Spectrum of cutaneous lesions in a cohort of patients with neurofibromatosis type 2.

BACKGROUND: Neurofibromatosis type 2 (NF2) is a rare autosomal dominant syndrome with a predisposition to the development of central nervous system tumors, ophthalmic manifestations, and dermatological lesions. The latter are present in 70-95% of patients and can precede the evolution of other tumors. However, they are not included in the diagnostic criteria and are frequently undervalued during follow-up. METHODS: An observational cross-sectional study characterizing cutaneous lesions in a cohort of NF2 patients was carried out. Dermatological examinations were performed, and lesions were classified into neural cutaneous tumors (superficial, SNCT, and deep, DNCT), hyperpigmented patches (HyperP), and hypopigmented patches (HypoP). The Dermatology Life Quality Index (DLQI) and EQ-5D questionnaires were applied to evaluate the impact on quality of life. RESULTS: Nineteen patients with a mean age of 36 years were included. Sixteen (84%) patients had cutaneous lesions, mostly developed 10 or more years before the diagnosis. SNCT, DNCT, and HyperP showed similar frequencies (58%). HypoP were observed in only one patient. HyperP developed, on average, earlier than NCT (9.6 vs. 16.5 SNCT, 17.0 DNCT; years). The excised lesions had different histological patterns, including neurofibromas, schwannomas, and a hybrid tumor. Most patients reported a low impact of cutaneous manifestations on the quality of life (DLQI 0 or 1). CONCLUSIONS: Cutaneous lesions are frequent in NF2 and may precede the diagnosis by several years. Their identification is important to establish the diagnosis earlier and potentially reduce morbidity and mortality.

Psychiatric Comorbidities in Neurologic Hospitalizations in Portugal: A Nationwide Retrospective Observational Study.

INTRODUCTION: Psychiatric comorbidities have a significant impact on patients' quality of life and often go undetected in neurologic practice. The aim of this study was to describe and characterize psychiatric comorbidities among patients hospitalized due to a neurologic disorder in mainland Portugal. METHODS: A retrospective observational study was performed by analyzing hospitalization with a primary diagnosis of neurologic disorder defined as categories 76, 77, 79 - 85, 95, 109 of the Clinical Classification Software for International Classification of Diseases, Ninth Revision, Clinical Modification, occurring between 2008 and 2015 in adult patients (≥ 18 years of age). Psychiatric comorbidities were determined as the presence of a secondary diagnosis belonging to the Clinical Classification Software categories 650 to 670. RESULTS: A total of 294 806 hospitalization episodes with a primary diagnosis of a neurologic disorder were recorded in adult patients between 2008 - 2015 in Portuguese public hospitals. Approximately 26.9% (n = 79 442) of the episodes had a recorded psychiatric comorbidity (22.1%; 32.2%, female versus male hospitalizations). Patients with registered psychiatric comorbidities were younger (66.2 ± 16.2 vs 68.6 ± 17.2 with no psychiatric comorbidities, p < 0.001), presented lower all-cause in-hospital mortality rates, and significantly longer mean hospital stays. 'Delirium, dementia, amnestic and other cognitive disorders' were recorded in 7.4% (n = 21 965) of the hospitalizations, followed by alcohol-related disorders in 6.5% (n = 19 302) and mood disorders in 6.1% (n = 18 079). Epilepsy/seizures were the neurologic disorders with the highest proportion of recorded psychiatric comorbidities (39.9%). CONCLUSION: Psychiatric comorbidities were recorded in more than a quarter of the hospitalizations with a primary diagnosis of a Neurologic disorder. Psychiatric comorbidities varied among neurological disorders and were associated with different demographic and clinical features.

Assessment of Subgingival Biofilm and its Relationship with the Status of Tumors in a Population with Breast Cancer

This study aimed to compare the subgingival microbiota of subjects with and without breast cancer (BC). Patients with BC (Group 1; n= 50) and without BC (Group 2; n=50) with periodontitis (A) and without periodontitis (B). The study was conducted in two phases (P1 and P2). One biofilm sample was collected from each subject and analyzed by DNA-DNA Hybridization (Checkerboard DNA-DNA). The relative abundance of the subgingival microbiota differed between the Case and Control groups. However, some species were higher in patients in the Case than in Control subjects and differed between the groups in both phases. Composition of the subgingival microbial community according to the Socransky complex was related to periodontal disease, followed by clinical attachment of level (CAL ≥4mm), age, and tooth loss, which were found to be abundant in Cases when compared with controls. Patients with Tumor Grade II and III had a higher prevalence of tooth loss and CAL≥4mm. It was concluded that in individuals with BC, the sub-gingival microbiota exhibited atypical changes, but they developed periodontal disease.

El objetivo de este estudio fue comparar la microbiota subgingival de sujetos con y sin cáncer de mama (CM). Pacientes con CM (Grupo 1; n= 50) y sin CM (Grupo 2; n=50) con periodontitis (A) y sin periodontitis (B). El estudio se realizó en das fases (P1 y P2). Se recogió una muestra de biopelícula de cada sujeto y se analizó mediante hibridación ADN-ADN (tablero de ajedrez ADN-ADN). La abundancia relativa de la microbiota subgingival difirió entre los grupos de Caso y Control. Sin embargo, algunas especies fueron más altas en los pacientes del Caso que en los sujetos del Control y difirieron entre los grupos en ambas fases. La composición de la comunidad microbiana subgingival según el complejo de Socransky se relacionó con la enfermedad periodontal, seguida por el nivel de inserción clínica (CAL≥4mm), la edad y la pérdida de dientes, que se mostró abundante en los casos en comparación con los controles. Los pacientes con Tumor Grado II y III tuvieron mayor prevalencia de pérdida dental y CAL≥4mm. Se concluyó que en individuos con CM la microbiota subgingival presentó cambios atípicos, pero sin embargo, desarrollaron enfermedad periodontal.

