance list, and the COVID-19 sick leave records recovered from the institutional RT-PCR database used to grant sick leave. The association between personal protective equipment training and COVID-19 was investigated using logistic regression, adjusted for sociodemographic and occupational characteristics., Results: The mean age was 36.9 years (± 8.3), and 72.6% of participants were female. A total of 5,502 (77.0%) professionals were trained: 3,012 (54.7%) through online training, 691 (12.6%) through face-to-face training, and 1,799 (32.7%) through both strategies. During the study period, 584 (8.2%) COVID-19 cases were diagnosed among these professionals. The number of positive RT-PCR tests was 180 (11.0%) for untrained professionals, 245 (8.1%) for those trained only online, 35 (5.1%) for those trained face-to-face, and 124 (6.9%) for those trained with both strategies (p<0.001). Participants who received face-to-face training had a 0.43 lower risk of contracting COVID-19., Conclusion: Personal protective equipment training decreased the odds of COVID-19 among healthcare professionals, with face-to-face simulation-based training being most effective.

Personalized medicine (PM) aims individualized approach to prevention, diagnosis, and treatment. Precision Medicine applies the paradigm of PM by defining groups of individuals with akin characteristics. Often the two terms have been used interchangeably. The quest for PM has been advancing for centuries as traditional nosology classification defines groups of clinical conditions with relatively similar prognoses and treatment options. However, any individual is characterized by a unique set of multiple characteristics and therefore the achievement of PM implies the determination of myriad demographic, epidemiological, clinical, laboratory, and imaging parameters. The accelerated identification of numerous biological variables associated with diverse health conditions contributes to the fulfillment of one of the pre-requisites for PM. The advent of multiplex analytical platforms contributes to the determination of thousands of biological parameters using minute amounts of serum or other biological matrixes. Finally, big data analysis and machine learning contribute to the processing and integration of the multiplexed data at the individual level, allowing for the personalized definition of susceptibility, diagnosis, prognosis, prevention, and treatment. Autoantibodies are traditional biomarkers for autoimmune diseases and can contribute to PM in many aspects, including identification of individuals at risk, early diagnosis, disease sub-phenotyping, definition of prognosis, and treatment, as well as monitoring disease activity. Herein we address how autoantibodies can promote PM in autoimmune diseases using the examples of systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis, Sjögren syndrome, systemic sclerosis, idiopathic inflammatory myopathies, autoimmune hepatitis, primary biliary cholangitis, and autoimmune neurologic diseases., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Peroxisome proliferator-activated receptors are promising therapeutic targets for metabolic diseases, including obesity, diabetes, and dyslipidemia. This study describes the design, synthesis and pharmacological evaluation of stilbene-based compounds as dual PPARα/γ partial agonists with potency in the nanomolar range. In vitro and in vivo assays revealed that the lead compound (E)-4-styrylphenoxy-propanamide (5b) removed 14 C-cholesterol from the foam cells through apolipoprotein A-I and High-Density Lipoprotein-2. In the high-fat diet-induced obesity mouse model, the oral administration of compound 5b increased HDL levels, paraoxonase-1 activity, and insulin sensitivity, and decreased glucose levels. Moreover, the adipogenesis pathway and triglyceride accumulation slightly changed in the adipocyte cells upon treatment with compound 5b, without affecting the body weight and adipose tissue in obese mice. Compound 5b did not affect the plasma levels of hepatic and renal injury biomarkers. Thus, stilbene-based compound 5b is a promising prototype for developing novel candidates to treat dyslipidemia and diabetes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: The association between brain-derived neurotrophic factor (BDNF) and neuropsychiatric systemic lupus erythematosus (NPSLE) is controversial in the literature. Cognitive dysfunction (CD) is a common, underdiagnosed NPSLE manifestation, but its pathophysiology is unknown. Thus, we investigate serum BDNF as a potential biomarker of CD in a cohort of SLE patients., Methods: We included 63 SLE patients, 48 NPSLE, and 57 age- and gender-matched controls (CON). All participants underwent neuropsychological assessment. Data on cardiovascular comorbidities, SLE disease activity index (SLEDAI), and Systemic Lupus International Collaborating Clinics damage index (SLICC-DI) were compiled. Multiple regression analyses evaluated predictors of serum BDNF levels., Results: Serum BDNF levels were lower in SLE and NPSLE patients than in CON (SLE 800.4 ± 502.7 vs. NPSLE 779.7 ± 426.3 vs. CON 1,345.5 ng/mL ± 438.4; p < 0.001). In addition, hypertension (B: - 192.5, SE: 84.3, 95% CI: - 359.7 to - 25.3, p = 0.024) and SLICC-DI score (B: - 75.9, SE: 27.2, 95% CI: - 129.8 to - 22, p = 0.006) were predictors of serum BDNF levels in SLE. There was no relation between BDNF levels and CD., Conclusion: BDNF levels are lower in SLE patients than CON and inversely associated with hypertension and SLICC-DI scores. No association between BDNF levels and CD or NPSLE was observed in this cohort. These findings indicate that BDNF may be associated with overall burden in SLE rather than specific manifestations such as cognition impairment. Key Points • BDNF is associated with an overall burden in SLE rather than specific manifestations such as cognition dysfunction. • BDNF levels are reduced in patients with SLE, and higher SLICC-DI scores and hypertension are independent predictors of lower serum BDNF levels. • The cognitive dysfunction rate is elevated (46%) among Brazilian SLE patients., (© 2021. International League of Associations for Rheumatology (ILAR).)

