TNF-alpha Production by Peripheral Blood Monocytes in Multiple Sclerosis Patients and Healthy Controls

Background: Aberrant immune responses are evident in the pathogenesis of multiple sclerosis (MS) and it has been proposed that the spectrum of cytokines influence disease outcomes. Leptin and lipopolysaccharide (LPS) of Gram-negative bacteria are both potent cellular stimulators for production of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α). The aim of this study was to compare the TNF-α production by peripheral blood monocytes from MS patients with healthy controls.

Methods: Peripheral blood samples were stimulated with LPS or leptin. After blocking the Golgi apparatus, intracellular cytokine production was assessed using a monoclonal antibody against human TNF-α by the flow cytometry technique. Moreover, plasma level measurement of cytokines was performed using enzyme-linked immunosorbent assay (ELISA).

Results: Intracellular levels of TNF-α were 16.80?±?8.21 and 16.52?±?8.23in MS patients and healthy controls which showed no statistically significant difference between them (p?=?0.850). Leptin-stimulated and LPS-stimulated TNF-α production showed no significant difference between MS patients and the control group (p?=?0.263 and p?=?0.191, respectively). However, after treatment with leptin, a weak significant difference was shown between cases and control group (p?=?0.049). There were significant differences between cases and controls regarding serum levels of IL-6 and Toll-like receptor-4 (TLR-4) before and after stimulation with leptin and LPS, separately (p?<?0.05).

Conclusion: Taken together, we cannot definitely conclude that TNF-α does not play an important role in pathogenesis of MS. However, other characteristics of monocyte activation such as IL-6 or TLRs can elucidate implication of peripheral blood monocytes in MS pathogenesis.     

Accelerometry Reveals Differences in Gait Variability Between Patients with Multiple Sclerosis and Healthy Controls

Variability of movement reflects important information for the maintenance of the health of the system. For pathological populations, changes in variability during gait signal the presence of abnormal motor control strategies. For persons with multiple sclerosis (PwMS), extensive gait problems have been reported including changes in gait variability. While previous studies have focused on footfall variability, the present study used accelerometers on the trunk to measure variability during walking. Thus, the purpose of this study was to examine the variability of the acceleration pattern of the upper and lower trunk in PwMS compared to healthy controls. We extracted linear and nonlinear measures of gait variability from 30 s of steady state walking for 15 PwMS and 15 age-matched healthy controls. PwMS had altered variability compared to controls with greater Lyapunov exponent in the ML (p < 0.001) and AP (p < 0.001) directions, and greater frequency dispersion in the ML direction (p = 0.034). PwMS also demonstrated greater mean velocity in the ML direction (p = 0.045) and lower root mean square of acceleration in the AP direction (p = 0.040). These findings indicate that PwMS have altered structure of variability of the trunk during gait compared to healthy controls and agree with previous findings related to changes in gait variability in PwMS.     

Characterization of Active T Cells in CSF and Blood in Multiple Sclerosis Patients and Controls

In thirty-two patients with multiple sclerosis (MS), significantly lower percentages of active T cells--that is, lymphocytes which have been incubated at 37 degrees C for 1 h before 5 min rosetting with sheep erythrocytes--were found in cerebrospinal fluid (CSF) than in blood, whereas the reverse was observed in twenty of twenty-two patients with other neurological diseases (OND). No significant difference was found between percentages of active T cells in blood in MS, OND, and healthy controls. Lymphocytes from MS CSF are extensively temperature-labile when examined under different test conditions; without incubation at 37 degrees C for 1 h, active T cell percentages in CSF of both patients with MS and OND were, in fact, higher than in peripheral blood. The mitogen response patterns of enriched active T cells and unseparated lymphocytes from peripheral blood did not discriminate between patients with MS and healthy controls. Although active T cell values have been shown to correlate with cell-mediated immunocompetence, they have not yet been defined functionally. One of the explanations for the present findings could be that lymphocytes themselves in MS patients' CSF are at least partly virus-infected.     