It's in the game: A review of neurological lesions associated with sports.

INTRODUCTION: The practice of sports may lead to neurological injuries. While relatively uncommon (overall incidence of approximately 2.5%), and mostly benign and transient, some conditions may be life-threatening and permanent. Thus, both clinical neurologists and sports physicians should be aware of their existence and relevance. We aimed to review all sports-related neurological injuries and illnesses reported in the literature. METHODS: Following SANRA guidelines, we performed a narrative review and searched PubMed and Scopus databases. Relevant sports were selected based on their recognition as an Olympic sport by the International Olympic Committee. Chronic traumatic encephalopathy (CTE) and other neurodegenerative disorders were not included. RESULTS: A total of 292 studies were included concerning 33 different sports. The most reported neurological injury was damage to the peripheral nervous system. Traumatic injuries have also been extensively reported, including cerebral haemorrhage and arterial dissections. Non-traumatic life-threatening events are infrequent but may also occur, e.g. posterior reversible encephalopathy syndrome, cerebral venous thrombosis, and arterial dissections. Some conditions were predominantly reported in specific sports, e.g. yips in baseball and golf, raising the possibility of a common pathophysiology. Spinal cord infarction due to fibrocartilaginous embolism was reported in several sports associated with minor trauma. CONCLUSION: Sports-related neurological injuries are increasingly receiving more social and medical attention and are an important cause of morbidity and mortality. This review may serve as a guide to physicians managing these challenging situations.

Wnt signaling is involved in crotalphine-induced analgesia in a rat model of neuropathic pain.

The aberrant activation of Wnt/ß-catenin and atypical Wnt/Ryk signaling pathways in the spinal cord is critical for the development and maintenance of neuropathic pain. Crotalphine is a structural analog to a peptide first identified in Crotalus durissus terrificus snake venom, which induces antinociception by activating kappa-opioid and CB2 cannabinoid receptors. Consistent with previous data, we showed that the protein levels of the canonical Wnt/ß-catenin and the atypical Wnt/Ryk signaling pathways are increased in neuropathic rats. Importantly, the administration of crotalphine downregulates these protein levels, including its downstream cascades, such as TCF4 from the canonical pathway and NR2B glutamatergic receptor and Ca2+-dependent signals, via the Ryk receptor. The CB2 receptor antagonist, AM630, abolished the crotalphine-induced atypical Wnt/Ryk signaling pathway activation. However, the selective CB2 agonist affects both canonical and non-canonical Wnt signaling in the spinal cord. Next, we showed that crotalphine blocked hypersensitivity and significantly decreased the concentration of IL-1ɑ, IL-1ß, IL-6, IL-10, IL-18, TNF-ɑ, MIP-1ɑ and MIP-2 induced by intrathecal injection of exogenous Wnt-3a agonist. Taken together, our findings show that crotalphine induces analgesia in a neuropathic pain model by down-regulating the canonical Wnt/ß-catenin and the atypical Wnt/Ryk signaling pathways and, consequently controlling neuroinflammation. This effect is, at least in part, mediated by CB2 receptor activation. These results open a perspective for new approaches that can be used to target Wnt signaling in the context of chronic pain. PERSPECTIVE: Our work identified that crotalphine-induced activation of CB2 receptors plays a critical role in the impairment of Wnt signaling during neuropathic pain. This work suggests that drugs with opioid/cannabinoid activity may be a useful strategy to target Wnt signaling in the context of chronic pain.

The impact of lipid metabolism on breast cancer: a review about its role in tumorigenesis and immune escape.

BACKGROUND: Breast cancer (BC) is the second most frequent type of cancer in the world and most common among women, configuring a major challenge to global health. BC is a complex and heterogeneous disease that can be subdivided into distinct tumor types based on the expression of molecular markers predicting patient outcomes and response to therapy. A growing number of studies have tried to expand the known markers by investigating the association of altered lipid metabolism with BC immune escape, progression, and metastasis. In this review, we describe the metabolic peculiarities of each BC subtype, understanding how this influences its aggressiveness and identifying whether these intrinsic vulnerabilities of each subtype can play a role in therapeutic management and may affect immune system cells in the tumor microenvironment. CONCLUSION: The evidence suggests so far that when changes occur in lipid pathways, it can affect the availability of structural lipids for membrane synthesis, lipid synthesis, and degradation that contribute to energy homeostasis and cell signaling functions. These findings will guide the next steps on the path to understanding the mechanisms underlying how lipids alterations are related to disparities in chemotherapeutic response and immune escape in BC. Video Abstract.

