Botulinum Toxin and Deep Brain Stimulation in Dystonia.

Deep Brain Stimulation (DBS) is a recognized treatment for different dystonia subtypes and has been approved by the Food and Drug Administration (FDA) since 2003. The European Federation of Neurological Societies (EFNS) and the International Parkinson and Movement Disorders Society (MDS) recommend DBS for dystonia after failure of botulinum toxin (BoNT) and other oral medications for dystonia treatment. In addition, several long-term studies have demonstrated the continuous efficacy of DBS on motor and quality of life (QoL) scores. However, there are only a few reports comparing the overall impact of surgical treatment in BoNT protocols (e.g., dosage and number of selected muscles before and after surgery). This retrospective multicenter chart-review study analyzed botulinum toxin total dosage and dosage per muscle in 23 dystonic patients before and after DBS surgery. The study's primary outcome was to analyze whether there was a reduction in BoNT dosage after DBS surgery. The mean BoNT dosages difference between baseline and post-surgery was 293.4 units for 6 months, 292.6 units for 12 months, and 295.2 units at the last visit. The median total dose of BoNT in the preoperative period was 800 units (N = 23). At the last visit, the median was 700 units (p = 0.05). This represents a 12.5% reduction in BoNT median dosage. In conclusion, despite the limitations of this retrospective study, there was a significant reduction in BoNT doses after DBS surgery in patients with generalized dystonia.

The Association of Nanostructured Carbonated Hydroxyapatite with Denatured Albumin and Platelet-Rich Fibrin: Impacts on Growth Factors Release and Osteoblast Behavior.

Platelet-rich Fibrin (PRF), a second-generation blood concentrate, offers a versatile structure for bone regeneration due to its composition of fibrin, growth factors, and cytokines, with adaptations like denatured albumin-enriched with liquid PRF (Alb-PRF), showing potential for enhanced stability and growth factor dynamics. Researchers have also explored the combination of PRF with other biomaterials, aiming to create a three-dimensional framework for enhanced cell recruitment, proliferation, and differentiation in bone repair studies. This study aimed to evaluate a combination of Alb-PRF with nanostructured carbonated hydroxyapatite microspheres (Alb-ncHA-PRF), and how this association affects the release capacity of growth factors and immunomodulatory molecules, and its impact on the behavior of MG63 human osteoblast-like cells. Alb-PRF membranes were prepared and associated with nanocarboapatite (ncHA) microspheres during polymerization. MG63 cells were exposed to eluates of both membranes to assess cell viability, proliferation, mineralization, and alkaline phosphatase (ALP) activity. The ultrastructural analysis has shown that the spheres were shattered, and fragments were incorporated into both the fibrin mesh and the albumin gel of Alb-PRF. Alb-ncHA-PRF presented a reduced release of growth factors and cytokines when compared to Alb-PRF (p < 0.05). Alb-ncHA-PRF was able to stimulate osteoblast proliferation and ALP activity at lower levels than those observed by Alb-PRF and was unable to positively affect in vitro mineralization by MG63 cells. These findings indicate that the addition of ncHA spheres reduces the biological activity of Alb-PRF, impairing its initial effects on osteoblast behavior.

Gerstmann-Sträussler-Scheinker Disease Presenting as Late-Onset Slowly Progressive Spinocerebellar Ataxia, and Comparative Case Series with Neuropathology.

BACKGROUND: Genetic prion diseases, including Gerstmann-Sträussler-Scheinker disease (GSS), are extremely rare, fatal neurodegenerative disorders, often associated with progressive ataxia and cognitive/neuropsychiatric symptoms. GSS typically presents as a rapidly progressive cerebellar ataxia, associated with cognitive decline. Late-onset cases are rare. OBJECTIVE: To compare a novel GSS phenotype with six other cases and present pathological findings from a single case. METHODS: Case series of seven GSS patients, one proceeding to autopsy. RESULTS: Case 1 developed slowly progressive gait difficulties at age 71, mimicking a spinocerebellar ataxia, with a family history of balance problems in old age. Genome sequencing revealed a heterozygous c.392G > A (p.G131E) pathogenic variant and a c.395A > G resulting in p.129 M/V polymorphism in the PRNP gene. Probability analyses considering family history, phenotype, and a similar previously reported point mutation (p.G131V) suggest p.G131E as a new pathogenic variant. Clinical features and imaging of this case are compared with those six additional cases harboring p.P102L mutations. Autopsy findings of a case are described and were consistent with the prion pathology of GSS. CONCLUSIONS: We describe a patient with GSS with a novel p.G131E mutation in the PRNP gene, presenting with a late-onset, slowly progressive phenotype, mimicking a spinocerebellar ataxia, and six additional cases with the typical P102L mutation.

