Patients with multiple sclerosis do not necessarily consume more alcohol or tobacco than the general population.

PubMed

Fragoso, Yara Dadalti; Gomes, Sidney; Goncalves, Marcus Vinicius M; Machado, Suzana C Nunes; Morales, Rogerio de Rizo; Oliveira, Francisco Tomas M de; Oliveira, João Filipe de; Olmo, Neide R Simoes; Parolin, Monica K Fiuza; Siquineli, Fabio; Stoney, Patrick N

2015-10-01

Purpose Recent papers suggest that patients with multiple sclerosis (MS) are prone to alcohol misuse. This may be due to the combination of a lifelong and disabling disease with a psychiatric profile typical of MS. The objective of the present study was to assess these findings in a culturally different population of patients with MS.Method The present case-control transversal study assessed 168 patients with MS and 168 control subjects from Brazil.Results There were no evidence that patients with MS drank more alcohol or, smoked more than did controls. In fact, control subjects had a significantly higher alcohol consumption. The only trait associated to higher alcohol consumption was anxiety, both for patients and controls.Conclusion Unlike previous reports in the literature, patients with MS in our study did not drink or smoked more than a control population.

Islamic fasting and multiple sclerosis

PubMed Central

2014-01-01

Background Month-long daytime Ramadan fasting pose s major challenges to multiple sclerosis (MS) patients in Muslim countries. Physicians should have practical knowledge on the implications of fasting on MS. We present a summary of database searches (Cochrane Database of Systematic Reviews, PubMed) and a mini-symposium on Ramadan fasting and MS. In this symposium, we aimed to review the effect of fasting on MS and suggest practical guidelines on management. Discussion In general, fasting is possible for most stable patients. Appropriate amendment of drug regimens, careful monitoring of symptoms, as well as providing patients with available evidence on fasting and MS are important parts of management. Evidence from experimental studies suggests that calorie restriction before disease induction reduces inflammation and subsequent demyelination and attenuates disease severity. Fasting does not appear to have unfavorable effects on disease course in patients with mild disability (Expanded Disability Status Scale (EDSS) score ≤3). Most experts believed that during fasting (especially in summer), some MS symptoms (fatigue, fatigue perception, dizziness, spasticity, cognitive problems, weakness, vision, balance, gait) might worsen but return to normal levels during feasting. There was a general consensus that fasting is not safe for patients: on high doses of anti-convulsants, anti-spastics, and corticosteroids; with coagulopathy or active disease; during attacks; with EDSS score ≥7. Summary These data suggest that MS patients should have tailored care. Fasting in MS patients is a challenge that is directly associated with the spiritual belief of the patient. PMID:24655543

Islamic fasting and multiple sclerosis.

PubMed

Jahromi, Soodeh Razeghi; Sahraian, Mohammad Ali; Ashtari, Fereshteh; Ayromlou, Hormoz; Etemadifar, Massoud; Ghaffarpour, Majid; Mohammadianinejad, Ehsan; Nafissi, Shahriar; Nickseresht, Alireza; Shaygannejad, Vahid; Togha, Mansoreh; Torabi, Hamid Reza; Ziaie, Shadi

2014-03-22

Month-long daytime Ramadan fasting pose s major challenges to multiple sclerosis (MS) patients in Muslim countries. Physicians should have practical knowledge on the implications of fasting on MS. We present a summary of database searches (Cochrane Database of Systematic Reviews, PubMed) and a mini-symposium on Ramadan fasting and MS. In this symposium, we aimed to review the effect of fasting on MS and suggest practical guidelines on management. In general, fasting is possible for most stable patients. Appropriate amendment of drug regimens, careful monitoring of symptoms, as well as providing patients with available evidence on fasting and MS are important parts of management. Evidence from experimental studies suggests that calorie restriction before disease induction reduces inflammation and subsequent demyelination and attenuates disease severity. Fasting does not appear to have unfavorable effects on disease course in patients with mild disability (Expanded Disability Status Scale (EDSS) score ≤3). Most experts believed that during fasting (especially in summer), some MS symptoms (fatigue, fatigue perception, dizziness, spasticity, cognitive problems, weakness, vision, balance, gait) might worsen but return to normal levels during feasting. There was a general consensus that fasting is not safe for patients: on high doses of anti-convulsants, anti-spastics, and corticosteroids; with coagulopathy or active disease; during attacks; with EDSS score ≥7. These data suggest that MS patients should have tailored care. Fasting in MS patients is a challenge that is directly associated with the spiritual belief of the patient.