Neurofibromatosis in the gluteus and posterior region of the thigh: case report / Neurofibromatose em glúteo e região posterior da coxa: relato de caso

Introduction: Neurofibromatosis is an autosomal dominant disorder, and type 1 is associated with an increased risk of tumor formation with neurocutaneous involvement. The variable evolution, often with limiting tumors, in addition to the significant incidence of cases requiring treatment, makes it fundamental to discuss procedures already performed in medical practice for early, careful, and individualized recognition of the diagnosis and treatment of the patient. The report aims to present a surgical case of neurofibromatosis, calling attention to the surgical technique, the characteristics of the disease, and the importance of the procedure in the quality of life of patients limited by the condition. Case Report: A 23-year-old male patient with a large mass neurofibroma in the gluteus and posterior surface of the right leg, in addition to café au lait stains in the distal third of the legs. He was treated with surgery to remove the tumor and a flap and graft in the affected region. The procedures were performed by a multidisciplinary team, allowing the total removal of the tumor mass, with subsequent skin grafting in the hip and thigh lesion on the right side and the fasciocutaneous flap in VY in the area. There were no significant complications in the immediate postoperative period. Conclusion: Neurofibromas can become limiting and impair patients' quality of life with neurofibromatosis type 1; therefore, early management and diagnosis are essential. Although the condition does not present a cure, there is a need for research into less invasive and preventive treatments for injuries.

Introdução: A neurofibromatose é um distúrbio autossômico dominante e o tipo 1 está associado a um aumento do risco de formação de tumores com acometimento neurocutâneo. A evolução variável, muitas vezes com tumorações limitantes, além da incidência significativa de casos que necessitam de tratamento, torna fundamental a discussão de condutas já realizadas na prática médica para um reconhecimento precoce, cuidadoso e individualizado do diagnóstico e do tratamento do enfermo. O relato objetiva apresentar um caso cirúrgico de neurofibromatose, chamando atenção para a técnica cirúrgica, as características da doença e a importância do procedimento na qualidade de vida de pacientes limitados pela afecção. Relato de Caso: Paciente de 23 anos, sexo masculino, com neurofibroma de grande massa em glúteo e face posterior da perna direita, além de manchas café com leite em terço distal de pernas. Foi tratado com uma cirurgia de retirada do tumor, além de retalho e enxerto na região acometida. Os procedimentos foram realizados por equipe multidisciplinar, possibilitando a retirada total da massa tumoral, com posterior realização de enxerto de pele na lesão do quadril e coxa em lado direito, e o retalho fasciocutâneo em V-Y na área. Não houve complicações significativas nos pós-operatórios imediatos.

High molecular weight adiponectin as a biomarker of hypertension in children and adolescents with obesity.

Lower HMW (high molecular weight) adiponectin levels are associated with obesity, insulin resistance, and metabolic syndrome in children and adolescents. However, data on HMW levels in pediatric population with hypertension are lacking. This study aimed to examine the association and predictive capacity of HMW levels, HMW/HOMA-IR, and HMW/APN ratio with hypertension in obese children and adolescents. The 299 pediatric subjects were grouped in obese hypertensive (OH), obese normotensive (ON), and normal weight normotensive (NN). Plasma concentrations of HMW were investigated by ELISA. ANOVA was used to compare study groups, and a binary logistic regression analysis was used to verify if HMW, HMW/HOMA-IR, HMW/APN, APN, APN/HOMA-IR, and HOMA-IR are associated to hypertension regardless obesity in children and adolescents. To compare the strength and performance of each biomarker to classify individuals with and without hypertension, the receiver-operating characteristic (ROC) curve, area under the curve (AUC), and Youden index (J) were evaluated. Both HMW plasma levels and the HMW/HOMA-IR ratio were significantly lower in the OH group when compared to the ON group (HMW: 2.00 ± 1.33 µg/mL vs 2.48 ± 1.48 µg/mL; HMW/HOMA-IR ratio: 0.87 ± 0.95 vs 1.27 ± 1.2; P < 0.05) and NN weight groups (HMW: 2.00 ± 1.33 µg/mL vs 4.02 ± 1.99 µg/mL; HMW/HOMA-IR ratio: 0.87 ± 0.95 vs 2.62 ± 1.86; P < 0.05). Hypertension was associated with lowest HMW (OR = 4.50; 95% CI = 1.41-15.84) and HMW/HOMA-IR (OR = 12.13; 95% CI = 2.51-92.93) regardless of obesity. However, HOMA-IR or the HMW/APN was not significant (P > 0.05). In the ROC curve analyses, the HMW and HMW/HOM-IR were more sensitive to detect hypertension in children and adolescents with obesity.    Conclusion: Low levels of HMW oligomer and HMW/HOM-IR are associated with hypertension in childhood obesity. Thus, these biomarkers could be clinically useful in identifying hypertension in childhood obesity. What is Known: • HMW has previously been reported as the most biologically active isoform of adiponectin, and lower HMW concentrations are associated with obesity, insulin resistance, and metabolic syndrome in children and adolescents. • HMW/HOMA-IR ratio is a sensitive predictor for metabolic syndrome in adults. What is New: • HMW levels are associated with hypertension in children and adolescents, independently of presence of obesity. • HMW was more sensitive to detect hypertension in children and adolescents with obesity when compared to HMW/HOMA-IR, HMW/APN, APN, APN/HOMA-IR, or HOMA-IR.