Biodegradable PBAT/PLA blend films incorporated with turmeric and cinnamomum powder: A potential alternative for active food packaging.

Active packaging made from biodegradable polymers and natural additives appears as an ecological alternative. In addition to having antioxidant activity and enhancing food preservation, it allows mitigating the negative impacts caused by improper disposal. This study pursued to produce biodegradable films based on a polymer blend PBAT/PLA (Ecovio®) using the flat extrusion method. The films were prepared with the incorporation of 5 wt% of powdered turmeric or cinnamon as natural additives. The films obtained, and those reprocessed twice, were characterized in terms of colorimetric, UV light transmittance, water contact angle, water vapor permeability, morphology, mechanical properties, and antioxidant activity. Cinnamon reduced the UV light transmittance and made a surface more hydrophobic. Reprocessing led to greater elongation and maximum load, associated with increased dispersion and distribution, as evidenced in the morphological analysis. The films developed have significant potential for applications in active food packaging, with emphasis on cinnamon-additivated films.

The Effects of Platelet-Rich Fibrin in the Behavior of Mineralizing Cells Related to Bone Tissue Regeneration-A Scoping Review of In Vitro Evidence.

Platelet-rich fibrin (PRF) is a second-generation blood concentrate that serves as an autologous approach for both soft and hard tissue regeneration. It provides a scaffold for cell interaction and promotes the local release of growth factors. PRF has been investigated as an alternative to bone tissue therapy, with the potential to expedite wound healing and bone regeneration, though the mechanisms involved are not yet fully understood. This review aims to explore the in vitro evidence of PRF's effects on the behavior of mineralizing cells related to bone tissue regeneration. A systematic electronic search was conducted up to August 2023, utilizing three databases: PubMed, Web of Science, and Scopus. A total of 76 studies were selected, which presented in vitro evidence of PRF's usefulness, either alone or in conjunction with other biomaterials, for bone tissue treatment. PRF membranes' influence on the proliferation, differentiation, and mineralization of bone cells is linked to the constant release of growth factors, resulting in changes in crucial markers of bone cell metabolism and behavior. This further reinforces their therapeutic potential in wound healing and bone regeneration. While there are some notable differences among the studies, the overall results suggest a positive effect of PRF on cell proliferation, differentiation, mineralization, and a reduction in inflammation. This points to its therapeutic potential in the field of regenerative medicine. Collectively, these findings may help enhance our understanding of how PRF impacts basic physiological processes in bone and mineralized tissue.

Physical fitness, hormonal profile, nutritional and psychological aspects assessment of transgender women volleyball players submitted to physical tests: protocol paper of a prospective cohort.

To evaluate aerobic capacity, strength and other physiological, nutritional, and psychological variables which may influence the performance of transgender women (TW) athletes and compare them to cisgender women (CW) and cisgender men (CM) athletes, as well as changes in TW performance over the course of a year. Prospective cohort study including three groups: TW, CW and CM volleyball athletes. Subjects will be comprehensively assessed at two different moments: baseline and after 6-12 months of adequate hormonal therapy. Evaluation will comprise clinical, medical, nutritional and psychological interviews, incremental treadmill cardiopulmonary exercise testing, hand grip strength test, vertical jump test, analysis of sleep quality (Pittsburgh Sleep Quality Index), hormonal profile, echocardiogram, analysis of resting energy expenditure, assessment of bone mass and body composition through dual-energy X-ray absorptiometry scans, and untargeted metabolomic analysis. CW and CM matched by age, body mass index and level of physical activity will undergo a similar evaluation. The assessment of the strength, aerobic capacity, haematological, nutritional and psychological status of TW using gold-standard tests will contribute to understanding the impact of oestrogen therapy on the exercise performance of these athletes and how they compare with CW and CM.

