4-Octyl itaconate inhibits inflammation via the NLRP3 pathway in neuromyelitis optica spectrum disorders.

OBJECTIVE: Neuromyelitis optica spectrum disorders (NMOSD) are rare inflammatory astrocytic diseases of the central nervous system (CNS). The roles of immune response gene-1 (IRG1) and the IRG1-itaconic acid-NLRP3 inflammatory pathway in the pathogenesis of NMOSD and the effects of 4-octyl itaconate (4-OI) on the NLRP3 inflammatory pathway in NMOSD are unclear. This study aimed to determine the role of IRG1 and the activation status of the NLRP3 inflammatory pathway in acute-onset NMOSD and to investigate the inhibitory effects of 4-OI on NLRP3 inflammasome activation via the IRG1-itaconic acid-NLRP3 pathway in monocytes and macrophages by using in vitro models. METHODS: Peripheral blood mononuclear cells (PBMCs) and serum were collected from patients with acute NMOSDs and healthy controls (HC), followed by monocyte typing and detection of the expression of NLRP3-related inflammatory factors. Subsequently, the effects of 4-OI on the IRG1-itaconic acid-NLRP3 pathway were investigated in peripheral monocytes from patients with NMOSD and in macrophages induced by human myeloid leukemia mononuclear cells (THP-1 cells) via in vitro experiments. RESULTS: Patients with acute NMOSD exhibited upregulated IRG1 expression. In particular, the upregulation of the expression of the NLRP3 inflammasome and proinflammatory factors was notable in monocytes in acute NMOSD patients. 4-OI inhibited the activation of the IRG1-itaconic acid-NLRP3 inflammatory pathway in the PBMCs of patients with NMOSD. INTERPRETATION: 4-OI could effectively inhibit NLRP3 signaling, leading to the inhibition of proinflammatory cytokine production in patients with NMOSD-derived PBMCs and in a human macrophage model. Thus, 4-OI and itaconate could have important therapeutic value for the treatment of NMOSD in the future.

Elevated levels of ß2-microglobulin in cerebrospinal fluid in adult patients with viral encephalitis/meningitis.

BACKGROUND: Increased cerebrospinal fluid (CSF) ß2-microglobulin (ß2-MG) values are attributed to immune activation, lymphoid cell turnover and release of tissue destruction in the central nervous system (CNS). We investigated plasma and CSF ß2-MG levels in adult patients with viral encephalitis/meningitis and their correlations with clinical parameters. METHOD: CSF samples from 26 patients with viral encephalitis/meningitis were collected. Moreover, 24 CSF samples from patients with non-inflammatory neurological disorders (NIND) as controls were collected. Plasma samples from 22 enrolled patients and 20 healthy individuals were collected. The ß2-MG levels were measured by immunoturbidimetry on an automatic biochemical analyzer. Clinical data were extracted from an electronic patient documentation system. RESULT: CSF levels of ß2-MG, adenosine deaminase (ADA), white blood cell (WBC), lactate dehydrogenase (LDH), protein and lactate were significantly increased in patients with viral encephalitis/meningitis respectively (p < 0.001, p < 0.001, p < 0.001, p = 0.001, p < 0.001, p = 0.013). In contrast, no statistically significant difference was found in plasma levels of ß2-MG. Furthermore, CSF levels of ß2-MG were weakly correlated with WBC (r = 0.426, p = 0.030), lymphocyte percentage (r = 0.599, p = 0.018), ADA (r = 0.545, p = 0.004) and LDH (r = 0.414, p = 0.036), but not with lactate (r = 0.381, p = 0.055), protein (r = 0.179, p = 0.381) and plasma levels of ß2-MG (r = -0.156, p = 0.537) in viral encephalitis/meningitis patients. CONCLUSION: CSF ß2-MG may be a potential inflammatory marker for viral encephalitis/meningitis in adult patients diagnosed with viral encephalitis/meningitis.

[Effect of Rehmanniae Radix Praeparata on energy metabolism in prefrontal cortex of rats with attention deficit hyperactivity disorder based on "static Yin and dynamic Yang" theory].