Association Between Sleep Problems and Perceived Cognitive Dysfunction Over 12 Months in Individuals with Multiple Sclerosis

Sleep problems are highly prevalent among individuals with multiple sclerosis (MS); however, the relationship between sleep problems and cognitive dysfunction is poorly understood in this population. In the present study, 163 individuals with MS and depression, fatigue, or pain completed self-report measures of sleep, cognitive dysfunction, and relevant demographic and clinical characteristics (e.g., disability severity, depressive symptomatology, pain intensity, fatigue impact) at four time points over 12 months. Mixed-effects regression demonstrated that poorer sleep was independently associated with worse perceived cognitive dysfunction (β = –0.05, p = .001), beyond the influence of depressive symptomatology. Fatigue impact was found to partially mediate this relationship. Results suggest that for individuals with MS and depression, fatigue, or pain, self-reported sleep problems are related to perceived cognitive dysfunction, and that fatigue impact accounts for part of this relationship.     

Validation of Machine Learning Models to Predict Adverse Outcomes in Patients with COVID-19: A Prospective Pilot Study

PurposeWe previously developed learning models for predicting the need for intensive care and oxygen among patients with coronavirus disease (COVID-19). Here, we aimed to prospectively validate the accuracy of these models.Materials and MethodsProbabilities of the need for intensive care [intensive care unit (ICU) score] and oxygen (oxygen score) were calculated from information provided by hospitalized COVID-19 patients (n=44) via a web-based application. The performance of baseline scores to predict 30-day outcomes was assessed.ResultsAmong 44 patients, 5 and 15 patients needed intensive care and oxygen, respectively. The area under the curve of ICU score and oxygen score to predict 30-day outcomes were 0.774 [95% confidence interval (CI): 0.614–0.934] and 0.728 (95% CI: 0.559–0.898), respectively. The ICU scores of patients needing intensive care increased daily by 0.71 points (95% CI: 0.20–1.22) after hospitalization and by 0.85 points (95% CI: 0.36–1.35) after symptom onset, which were significantly different from those in individuals not needing intensive care (p=0.002 and <0.001, respectively). Trends in daily oxygen scores overall were not markedly different; however, when the scores were evaluated within <7 days after symptom onset, the patients needing oxygen showed a higher daily increase in oxygen scores [1.81 (95% CI: 0.48–3.14) vs. -0.28 (95% CI: 1.00–0.43), p=0.007].ConclusionOur machine learning models showed good performance for predicting the outcomes of COVID-19 patients and could thus be useful for patient triage and monitoring.     

钢琴学习对老年人的加工速度、工作记忆及流体智力的影响

目的:了解老年开始钢琴学习对老年人认知能力的影响.方法:采用实验法和测验法,对老年被试的认知加工速度、工作记忆容量和流体智力进行测量.结果:老年时开始钢琴学习有利于老年人视听材料加工速度和听觉材料工作记忆容量的保持;流体智力与视觉材料加工速度和工作记忆容量相关显著,老年钢琴学习者在流体智力上的优势不明显.结论:老年时开始钢琴学习对老年人的认知能力发展有一定的积极作用.     

Editorial commentary on special issue of Advances in EEG Signal Processing and Machine Learning for Epileptic Seizure Detection and Prediction

This special issue of The Journal of Biomedical Research features novel studies on epileptic seizure detection and prediction based on advanced EEG signal processing and machine learning algorithms. The articles selected present important findings including new experimental results and theoretical studies.     

Antibodies to Interferon beta in Patients with Multiple Sclerosis Receiving CinnoVex,Rebif, and Betaferon

Treatment with interferon beta (IFN-β) induces the production of binding antibodies (BAbs) and neutralizing antibodies (NAbs) in patients with multiple sclerosis (MS). NAbs against IFN-β are associated with a loss of IFN-β bioactivity and decreased clinical efficacy of the drug. The objective of this study was to evaluate the incidence and the prevalence of binding antibodies (BAbs) and neutralizing antibodies (NAbs) to IFN-β in MS patients receiving CinnoVex, Rebif, or Betaferon. The presence of BAbs was studied in serum samples from 124 MS patients using one of these IFN-β medications by ELISA. The NAbs against IFN-β were measured in BAb-positive MS patients receiving IFN-β using an MxA gene expression assay (real-time RT-PCR). Of the 124 patients, 36 (29.03%) had BAbs after at least 12 months of IFN-β treatment. The proportion of BAb+ was 38.1% for Betaferon, 21.9% for Rebif, and 26.8% for CinnoVex. Five BAb-positive MS patients were lost to follow-up; thus 31 BAb-positive MS patients were studied for NAbs. NAbs were present in 25 (80.6%) of BAb-positive MS patients receiving IFN-β. In conclusion, the three IFN-β preparations have different degrees of immunogenicity.     