Background: IgG4 is associated with two emerging groups of rare diseases: 1) IgG4 autoimmune diseases (IgG4-AID) and 2) IgG4-related diseases (IgG4-RLD). Anti-neuronal IgG4-AID include MuSK myasthenia gravis, LGI1- and Caspr2-encephalitis and autoimmune nodo-/paranodopathies (CNTN1/Caspr1 or NF155 antibodies). IgG4-RLD is a multiorgan disease hallmarked by tissue-destructive fibrotic lesions with lymphocyte and IgG4 plasma cell infiltrates and increased serum IgG4 concentrations. It is unclear whether IgG4-AID and IgG4-RLD share relevant clinical and immunopathological features., Methods: We collected and analyzed clinical, serological, and histopathological data in 50 patients with anti-neuronal IgG4-AID and 19 patients with IgG4-RLD., Results: A significantly higher proportion of IgG4-RLD patients had serum IgG4 elevation when compared to IgG4-AID patients (52.63% vs. 16%, p = .004). Moreover, those IgG4-AID patients with elevated IgG4 did not meet the diagnostic criteria of IgG4-RLD, and their autoantibody titers did not correlate with their serum IgG4 concentrations. In addition, patients with IgG4-RLD were negative for anti-neuronal/neuromuscular autoantibodies and among these patients, men showed a significantly higher propensity for IgG4 elevation, when compared to women ( p = .005). Last, a kidney biopsy from a patient with autoimmune paranodopathy due to CNTN1/Caspr1-complex IgG4 autoantibodies and concomitant nephrotic syndrome did not show fibrosis or IgG4 + plasma cells, which are diagnostic hallmarks of IgG4-RLD., Conclusion: Our observations suggest that anti-neuronal IgG4-AID and IgG4-RLD are most likely distinct disease entities., Competing Interests: LD received a grant from Fleury Laboratory for the Brazilian Autoimmune Encephalitis Project without personal compensation. CL served as a consultant for Roche. K-NP received a travel grant from Merck. RH reports speakers’ honoraria from Novartis and Biogen. The Medical University of Vienna (Austria; employer of Dr. Höftberger) receives payment for antibody assays and for antibody validation experiments organized by Euroimmun (Lübeck, Germany). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Endmayr, Tunc, Ergin, De Rosa, Weng, Wagner, Yu, Fichtenbaum, Perkmann, Haslacher, Kozakowski, Schwaiger, Ricken, Hametner, Klotz, Dutra, Lechner, de Simoni, Poppert, Müller, Pirker, Pirker, Angelovski, Valach, Maestri, Guida, Ricciardi, Frommlet, Sieghart, Pinter, Kircher, Artacker, Höftberger and Koneczny.)