The present study investigated the effect of Rehmanniae Radix Praeparata(RRP) on the energy metabolism of prefrontal cortex(PFC) of spontaneously hypertensive rats with attention deficit hyperactivity disorder(ADHD) based on the "static Yin and dynamic Yang" theory.Thirty spontaneously hypertensive male rats aged 3 weeks were randomly divided into a model group, a methylphenidate(MPH) group(2 mg·kg~(-1)), and an RRP group(2.4 g·kg~(-1)).Wistar-Kyoto(WKY) male rats of the same age were assigned to the normal group.Rats were treated with corresponding drugs twice per day, and those in the model group and the normal group received the same volume of 0.9% sodium carboxymethyl cellulose(CMC-Na) solution by gavage.The open-field test was performed to evaluate the spontaneous and impulsive behaviors of rats before treatment and on the 4~(th) week after treatment.Four weeks after treatment, PFC was isolated and mitochondria were prepared.The content of adenosine triphosphate(ATP), adenosine diphosphate(ADP), and adenosine monophosphate(AMP) in the PFC was determined by high-performance liquid chromatography(HPLC), and energy charge(EC) was calculated.The parameters related to mitochondrial respiratory function were measured by the Clark oxygen electrode, specifically, state 3 respiration(ST3), state 4 respiration(ST4), and respiratory control rate(RCR).Enzymatic activities of succinate dehydrogenase(SDH), cytochrome C oxidase(COX), Na~+-K~+-ATPase, and Ca~(2+)-Mg~(2+)-ATPase were measured by chemical colorimetry.Mitochondrial permeability transition pore(mPTP) opening was measured by spectrophotometry.Protein expression of glucose transporter 1(GLUT1) and GLUT3 in PFC was tested by Western blot.Compared with the results in the model group, RRP could significantly reduce the total distance of movement, vertical times, and distance in the central area in the open field test(P<0.05 or P<0.01), increase the content of ATP and EC, decrease the content of AMP(P<0.05), elevate ST3 and RCR(P<0.05), potentiate activities of SDH, COX, Na~+-K~+-ATPase, and Ca~(2+)-Mg~(2+)-ATPase(P<0.05 or P<0.01), inhibit the opening of mPTP, and increase the expression levels of GLUT1 and GLUT3 proteins(P<0.05).It was inferred that RRP could inhibit hyperacti-vity and impulsivity by improving the energy metabolism disorder in PFC of ADHD rats, and its mechanism may be related to the improvement of mitochondrial respiratory function, potentiation of Na~+-K~+-ATPase, Ca~(2+)-Mg~(2+)-ATPase, and mitochondrial respiratory enzymes, inhibition of the opening of mPTP, and up-regulation of the expression of glucose transporter proteins.This study initially reveals the biological connotation of the "static Yin and dynamic Yang" theory in ADHD.

A new risk stratification strategy for fatty liver disease by incorporating MAFLD and fibrosis score in a large US population.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newly proposed definition of fatty liver disease (FLD) independent of excessive alcohol consumption (EAC) and hepatitis viral infection. Evidence on the mortality risk in different types of FLD [nonalcoholic FLD (NAFLD), alcoholic FLD (AFLD), and MAFLD] is sparse, hindering the identification of high-risk populations for preferential clinical surveillance. METHODS: A total of 11,000 participants in the Third National Health and Nutrition Examination Survey were enrolled. Participants were categorized into three groups [FLD( - ), MAFLD( - ), and MAFLD( +)] according to FLD and MAFLD criteria, and further categorized into six groups by EAC. Multivariate Cox proportional hazard model was used to estimate the risk of all-cause, cardiovascular-related, and cancer-related mortality. RESULTS: During a median follow-up of 23.2 years, a total of 3240 deaths were identified. Compared with FLD( - )/EAC( - ) participants, MAFLD( +) individuals had higher all-cause mortality risk [hazard ratio (HR) = 1.28, 95% confidence interval (CI) = 1.18-1.39] regardless of EAC status [MAFLD( +)/NAFLD: HR = 1.22, 95%CI = 1.11-1.34; MAFLD( +)/AFLD: HR = 1.83, 95%CI = 1.46-2.28], while not for MAFLD( - ) individuals. Furthermore, diabetes-driven-MAFLD had higher mortality risk (HR = 2.00, 95%CI = 1.77-2.27) followed by metabolic dysregulation-driven-MAFLD (HR = 1.30, 95%CI = 1.06-1.60) and overweight/obesity-driven-MAFLD (HR = 1.11, 95%CI = 1.00-1.22). Additionally, MAFLD( - ) participants with elevated fibrosis score were also associated with statistically significantly higher mortality risk (HR = 3.23, 95%CI = 1.63-6.40). CONCLUSIONS: Utilizing a representative sample of the US population, we proved the validity of MAFLD subtype and fibrosis score, rather than the traditional definition (NAFLD and AFLD), in the risk stratification of FLD patients. These findings may be applied to guide the determination of surveillance options for FLD patients.

Roles of IL-35-producing T and B cells in anti-acetylcholine receptor antibody-positive myasthenia gravis.

