Mccormickjonasson7609

OBJECTIVES Alexithymia is a multicomponent personality construct that could occur in up to 53% of patients with multiple sclerosis (MS), with recent works proposing higher rates of alexithymia in progressive MS. Among the available models of alexithymia, some propose a deficient interhemispheric communication and an aberrant GABAergic transmission at its origin. However, no single study has addressed the underlying physiological mechanisms of alexithymia in MS. The aim of this work was to assess the relationship between GABAergic neurotransmission and alexithymia in progressive MS by means of transcranial magnetic stimulation (TMS). METHODS Twelve patients with high alexithymia and fifteen patients with low alexithymia were included based on Toronto Alexithymia Scale (TAS). Sociodemographic, clinical and neuropsychological data were recorded. The following corticospinal excitability measures were obtained resting motor threshold, cortical silent period (CSP which reflects cortical GABAergic function), and interhemispheric inhibition (i.e., GABAergic function mediated by interhemispheric fibers). RESULTS No significant group differences were observed regarding sociodemographic, clinical or neuropsychological variables. Patients with high alexithymia scores exhibited shorter CSP than those with low alexithymia scores (81.87 ± 45.72 ms vs. 145.27 ± 77.26 ms, respectively, p  less then  0.05). A significant inverse correlation was also found between TAS scores and CSP duration (r = -0.59, p  less then  0.05). CONCLUSION This study offers insights into the neurophysiological mechanisms of alexithymia in MS. Reduced GABAergic transmission, as reflected by short CSP, seems to be associated with alexithymia in this population. Future studies would benefit from a more comprehensive evaluation of cortical and interhemispheric mechanisms in MS patients with alexithymia. BACKGROUND Rapid tapping tests have been shown to be reliable measures of upper motor neuron disease, and effectively examine motor function differences between multiple sclerosis (MS) and non-MS controls (CON), and between relapsing-remitting and progressive MS subtypes. To successfully perform rapid repetitive movements such as tapping, a person must be able to consistently turn on and off motor units to switch between the up and down movement phases. However, it is not clear which specific movement phase that occurs during tapping is different between MS subtypes. The objective of this study was to quantify and characterize performance differences during rapid hand- and foot-tapping tests between relapsing-remitting (RRMS) and progressive (PMS) forms of MS, as well as how both subtypes differ from non-MS controls. METHODS Participants in this study included 30 non-MS controls, 32 RRMS, and 31 PMS. Participants wore inertial sensors on all hands and feet and were instructed to tap as fast as possible for 10between subtypes. Performance in the up-movement showed larger group differences than the down-movement, suggesting that the anti-gravity up-movement during tapping may be more important diagnostically. Future studies should be conducted on the nature of the physiological mechanisms underlying impairments in anti-gravity movements in people with MS. Endoplasmic reticulum (ER) stress is strictly linked to neuroinflammation and involves in the development of neurodegenerative disorders. Protein disulfide isomerase (PDI) is an enzyme that catalyzes formation and isomerization of disulfide bonds and also acts as a chaperone that survives the cells against cell death by removal of misfolded proteins. Our previous work revealed that PDI is explicitly upregulated in response to myelin oligodendrocyte glycoprotein (MOG)-induced ER stress in the brain of experimental autoimmune encephalomyelitis (EAE) mice. Selleck Veliparib The significance of overexpression of PDI in the apoptosis of neural cells prompted us to study the effect of CCF642, efficient inhibitor of PDI, in the recovery of EAE clinical symptoms. Using this in vivo model, we characterized the ability of CCF642 to decrease the expression of ER stress markers and neuroinflammation in the hippocampus of EAE mice. Our observations suggested that CCF642 administration attenuates EAE clinical symptomsand the expression of ER stress-related proteins. Further, it suppressed the inflammatory infiltration of CD4 + T cells and the activation of hippocampus-resident microglia and Th17 cells. We reported here that the inhibition of PDI protected EAE mice against neuronal apoptosis induced by prolonged ER stress and resulted in neuroprotection. V.Analysis of reported outcomes of treatment of pemphigus vulgaris (PV) patients demonstrated that the multidrug approach offers a lower relapse rate compared to the FDA-approved prednisone/rituximab regimen. The multidrug protocol protects keratinocytes from autoantibody attack by systemic corticosteroids and mitochondrion-protecting drugs, selectively eliminates pathogenic autoantibodies by intravenous immunoglobulin (IVIg) and inhibits autoantibody production by cytotoxic immunosuppressors. Therefore, IVIg should be always added to the prednisone/rituximab regimen that does not eliminate circulating autoantibodies. To decrease risk for relapse to a minimum, PV should be maintained in full clinical remission until the critical mass of autoreactive plasma cells dies off. The two major factors that determine patient's risk for a relapse are the composition of the pool of pathogenic autoantibodies and the innate abilities of keratinocytes to sustain an autoantibody attack. As it is currently impossible to evaluate the risk for a relapse, development of a biomarker assay that could do so would be helpful in a long-term management of PV patients. We compared the magnitude of cytochrome c (CytC) release in keratinocytes by serum from PV patients in acute disease stage vs. remission and identified very strong positive correlation with disease severity. PV patients whose serum contained autoantibodies requiring higher amounts of normal IgG to neutralize their ability to release CytC were found to be at a higher risk for disease relapse. However, lack of very strong statistical correlation suggested that CytC is not an ideal biomarker to predict disease relapse, which should prompt a search for alternative candidates.