Cyclooxygenase (COX) and lipoxygenase (LOX) are key targets for the development of new anti-inflammatory agents. LOX, which is involved in the biosynthesis of mediators in inflammation and allergic reactions, was selected for a biochemical screening campaign to identify LOX inhibitors by employing the main natural product library of Brazilian biodiversity. Two prenyl chalcones were identified as potent inhibitors of LOX-1 in the screening. The most active compound, ( E )-2- O -farnesyl chalcone, decreased the rate of oxygen consumption to an extent similar to that of the positive control, nordihydroguaiaretic acid. Additionally, studies on the mechanism of the action indicated that ( E )-2- O -farnesyl chalcone is a competitive LOX-1 inhibitor. Molecular modeling studies indicated the importance of the prenyl moieties for the binding of the inhibitors to the LOX binding site, which is related to their pharmacological properties.

Objective: To clinically characterize patients with anti-metabotropic glutamate receptor (mGluR) 1 encephalitis, to identify prognostic factors, and to study the immunoglobulin G (IgG) subclasses and effects of antibodies on neuronal mGluR1 clusters., Methods: Clinical information on new and previously reported patients was reviewed. Antibodies to mGluR1 and IgG subclasses were determined with brain immunohistochemistry and cell-based assays, and their effects on mGluR1 clusters were studied on rat hippocampal neurons., Results: Eleven new patients were identified (10 adults, 1 child);4 were female. In these and 19 previously reported cases (n = 30, median age 55 years), the main clinical manifestation was a subacute cerebellar syndrome that in 25 (86%) patients was associated with behavioral/cognitive changes or other neurologic symptoms. A tumor was found in 3 of 26 (11%). Brain MRI was abnormal in 7 of 19 (37%) at onset and showed cerebellar atrophy in 10 of 12 (83%) at follow-up. Twenty-five of 30 (83%) patients received immunotherapy. Follow-up was available for 25: 13 (52%) had clinical stabilization; 10 (40%) showed significant improvement; and 2 died. At the peak of the disease, patients with bad outcome at 2 years (modified Rankin Scale score > 2, n = 7) were more likely to have higher degree of initial disability, as reflected by a worse Scale for Assessment and Rating of Ataxia score, and more frequent need of assistance to walk. Antibodies to mGluR1 were mainly IgG1 and caused a significant decrease of mGluR1 clusters in cultured neurons., Conclusions: Anti-mGluR1 encephalitis manifests as a severe cerebellar syndrome, often resulting in long-term disability and cerebellar atrophy. The antibodies are pathogenic and cause significant decrease of mGluR1 clusters in cultured neurons., (© 2020 American Academy of Neurology.)

Aim: This study aimed to evaluate the activity of 2'-hydroxychalcone-loaded in nanoemulsion (NLS + 2'chalc), the cytotoxic effect and toxicity against Paracoccidioides brasiliensis and Paracoccidioides lutzii using a zebrafish model. Materials & methods: Preparation and physical-chemical characterization of nanoemulsion (NLS) and NLS + 2'chalc were performed. MIC and minimum fungicide concentration, cytotoxicity and toxicity were also evaluated in the Danio rerio model. Results: NLS + 2'chalc showed fungicidal activity against Paracoccidioides spp. without cytotoxicity in MRC5 and HepG2 lines. It also had high selectivity index values and no toxicity in the zebrafish model based on MIC values. Conclusion: NLS + 2'chalc is a potential new alternative treatment for paracoccidioidomycosis.