BACKGROUND: Interleukin 35 (IL-35) plays an anti-inflammatory in numerous autoimmune diseases. However, the potential roles of IL-35-producing T and B cells and serum IL-35 levels in the pathogenesis of myasthenia gravis (MG) and its association with disease activity in patients with MG remain unclear. METHODS: The percentages of IL-35-producing CD4 + CD25 + T cells and CD19 + B cells among peripheral blood mononuclear cells were determined in 37 patients with anti-acetylcholine receptor (AChR) antibody-positive MG and 35 healthy controls (HCs) by performing a flow cytometry analysis. Serum IL-35 levels in participants were determined using an enzyme-linked immunosorbent assay. Further, the correlations between IL35 levels and disease activity were analysed. RESULTS: The percentages of IL-35-producing CD4 + CD25 + T cells and CD19 + B cells were significantly lower in patients with anti-AChR antibody-positive MG than in HCs (p = 0.001 and p = 0.002, respectively). Furthermore, patients with thymoma and patients with generalized MG had lower percentages of IL-35-producing CD4 + CD25 + T cells and CD19 + B cells than those without thymoma and those with ocular MG (p = 0.001 and p = 0.003; p = 0.008 and p = 0.001, respectively). Interestingly, the suppression of IL-35 secretion correlated negatively with the activities of daily living scores of patients with MG (r = -0.4774, p = 0.0028) and the quantitative MG scores (r = -0.4656, p = 0.0037). The proportions of IL-35-producing T cells and B cells and serum levels of IL-35 increased after treatment. CONCLUSIONS: IL-35 may represent a potential biomarker for the clinical evaluation of MG.

Acute effect of high-definition and conventional tDCS on exercise performance and psychophysiological responses in endurance athletes: a randomized controlled trial.

Transcranial direct current stimulation (tDCS) has been used aiming to boost exercise performance and inconsistent findings have been reported. One possible explanation is related to the limitations of the so-called "conventional" tDCS, which uses large rectangular electrodes, resulting in a diffuse electric field. A new tDCS technique called high-definition tDCS (HD-tDCS) has been recently developed. HD-tDCS uses small ring electrodes and produces improved focality and greater magnitude of its aftereffects. This study tested whether HD-tDCS would improve exercise performance to a greater extent than conventional tDCS. Twelve endurance athletes (29.4 ± 7.3 years; 60.15 ± 5.09 ml kg-1 min-1) were enrolled in this single-center, randomized, crossover, and sham-controlled trial. To test reliability, participants performed two time to exhaustion (TTE) tests (control conditions) on a cycle simulator with 80% of peak power until volitional exhaustion. Next, they randomly received HD-tDCS (2.4 mA), conventional (2.0 mA), or active sham tDCS (2.0 mA) over the motor cortex for 20-min before performing the TTE test. TTE, heart rate (HR), associative thoughts, peripheral (lower limbs), and whole-body ratings of perceived exertion (RPE) were recorded every minute. Outcome measures were reliable. There was no difference in TTE between HD-tDCS (853.1 ± 288.6 s), simulated conventional (827.8 ± 278.7 s), sham (794.3 ± 271.2 s), or control conditions (TTE1 = 751.1 ± 261.6 s or TTE2 = 770.8 ± 250.6 s) [F(1.95; 21.4) = 1.537; P = 0.24; η2p = 0.123]. There was no effect on peripheral or whole-body RPE and associative thoughts (P > 0.05). No serious adverse effect was reported. A single session of neither HD-tDCS nor conventional tDCS changed exercise performance and psychophysiological responses in athletes, suggesting that a ceiling effect may exist.

Interleukin-27 levels in patients with myasthenia gravis.

Interleukin-27 (IL-27), which belongs to IL-12 family, influences the function of T cells (Tregs) through regulating the expression, and function of forkhead box P3 (FoxP3). In this study, we detected the IL-27 serum levels in 59 myasthenia gravis (MG) patients and 35 healthy controls (HCs). Among them, 32 MG patients received immunoglobulin intravenous (IVIG) injections (0.4 g/kg per day for 5 consecutive days). IL-27 levels were collected before and after the treatments and subjected to a comparative study. Finally, we assessed the correlations of IL-27 levels with the clinical characteristics of MG. As a result, serum IL-27 levels were significantly higher in MG patients than those in the HCs. Meanwhile, significant reduction was detected after the IVIG treatment. IL-27 levels positively correlated with both MG activities of daily living and quantitative MG score. IL-27 may participate in the pathogenesis of MG and can be used as an early marker for the diagnosis and prognosis of MG. In addition, IL-27 can be used as a target for MG treatment through the regulation of specific immune signaling and maintaining immune homeostasis.

Long noncoding RNA ZNF800 suppresses proliferation and migration of vascular smooth muscle cells by upregulating PTEN and inhibiting AKT/mTOR/HIF-1α signaling.