Percepção dos alunos de graduação em Odontologia da Universidade de Brasília acerca da escolha de técnicas de manejo comportamental em Odontopediatria / Percepción de estudiantes de la carrera de Odontología de la Universidad de Brasilia sobre la elección de técnicas de manejo de conducta en Odontopediatría / Perception of undergraduate Dentistry students at the University of Brasília about the choice of behavioral management techniques in Pediatric Dentistry

O objetivo deste estudo foi analisar a aceitação das técnicas de manejo de comportamento infantil por estudantes de primeiro, sexto e nono semestres de um curso de graduação em Odontologia, e a influência que as disciplinas ministradas podem exercer sobre esta. Para isso, foi aplicado um questionário (n=55) contendo questões sobre técnicas de orientação comportamental em Odontopediatria. A aceitação sobre as mesmas, foi avaliada por meio de escala Likert. O teste H de Kruskal-Wallis foi utilizado para avaliar diferença entre os três grupos de estudantes seguido do teste de Dunn. Além disso, foi realizada a correlação de Spearmanpara avaliar possíveis fatores de confusão. De forma geral, notou-se que as técnicas básicas foram mais aceitas entre todos os estudantes, já as técnicas de controle de voz, estabilização protetora e as farmacológicas foram menos aceitas. Os participantes do nono semestre aceitaram mais em média "estabilização protetora pais/equipe", "controle de voz"e "estabilização protetora wrap", e menos "presença permitida dos pais" e "recompensa prometida" em relação aos do primeiro semestre. Em comparação ao sexto, os alunos do nono semestres tiveram menor aceitação para "presença permitida dos pais", "recompensa prometida" e "explicar que pode envolver dor", e maior para "estabilização protetora pais/equipe" e "estabilização protetora wrap". A única técnica que demonstrou diferença entre o primeiro e sexto semestres foi "não deixar falar" com menor aceitabilidade entre os estudantes do sexto semestre. A posição do aluno no percurso curricular parece, portanto, influenciar na aceitação das técnicas de manejo comportamental usadas na Odontopediatria (AU).

El objetivo de este estudio fue analizar la aceptación de técnicas de manejo de la conducta infantil por parte de estudiantes de primero, sexto y noveno semestre de la carrera de Odontología, y la influencia que las materias impartidas pueden tener en esto. Para ello se aplicó un cuestionario (n=55) que contenía preguntas sobre técnicas de orientación conductual en odontopediatría. La aceptación de los mismos se evaluó mediante una escala Likert. Para evaluar las diferencias entre los tres grupos de estudiantes se utilizó la prueba H de Kruskal-Wallis seguida de la prueba de Dunn. Además, se realizó la correlación de Spearman para evaluar posibles factores de confusión. En general, se observó que las técnicas básicas fueron más aceptadas entre todos los estudiantes, mientras que el control de la voz, la estabilización protectora y las técnicas farmacológicas fueron menos aceptadas. Los participantes del noveno semestre aceptaron más en promedio "estabilización protectora de padres/equipo", "control de voz" y "estabilización protectora envolvente", y menos "presencia parental permitida" y "recompensa prometida" en comparación con los del primer semestre. En comparación con el sexto, los estudiantes del noveno semestre tuvieron una menor aceptación de "presencia parental permitida", "recompensa prometida" y "explicar que puede implicar dolor", y mayor de "estabilización protectora padres/equipo" y "envoltura protectora de estabilización". La única técnica que demostró una diferencia entre el primer y el sexto semestre fue "no dejar hablar" con menor aceptabilidad entre los estudiantes del sexto semestre. Por lo tanto, la posición del estudiante en el plan Percepção dos alunos de graduação em Odontologia da Universidade de Brasília acerca da escolha de técnicas de manejo comportamental em Odontopediatria de estudios parece influir en la aceptación de las técnicas de manejo conductual utilizadas en odontología pediátrica (AU).

This study aimed to analyze the acceptance of undergraduate students in the first, sixth, and ninth semesters about the child behavioral management techniques and to explore the potential influence of the curriculum path on their perception. An online questionnaire (n=55) with questions about mental guidance techniques in Pediatric Dentistry was applied. Their accessibility was assessed using a Likert scale. The Kruskal-Wallis and the Dunn testwere used to analyze the difference between the three groups of students. Spearman's correlationwas used to analyze confounding factors. In general, all students exhibited greater acceptance of basic techniques when compared with voice control, protective stabilization, and pharmacological techniques. Participants in the ninth semester showed greater acceptance of "parent/team protective stabilization", "voice control" and "wrap protective stabilization" techniques, and less acceptance of "parental presence/absence" and "promised reward" compared to the first semester. Compared to the sixth, students in the ninth semester had greater acceptance of "parent/team protective stabilization" and "wrap protective stabilization" techniques and less acceptance of "parental presence/absence", "promised reward" and "explain that it may involve pain". "Don't let people talk" was the only technique that demonstrated a difference between the first and sixth semesters, with lower acceptance among students in the sixth semester. The student's semesters seem, therefore, to influence the acceptance of behavioral management techniques used in Pediatric Dentistry (AU).

Overexpression of CLDN16 in ovarian cancer is modulated by PI3K and PKC pathways.

Epithelial ovarian cancer (EOC) is the gynecological malignant tumor of poorest prognosis and higher mortality rate. Chemotherapy is the base of high-grade serous ovarian cancer (HGSOC) treatment; however, it favors the emergence of chemoresistance and metastasis. Thus, there is an urge to search for new therapeutic targets, such as proteins related to cellular proliferation and invasion. Herein, we investigated the expression profile of claudin-16 (CLDN16 protein and CLDN16 transcript) and its possible functions in EOC. In silico analysis of CLDN16 expression profile was performed using data extracted from GENT2 and GEPIA2 platforms. A retrospective study was carried out with 55 patients to evaluate the expression of CLDN16. The samples were evaluated by immunohistochemistry, immunofluorescence, qRT-PCR, molecular docking, sequencing, and immunoblotting assays. Statistical analyzes were performed using Kaplan-Meier curves, one-way ANOVA, Turkey posttest. Data were analyzed using GraphPad Prism 8.0. In silico experiments showed that CLDN16 is overexpressed in EOC. 80.0% of all EOC types overexpressed CLDN16, of which in 87% of the cases the protein is restricted to cellular cytoplasm. CLDN16 expression was not related to tumor stage, tumor cells differentiation status, tumor responsiveness to cisplatin, or patients' survival rate. When compared to data obtained from in silico analysis regarding EOC stage and degree of differentiation, differences were found in the former but not in the later, neither in survival curves. CLDN16 expression in HGSOC OVCAR-3 cells increased by 1.95-fold (p < 0.001), 2.32-fold (p < 0.001), and 6.57-fold (p < 0.001) via PKC, PI3K, and estrogen pathways, respectively. Altogether, our results suggest that despite the low number of samples included in our in vitro studies, adding to the expression profile findings, we provided a comprehensive study of CLDN16 expression in EOC. Therefore, we hypothesize that CLDN16 is a potential target in the diagnosis and treatment of the disease.

