COVID-19 has spread to most countries in the world. However, there are differences in the rate of infection in different countries. Specifically, high incidence was reported in specific areas in ...China (Wuhan) and Italy (Lombardy). These differences may be related to different Human Leucocyte Antigen (HLA) patterns in various geographic areas. We suggest HLA spreading between Italy and China is related to the travels of Marco Polo through the Silk Road as a potential historic explanation to COVID-19 spreading.
: Differential expression of apoptotic genes may influence the susceptibility of activated lymphocytes to expand and induce acute relapse and persistent inflammation in patients with ...relapsing–remitting multiple sclerosis (RRMS). The exact relationship between alterations in apoptotic‐related gene expression and clinical disease activity has not been broadly evaluated. In this study we studied peripheral blood mononuclear cells (PBMCs) expression of pro‐ and antiapoptotic genes in RRMS patients during acute relapse in comparison to patients in remission. Using cDNA Affymetrix microarrays platform (U133A2 microarrays) we analyzed the gene expression profile of PBMC derived from 22 RRMS patients in acute relapse (15 females, mean age 34.6 ± 1.8 years, disease duration 5.6 ± 0.8 years) in comparison to 20 sex‐ and age‐matched RRMS patients in remission. One thousand five hundred seventy‐eight gene transcripts significantly differentiated acute multiple sclerosis (MS) relapse from remission. This characteristic gene expression signature was enriched by an apoptotic‐related pathway. The 1578 gene transcripts that significantly differentiated acute relapse from remission were enriched by 55 apoptotic‐related genes in that reflected different operating pathways during the acute phase of the disease. These genes mainly involved the caspase‐dependent pathway and included overexpression of the negative regulator of FAS‐induced apoptosis (TOSO) and the BCL2 antiapoptotic family members (BCL2, BCL2 AA) as well as downexpression of proapoptotic genes like BAX, apoptotic protease‐activating factor 1 (APAF1) and caspases 1, 2, 8, 9. and 10. An additional group of antiapoptotic genes related to T cell receptor‐mediated apoptosis was also found to be overexpressed in acute relapse and included TCR‐binding CD3E antigen, antiapoptotic serine threonin kinase (AKT), and NFκB‐associated genes like reticuloendotheliosis viral oncogene homolog A (RELA) and human T cell leukemia virus type I‐binding protein (Tax1BP) known to inhibit tumor necrosis factor (TNF)‐induced apoptosis. Our findings demonstrate impaired apoptotic mechanisms in peripheral lymphocytes from RRMS patients during acute relapse. This suggests that the inflammatory process in active disease is targeted by inhibition of proapoptotic and repression of antiapoptotic genes that allow prolonged abnormal immune responses.
Abstract The purpose of the study was to determine the relationship between static postural control parameters to fear of falling and falling history in people with multiple sclerosis (MS) without ...mobility assistive devices. One-hundred and seven relapsing–remitting patients diagnosed with MS, 62 women aged 42.8 (S.D. = 12.0), participated in this investigation. Participants were divided into groups based on fall history; 47 had no history during the past 6 months and 60 had a history of at least one fall within the same period. Static postural control parameters were obtained from the Zebris FDM-T Treadmill (zebris® Medical GmbH, Germany). The patient's self-reported questionnaire, the Falls Efficacy Scale International (FES-I), was used to assess the level of concern relating to falls. People with MS classified as fallers exhibited increased center of pressure (CoP) path length, sway velocity and greater overall sway area. CoP path length performed with eyes open was found to explain 42% of the variance related to at least one fall during the past six months; R2 = 0.424, χ2(1) = 40.727, P < 0.01. The correlation between the FES-I and CoP path length was 0.620 ( P < 0.001). Measurement of the CoP trajectories with instrumented posturography should be considered in managing fall risk in the MS population.
