CD4(+) T cells of myasthenia gravis patients are characterized by ıncreased IL-21, IL-4, and IL-17A productions and higher presence of PD-1 and ICOS

Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies predominantly against the acetylcholine receptor (AChR). Specific T cell subsets are required for long-term antibody responses, and cytokines secreted mainly from CD4(+) T cells regulate B cell antibody production. The aim of this study was to assess the differences in the cytokine expressions of CD4(+) T cells in MG patients with AChR antibodies (AChR-MG) and the effect of immunosuppressive (IS) therapy on cytokine activity and to test these findings also in MG patients without detectable antibodies (SN-MG). Clinically diagnosed AChR-MG and SN-MG patients were included. The AChR-MG patients were grouped as IS-positive and -negative and compared with age- and sex-matched healthy controls. Peripheral blood mononuclear cells were used for ex vivo intracellular cytokine production, and subsets of CD4(+) T cells and circulating follicular helper T (cTfh) cells were detected phenotypically by the expression of the chemokine and the costimulatory receptors. Thymocytes obtained from patients who had thymectomy were also analyzed. IL-21, IL-4, IL-10, and IL-17A productions in CD4(+) T cells were increased in AChR-MG compared to those in healthy controls. IS treatment enhanced IL-10 and reduced IFN-gamma production in AChR-MG patients compared to those in IS-negative patients. Increased IL-21 and IL-4 productions were also demonstrated in SN-MG patients. Among CD4(+) T cells, Th17 cells were increased in both disease subgroups. Treatment induced higher proportions of Th2 cells in AChR-MG patients. Both CXCR5(+) and CXCR5(-) CD4(+) T cells expressed higher programmed cell death protein 1 (PD-1) and inducible costimulatory (ICOS) in AChR-MG and SN-MG groups, mostly irrespective of the treatment. Based on chemokine receptors on CXCR5(+)PD-1(+) in CD4(+) T (cTfh) cells, in AChR-MG patients without treatment, the proportions of Tfh17 cells were higher than those in the treated group, whereas the Tfh1 cells were decreased compared with those in the controls. The relevance of CXCR5 and PD-1 in the pathogenesis of AChR-MG was also suggested by the increased presence of these molecules on mature CD4 single-positive thymocytes from the thymic samples. The study provides further evidence for the importance of IL-21, IL-17A, IL-4, and IL-10 in AChR-MG. Disease-related CD4(+)T cells are identified mainly as PD-1(+) or ICOS+ with or without CXCR5, resembling cTfh cells in the circulation or probably in the thymus. AChR-MG and SN-MG seem to have some similar characteristics. IS treatment has distinctive effects on cytokine expression.Istanbul Universit

OPERASYON ÖNCESI FONKSIYONEL MR’IN TEMPORAL LOBEKTOMI SONRASI BELLEK PERFORMANSINI YORDAMADA KULLANIMI: SISTEMATIK BIR DERLEME

Most of the patients with temporal lobe epilepsy suffer from memory decline following anterior temporal lobectomy (ATL). Studies examining memory decline following ATL show that post operative memory decline can be predicted in advance through the pre operative determination of memory lateralisation. Therefore, preoperative memory lateralisation plays a crucial role for epileptic surgery. Recent research suggests that instead of WADA test which is known as an invasive and high-risk operation, functional MRI can be used as a non-invasive and repeatable method to lateralize memory in the brain and to predict post operative memory decline. The aim of this article is to review the utility of fmri in prediction of post operative memory decline and to summarize the results of recent memory lateralisation studies using fmri

The use of quantitative eeg for differentiating frontotemporal dementia from late-onset bipolar disorder

WOS: 000430198600004PubMed ID: 29284291The behavioral variant frontotemporal dementia (bvFTD) usually emerges with behavioral changes similar to changes in late-life bipolar disorder (BD) especially in the early stages. According to the literature, a substantial number of bvFTD cases have been misdiagnosed as BD. Since the literature lacks studies comparing differential diagnosis ability of electrophysiological and neuroimaging findings in BD and bvFTD, we aimed to show their classification power using an artificial neural network and genetic algorithm based approach. Eighteen patients with the diagnosis of bvFTD and 20 patients with the diagnosis of late-life BD are included in the study. All patients' clinical magnetic resonance imaging (MRI) scan and electroencephalography recordings were assessed by a double-blind method to make diagnosis from MRI data. Classification of bvFTD and BD from total 38 participants was performed using feature selection and a neural network based on general algorithm. The artificial neural network method classified BD from bvFTD with 76% overall accuracy only by using on EEG power values. The radiological diagnosis classified BD from bvFTD with 79% overall accuracy. When the radiological diagnosis was added to the EEG analysis, the total classification performance raised to 87% overall accuracy. These results suggest that EEG and MRI combination has more powerful classification ability as compared with EEG and MRI alone. The findings may support the utility of neurophysiological and structural neuroimaging assessments for discriminating the 2 pathologies