Persistent headache attributed to past cervicocephalic artery dissection: clinical characteristics and contributors to headache persistence.

BACKGROUND: Persistent headache/facial/neck pain attributed to past cervicocephalic arterial dissection is under-documented in literature. Our main goal was to evaluate clinical characteristics and contributors to this persistence. METHODS: A retrospective cohort study which included patients with a radiologically confirmed cervicocephalic arterial dissection (2015-2020) in a Portuguese tertiary hospital. Headache persistence was identified through clinical records. A questionnaire aimed to characterize headache in three moments: previous, persistent, and headache at the time of the interview (on average 2.5 years post-event). RESULTS: Ninety-two patients were identified; 24 (26.1%) had headache persistence ≥3 months, and 20 (22.2%) on average after 2.5 years post-event. There were no differences regarding demographics and vascular risk factors among patients with (n = 22) and without (n = 68) headache persistence. The first group had higher previous headache history (68.2% vs 4.4%, p < 0.001), delay in diagnosis (3.6 vs 1.9 days, p < 0.001), and headache/cervicalgia as the first symptom (81.8% vs 41.2%, p < 0.001). At the time of the interview, 20% still reported daily headache. A logistic regression model depicted headache history (OR = 59.8, p < 0.001), acute headache/cervicalgia (odds ratio, OR = 25.4, p = 0.005), posterior circulation dissection (OR = 7.6, p < 0.001), and less than 4 points by National Institutes of Health Stroke Scale score (OR = 5.0, p = 0.025) as contributors to headache persistence. CONCLUSION: Headache persistence post-cervicocephalic arterial dissection is common, and frequently affects patients daily. As it potentially affects functional outcomes and quality of life, the contributors identified in this study may help clinicians manage patients after the acute event.

Repercussões das Conferências Nacionais de Segurança Alimentar e Nutricional nas propostas legislativas para o Programa Nacional de Alimentação Escolar / Repercussions of the National Food and Nutrition Security Conferences on legislative proposals for the National School Feeding Program

Introdução: As Conferências Nacionais de Segurança Alimentar e Nutricional (CNSAN) foram realizadas no Brasil no período de 1994 a 2015. Por seu caráter intersetorial e multidimensional, as CNSAN debateram um amplo conjunto de temas e recomendações de políticas e programas, dentre eles, o Programa Nacional de Alimentação Escolar (PNAE). Objetivo: Analisar as repercussões das recomendações das CNSAN direcionadas ao PNAE no processo legislativo. Métodos: Trata-se de estudo documental, realizado em duas fases: a primeira consistiu na identificação de recomendações para políticas públicas de SAN contempladas nos relatórios das cinco CNSAN direcionadas ao PNAE; a segunda, na busca de projetos legislativos que tivessem pertinência temática com as demandas das CNSAN no período de 24 meses após cada evento. Resultados: Identificou-se, nas CNSAN, um total de 24 recomendações para atualização do PNAE e 24 projetos legislativos que tratam integral ou parcialmente dos temas e se distribuem de forma desigual entre as CNSAN. Foram encontrados projetos legislativos para 41,7% das recomendações das CNSAN para o PNAE, indicando que há convergência entre a agenda das CNSAN e do Legislativo brasileiro; as recomendações de universalização do programa e de reajuste dos valores repassados pela União para estados e municípios sobressaíram quanto ao número de projetos no Legislativo, indicando foco na garantia do direito à alimentação escolar; duas leis foram aprovadas para o período estudado. Conclusão: Tais resultados podem estar relacionados à abertura do congresso para as recomendações das CNSAN, devido ao modelo de governança adotado no período analisado.

Introduction: The National Food and Nutrition Security Conferences (from Portuguese: Conferências Nacionais de Segurança Alimentar e Nutricional (CNSAN), were held in Brazil from 1994 to 2015. Due to its intersectoral and multidimensional nature, the CNSAN debated a wide range of themes, policy and program recommendations, among it, the National School Feeding Program (from Portuguese: Programa Nacional de Alimentação Escolar (PNAE)). Objective: To analyze the repercussions of CNSAN recommendations directed to PNAE in the legislative process. Methods: This is a documentary study, carried out in two phases: the first consisted of identifying recommendations for public policies included in the reports of the five CNSAN directed to the PNAE; the second, in the search for legislative projects that had thematic relevance with the demands of CNSAN in the 24-month period after each event. Results: A total of 24 recommendations for updating the PNAE and 24 legislative projects were identified in the CNSAN, which fully or partially address the topics and are unevenly distributed among it. Legislative projects were found for 41.7% of the CNSAN recommendations for the PNAE, indicating that there is convergence between the CNSAN agenda and the Brazilian Legislature; the recommendations for universalizing the program and readjusting the amounts transferred by the Union to states and municipalities stood out in terms of the number of projects in the Legislature, indicating a focus on guaranteeing the right to school meals; two laws were approved for the period studied. Conclusion: The results may be related to the opening of the congress to the CNSAN recommendations, due to the governance model adopted in the period analyzed.