The larval midgut of Anopheles, Aedes, and Toxorhynchites mosquitoes (Diptera, Culicidae): a comparative approach in morphophysiology and evolution.

The mosquito larval midgut is responsible for acquiring and storing most of the nutrients that will sustain the events of metamorphosis and the insect's adult life. Despite its importance, the basic biology of this larval organ is poorly understood. To help fill this gap, we carried out a comparative morphophysiological investigation of three larval midgut regions (gastric caeca, anterior midgut, and posterior midgut) of phylogenetically distant mosquitoes: Anopheles gambiae (Anopheles albimanus was occasionally used as an alternate), Aedes aegypti, and Toxorhynchites theobaldi. Larvae of Toxorhynchites mosquitoes are predacious, in contrast to the other two species, that are detritivorous. In this work, we show that the larval gut of the three species shares basic histological characteristics, but differ in other aspects. The lipid and carbohydrate metabolism of the An. gambiae larval midgut is different compared with that of Ae. aegypti and Tx. theobaldi. The gastric caecum is the most variable region, with differences probably related to the chemical composition of the diet. The peritrophic matrix is morphologically similar in the three species, and processes involved in the post-embryonic development of the organ, such as cell differentiation and proliferation, were also similar. FMRF-positive enteroendocrine cells are grouped in the posterior midgut of Tx. theobaldi, but individualized in An. gambiae and Ae. aegypti. We hypothesize that Tx. theobaldi larval predation is an ancestral condition in mosquito evolution.

The impact of early-life exposure to three agrochemicals on survival, behavior, and gut microbiota of stingless bees (Partamona helleri).

Over the last few decades, agrochemicals have been partially associated with a global reduction in bees' population. Toxicological assessment is therefore crucial for understanding the overall agrochemical risks to stingless bees. Therefore, the lethal and sublethal effects of agrochemicals commonly used in crops (copper sulfate, glyphosate, and spinosad) on the behavior and gut microbiota of the stingless bee, Partamona helleri, were assessed using chronic exposure during the larval stage. When used at the field-recommended rates, both copper sulfate (200 µg of active ingredient/bee; a.i µg bee-1) and spinosad (8.16 a.i µg bee-1) caused a decrease in bee survival, while glyphosate (148 a.i µg bee-1) did not show any significant effects. No significant adverse effects on bee development were observed in any treatment with CuSO4 or glyphosate, but spinosad (0.08 or 0.03 a.i µg bee -1) increased the number of deformed bees and reduced their body mass. Agrochemicals changed the behavior of bees and composition of the gut microbiota of adult bees, and metals such as copper accumulated in the bees' bodies. The response of bees to agrochemicals depends on the class or dose of the ingested compound. In vitro rearing of stingless bees' larvae is a useful tool to elucidate the sublethal effects of agrochemicals.

Differences in augmented reality games performance between individuals with down syndrome and individuals with typical development

Introduction: Down syndrome is the most common genetic cause of intellectual disability, and the use of augmented reality can be improving the cognitive, motor, and literacy skills of this population Objective: to compare statistical differences in learning between individuals with Down syndrome and individuals with typical development using augmented reality games.Methods: we compared the reaction time before and after the virtual reality tasks, in addition to the performance in these tasks, which consisted of correctly identifying numbers and letters in 46 people with Down syndrome and 46 controls with typical development.Results: our results indicate that the total points for the typical development group were higher (M = 13.0 and 11.9) when compared to the Down syndrome group (M = 6.6 and 4.6) for letters of the alphabet and numbers, respectively. Furthermore, the results indicated that participants in both groups were more accurate in identifying alphabetic symbols when compared to numerical symbols, and both groups were sensitive to the number of symbols presented in each phase. The down syndrome group had a lower performance when compared to the typical development group.Conclusion: despite the need for further studies, our results support the outcome that there is clinical utility of an intervention based on virtual reality tasks for people with Down syndrome. In conclusion, the use of this technology to improve the reaction time of this population is considered useful