Enerji Alanında Araştırma Üniversiteleri Odaklı Yön-Eylem Belirleme Çalışması

Teknoloji izleme, öngörü çalışmalarının doğal eşleniği olmasının yanında mevcutta ve gelecekte olası tehditlerinbertarafı ve gelişme fırsatlarını artırmak için bilimsel, teknik ve teknolojik ortamın gözlenmesi ve analiz edilmesiolarak ifade edilmektedir. Teknoloji izleme aynı zamanda kuruluşların belirli bir alanda içgörü ve rekabet avantajı eldeetmek amacıyla teknik bilgilerini sürekli olarak sistematik bir şekilde analiz etmeleri için kullanılan ve temel olarakyayınlanan bilgilerin istatistiksel analizine dayanan bir yöntemdir. Bu çalışma mevcut literatür bilgilerine dayalı enerjialanındaki çalışmaların gözden geçirilmesi ve ilgili yayınlara bağlı olarak araştırma yöntemlerini de içeren teknolojikeğilimin belirlenmesini amaçlamaktadır. Özellikle enerji, yenilenebilir enerji, güç ve yakıt anahtar kelimeleriyletanımlanan Türkiye adresli son on yılda (2009–2018) yayımlanmış olan makale, patent, tez ve gerçekleştirilen projelerinbibliyometrik yöntem kullanılarak analiz edilmesine odaklanmaktadır. Çalışmada yararlanılan bibliyometrik yaklaşımtüm enerji araştırmalarını değerlendirmek için kullanılmıştır. Gerçekleştirilen çalışmada ulusal ve uluslararası işbirlikleri de incelenmiştir

Relation of HLA-DRB1 to IgG4 autoantibody and cytokine production in muscle-specific tyrosine kinase myasthenia gravis (MuSK-MG)

A small subset of myasthenia gravis (MG) patients develop autoantibodies against muscle-specific kinase (MuSK), which are predominantly of the immunoglobulin (Ig)G4 isotype. MuSK-MG is strongly associated with HLA-DRB1*14, HLA-DRB1*16 and HLA-DQB1*05. In this study, the possible effects of these HLA associations on MuSK IgG autoantibody or cytokine production were investigated. Samples from 80 MG patients with MuSK antibodies were studied. The disease-associated HLA types were screened in the DNA samples. The IgG1, IgG2, IgG3 and IgG4 titres of the MuSK antibodies and the levels of interleukin (IL)-4, IL-6, IL-17A and IL-10 were measured in the sera. Comparisons were made among the groups with or without HLA-DRB1*14, HLA-DRB1*16 or HLA-DQB1*05. The IgG4 titres of the MuSK antibodies were higher than those of the IgG1, IgG2 and IgG3 isotypes among the whole group of patients. DRB1*14 (+) DRB1*16 (–) patients had higher levels of IgG4 antibodies than those of DRB1*14 (–) DRB1*16 (+) patients. DRB1*14 (+) DRB1*16 (+) patients also had higher levels of IgG4 antibodies than those of DRB1*14 (–) DRB1*16 (+) and DRB1*14 (–) DRB1*16 (–) patients. Higher IL-10 and lower IL-17A levels were measured in DRB1*14 (+) DRB1*16 (–) patients than in DRB1*14 (–) DRB1*16 (–) patients. The higher IgG4 titres of MuSK autoantibodies in patients carrying HLA-DRB1*14 than those in the other patients suggest a role for HLA in the production of the antibodies. The differences in IL-10 and IL-17A support the role of DRB1 in the etiopathogenesis of this autoimmune response.Istanbul Universit

Epigenetics of Multiple Sclerosis: An Updated Review

Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease characterized with autoimmune response against myelin proteins and progressive axonal loss. The heterogeneity of the clinical course and low concordance rates in monozygotic twins have indicated the involvement of complex heritable and environmental factors in MS pathogenesis. MS is more often transmitted to the next generation by mothers than fathers suggesting an epigenetic influence. One of the possible reasons of this parent-of-origin effect might be the human leukocyte antigen-DRB1*15 allele, which is the major risk factor for MS and regulated by epigenetic mechanisms such as DNA methylation and histone deacetylation. Moreover, major environmental risk factors for MS, vitamin D deficiency, smoking and Ebstein-Barr virus are all known to exert epigenetic changes. In the last few decades, compelling evidence implicating the role of epigenetics in MS has accumulated. Increased or decreased acetylation, methylation and citrullination of genes regulating the expression of inflammation and myelination factors appear to be particularly involved in the epigenetics of MS. Although much less is known about epigenetic factors causing neurodegeneration, epigenetic mechanisms regulating axonal loss, apoptosis and mitochondrial dysfunction in MS are in the process of identification. Additionally, expression levels of several microRNAs (miRNAs) (e.g., miR-155 and miR-326) are increased in MS brains and potential mechanisms by which these factors might influence MS pathogenesis have been described. Certain miRNAs may also be potentially used as diagnostic biomarkers in MS. Several reagents, especially histone deacetylase inhibitors have been shown to ameliorate the symptoms of experimental allergic encephalomyelitis. Ongoing efforts in this field are expected to result in characterization of epigenetic factors that can be used in prediction of treatment responsive MS patients, diagnostic screening panels and treatment methods with specific mechanism of action