Wnt signaling is involved in crotalphine-induced analgesia in a rat model of neuropathic pain

The aberrant activation of Wnt/β-catenin and atypical Wnt/Ryk signaling pathways in the spinal cord is critical for the development and maintenance of neuropathic pain. Crotalphine is a structural analog to a peptide first identified in Crotalus durissus terrificus snake venom, which induces antinociception by activating kappa-opioid and CB2 cannabinoid receptors. Consistent with previous data, we showed that the protein levels of the canonical Wnt/β-catenin and the atypical Wnt/Ryk signaling pathways are increased in neuropathic rats. Importantly, the administration of crotalphine downregulates these protein levels, including its downstream cascades, such as TCF4 from the canonical pathway and NR2B glutamatergic receptor and Ca2+-dependent signals, via the Ryk receptor. The CB2 receptor antagonist, AM630, abolished the crotalphine-induced atypical Wnt/Ryk signaling pathway activation. However, the selective CB2 agonist affects both canonical and non-canonical Wnt signaling in the spinal cord. Next, we showed that crotalphine blocked hypersensitivity and significantly decreased the concentration of IL-1ɑ, IL-1β, IL-6, IL-10, IL-18, TNF-ɑ, MIP-1ɑ and MIP-2 induced by intrathecal injection of exogenous Wnt-3a agonist. Taken together, our findings show that crotalphine induces analgesia in a neuropathic pain model by down-regulating the canonical Wnt/β-catenin and the atypical Wnt/Ryk signaling pathways and, consequently controlling neuroinflammation. This effect is, at least in part, mediated by CB2 receptor activation. These results open a perspective for new approaches that can be used to target Wnt signaling in the context of chronic pain.

Common variable immunodeficiency and its inflammatory neurological manifestations: A case report and literature review.

BACKGROUND: Common variable immunodeficiency disorders (CVID) are a group of primary immunodeficiencies characterized by impaired immunoglobulin production and dysregulated immune response. Neurological manifestations have been described in a few patients, and little is known about its clinic and therapeutic approach. Thus, this work aimed to review the literature on it and to help differentiate CVID from its mimics, especially sarcoidosis. METHODS: We described a case report and included a literature review of inflammatory neurological involvement in CVID. RESULTS: A 32-year-old female patient with a medical history of recurrent bacterial infections, temporal focal epilepsy and granulomatous lung disease under study, and cervix squamous cell carcinoma, was initially admitted to the emergency department due to intracranial hypertension. After excluding infectious and neoplastic etiologies, the most likely hypothesis was that granulomatous pulmonary, cerebral, and leptomeningeal inflammatory involvement were associated with sarcoidosis. Two years later, a diagnosis of CVID was made, and the patient was secondarily diagnosed with Granulomatous and Lymphocytic Interstitial Lung Disease (GLILD) and related inflammatory brain disease - both complications of CVID. After starting targeted treatment with immunoglobulin replacement and pulse glucocorticoids followed by a chronic taper, the patient became stable. However, three consecutive failures in immunoglobulin intake during the COVID-19 pandemic led to disease recurrence with relapse of neurological manifestations. CONCLUSION: This case illustrates the complex multiple organ manifestations of CVID. When granulomatous conditions arise in these patients, a rare lung disease arising in the context of CVID, the GLILD disease with multisystem involvement, should be taken into consideration. Early treatment with combined steroids and immunotherapy seems to be effective in controlling CVID's neurological manifestations.

Use of Social Networks in the Context of the Dietitian's Practice in Brazil and Changes During the COVID-19 Pandemic: Exploratory Study.

BACKGROUND: Social networks have been pointed out as 1 of the greatest means of spreading information. A large part of the population is already present on these platforms, looking up subjects such as health, nutrition, and food. To reach this audience, it may be important for dietitians to explore social networks. However, there is a gap in scientific studies on exploring the ways in which these platforms are used by dietitians in Brazil, and the roles they play in the profession have not been well defined. OBJECTIVE: This study aims to describe the roles that social networks play in dietitians' practice in Brazil and their mode of use of social networks. This study also aims to identify professionals' perceptions and opinions regarding the use of these tools, as well as changes in behavior on social network usage caused by the COVID-19 pandemic. METHODS: We carried out a quantitative cross-sectional study, collecting data through an online questionnaire, submitted between October 2020 and January 2021 to dietitians registered on the Federal Council of Dietitians. All participants included in the study answered questions about the use of social networks in their professional context. RESULTS: In total, 264 (91.7%) of the 288 participants reported using social networks for professional practice. Instagram was the social network most often used by professionals (224/264, 84.8%). Dietitians (N=288) related to the use of social networks (always to almost always) for sharing information about their services (n=114-72 [39.6%-25%], respectively), following the work of other dietitians (n=172-64 [59.7%-22.2%], respectively), and writing about topics related to food and nutrition (n=166-53 [57.6%-18.4%], respectively). The roles played by social networks in the professional context of dietitians were attracting more clients (210/289, 72.7%) and keeping in touch with them (195/289, 67.5%). Furthermore, 227 (78.5%) of the 289 dietitians strongly agreed that social networks are good tools to promote their services. During the COVID-19 pandemic, 216 (74.7%) of the 289 participants noticed changes in their behavior, feelings, or beliefs on the use of social networks related to professional practice, and 149 (51.6%) have increased the frequency of sharing information about nutrition and health in general on social networks. CONCLUSIONS: The main roles of social networks in the professional context of dietitians are to attract clients and to facilitate the contact between professional and client. The modes of use reported by the professionals included sharing information about their services, following the work of professional colleagues, and writing about topics related to nutrition. Most of them reported believing that social networks are an effective way to disseminate their services. Moreover, most professionals claimed to have noticed changes in their behaviors or beliefs on social media during the COVID-19 pandemic.