BACKGROUND AND AIMS: Long noncoding RNAs (lncRNAs) have recently been implicated in many biological and disease processes, but the exact mechanism of their involvement in atherosclerosis is unclear. The aberrant proliferation and migration of vascular smooth muscle cells (VSMCs) is a major contributor to the development of atherosclerotic lesions. This study aimed to investigate the potential effects of lncRNA ZNF800, a previously uncharacterized lncRNA, on VSMC proliferation and migration. METHODS: The expression of lncRNA ZNF800 in atherosclerotic plaque tissues was detected using reverse transcription-quantitative PCR (RT-qPCR), while the role and mechanism of lncRNA ZNF800 in proliferation and migration of VSMCs were investigated by CCK8 assay, transwell assay, scratch wound assay, RT-qPCR and Western blot. RESULTS: We found that lncRNA ZNF800 was significantly more abundant in atherosclerotic plaque tissues, and substantially suppressed the proliferation and migration of VSMCs. LncRNA ZNF800 had no effect on phosphatase and tensin homolog deleted on chromosome 10 (PTEN) mRNA expression but dramatically increased the levels of PTEN protein. Enhanced lncRNA ZNF800 expression inhibited the activity of the AKT/mTOR/HIF-1α signaling pathway, downregulated the expression of vascular endothelial growth factor α (VEGF-α) and matrix metalloproteinase 1 (MMP1), and suppressed VSMC proliferation and migration. These inhibitory effects of lncRNA ZNF800 were abolished by knockdown of PTEN. The inhibitory effects of lncRNA ZNF800 on cell proliferation and migration and the expression of VEGF-α and MMP1 were exacerbated by HIF-1α knockdown in VSMCs. CONCLUSIONS: These findings demonstrated that lncRNA ZNF800 suppressed VSMC proliferation and migration by interacting with PTEN through a mechanism involving AKT/mTOR/HIF-1α signaling. Therefore, it may play a key atheroprotective role and represent a potential therapeutic target for atherosclerosis-related diseases.

[Influencing Factors and Prevation of Infection in Leukemia Patients after Allogeneic Peripheral Blood Stem Cell Transplantation].

OBJECTIVE: To explore the influencing factors and countermeasures of infection in leukemia patients after allogeneic peripheral blood hematopoietic stem cell transplantation. METHODS: A total of 126 patients with leukemia admitted in our hospital from August 2016 to March 2018 were selected. The number of infected patients after transplantation was recorded, and the causes of infection were analyzed. RESULTS: Among the 126 patients, 43 were positive for infection, and the infection rate was 34.13%. A total of 89 pathogens were detected, of which bacteria accounted for 64.05%; virus accounted for 22.47%, and fungi accounted for 13.48%. The patient's age, donor type, pre-transplant infection, prophylactic use of antibiotics and aGVHD all were factors influencing the patient's infection (P＜0.05). The follow-up results showed that the incidence of infection in the intervention group significantly decreased after intervention with prevention program (P＜0.05). After reasonable nursing intervention, the incidence of infection in the intervention group after follow-up for 12 months was lower than that in the control group (P＜0.05). CONCLUSION: Pre-transplant infection and prophylactic use of antibiotics are factors influencing the infection after allogeneic hematopoietic stem cell transplantation. The incidence of infection can be reduced by reasonable infection prevention.

[The cell cycle pathway regulates chicken abdominal fat deposition as revealed by transcriptome sequencing].

With the improvement of growth traits and feed conversion rate, the abdominal fat rate of Chinese local breeds of broilers has been increasing. Excessive abdominal fat deposition not only reduces the slaughter rate and disease resistance of broiler chickens, but also produces waste due to the difficulty of fat treatment. In order to study the regulatory genes and pathways involved in abdominal fat deposition of broilers, we used high-fat diets to feed the Xinghua Chicken, which is a Chinese local breed. Two weeks after feeding, we found that the abdominal fat weight and rate of broilers in the high-fat diet group increased significantly, and the diameter and area of abdominal fat cells also increased significantly. Transcriptome sequencing of abdominal fat and livers showed that the differentially expressed genes in the abdominal fat were mainly enriched in the cell cycle, peroxisome proliferator- activated receptor (PPAR) and extracellular matrix (ECM) receptor signaling pathways. The differentially expressed genes in livers were also significantly enriched in the cell cycle pathway, as well as in the steroid biosynthesis and PPAR signaling pathway. By analyzing the common differentially expressed genes in abdominal fat and liver tissues, we found that these genes were also enriched in cell cycle. Finally, we used the chicken LMH (chicken hepatoma cell) cell line and chicken ICP (immortalized chicken preadipocytes) cell line to do the in vitro validation assays. We used high-fat and common medium to culture the cells. The results showed that after 48 hours, the high-fat medium could significantly promote cell cycle and increase the number of cells in S phase. Additionally, qRT-PCR results showed that the high-fat medium could significantly promote the expression of genes related to cell cycle. In conclusion, we found that high-fat diets activate the cell cycle progression of chicken hepatocytes and preadipocytes, promote cell proliferation, and then increase abdominal fat deposition.