Vaccinia-related kinases 1 and 2 (VRK1 and VRK2) are human Ser/Thr protein kinases associated with increased cell division and neurological disorders. Nevertheless, the cellular functions of these proteins are not fully understood. Despite their therapeutic potential, there are no potent and specific inhibitors available for VRK1 or VRK2. We report here the discovery and elaboration of an aminopyridine scaffold as a basis for VRK1 and VRK2 inhibitors. The most potent compound for VRK1 ( 26 ) displayed an IC 50 value of 150 nM and was fairly selective in a panel of 48 human kinases (selectivity score S(50%) of 0.04). Differences in compound binding mode and substituent preferences between the two VRKs were identified by the structure-activity relationship combined with the crystallographic analysis of key compounds. We expect our results to serve as a starting point for the design of more specific and potent inhibitors against each of the two VRKs., Competing Interests: The authors declare the following competing financial interest(s): The authors F.H.S.G., H.A., A.M., C.R.W.G. are employed by Aché Laboratórios Farmacêuticos. All other authors declare no competing financial interest.

SYNE1 gene mutations were identified as a cause of late-onset pure cerebellar syndrome. Non-cerebellar symptoms, including cognitive impairment, were already described in this condition. The aim of this study was to perform a detailed cognitive and psychiatric description of patients with SYNE1 gene mutations. We performed neuropsychological and psychiatric evaluations of six patients with SYNE1 ataxia and compared their performance with 18 normal controls paired for age and education level. SYNE1 ataxia patients present cognitive dysfunction, characterized by impairment in attention and processing speed domains. Otherwise, the psychiatric assessment reported low levels of overall behavioral symptoms with only some minor anxiety-related complaints. Although this is a small sample of patients, these results suggest that SYNE1 ataxia patients may represent a model to investigate effects of cerebellar degeneration in higher hierarchical cognitive functions. For further studies, abstract thinking impairment in schizophrenia may be related to dysfunction in cerebellum pathways.

Introduction: Transcranial Doppler is a method that enables the assessment of different cerebral hemodynamic parameters. It also allows for the evaluation of the presence of right-to-left circulation shunts (RLS) and for the detection of microembolic signals (MESs), which might be associated with an increased risk of cerebrovascular events. For instance, the presence of MESs on transcranial Doppler in patients with systemic lupus erythematous (SLE) and antiphospholipid syndrome (APS) is associated with an increased risk of stroke. Therefore, transcranial Doppler could be a useful tool for stroke risk stratification in these patients., Objective: Our objective was to evaluate transcranial Doppler cerebral mean blood flow velocities as well as the presence of MESs and RLS in patients with antiphospholipid syndrome and SLE., Patients and Methods: Twenty-two patients with primary APS (PAPS), 24 patients with secondary APS (SAPS), 27 patients with SLE without APS and 21 healthy controls were evaluated. Clinical and epidemiological data were compiled from medical charts, and all subjects underwent transcranial Doppler examination with breath-holding index calculation. Both middle cerebral arteries were monitored for 60 min for the detection of MESs. RLS was investigated with agitated saline injected as a bolus., Results: There were no significant differences in mean blood flow velocities among the groups. MESs were more frequently found in patients with SLE when compared with controls and patients with APS (SLE: 17.4%, SAPS: 4.3%, PAPS: 0%, controls: 0%, p = 0.03). Anticoagulant therapy was more frequently used in the APS group (PAPS: 81.8%, SAPS: 75.2%, SLE: 1.7%, p < 0.001). Patients with APS had a higher frequency of RLS when compared with volunteers (63.6% versus 38.1%, p = 0.05). Breath-holding index values tended to be lower in patients with SAPS than in control subjects and patients with PAPS and SLE ( p = 0.06)., Conclusions: Patients with APS had a higher frequency of RLS than healthy controls. This finding alerts to the importance of cardiac investigation in patients with stroke and APS, because further therapies such as RLS occlusion might eventually add protection. The higher frequency of MES in patients with SLE could suggest an effect of anticoagulant therapy on MES prevention, more frequently used in patients with APS.