Multiple sclerosis (MS) is a central nervous system autoimmune inflammatory T-cell-mediated disease with a relapsing-remitting course in the majority of patients. In this study, we performed a ...high-resolution systems biology analysis of gene expression and physical interactions in MS relapse and remission. To this end, we integrated 164 large-scale measurements of gene expression in peripheral blood mononuclear cells of MS patients in relapse or remission and healthy subjects, with large-scale information about the physical interactions between these genes obtained from public databases. These data were analyzed with a variety of computational methods. We find that there is a clear and significant global network-level signal that is related to the changes in gene expression of MS patients in comparison to healthy subjects. However, despite the clear differences in the clinical symptoms of MS patients in relapse versus remission, the network level signal is weaker when comparing patients in these two stages of the disease. This result suggests that most of the genes have relatively similar expression levels in the two stages of the disease. In accordance with previous studies, we found that the pathways related to regulation of cell death, chemotaxis and inflammatory response are differentially expressed in the disease in comparison to healthy subjects, while pathways related to cell adhesion, cell migration and cell-cell signaling are activated in relapse in comparison to remission. However, the current study includes a detailed report of the exact set of genes involved in these pathways and the interactions between them. For example, we found that the genes TP53 and IL1 are 'network-hub' that interacts with many of the differentially expressed genes in MS patients versus healthy subjects, and the epidermal growth factor receptor is a 'network-hub' in the case of MS patients with relapse versus remission. The statistical approaches employed in this study enabled us to report new sets of genes that according to their gene expression and physical interactions are predicted to be differentially expressed in MS versus healthy subjects, and in MS patients in relapse versus remission. Some of these genes may be useful biomarkers for diagnosing MS and predicting relapses in MS patients.
Background
Relapsing-remitting multiple sclerosis (RRMS) affects predominantly young women within reproductive years. As an increased risk of relapses is known to occur during the post-partum period, ...it is important to consider treatment options.
Aim
Evaluate the effects of intravenous immunoglobulins (IVIg) to prevent post-partum relapses.
Methods
We prospectively followed 198 pregnant female RRMS patients, 67 treated with IVIg during pregnancy and the three months post-partum, and 131 untreated patients that served as controls.
Results
During the pre-gestation year, 41.4% were treated with immunomodulatory drugs, and 28.3% experienced a relapse. During pregnancy and the post-partum period, the number of relapsing patients significantly decreased in the IVIg group (37.3%, 10.4%, 8.9%, respectively, p = 0.0003), while no significant change was observed in the untreated group (23.7%, 17.6%, and 22.1%). During the three-month post-partum period, there were only mild and moderate relapses in the IVIg group, while in the untreated group, there were also severe relapses. Stepwise logistic regression that assessed the relation between three-month post-partum relapse and explanatory variables demonstrated that untreated patients had increased risk for post-partum relapse (odds ratio = 4.6, 95% CI 1.69, 12.78, p = 0.033).
Conclusions
IVIg treatment proved efficient to reduce the rate and severity of relapses during pregnancy and the three-month post-partum.
Multiple sclerosis (MS) is a central nervous system disease with an unpredictable course and outcome. Peripheral blood mononuclear cells (PBMCs) are involved in the disease pathogenesis and induce ...active demyelination. Using oligonucleotide microarrays, we identified a statistically significant transcriptional signature of 1,109 genes in PBMCs from 26 MS patients, irrespective of disease activation state or immunomodulatory treatment. This signature contains genes that implicate underlying processes involved in MS pathogenesis including T‐cell activation and expansion, inflammation, and apoptosis. Another transcriptional signature of 721 genes involved in cellular recruitment, epitope spreading, and escape from regulatory immune surveillance identified MS patients in acute relapse compared with remission. Our results offer new opportunity for understanding the mechanisms involved in MS and indicate that gene expression patterns in PBMCs contain information about a remote‐target disease process that may be useful for diagnosis and future tailoring of therapeutic strategies for MS.
Multiple sclerosis (MS) is a chronic disease marked by progressive disability and decreased mobility over time. We studied whether individuals with MS of higher disability levels will be more ...overweight/obese as a result of their immobility and/or recurrent steroid treatments. In a prospective study, 130 individuals with MS and significant disability were classified according to the Expanded Disability Status Scale (EDSS) score as belonging to four groups: EDSS 3.0–4.0 (n = 31, 24%), EDSS 4.5–5.5 (n = 24, 18%), EDSS = 6.0 (n = 44, 34%) and EDSS ≥ 6.5 (n = 31, 24%). Medical history, body mass index (BMI), waist circumference and the level of engagement in physical activity were obtained. The mean ± standard error age was 55.8 ± 0.5 years, disease duration 18.2 ± 1.0 years and EDSS score 5.5 ± 0.1. Disease duration, the number of steroid courses per disease duration, weight, BMI and physical activity did not differ according to the four disability groups. The mean waist circumference increased significantly with increased severity of EDSS, p = 0.03. Increased disability in individuals with MS was not correlated with disease duration, lifestyle habits or overweight/obesity. However, increased disability was associated with central obesity.