Introdução: a síndrome de Down é uma das principais doenças genéticas que causam deficiência intelectual, e o uso da realidade aumentada pode aumentar as habilidades cognitivas, motoras e de aprendizado dessa população. Objetivo: comparar diferenças estatísticas na aprendizagem entre indivíduos com síndrome de Down e indivíduos com desenvolvimento típico usando jogos de realidade aumentada.Métodos: comparamos o tempo de reação antes e depois das tarefas de realidade virtual, além do desempenho nessas tarefas, que consistiam em identificar corretamente números e letras em 46 pessoas com síndrome de Down e 46 controles com desenvolvimento típico.Resultados: nossos resultados indicam que o total de pontos para o grupo de desenvolvimento típico foi maior (M = 13,0 e 11,9) quando comparado ao grupo com síndrome de Down (M = 6,6 e 4,6) para letras do alfabeto e números, respectivamente. Além disso, os resultados indicaram que os participantes de ambos os grupos foram mais precisos na identificação de símbolos alfabéticos quando comparados aos símbolos numéricos, e ambos os grupos foram sensíveis ao número de símbolos apresentados em cada fase. O grupo com síndrome de Down teve desempenho inferior quando comparado ao grupo de desenvolvimento típico.Conclusão: apesar da necessidade de mais estudos, nossos resultados suportam a utilidade clínica de uma intervenção baseada em tarefas de realidade virtual para pessoas com síndrome de Down. Em conclusão, considera-se útil o uso dessa tecnologia para melhorar o tempo de reação dessa população

Association between illness perception and clinical control, quality of life, physical activity, and psychosocial status in subjects with moderate to severe asthma: a cluster analysis.

Background: Illness perception (IP) is a psychosocial factor involved in several chronic diseases and is associated with relevant clinical outcomes. However, the relationship between IP and health-related quality of life (HRQoL), psychosocial status, and physical activity in daily life (PADL) in subjects with asthma is poorly understood.Objective: To identify groups of subjects with asthma based on their IPs and to assess their association with clinical control, HRQoL, psychosocial disturbances, and PADL.Methods: This cross-sectional study included 149 subjects with moderate to severe asthma. IP, anthropometric data, Asthma Control Questionnaire-7, Asthma Quality of Life Questionnaire, Hospital Anxiety and Depression Scale, PADL (accelerometry), and general self-efficacy (GSE) were assessed. Cluster analysis was performed to identify clusters with similar profiles and investigate their characteristics and differences. Pearson's correlation coefficient was used to test the associations between IP and other variables.Results: Statistical analyses identified two clusters of subjects with asthma based on IP. Cluster 1 presented worse IP in seven out of eight domains than Cluster 2. Cluster 1 had more negative consequences of the disease, worse understanding, and a high emotional representation of the disease than Cluster 2. Cluster 1 also had a greater extent of asthma symptoms, poor clinical control, worse HRQoL, and more symptoms of anxiety and depression. No difference between clusters was found for PADL or self-efficacy.Conclusion: Subjects with asthma who have worse IP have more negative symptoms, worse clinical control, HRQoL, and symptoms of anxiety and depression.

Extract from Opuntia ficus-indica cladode delays the Aedes aegypti larval development by inducing an axenic midgut environment.

This study evaluated the effects of acute exposure of Aedes aegypti third instar (L3 ) larvae to the saline extract of Opuntia ficus-indica cladodes on the biological cycle and fertility of the emerging adults. For this, larvae were treated for 24 h with the extract at » LC50 (lethal concentration to kill 50% of larvae), ½ LC50 or LC50 ; the development and reproduction of the emerged adults were evaluated after a recovery period of 9 days. The resistance of proteins in the extract to hydrolysis by L3 digestive enzymes and histomorphological alterations in the larval midgut were also investigated. The extract contained lectin, flavonoids, cinnamic derivatives, terpenes, steroids, and reducing sugars. It showed a LC50 of 3.71% for 48 h. The data indicated mean survival times similar in control and extract treatments. It was observed development delay in extract-treated groups, with a lower number of adults than in control. However, the females that emerged laid similar number of eggs in control and treatments. Histological evaluation revealed absence of bacterial and fungal microorganisms in the food content in midguts from larvae treated with cladode extract. Electrophoresis revealed that three polypeptides in the extract resisted to hydrolysis by L3 digestive proteases for 90 min. The lectin activity was not altered even after 24-h incubation with the enzymes. In conclusion, the extract from O. ficus-indica can delay the development of Ae. aegypti larvae, which may be linked to induction of an axenic environment at larval midgut and permanence of lectin activity even after proteolysis.