Cerebellar ataxia is a common finding in neurological practice and has a wide variety of causes, ranging from the chronic and slowly-progressive cerebellar degenerations to the acute cerebellar lesions due to infarction, edema and hemorrhage, configuring a true neurological emergency. Acute cerebellar ataxia is a syndrome that occurs in less than 72 hours, in previously healthy subjects. Acute ataxia usually results in hospitalization and extensive laboratory investigation. Clinicians are often faced with decisions on the extent and timing of the initial screening tests, particularly to detect treatable causes. The main group of diseases that may cause acute ataxias discussed in this article are: stroke, infectious, toxic, immune-mediated, paraneoplastic, vitamin deficiency, structural lesions and metabolic diseases. This review focuses on the etiologic and diagnostic considerations for acute ataxia.

Background: Postzygotic de novo mutations lead to the phenomenon of gene mosaicism. The 3 main types are called somatic, gonadal, and gonosomal mosaicism, which differ in terms of the body distribution of postzygotic mutations. Mosaicism has been reported occasionally in patients with primary immunodeficiency diseases (PIDs) since the early 1990s, but its real involvement has not been systematically addressed., Objective: We sought to investigate the incidence of gene mosaicism in patients with PIDs., Methods: The amplicon-based deep sequencing method was used in the 3 parts of the study that establish (1) the allele frequency of germline variants (n = 100), (2) the incidence of parental gonosomal mosaicism in families with PIDs with de novo mutations (n = 92), and (3) the incidence of mosaicism in families with PIDs with moderate-to-high suspicion of gene mosaicism (n = 36). Additional investigations evaluated body distribution of postzygotic mutations, their stability over time, and their characteristics., Results: The range of allele frequency (44.1% to 55.6%) was established for germline variants. Those with minor allele frequencies of less than 44.1% were assumed to be postzygotic. Mosaicism was detected in 30 (23.4%) of 128 families with PIDs, with a variable minor allele frequency (0.8% to 40.5%). Parental gonosomal mosaicism was detected in 6 (6.5%) of 92 families with de novo mutations, and a high incidence of mosaicism (63.9%) was detected among families with moderate-to-high suspicion of gene mosaicism. In most analyzed cases mosaicism was found to be both uniformly distributed and stable over time., Conclusion: This study represents the largest performed to date to investigate mosaicism in patients with PIDs, revealing that it affects approximately 25% of enrolled families. Our results might have serious consequences regarding treatment and genetic counseling and reinforce the use of next-generation sequencing-based methods in the routine analyses of PIDs., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Neurological involvement in antiphospholipid antibody syndrome (APS) is common, and its occurrence increases morbidity and mortality. Patients may present variable neurological involvement, such as cerebrovascular disease, cognitive dysfunction, headache, seizures, movement disorders, multiple sclerosis-like syndrome, transverse myelitis and ocular symptoms. Most neurological manifestations are associated with thrombosis of the microcirculation or of large vessels; nonetheless, there is compelling evidence suggesting that, in some cases, symptoms are secondary to an immune-mediated pathogenesis, with direct binding of aPL on neurons and glia. Herein we describe clinical characteristics and management of neurological APS manifestations.

Autoimmune encephalitis (AIE) is one of the most common causes of noninfectious encephalitis. It can be triggered by tumors, infections, or it may be cryptogenic. The neurological manifestations can be either acute or subacute and usually develop within six weeks. There are a variety of clinical manifestations including behavioral and psychiatric symptoms, autonomic disturbances, movement disorders, and seizures. We reviewed common forms of AIE and discuss their diagnostic approach and treatment.