Elevated resistin levels may regulate high mobility group box 1 expression in Guillain-Barré syndrome.

Interactions among cytokines have important roles in the inflammatory processes underlying Guillain-Barré syndrome (GBS). Resistin and high mobility group box 1 (HMGB1) are involved in many inflammatory processes. This study examined 51 GBS patients, and found that serum resistin levels were elevated in 51 patients with GBS and correlated with HMGB1 levels. In vitro, resistin induced the release of HMGB1, interleukin (IL)-1ß, and IL-6 in THP-1 macrophages. This process was dependent on activation of p38 mitogen-activated protein kinase and NF-κB signaling pathways. These results suggest that signaling between resistin and HMGB1 might be a potential therapeutic target in GBS.

Web-Based Undergraduate Medical Education in a Virtual Learning Environment Using an Original Pedagogical Approach: an Observational Longitudinal Study / Educação médica de graduação via web em um ambiente virtual de aprendizagem utilizando uma abordagem pedagógica original: um estudo observacional longitudinal

ABSTRACT Background Asynchronous Web-based Medical Education in Virtual Learning Environments (VLEs) has grown steadily because of its many advantages. Various configurations and instructional methods are presently available. The existing proposals are poorly structured and/or not very effectively used for teaching diagnostic skills to undergraduate medical students in Brazil. A robust instructional method with positive pedagogical characteristics is needed. Thus, we have proposed a pedagogically-structured method for VLEs that includes a motivating initial reading (Medical Chronicle - MC), and a knowledge building program, using real cases coupled with audiovisual resources (Diagnostic Workshop - DW). We aimed to verify its acceptance, as well as the efficacy of the MC/DW method in improving the diagnostic ability of medical students, in the long term. Methods An opinion survey, two MC/DW materials and two Knowledge and Diagnostic Skills (KDS) questionnaires on stroke and epilepsy were developed, and two medical student groups were followed up in this 2013 longitudinal observational study. The students answered a KDS1, and attended a traditional lecture on one of the topics. They also accessed a VLE to apply the MC/DW method on stroke or epilepsy. We applied the same questionnaire (KDS2 and KDS3, respectively), one month and 5-6 months after the KDS1. We analyzed the mean KDS1 score of all the students, and the mean pairwise of those who accessed and those who did not access the VLEs during these three stages. An opinion survey was applied, and the results were analyzed by descriptive statistics. Results 87 students participated in the study, but six were excluded as they did not answer the questionnaires. The KDS1 general mean score was 1.59 (SD0.71). We found that 66 students (81.5%) accessed the VLE, showing a significant improvement in diagnostic skills in the KDS2 (mean5.65, p<0.05) and KDS3 (mean 4.57, p<0.05), with non-significant variations for those who did not access it. The MC was considered at least good for 62 students (94%), with 52 students (78.8%) finding that a checklist was sufficient to clear up all their DW doubts. Conclusions The MC/DW method in VLE proved to be effective for improving the diagnostic capability of the undergraduate medical students in the long term, and it was well accepted by the students. It presents several positive pedagogical characteristics and can be replicated.

RESUMO Contexto A educação médica assíncrona via web, em Ambientes de Aprendizagem Virtual (AVA), cresceu muito, em virtude de suas diversas vantagens. Há várias configurações e métodos de instrução disponíveis. As propostas existentes são pouco estruturadas e/ou não são efetivamente utilizadas para o ensino de habilidades de diagnóstico para estudantes de graduação em Medicina, no Brasil. É necessário um método instrutivo robusto, com características pedagógicas positivas. Assim, propomos um método pedagogicamente estruturado para AVA, que inclui uma leitura inicial motivadora (Crônica Médica - CM) e um programa de construção de conhecimento, utilizando casos reais juntamente com recursos audiovisuais (Oficina Diagnóstica - OD). Objetivamos verificar a aceitação e a eficácia do método proposto na melhoria da capacidade diagnóstica dos estudantes de Medicina, em longo prazo. Métodos Foi desenvolvido um questionário de opiniões, dois materiais CM/OD e dois questionários de Conhecimento e Habilidades Diagnósticas (CHD) sobre acidente vascular encefálico e epilepsia. Dois grupos de estudantes de Medicina foram acompanhados neste estudo observacional longitudinal, em 2013. Os alunos responderam ao CHD1 e participaram de uma aula teórica tradicional, sobre um dos tópicos. Eles também acessaram um AVA para realizar o método CM/OD sobre um dos dois temas. O mesmo questionário (CHD2 e CHD3) foi aplicado, respectivamente, um mês e cinco-seis meses após o CHD1. Analisamos a média CHD1 de todos os alunos e as médias pareadas nos três momentos, dos que acessaram e daqueles que não acessaram o AVA. O questionário de opiniões foi aplicado e analisado por estatística descritiva. Resultados Oitenta e sete alunos participaram, mas seis foram excluídos por não responderem a todos os questionários. A média geral do CHD1 foi de 1,59 (desvio-padrão 0,71). Dos 81 participantes, 66 (81,5%) acessaram o AVA, mostrando melhora significativa nas habilidades de diagnóstico no CHD2 (média 5,65, p <0,05) e CHD3 (média 4,57, p < 0,05), com variações não significativas para aqueles que não acessaram. A CM foi considerada pelo menos boa para 62 alunos (94%), e 52 alunos (78,8%) julgaram que o gabarito disponível foi suficiente para sanar todas as dúvidas da OD. Conclusões O método CM/OD no AVA provou ser eficaz para melhorar a capacidade de diagnóstico dos estudantes de graduação em Medicina, em longo prazo, e foi bem aceito pelos alunos. Ele apresenta várias características pedagógicas positivas e pode ser replicado.