Development of Biodegradable PLA/PBAT-Based Filaments for Fertilizer Release for Agricultural Applications.

The aim of this work was to produce filaments of PLA/PBAT and NPK fertilizer adsorbed on organophilized bentonite intended for application in the prototyping of biodegradable agricultural artifacts in 3D printing, using the Fused Deposition Modeling (FDM) technique. This is the first time that we have reported this composite for a 3D printing approach. Systems containing PLA/PBAT, organobentonite and NPK were initially processed in an internal mixer and later extruded as filaments in a single-screw extruder. The prototypes were printed by FDM. Structural, morphological and thermal properties, as well as NPK releasing, were investigated. The results suggest that exfoliated and/or intercalated nanocomposites were obtained by the organoclay addition to the PLA/PBAT blend. The morphological analysis revealed a good surface quality of the impressions. Systems containing organobentonite released approximately 22% less fertilizer in 24 h compared to the systems without organobentonite. This difference is due to the higher concentration of nanoparticles that generate more barriers to the diffusion of NPK. The release data for these systems had a better fit to the kinetic model of Korsmeyer-Peppas. Thus, studied filaments have the potential to retard the release of fertilizer and are suitable for further development of structures for agricultural applications by FDM.

Effects of Foot Orthoses on Pain and the Prevention of Lower Limb Injuries in Runners: Systematic Review and Meta-Analysis.

CONTEXT: A variety of approaches have been proposed to prevent lower limb injuries in runners. However, the evidence for the effectiveness of interventions to reduce lower limb pain and injury after intensive running is very weak. OBJECTIVE: The authors performed a systematic review to investigate the effects of foot orthoses on pain and the prevention of lower limb injuries in runners. EVIDENCE ACQUISITION: The authors searched the MEDLINE/PubMed, Physiotherapy Evidence Database, Scielo, and Cochrane Central (from inception to February 2022) databases for randomized controlled trials that evaluated the effects of foot orthoses in runners. The authors then calculated mean differences and 95% confidence intervals from these trials. Heterogeneity was assessed using the I2 test. Furthermore, the authors compared the criteria between runners with foot orthoses and ones with no intervention (control group). EVIDENCE SYNTHESIS: Twelve studies (5321 runners) met our review criteria. The control and the foot orthoses group sustained 721 (37%) and 238 (24%) injuries, respectively. Compared with the control group, the use of foot orthoses resulted in a significant reduction in lower limb injury risk (risk ratio = 0.6; 95% confidence interval, 0.5-0.7; P = .00001, I2 = 54%; 7 studies, N = 2983: moderate-quality evidence). Moreover, the foot orthoses group corresponded to a 40% reduction in the risk of developing lower limb injuries. CONCLUSIONS: The use of foot orthoses may help reduce the incidence of lower limb injuries and pain in runners.

Granuloma annulare and necrobiosis lipoidica in a patient with HNF1A-MODY

SUMMARY Maturity-onset diabetes of the young (MODY) is a heterogeneous group of monogenic forms of diabetes mellitus with distinct clinical features. Clinical dermatological phenotypes in MODY patients are very rare in literature. This report describes a patient with HNF1A-MODY presenting with necrobiosis lipoidica (NL) and granuloma annulare (GA). A 39-year-old asymptomatic woman, with atypical diabetes diagnosed at age 17, has a confirmed HNF1A mutation on exon 2 (c.392G>A, p.R131Q), classified as Pathogenic by the ACMG guidelines. She has reasonable metabolic control using oral anti-diabetic medications and has no chronic diabetic complications. Clinical and histologic diagnoses of both NL and GA were made. We discuss these conditions and their association with MODY.

Granuloma annulare and necrobiosis lipoidica in a patient with HNF1A-MODY.

Maturity-onset diabetes of the young (MODY) is a heterogeneous group of monogenic forms of diabetes mellitus with distinct clinical features. Clinical dermatological phenotypes in MODY patients are very rare in literature. This report describes a patient with HNF1A-MODY presenting with necrobiosis lipoidica (NL) and granuloma annulare (GA). A 39-year-old asymptomatic woman, with atypical diabetes diagnosed at age 17, has a confirmed HNF1A mutation on exon 2 (c.392G>A, p.R131Q), classified as Pathogenic by the ACMG guidelines. She has reasonable metabolic control using oral anti-diabetic medications and has no chronic diabetic complications. Clinical and histologic diagnoses of both NL and GA were made. We discuss these conditions and their association with MODY.