N-oxide derivatives compounds such as furoxan and benzofuroxan are promising scaffolds for designing of new antileishmanial drugs. A series of furoxan (1,2,5-oxadiazole 2-N-oxide) (compounds 4a-b, and 14a-f) and benzofuroxan (benzo[c][1,2,5]oxadiazole1-N-oxide) (compounds 8a-c) derivatives were evaluated against in vitro cultured L. infantum promastigotes and amastigotes. The compounds exhibited activity against promastigote and intracellular amastigote forms with EC 50 values ranging from 2.9 to 71.2μM and 2.1 to 18.2μM, respectively. The most promising compound, 14e, showed good antileishmanial activity (EC 50 =3.1μM) against intracellular amastigote forms of L. infantum with a selectivity index, based on murine macrophages (SI=66.4), almost 3-times superior to that presented by the standard drug amphotericin B (AmpB). The efficacy of 14e to eliminate the parasites in vivo was also demonstrated. Treatment of L. infantum-infected hamsters with compound 14e at 3.0mg/Kg/day led to a meaningful reduction of parasite load in spleen (49.9%) and liver (54.2%), respectively; these data were corroborated by histopathological analysis, which also revealed reduction in the number of inflammatory cells in the liver of the treated animals. Moreover, histological analysis of the spleen and kidney of treated animals did not reveal alterations suggestive of toxic effects. The parasite load reduction might be related to NO production, since this molecule is a NO-donor. We observed neither side effects nor elevation of hepatic/renal biomarker levels in the plasma. The data herein presented suggest that the compound should be considered in the development of new drugs for treatment of visceral leishmaniasis., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

The chemopreventive and anticancer effects of resveratrol (RSV) are widely reported in the literature. Specifically, mechanisms involving epigenetic regulation are promising targets to regulate tumor development. Bromodomains act as epigenetic readers by recognizing lysine acetylation on histone tails and boosting gene expression in order to regulate tissue-specific transcription. In this work, we showed that RSV is a pan-BET inhibitor. Using Differential Scanning Fluorimetry (DSF), we showed that RSV at 100 µM increased the melting temperature (∆Tm) of BET bromodomains by around 2.0 °C. The micromolar dissociation constant ( K d ) range was characterized using Isothermal Titration Calorimetry (ITC). The RSV K d value accounted to 6.6 µM in case of BRD4(1). Molecular docking proposed the binding mode of RSV against BRD4(1) mimicking the acetyl-lysine interactions. All these results suggest that RSV can also recognize epigenetic readers domains by interacting with BET bromodomains., Competing Interests: The authors declare no conflict of interest.

Aim: This work aimed to evaluate the activity of 3'-hydroxychalcone against Cryptococcus gattii in planktonic and biofilm forms and their toxicity using alternative animal models., Materials & Methods: Minimum inhibitory concentration and minimum fungicide concentration were determined. Biofilm formation and the susceptibility tests were performed by the 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-5-[carbonyl(phenylamino)]-2H-tetrazolium hydroxide assay. Toxicity and efficacy were checked in Danio rerio and Galleria mellonella models., Results: The compound 3'-hydroxychalcone showed fungicidal activity against C. gattii in both planktonic and biofilm forms. The toxicity in zebrafish embryos revealed a low lethal concentration. In G. mellonella, the compound did not show antifungal activity and larvae toxicity., Conclusion: Because of the activity of 3'-hydroxychalcone against C. gattii in vitro, molecular modifications should be made to improve efficacy and to reduce toxicity in vivo. [Formula: see text].

Solid organ transplantation is a significant development in the treatment of chronic kidney, liver, heart and lung diseases. This therapeutic approach has increased patient survival and improved quality of life. New surgical techniques and immunosuppressive drugs have been developed to achieve better outcomes. However, the variety of neurological complications following solid organ transplantation is broad and carries prognostic significance. Patients may have involvement of the central or peripheral nervous system due to multiple causes that can vary depending on time of onset after the surgical procedure, the transplanted organ, and the intensity and type of immunosuppressive therapy. Neurological manifestations following solid organ transplantation pose a diagnostic challenge to medical specialists despite extensive investigation. This review aimed to provide a practical approach to help neurologists and clinicians assess and manage solid organ transplant patients presenting with acute or chronic neurological manifestations.