Integrating Natural Language Processing and Machine Learning Algorithms to Categorize Oncologic Response in Radiology Reports

Journal of Digital Imaging - A significant volume of medical data remains unstructured. Natural language processing (NLP) and machine learning (ML) techniques have shown to successfully extract...     

Lower Serum Levels of Th2-Related Chemokine CCL22 in Women Patients with Multiple Sclerosis: A Comparison Between Patients and Healthy Women

Chemokines play a major role in autoimmune diseases such as multiple sclerosis (MS). Gender also affects the susceptibility and course of MS. The aim of this study was to investigate the serum levels of the macrophage-derived chemokine (CCL22) in women and men patients with MS. Blood samples were collected from 135 healthy subjects (35 men and 100 women) and 135 MS patients (29 men and 136 women; 47 newly diagnosed and 88 treated patients and have relapsing-remitting (RRMS; n?=?65), secondary progressive (SPMS; n?=?37), primary progressive (PPMS; n?=?19), or progressive relapsing (PRMS; n?=?14) patterns). The serum levels of CCL22 were measured by ELISA. The difference of the mean serum levels of CCL22 between the newly diagnosed MS men and healthy men was not significant, but in newly diagnosed MS women, the mean serum levels of CCL22 were significantly lower than those in treated MS women and healthy women (P?<?0.006 and P?<?0.0001, respectively). The differences of the mean CCL22 levels between men patients with different treatment programs were not significant, but the mean CCL22 levels were significantly higher in women treated with interferon-β or the combination of interferon-β plus methylprednisolone as compared to untreated women patients (P?<?0.01 and P?<?0.05, respectively). The CCL22 levels were also significantly higher in women with RRMS and PRMS patterns in comparison to healthy women (P?<?0.05 and P?<?0.01, respectively). These results showed lower levels of CCL22 in women patients which represents that the reduction in CCL22 levels may play an important role in the pathogenesis of the disease in women. In women patients, the levels of CCL22 were influenced by disease pattern and treatment.     

Clinical and Etiological Characteristics of Enterovirus 71-Related Diseases during a Recent 2-Year Period in Korea

Human enterovirus 71 (EV 71) has caused large-scale outbreaks of hand-foot-and-mouth disease (HFMD), particularly in the Asian-Pacific region. In this study, we report a major outbreak of EV 71 infection in Korea and describe the clinical differences between EV 71 and non-EV 71 enterovirus infections. We prospectively enrolled patients with suspected viral infections during a recent 2-year period through a nationwide surveillance system. We identified 719 patients with suspected HFMD or herpangina using real-time PCR and genotyping based on VP1 sequence analysis. The major pathogen causing HFMD changed substantially from 2008 to 2009, with EV 71 becoming the most common cause of HFMD in Korea in 2009. We successfully identified the enteroviral genotypes for 218 of the 719 patients. Patients with EV 71 infections tended to be younger than those with non-EV 71 enteroviral infections and presented with HFMD and meningoencephalitis. In addition, the occurrence of fever, headache, and neck stiffness was significantly higher in patients with EV 71 infections. Multivariable analysis showed that for patients presenting with HFMD, fever, or a sore throat, each covariate was independently associated with EV 71 infection; the adjusted odds ratios (with 95% confidence intervals in parentheses) for these variables were 31.86 (10.04 to 101.09), 4.76 (1.71 to 13.25), and 0.18 (0.04 to 0.77), respectively. Our results indicate that EV 71 was a major cause of HFMD in Korea during the study period. In addition, we found that clinical symptoms may be helpful in the early identification of patients with EV 71 infections.Human enterovirus 71 (EV 71) is an important emerging pathogen of hand-foot-and-mouth disease (HFMD) (1, 6, 30). In particular, several major outbreaks of EV 71 have been documented in the Asia-Pacific region since 1997 (3, 4, 7, 9, 25). EV 71 infection causes HFMD, a common exanthema of young children that is characterized by a fever, rashes on the palms and the bottoms of the feet, and ulcers in the oral cavity. In general, patients with HFMD experience a mild course of disease; however, some patients develop severe neurological complications, especially as a result of EV 71 (18).Given that EV 71 infection could cause severe neurological complications, its early detection in patients with HFMD is an important part of intensive care efforts and efforts to prevent mortality. Unfortunately, current methods for the detection of EV 71 do not enable early detection (23). Here we report an outbreak of EV 71 infection in Korea. As part of this nationwide surveillance study, we examined the clinical differences between EV 71 and non-EV 71 enteroviral infections, and we investigated whether these differences are clinically applicable to the early detection of EV 71 in patients with complications of HFMD.     