Carga de comorbidade e qualidade de vida em indivíduos portadores de insuficiência cardíaca com fração de ejeção preservada / Comorbidity burden and quality of life in individuals with heart failure with preserved ejection fraction

INTRODUÇÃO: A Insuficiência cardíaca com fração de ejeção preservada (ICFEP) corresponde a uma síndrome clínica caracterizada por fração de ejeção maior que 50%. Apesar disso, os portadores dessa afecção apresentam diversos sinais e sintomas limitantes, com destaque para a dispneia e a fadiga, contribuindo para um comprometimento da funcionalidade com impacto negativo na qualidade de vida. Adicionalmente, essa condição pode ser agravada com a carga de comorbidade apresentada pelo indivíduo portador dessa doença. OBJETIVO: Avaliar a influência da carga de comorbidade na qualidade de vida de indivíduos com ICFEP. MÉTODOS: Foi realizado um estudo transversal com 67 pacientes de ambos os gêneros, com idade entre 18 e 75 anos, assistidos em um ambulatório de medicina cardiovascular personalizada de um hospital público. Os indivíduos foram divididos em: grupo com duas comorbidades simultâneas (G2), grupo com três comorbidades simultâneas (G3) e grupo com quatro ou mais comorbidades simultâneas (G4+). A qualidade de vida foi estimada por meio da pontuação no questionário de Minnesota. A normalidade dos dados foi avaliada por meio do teste Shapiro Wilk e os dados não paramétricos por meio do teste Kruskal. CAAE: 39592920.3.0000.5462 RESULTADOS: A pontuação no questionário de qualidade de vida variou conforme a carga de comorbidade (G1 = 23,3 ± 21,0; G2 = 24,2 ± 20,0; G3 = 44,1 ± 28,2) com diferença estatística entre os GCM2 e o GCM4. CONCLUSÃO: O presente estudo sugere que a carga de comorbidade influencia negativamente na qualidade de vida, visto que os indivíduos com um número maior de comorbidades simultâneas apresentaram maior comprometimento da qualidade de vida.

Digital Management Systems in Academic Health Sciences Laboratories: A Scoping Review.

Good laboratory practices (GLP) increase the quality and traceability of results in health sciences research. However, factors such as high staff turnover, insufficient resources, and a lack of training for managers may limit their implementation in research and academic laboratories. This Scoping Review aimed to identify digital tools for managing academic health sciences and experimental medicine laboratories and their relationship with good practices. Following the PRISMA-ScR 2018 criteria, a search strategy was conducted until April 2021 in the databases PUBMED, Web of Sciences, and Health Virtual Library. A critical appraisal of the selected references was conducted, followed by data charting. The search identified twenty-one eligible articles, mainly originated from high-income countries, describing the development and/or implementation of thirty-two electronic management systems. Most studies described software functionalities, while nine evaluated and discussed impacts on management, reporting both improvements in the workflow and system limitations during implementation. In general, the studies point to a contribution to different management issues related to GLP principles. In conclusion, this review identified evolving evidence that digital laboratory management systems may represent important tools in compliance with the principles of good practices in experimental medicine and health sciences research.

Inflammatory and neurotrophic factor plasma levels are related to epilepsy independently of etiology.