Activation of PKCε-ALDH2 Axis Prevents 4-HNE-Induced Pain in Mice.

Protein kinase Cε (PKCε) is highly expressed in nociceptor neurons and its activation has been reported as pro-nociceptive. Intriguingly, we previously demonstrated that activation of the mitochondrial PKCε substrate aldehyde dehydrogenase-2 (ALDH2) results in anti-nociceptive effects. ALDH2 is a major enzyme responsible for the clearance of 4-hydroxy-2-nonenal (4-HNE), an oxidative stress byproduct accumulated in inflammatory conditions and sufficient to induce pain hypersensitivity in rodents. Here we determined the contribution of the PKCε-ALDH2 axis during 4-HNE-induced mechanical hypersensitivity. Using knockout mice, we demonstrated that PKCε is essential for the nociception recovery during 4-HNE-induced hypersensitivity. We also found that ALDH2 deficient knockin mice display increased 4-HNE-induced nociceptive behavior. As proof of concept, the use of a selective peptide activator of PKCε (ΨεHSP90), which favors PKCε translocation to mitochondria and activation of PKCε-ALDH2 axis, was sufficient to block 4-HNE-induced hypersensitivity in WT, but not in ALDH2-deficient mice. Similarly, ΨεHSP90 administration prevented mechanical hypersensitivity induced by endogenous production of 4-HNE after carrageenan injection. These findings provide evidence that selective activation of mitochondrial PKCε-ALDH2 axis is important to mitigate aldehyde-mediated pain in rodents, suggesting that ΨεHSP90 and small molecules that mimic it may be a potential treatment for patients with pain.

Crotalphine Attenuates Pain and Neuroinflammation Induced by Experimental Autoimmune Encephalomyelitis in Mice.

Multiple sclerosis (MS) is a demyelinating disease of inflammatory and autoimmune origin, which induces sensory and progressive motor impairments, including pain. Cells of the immune system actively participate in the pathogenesis and progression of MS by inducing neuroinflammation, tissue damage, and demyelination. Crotalphine (CRO), a structural analogue to a peptide firstly identified in Crotalus durissus terrificus snake venom, induces analgesia by endogenous opioid release and type 2 cannabinoid receptor (CB2) activation. Since CB2 activation downregulates neuroinflammation and ameliorates symptoms in mice models of MS, it was presently investigated whether CRO has a beneficial effect in the experimental autoimmune encephalomyelitis (EAE). CRO was administered on the 5th day after immunization, in a single dose, or five doses starting at the peak of disease. CRO partially reverted EAE-induced mechanical hyperalgesia and decreased the severity of the clinical signs. In addition, CRO decreases the inflammatory infiltrate and glial cells activation followed by TNF-α and IL-17 downregulation in the spinal cord. Peripherally, CRO recovers the EAE-induced impairment in myelin thickness in the sciatic nerve. Therefore, CRO interferes with central and peripheral neuroinflammation, opening perspectives to MS control.

O tempo de balanço como variável preditiva da doença de Parkinson / El tiempo de equilibrio como variable predictora de la enfermedad de Parkinson / Swing time as a predictive variable for Parkinson's disease

RESUMO Atualmente, a doença de Parkinson (DP) tem seu diagnóstico baseado apenas na observação clínica de uma combinação de sintomas, o que pode levar ao diagnóstico tardio. Alguns indivíduos podem, em decorrência disso, ter a doença por 5 a 10 anos antes de serem diagnosticados. O objetivo deste estudo foi identificar as variáveis cinemáticas temporais da marcha, pois estas são capazes de discriminar idosos com e sem DP. Como método, 40 indivíduos foram divididos em dois grupos: grupo de idosos sem DP (n=21) e com DP (n=19). Foram obtidos dez ciclos de marcha consecutivos durante a marcha em velocidade de preferência, sendo utilizados para a análise dos dados. Realizou-se uma análise discriminativa para determinar um modelo preditor de alterações na marcha característico da DP. O modelo foi calculado com base na especificidade e sensibilidade de cada variável analisada, utilizando-se variáveis cinemáticas temporais. A variável com valor discriminativo de sensibilidade e especificidade foi o tempo de balanço, o que pode classificá-lo como a variável que possui grande potencial preditivo da presença ou não da DP, e o ponto de corte encontrado para essa variável foi de 0,48 segundos. A pesquisa concluiu que a análise cinemática da marcha permite discriminar um grupo de indivíduos com a doença de Parkinson de um grupo de indivíduos saudáveis, com alta sensibilidade e especificidade, por meio do tempo de balanço, visto que ele é menor no grupo acometido pela doença.