Multi-view autostereoscopic system for 3D visualization in anatomy

Abstract Introduction The use of 3D imaging in the medical field has proven to be a benefit to doctors when diagnosing patients. As for different medical applications, 3D visualization systems have advantages in terms of a better spatial understanding of anatomical structures, better performance of tasks that require high level of dexterity, increased learning performance, and improved communications with patients or between doctors. Methods In this technical report, we show how to employ a multi-view autostereoscopic system to provide 3D images without any special glasses or equipment, describing a new way to obtain 3D visualization using sets of 2D images instead of real volumetric data such as magnetic resonance imaging (MRI) or computed tomography (CT). We also propose an application of the images in neuroanatomy. Results We obtained three-dimensional images of anatomical parts for visualization without glasses with resolution of 336 × 210 pixels'. Conclusion The proposed method was able to generate three-dimensional high-resolution images and has great potential to be used in various areas such as anatomy and physiological studies.

Increased resistin levels in the serum and cerebrospinal fluid of patients with neuromyelitis optica.

INTRODUCTION: Resistin, which acts as a pro-inflammatory cytokine, has been implicated in the pathogenesis of several autoimmune diseases. However, the involvement of resistin in neuromyelitis optica (NMO), a severe inflammatory central nervous system disorder that targets the optic nerve and spinal cord, remains unclear. METHODS: We measured serum and cerebrospinal fluid (CSF) resistin levels in patients with NMO and controls matched by age and sex. The link between resistin levels and clinical variables in NMO was subsequently assessed. RESULTS: The concentrations of serum and CSF resistin were significantly higher in patients with NMO than in controls, and decreased following treatment with methylprednisolone. High sensitivity C-reactive protein (hs-CRP) levels and annualized relapse rate positively correlated with resistin levels in patients with NMO. CONCLUSION: Resistin might be a useful biomarker of inflammation in NMO, and a potential target for the treatment of NMO.

Hackathon as a way to raise awareness and foster innovation for stroke / Hackathon como uma maneira de aumentar a conscientização e promover a inovação no AVC

ABSTRACT The ‘Time is Brain” concept has been a major focus in the World Stroke Awareness Campaign. Objective We describe our experience with a Hackathon (junction of hack+marathon), a 24 hour event of innovation- and technology-based project development, focused around detecting stroke. Method The Hackathon was held during a Brazilian Student’s union (BRASA) congress involving students from engineering and other technological disciplines. Results Four teamscompleted the 24-hour challenge; two teams opted the stroke challenge. One team proposed improving detection using a mobile sensor Fit-Bit combined with a smart-phone to contact emergency dispatch. The other team developed a game, in which kids would play a role as a neurologist; to diagnosis stroke with objective to increase awareness. Conclusion Hackathons can focus attention on innovation and improvement opportunities to support the World Stroke Campaign, as well as other campaigns to raise awareness for other health or social problems.

RESUMO O conceito ‘Tempo é Cérebro “tem sido um grande foco na Campanha Mundial de conscientização sobre AVC. Objetivo Nós descrevemos experiência com Hackathon (junção das palavras hack+marathon) , um evento de 24 horas voltado a desenvolvimento de inovação tecnológica, centrada em torno de detecção de AVC. Método O Hackathon aconteceu durante o congresso da Associação de Estudante Brasileiros no Exterior (BRASA), envolvendo estudantes de engenharia e disciplinas tecnológicas. Resultados Quatro equipes completaram o desafio, duas optaram pelo desafio sobre AVC, uma propôs a detecção usando um sensor Fit-Bit e um telefone móvel para detecção e contato com a emergência. A outra equipe desenvolveu um jogo para as crianças detectarem AVC. Conclusão Hackathon pode focar a atenção em inovações e oportunidades de melhorias como um adicional a Campanha Mundial contra AVC, bem como em outras campanhas de conscientização para outras doenças ou problemas sociais.