OBJECTIVE: Inflammation plays an essential role in epilepsy. Studies indicate that cytokines and neurotrophic factors can act in neuroexcitability and epileptogenesis. We aimed to investigate the association between plasma inflammatory and neurotrophic markers, seizure frequency, and chronic epilepsy subtypes. METHODS: We studied 446 patients with epilepsy and 166 healthy controls. We classified patients according to etiology and seizure frequency. We measured plasma levels of interleukin-1 (IL-1), IL-2, IL-4, IL-6, IL-10, IL-17, interferon-γ (IFNγ), tumor necrosis factor α (TNFα), soluble TNF receptor 1 (sTNFr1), sTNFr2, brain-derived neurotrophic factor (BDNF), neurotrophic factor 3 (NT3), NT4/5, ciliary neurotrophic factor (CNTF), nerve growth factor (NGF), and glial cell line-derived neurotrophic factor (GDNF) by enzyme-linked immunosorbent assay or cytometric bead array. RESULTS: The plasma levels of BDNF, NT3, NGF, and sTNFr2 were higher, whereas IL-2, IL-4, IL-6, IL-10, IL-17, IFNγ, TNFα, CNTF, and sTNFr1 were lower in patients than controls. IL1, GDNF, and NT4/5 were similar between groups. These markers did not correlate with age, sex, and epilepsy duration. The molecule sTNFr2 was the best marker to discriminate patients from controls (area under the curve = .857), also differing between patients with frequent and infrequent seizures. SIGNIFICANCE: This large cohort confirmed that patients with epilepsy have abnormal levels of plasma inflammatory and neurotrophic markers independent of the underlying etiology. Plasma level of sTNFr2 was related to seizure frequency and discriminated people with or without epilepsy with good accuracy, making it a potential biomarker for epilepsy and seizure burden.

FMRF-related peptides in Aedes aegypti midgut: neuromuscular connections and enteric nervous system.

FMRFamide-related peptides (FaRPs) are a class of neuropeptides that participate in a variety of physiological processes in invertebrates. They occur in nerves of stomatogastric ganglia and enteroendocrine cells of the insect digestive tract, where they may control muscle functions. However, their direct involvement in muscle function has never been shown in situ. We studied the relationship between FaRPs and midgut muscle during larval-pupal transition of the mosquito Aedes aegypti. In late L4, FaRP-positive neuronal extensions attach to the bundles of the external circular muscle layer, and muscle stem cells start to undergo mitosis in the internal circular layer. Thereafter, the external muscle layer degenerates, disappearing during early pupal development, and is completely absent in the adult mosquito. Our results indicate that FaRP-based neural signals are involved in the reorganization of the muscle fibers of the mosquito midgut during the larval-pupal transition. In addition to confirming FaRP involvement in muscle function, we show that the mosquito midgut muscles are largely innervated, and that circular and longitudinal muscle have specific neuron bodies associated with them.

Clinical variables that help in predicting the presence of autoantibodies in patients with acute encephalitis.

OBJECTIVE: To identify clinical variables that could predict the presence of autoantibodies in patients with acute encephalitis. METHODS: An observational, retrospective study from May 2011 to May 2017. Clinical, EEG, brain MRI data, and antibodies against human neuronal antigens (NMDAR, GABAR, AMPAR, LGI1, CASPR2, and GAD) from 158 patients with criteria for possible autoimmune encephalitis were analyzed to create a predictive model for this disease. RESULTS: We analyzed 158 samples, of which 18 cases were positive for anti-NMDAR, 2 for anti-LGI1, and 2 for anti-GAD. Seven of the 18 positive NMDAR patients were children, and 12 were female. Behavioral disorder, epileptic seizures, movement disorder, and altered level of consciousness were the frequent symptoms with >75 % sensitivity in positive anti-NMDAR patients. Other symptoms, such as language disorder, psychosis, hypoventilation, altered wake and sleep cycle, and cognitive impairment, had a sensitivity >55 %. Abnormal EEG findings had a high sensitivity (99.4 %). Brain MRI suggestive of encephalitis was observed in 7 of the positive cases for NMDAR. Abnormal CSF findings were reported in 12 patients positive for this receptor (sensitivity 70.6 %). With 7 of these symptoms, we obtained a sensitivity of 70 % and specificity of 81 % for the presence of anti-NMDAR antibodies (ROC Area 82 %). However, to predict that a patient with subacute encephalitis may have an autoimmune cause, the patient should include clinical manifestations such as movement disorder, behavioral disorder, hypoventilation, dysautonomia, and alteration of the wake and sleep cycle. Children were significantly more likely than adults with autoimmune encephalitis to experience chorea and status epilepticus (p < 0.05). CONCLUSIONS: Anti-NMDAR encephalitis was more frequent in females and children. The repertoire of autoimmune encephalitis in children is different from adults. The presence of subacute behavioral changes, epileptic seizures, movement disorders, altered consciousness, hypoventilation, dysautonomia, and altered wake and sleep cycle predicted autoimmune encephalitis in our series.