Resveratrol (RVT) is a stilbene with a protective effect on the cardiovascular system; however, drawbacks including low bioavailability and fast metabolism limit its efficacy. In this work we described new resveratrol derivatives with nitric oxide (NO) release properties, ability to inhibit platelet aggregation and in vivo antithrombotic effect. Compounds (4a-f) were able to release NO in vitro, at levels ranging from 24.1% to 27.4%. All compounds (2a-f and 4a-f) have exhibited platelet aggregation inhibition using as agonists ADP, collagen and arachidonic acid. The most active compound (4f) showed reduced bleeding time compared to acetylsalicylic acid (ASA) and protected up to 80% against in vivo thromboembolic events. These findings suggest that hybrid resveratrol-furoxan (4f) is a novel lead compound able to prevent platelet aggregation and thromboembolic events., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Vaccinia virus (VACV) is responsible for outbreaks in Brazil and has immense potential as an emerging virus. VACV can be found naturally circulating in India, Pakistan and South America, where it causes infections characterised by exanthematic lesions in buffaloes, cattle and humans. The transmission cycle of Brazilian VACV has still not been fully characterised; one of the most important gaps in knowledge being the role of wild animals. Capybaras, which are restricted to the Americas, are the world's largest rodents and have peculiar characteristics that make them possible candidates for being part of a natural VACV reservoir. Here, we developed a method for detecting orthopoxvirus DNA in capybara stool samples, and have described for the first time the detection of orthopoxvirus DNA in capybaras samples from three different regions in Brazil. These findings strongly suggest that capybaras might be involved in the natural transmission cycle of VACV and furthermore represent a public health problem, when associated with Brazilian bovine vaccinia outbreaks. This makes infected animals an important factor to be considered when predicting and managing Brazilian VACV outbreaks.

Primary central nervous system vasculitis (PCNSV) is a challenging diagnosis due to broad clinical manifestations and variable specificity and sensitivity of laboratory and imaging diagnostic tools. Differential diagnosis includes reversible cerebral vasoconstriction syndrome (RCVS), secondary vasculitis of the CNS and other noninflammatory vasculopathies. Brain biopsy is essential for definitive diagnosis and to exclude mimickers. Recent data show that data large-vessel PCNSV present worse prognosis when compared to small-vessel PCNSV. Herein we review diagnosis and management of PCNSV, secondary vasculitis of CNS and RCVS., (Copyright © 2016. Published by Elsevier B.V.)

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease involving multiple organs, characterized by the production of autoantibodies and the development of tissue injury. The etiology of SLE is partially known, involving multiple genetic and environmental factors. As many as 50% of patients with SLE have neurological involvement during the course of their disease. Neurological manifestations are associated with impaired quality of life, and high morbidity and mortality rates. Nineteen neuropsychiatric syndromes have been identified associated with SLE, and can be divided into central and peripheral manifestations. This article reviews major neuropsychiatric manifestations in patients with SLE and discusses their clinical features, radiological findings and treatment options.

Neurodegeneration with brain iron accumulation (NBIA) represents a heterogeneous and complex group of inherited neurodegenerative diseases, characterized by excessive iron accumulation, particularly in the basal ganglia. Common clinical features of NBIA include movement disorders, particularly parkinsonism and dystonia, cognitive dysfunction, pyramidal signs, and retinal abnormalities. The forms of NBIA described to date include pantothenase kinase-associated neurodegeneration (PKAN), phospholipase A2 associated neurodegeneration (PLAN), neuroferritinopathy, aceruloplasminemia, beta-propeller protein-associated neurodegeneration (BPAN), Kufor-Rakeb syndrome, mitochondrial membrane protein-associated neurodegeneration (MPAN), fatty acid hydroxylase-associated neurodegeneration (FAHN), coenzyme A synthase protein-associated neurodegeneration (CoPAN) and Woodhouse-Sakati syndrome. This review is a diagnostic approach for NBIA cases, from clinical features and brain imaging findings to the genetic etiology.

Objective: Ischemic stroke (IS) prognostic scales may help clinicians in their clinical decisions. This study aimed to assess the performance of four IS prognostic scales in a Brazilian population., Method: We evaluated data of IS patients admitted at Hospital Paulistano, a Joint Commission International certified primary stroke center. In-hospital mortality and modified Rankin score at discharge were defined as the outcome measures. The performance of National Institutes of Health Stroke Scale (NIHSS), Stroke Prognostication Using Age and NIHSS (SPAN-100), Acute Stroke Registry and Analysis of Lausanne (ASTRAL), and Totaled Health Risks in Vascular Events (THRIVE) were compared., Results: Two hundred six patients with a mean ± SD age of 67.58 ± 15.5 years, being 55.3% male, were included. The four scales were significantly and independently associated functional outcome. Only THRIVE was associated with in-hospital mortality. With area under the curve THRIVE and NIHSS were the scales with better performance for functional outcome and THRIVE had the best performance for mortality., Conclusion: THRIVE showed the best performance among the four scales, being the only associated with in-hospital mortality.