Tongxinluo (TXL), a Traditional Chinese Medicinal Compound, Improves Endothelial Function After Chronic Hypoxia Both In Vivo and In Vitro.

Vascular injury after chronic hypoxia leads to endothelial injury and structural damage to tight junctions (TJs), thereby resulting in a variety of cardiovascular diseases. Thus, attenuating hypoxia-induced damage has great significance for the prevention and treatment of cardiovascular disease. The aim of this study was to investigate whether the endothelial protection conferred by tongxinluo (TXL), a traditional Chinese medicinal compound, is related to its regulation of TJ protein expression. In vivo, we found that TXL could promote hypoxia-induced angiogenesis in lung and liver tissue. In vitro, we found that CoCl2 treatment significantly reduced the expression of the TJ proteins occludin, claudin-1, VE-cadherin, and beta-catenin in cultured human cardiac microvascular endothelial cells. TXL pretreatment abrogated the CoCl2-induced downregulation of these TJ proteins. Conversely, overexpression of Krüppel-like factor 4 (KLF4) inhibited the expression of TJ proteins in human cardiac microvascular endothelial cells, an effect that was reversed by TXL pretreatment. Further experiments showed that TXL could promote endothelial cell proliferation by increasing KLF4 phosphorylation, thereby reversing the effect of KLF4 on the expression of TJ proteins. These findings provide a new molecular mechanism for the TXL-induced increase in TJ protein expression.

Lean thinking turns ‘time is brain’ into reality / Pensamento enxuto faz ‘tempo é cérebro’ virar realidade

Intravenous rt-PA is an effective recanalizing treatment for ischemic stroke within 4 and half hours from its onset (Onset-to-Treatment [OTT]), with the best result seen in those treated within 90 minutes OTT. Yet few patients currently are treated in this time frame. From the standpoint of process improvement or a lean thinking perspective, there is a potential opportunity to reduce the time by eliminating non-value-added steps in each element of the stroke survival chain. The reduction in one time element does not necessarily shift the OTT under 90 minutes. Most likely, the reduction in OTT requires a coordinated approach to track and improve all elements of OTT, from the patient’s ability to recognize the onset of stroke up to delivery of medication. Shortening this total time should be a considered an indicator of quality improvement in acute stroke care.

Tratamento intravenoso com rt- PA é eficaz na recanalização do acidente vascular cerebral isquêmico (AVCI) no prazo de até 4 horas e meia de seu início (OTT), com o melhor resultado visto naqueles tratados dentro de 90 minutos OTT. Apesar disso, poucos são tratados neste período de tempo. Do ponto de vista da melhoria de processos ou uma perspectiva de pensamento enxuto, há uma oportunidade potencial para reduzir o tempo ao eliminar etapas que não agregam valor em cada elemento da cadeia de sobrevivência do paciente com acidente vascular cerebral. A diminuição da OTT requer uma abordagem coordenada em conjunto para controlar e melhorar todos os elementos de OTT, a capacidade do paciente para reconhecer o início do icto até à administração da medicação. Encurtar esse tempo total deve ser um considerado um indicador da melhoria da qualidade no atendimento AVCI agudo.

Predictors of pneumonia in acute stroke in patients in an emergency unit / Preditores de pneumonia em pacientes com AVC isquêmico numa unidade de emergência

Objective To evaluate the risk factors and comorbid conditions associated with the development of pneumonia in patients with acute stroke. To determine the independent predictors of pneumonia. Method Retrospective study from July to December 2011. We reviewed all medical charts with diagnosis of stroke. Results 159 patients (18-90 years) were admitted. Prevalence of pneumonia was 32%. Pneumonia was more frequent in patients with hemorrhagic stroke (OR: 4.36; 95%CI: 1.9-10.01, p < 0.001), higher National Institute of Health Stroke Scale (NIHSS) (p = 0.047) and, lower Glasgow Coma Score (GCS) (p < 0.0001). Patients with pneumonia had longer hospitalization (p < 0.0001). Multivariable logistic regression analysis identified NIHSS as an independent predictor of pneumonia (95%CI: 1.049-1.246, p = 0.002). Conclusion Pneumonia was associated with severity and type of stroke and length of hospital stay. The severity of the deficit as evaluated by the NIHSS was shown to be the only independent risk factor for pneumonia in acute stroke patients. .