RESUMEN Actualmente, el diagnóstico de la enfermedad de Parkinson (EP) se obtiene desde la observación clínica de una combinación de síntomas, lo que puede llevar a un diagnóstico tardío. Como resultado, algunas personas pueden haber adquirido la enfermedad entre 5 y 10 años antes de que fuesen diagnosticadas. El objetivo de este estudio fue identificar las variables cinemáticas temporales de la marcha, ya que son capaces de diferenciar a los ancianos con EP y a los ancianos sin EP. Se dividieron los 40 participantes en dos grupos: ancianos sin EP (n=21) y ancianos con EP (n=19). Se obtuvieron diez ciclos de marcha consecutivos durante la marcha a la velocidad preferida para el análisis de datos. Se realizó un análisis discriminante para determinar un modelo predictivo de cambios en la marcha característicos de la EP. El modelo se calculó con base en la especificidad y sensibilidad de cada variable analizada, utilizando variables cinemáticas temporales. La variable con valor discriminante de sensibilidad y especificidad fue el tiempo de equilibrio, que puede clasificarse como la variable con mayor potencial para predecir la presencia o no de EP; y el punto de cohorte encontrado para esta variable fue de 0,48 segundos. Se concluye que el análisis cinemático de la marcha puede discriminar a un grupo de individuos con enfermedad de Parkinson de un grupo de individuos sanos, con alta sensibilidad y especificidad, por medio del tiempo de equilibrio, que fue menor en el grupo afectado por la enfermedad.

ABSTRACT Currently, Parkinson's Disease (PD) is diagnosed based only on the clinical observation of a combination of symptoms, which can lead to late diagnosis, since some individuals may have the disease for 5 to 10 years before being diagnosed. The aim was to identify temporal kinematic variables of walking, capable of discriminating elderly people with and without PD. 40 individuals were divided into two groups: elderly group without PD (n=21) and with PD (n=19). Ten consecutive gait cycles were obtained during walking at a preferred speed and used for data analysis. A discriminative analysis was performed to determine a predictor model of gait changes, characteristic of PD and calculated based on the specificity and sensitivity of each variable analyzed, using temporal kinematic variables. The variable with discriminative value of sensitivity and specificity was the time of balance, which can be classified as the variable with most predictive potential of the presence or not of PD, and the cut of found for this variable was 0,48 seconds. The kinematic gait analysis allows to discriminate a group of individuals with PD from a group of healthy individuals with high sensitivity and specificity, through the time of balance that is lower in the group affected by the disease (cut of 0,48 seconds).

Headache teleconsultation in the era of COVID-19: Patients' evaluation and future directions.

BACKGROUND AND PURPOSE: Literature regarding headache teleconsultation and patient satisfaction is scarce. The SARS-CoV-2 pandemic led to the restructuring of traditional clinical activity by adopting telemedicine. Our objectives were to evaluate patients' satisfaction with headache teleconsultation by telephone during the SARS-CoV-2 pandemic and assess patients' preferred model of appointment (face-to-face, teleconsultation by telephone, or both). METHODS: Patients with a previous diagnosis of primary headache or neuropathies and facial pain disorders, and at least one telephone headache visit during the first wave of COVID-19, filled out an online questionnaire regarding sociodemographic parameters, satisfaction with teleconsultation, and preferred model of appointment. RESULTS: We included 83 patients (valid response rate of 64.3%); most had migraine (83.1%). Regarding teleconsultation, 81.9% considered this model adequate for follow-up, 88.0% were satisfied with the information provided about the disease/treatment, and 73.5% were satisfied with the medication modification. Ninety percent would agree with a new tele-evaluation if stable after the pandemic. The mixed model was the preferred medical consultation type for the postpandemic period (43.4%), followed by face-to-face visits (33.7%). CONCLUSIONS: Patients were satisfied with the headache teleconsultation during the COVID-19 era. However, an exclusive model of telemedicine does not seem suitable for monitoring all patients. A mixed approach could be integrated into clinical practice after the pandemic to optimize health care.

Neuro-COVID frequency and short-term outcome in the Northern Portuguese population.

BACKGROUND AND PURPOSE: COVID-19-related acute neurological phenotypes are being increasingly recognised, with neurological complications reported in more than 30% of hospitalised patients. However, multicentric studies providing a population-based perspective are lacking. METHODS: We conducted a retrospective multicentric study at five hospitals in Northern Portugal, representing 45.1% of all hospitalised patients in this region, between 1 March and 30 June 2020. RESULTS: Among 1261 hospitalised COVID-19 patients, 457 (36.2%) presented neurological manifestations, corresponding to a rate of 357 per 1000 in the North Region. Patients with neurologic manifestations were younger (68.0 vs. 71.2 years, p = 0.002), and the most frequent neurological symptoms were headache (13.4%), delirium (10.1%), and impairment of consciousness (9.7%). Acute well-defined central nervous system (CNS) involvement was found in 19.1% of patients, corresponding to a rate of 217 per 1000 hospitalised patients in the whole region. Assuming that all patients with severe neurological events were hospitalised, we extrapolated our results to all COVID-19 patients in the region, estimating that 116 will have a severe neurological event, corresponding to a rate of nine per 1000 (95% CI = 7-11). Overall case fatality in patients presenting neurological manifestations was 19.8%, increasing to 32.6% among those with acute well-defined CNS involvement. CONCLUSIONS: We characterised the population of hospitalised COVID-19 patients in Northern Portugal and found that neurological symptoms are common and associated with a high degree of disability at discharge. CNS involvement with criteria for in-hospital admission was observed in a significant proportion of patients. This knowledge provides the tools for adequate health planning and for improving COVID-19 multidisciplinary patient care.