Abstract Background Balance and gait deficits are common in people with multiple sclerosis (MS). Physical interventions directed at improving balance and walking abilities have been implemented using ...various approaches. Nonetheless, no mode of training has been universally agreed upon. Objectives To determine whether textured insoles have immediate effects on postural control and spatiotemporal parameters of gait and plantar sensation in people with people with MS and to explore effects 4 weeks after insole wear as to whether any immediate effects are maintained over time. Design Within-subject experimental study with a 4-week intervention phase. Settings Multiple Sclerosis Center, Center of Advanced Technologies in Rehabilitation, Sheba Medical Center, Tel-Hashomer, Israel. Participants Twenty-five relapsing-remitting patients diagnosed with MS, 16 women and 9 men, aged 49.6 years (standard deviation = 6.5 years). Intervention Textured insoles customized according to foot size and adapted to the participant's casual shoes. Main outcome measures Spatiotemporal parameters of gait and center of pressure (CoP) excursions during static postural control were studied using the Zebris FDM-T Treadmill. Light-touch and pressure-sensation thresholds were determined using the Semmes-Weinstein monofilaments test. Results Textured insoles did not alter static postural control parameters when examined with eyes open. Examination during the eyes-closed task demonstrated an immediate reduction in the CoP path length (298.4 mm, standard error = 49.7 mm, versus 369.9 mm, SE = 56.3 mm; P = .04) and sway rate (12.0 mm/s, standard error = 1.4 mm/s, versus 15.1 mm/s, standard error = 1.6 mm/s; P = .03) after insertion of the textured insoles compared to casual shoes alone. These findings were maintained at termination of the insole 4-week intervention period. In terms of spatiotemporal parameters of gait, differences were not observed between casual shoes and shoes with textured insoles at baseline. Likewise, no differences were observed between initial and concluding gait trials. Significant differences in plantar sensitivity measures were not observed after the insole 4-week intervention phase. Conclusions Although there were improvements in some aspects of balance, the efficacy of textured insoles in the MS population remains unclear.
Highlights • Fear of falling is related to spatial and temporal gait parameters in people with MS. • Fearful patients demonstrated a larger variability of the CoP trajectory during gait. • CoP ...variability in the lateral plane was significantly correlated to fear of falling.
•Pro-inflammatory cytokines were enormously elevated in patients with COVID19.•IL6 and TNFα were higher in patients that did not survive.•IL6 expression predicted 30-day mortality with high ...sensitivity and specificity.
Coronavirus disease 2019 (COVID19) is a life-threatening infection with uncertain progression and outcome. Assessing the severity of the disease for worsening patients is of importance in making decisions related to supportive mechanical ventilation and aggressive treatments. This was a prospective, non-randomized study that included hospitalized patients diagnosed with COVID19. Pro-inflammatory cytokines were assessed during hospitalization, and we calculated a prediction paradigm for 30-day mortality based on the serum levels of interleukin1β (IL1β), interleukin6 (IL6), interleukin8 (IL8), and tumor necrosis factor alpha (TNFα) measured by next-generation ELISA.
Data of 71 COVID19 patients, mean age 62 years, SD13.8, 50 males, 21 females, were analyzed. Twelve (16.9%) patients died within 7–39 days of their first COVID19 positive nasopharyngeal test. Levels of IL6 and TNFα were significantly higher in patients that did not survive. IL6 predicted mortality at the cut-off value of 163.4 pg/ml, with a sensitivity of 91.7% and specificity of 57.6%.
Our findings demonstrate that IL6 expression is significant for the prediction of 30-day mortality in hospitalized COVID19 patients and, therefore, may assist in treatment decisions.
PDF