Melioidosis in Odisha: A Clinico-Microbiological and Epidemiological Description of Culture-Confirmed Cases over a 2-Year Period

Melioidosis is an emerging infectious disease in India mostly reported from South-western coastal Karnataka and North-eastern Tamil Nadu. We speculate the existence of another major hidden focus in Odisha, one of the eastern coastal states. The clinico-epidemiological features of 47 culture-confirmed melioidosis at a tertiary care teaching hospital over a period of 2 years are reported. Septicaemia was the most common clinical presentation. Diabetes mellitus (DM) was present in 72.3% of our cases. The geo-climatic conditions of Odisha and other coastal states of India and the rise in the incidence of DM demand a nationwide surveillance of melioidosis and creation of melioidosis registry.     

Lack of Association between PRNP M129V Polymorphism and Multiple Sclerosis,Mild Cognitive Impairment,Alcoholism and Schizophrenia in a Korean Population

The genetic variant at codon 129 (M129V) of the prion protein gene (PRNP) is considered to be a major genetic risk factor for prion diseases. In this study, we examined the possible genetic association of PRNP*129Val with multiple sclerosis (MS, n = 681), mild cognitive impairment (MCI, n = 801), alcoholism (n = 761) and schizophrenia (n = 715) in a Korean population, and compared the data with previous genetic association studies of the variant. The minor allele frequency of PRNP*129Val (MAF = 0.025) was significantly lower in Korean population (n = 2,479) compared to Caucasian populations (P < 0.0001), suggestive of a weak influence of the variant in the previous population. Statistical analysis revealed no significant association between PRNP*129Val and MS (P = 0.76), MCI (P = 0.46), alcoholism (P = 0.84) and schizophrenia (P = 0.69). These findings were discussed in the context of prior inconsistent reports on the role of PRNP*129Val polymorphism in several diseases. Results from this study may provide further evidence that PRNP M129V is not a genetic susceptibility factor for MS, MCI, alcoholism and schizophrenia in a Korean population.     

The Association of Illness Severity,Self-Reported Cognitive Impairment,and Perceived Illness Management with Depression and Anxiety in a Multiple Sclerosis Clinic Population

Within the multiple sclerosis (MS) population, high prevalence of psychiatric concerns, such as depression and anxiety, has been well documented. The purpose of this study was to examine factors contributing to higher depression and anxiety levels in a sample of 82 patients utilizing MS clinic services. Independent variables included MS physical severity, self-reported cognitive impairment, and perceived illness management, respectively. Results from hierarchical regression analyses indicated that depression was related to the physical severity, self-reported cognitive impairment, and perceived illness management variables. Anxiety was also related to the physical severity and self-reported cognitive impairment variables but not to the perceived illness management ones, suggesting that depression and anxiety symptoms may involve somewhat different processes within MS. The findings of this study support further clinical consideration and additional investigation of these variables in the treatment of anxiety and depression in an MS clinic population.     

The Association of HLA Antigens A3, B7, and DW2 with 330 Multiple Sclerosis Patients in the United States

Reported associations of HLA antigens with MS have varied considerably. In this study we have examined 330 clinically definite MS patients from the United States. The frequency of DW2 (52%) was highly statistically significant in MS patients as compared to controls (p < 0.00001). Neither A3 nor B7 was significantly increased in MS; however, the joint occurrences of A3-DW2 (20% vs 7%, p < 0.001) and B7-DW2 (30% vs 13%, p < 0.0002) are highly associated with MS.     

IgG1 Subclass Restriction of Oligoclonal Measles Virus-Specific IgG Antibodies in Patients with Subacute Sclerosing Panencephalitis and in a Patient with Multiple Sclerosis

A restriction to the IgG1 subclass was demonstrated for measles virus-specific IgG antibodies isolated from the sera of five patients with subacute sclerosing panencephalitis, from the cerebrospinal fluid of one of the patients, and from brain extract from a sixth patient. A predominance of IgG1 was also observed in measles antibodies isolated from the serum and brain extract of a patient with multiple sclerosis. Evidence is presented that the IgG1 restriction is associated with the occurrence of oligoclonal measles antibodies in these patients. A similar restriction to the IgG1 subclass was not observed in measles antibodies isolated from the serum of a measles-convalescent child or from pooled normal serum and IgG.