Non-traumatic myelopathies represent a heterogeneous group of neurological conditions. Few studies report clinical and epidemiological profiles regarding the experience of referral services. Objective To describe clinical characteristics of a non-traumatic myelopathy cohort. Method Epidemiological, clinical, and radiological variables from 166 charts of patients assisted between 2001 and 2012 were compiled. Results The most prevalent diagnosis was subacute combined degeneration (11.4%), followed by cervical spondylotic myelopathy (9.6%), demyelinating disease (9%), tropical spastic paraparesis (8.4%) and hereditary spastic paraparesis (8.4%). Up to 20% of the patients presented non-traumatic myelopathy of undetermined etiology, despite the broad clinical, neuroimaging and laboratorial investigations. Conclusion Regardless an extensive evaluation, many patients with non-traumatic myelopathy of uncertain etiology. Compressive causes and nutritional deficiencies are important etiologies of non-traumatic myelopathies in our population.

Glutamic acid decarboxylase (GAD) is the enzyme that catalyzes the conversion of glutamic acid to the neurotransmitter gamma-amino butyric acid. Antibodies against GAD (anti-GAD-Ab) are associated with an array of autoimmune-related neurological conditions, such as stiff-person syndrome, cerebellar ataxia, epilepsy and limbic encephalitis. The clinical spectrum of ataxia associated with anti-GAD-Ab comprises slowly progressive cerebellar ataxia syndrome evolving in months or years, associated with cerebellar atrophy on brain MRI. There are few reports of patients with ataxia associated with anti-GAD-Ab presenting with abnormal ocular movements, such as downbeat nystagmus (DBN).We present two patients with ataxia associated with anti-GAD-Ab from a large series of ataxic subjects who presented with cerebellar ataxia combined with spontaneous DBN. All patients underwent a thorough neurological evaluation with the use of ataxia scales, brain MRI scans, cerebrospinal fluid examination, 18FDG-PET/CT scans, laboratory work-up with on coneural and immune encephalitis antibodies, serum and cerebrospinal fluid levels of anti-GAD-Ab, and the antibody specificity index to measure the intrathecal synthesis of anti-GAD-Ab. All patients were treated with cycles of intravenous immunoglobulin and had mild/partial ataxia improvement and no improvement of DBN. The finding of DBN may work as a diagnostic clue in the context of adult-onset non-hereditary ataxias.

The enzyme glycerol-3-phosphate dehydrogenase (G3PDH) from Leishmania species is considered as an attractive target to design new antileishmanial drugs and a previous in silico study reported on the importance of chalcones to achieve its inhibition. Here, we report the identification of a synthetic chalcone in our in vitro assays with promastigote cells from Leishmania amazonensis, its biological activity in animal models, and docking followed by molecular dynamics simulation to investigate the molecular interactions and structural patterns that are crucial to achieve the inhibition complex between this compound and G3PDH. A molecular fragment of this natural product derivative can provide new inhibitors with increased potency and selectivity., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Chalcones form a class of compounds that belong to the flavonoid family and are widely distributed in plants. Their simple structure and the ease of preparation make chalcones attractive scaffolds for the synthesis of a large number of derivatives enabling the evaluation of the effects of different functional groups on biological activities. In this Letter, we report the successful synthesis of a series of novel prenylated chalcones via Claisen-Schmidt condensation and the evaluation of their effect on the viability of the Trypanosomatidae parasites Leishmania amazonensis, Leishmania infantum and Trypanosoma cruzi., (Copyright © 2015 Elsevier Ltd. All rights reserved.)