Objetivo Avaliar os fatores de risco e as comorbidades associadas ao desenvolvimento de pneumonia em pacientes com acidente vascular cerebral (AVC) agudo. Determinar os preditores independentes de pneumonia. Método Estudo retrospectivo, realizado entre julho e dezembro de 2011. Foi revisado todos os prontuários dos pacientes com diagnóstico de AVC. Resultados 159 pacientes (18-90 anos) foram admitidos. A incidência de pneumonia foi de 32%. A incidência de pneumonia foi maior em pacientes com AVC hemorrágico (OR: 4,36; IC95%: 1,9-10,01, p < 0,001) e em pessoas com escore alto National Institute of Health Stroke Scale (NIHSS) (p = 0,047) e escores mais baixos da Escala de Coma de Glasgow (ECG) (p < 0,0001). Os pacientes com pneumonia tiveram maior tempo de internação (p < 0,0001). A análise de regressão logística identificou apenas o NIHSS como um preditor independente de pneumonia (IC95%: 1,049-1,246, p = 0,002). Conclusão O diagnóstico de pneumonia foi associado a tipo e gravidade do AVC e com tempo de hospitalização. A gravidade do déficit, avaliada pela escala NIHSS mostrou ser o único fator de risco independente para pneumonia em pacientes com AVC agudo. .

Chinese medicine Tongxinluo increases tight junction protein levels by inducing KLF5 expression in microvascular endothelial cells.

Tongxinluo (TXL) is a compound prescription formulated according to the meridian theory of traditional Chinese medicine. It may play an important role in cardiovascular protection by improving endothelial cell function. The aim of present study was to investigate whether endothelial protection with TXL is related to its regulation of tight junction protein expression. Human cardiac microvascular endothelial cells (HCMECs) were cultured and treated with 10(-7) mol l(-1) angiotensin II (Ang II) and the different doses of TXL; the expression of tight junction proteins occludin, claudin, VE-cadherin and beta-catenin was determined by Western blotting and real-time PCR. Gain-of-function and loss-of-function of Krüppel-like factor 5 (KLF5) were carried out in HCMEC transfected with either KLF5 adenovirus pAd-KLF5 or siRNA specific for KLF5. Angiotensinogen transgenic mice were treated with TXL by oral administration of TXL of 0.75 g kg(-1) day(-1) , and immunohistochemical staining was performed with antioccludin, anticlaudin, anti-VE-cadherin, antibeta-catenin and anti-KLF5 antibodies. Ang II treatment significantly reduced the expression of tight junction proteins occludin, claudin, VE-cadherin and beta-catenin in cultured HCMECs. TXL pretreatment could abrogate the down-regulation of these tight junction proteins induced by Ang II. Ang II treatment also decreased KLF5 expression at the mRNA and protein levels; TXL pretreatment markedly reversed the inhibitory effect of Ang II on KLF5 expression. Gain-of-function and loss-of-function of KLF5 showed that KLF5 mediated the expression of tight junction proteins in HCMECs. TXL-enhanced expression of the tight junction proteins was mediated by KLF5. In angiotensinogen transgenic mice, TXL also increased the tight junction protein levels by inducing KLF5 expression. Chinese medicine TXL increases tight junction protein levels by inducing KLF5 expression in microvascular endothelial cells.

Circadian rhythm and profile in patients with juvenile myoclonic epilepsy and temporal lobe epilepsy / Ritmo e perfil circadiano em pacientes com epilepsia mioclônica juvenil e epilepsia de lobo temporal

Objective This study intended to compare the circadian rhythm and circadian profile between patients with juvenile myoclonic epilepsy (JME) and patients with temporal lobe epilepsy (TLE). Method We enrolled 16 patients with JME and 37 patients with TLE from the Outpatient Clinic of UNICAMP. We applied a questionnaire about sleep-wake cycle and circadian profile. Results Fourteen (87%) out of 16 patients with JME, and 22 out of 37 (59%) patients with TLE reported that they would sleep after seizure (p < 0.05). Three (19%) patients with JME, and 17 (46%) reported to be in better state before 10:00 AM (p < 0.05). Conclusion There is no clear distinct profile and circadian pattern in patients with JME in comparison to TLE patients. However, our data suggest that most JME patients do not feel in better shape early in the day. .

Objetivo Este estudo pretende comparar o ritmo circadiano e o perfil circadiano entre pacientes com epilepsia mioclônica juvenil (EMJ) e epilepsia de lobo temporal (ELT). Método Nós entrevistamos 16 pacientes com EMJ e 37 com ELT do ambulatório da UNICAMP. Nós aplicamos um questionário sobre ciclo sono-vigília e perfil circadiano. Resultados Quatorze (87%) de 16 pacientes com EMJ e 22 de 37 (59%) pacientes com ELT relataram que eles apresentam sonolência pós-crise (p < 0,05). Três (19%) pacientes com EMJ e 17 (46%) relataram um melhor estado geral antes das 10h00min (p < 0,05). Conclusão Não há uma clara diferença de ritmo e de perfil circadiano entre pacientes com EMJ e ELT. No entanto, nossos dados sugerem que a maioria dos pacientes com EMJ não se sentem em sua melhor forma cedo pela manhã. .