Is Geo-Environmental Exposure a Risk Factor for Multiple Sclerosis? A Population-Based Cross-Sectional Study in South-Western Sardinia.

PubMed

Monti, Maria Cristina; Guido, Davide; Montomoli, Cristina; Sardu, Claudia; Sanna, Alessandro; Pretti, Salvatore; Lorefice, Lorena; Marrosu, Maria Giovanna; Valera, Paolo; Cocco, Eleonora

South-Western Sardinia (SWS) is a high risk area for Multiple Sclerosis (MS) with high prevalence and spatial clustering; its population is genetically representative of Sardinians and presents a peculiar environment. We evaluated the MS environmental risk of specific heavy metals (HM) and geographical factors such as solar UV exposure and urbanization by undertaking a population-based cross-sectional study in SWS. Geochemical data on HM, UV exposure, urbanization and epidemiological MS data were available for all SWS municipalities. Principal Component Analysis (PCA) was applied to the geochemical data to reduce multicollinearity and confounding criticalities. Generalized Linear Mixed Models (GLMM) were applied to evaluate the causal effects of the potential risk factors, and a model selection was performed using Akaike Information Criterion. The PCA revealed that copper (Cu) does not cluster, while two component scores were extracted: 'basic rocks', including cobalt, chromium and nickel, and 'ore deposits', including lead and zinc. The selected multivariable GLMM highlighted Cu and sex as MS risk factors, adjusting for age and 'ore deposits'. When the Cu concentration increases by 50 ppm, the MS odds are 2.827 (95% CI: 1.645; 5.07) times higher; females have a MS odds 2.04 times (95% CI: 1.59; 2.60) higher than males. The high frequency of MS in industrialized countries, where pollution by HM and CO poisoning is widespread, suggests a relationship between environmental exposure to metals and MS. Hence, we suggested a role of Cu homeostasis in MS. This is a preliminary study aimed at generating hypotheses that will need to be confirmed further.

Maternal methyl supplemented diets and effects on offspring health

PubMed Central

O'Neill, Rachel J.; Vrana, Paul B.; Rosenfeld, Cheryl S.

2014-01-01

Women seeking to become pregnant and pregnant women are currently advised to consume high amounts of folic acid and other methyl donors to prevent neural tube defects in their offspring. These diets can alter methylation patterns of several biomolecules, including nucleic acids, and histone proteins. Limited animal model data suggests that developmental exposure to these maternal methyl supplemented (MS) diets leads to beneficial epimutations. However, other rodent and humans studies have yielded opposing findings with such diets leading to promiscuous epimutations that are likely associated with negative health outcomes. Conflict exists to whether these maternal diets are preventative or exacerbate the risk for Autism Spectrum Disorders (ASD) in children. This review will discuss the findings to date on the potential beneficial and aversive effects of maternal MS diets. We will also consider how other factors might influence the effects of MS diets. Current data suggest that there is cause for concern as maternal MS diets may lead to epimutations that underpin various diseases, including neurobehavioral disorders. Further studies are needed to explore the comprehensive effects maternal MS diets have on the offspring epigenome and subsequent overall health. PMID:25206362

Association of Common Mitochondrial DNA Variants with Multiple Sclerosis and Systemic Lupus Erythematosus

PubMed Central

Vyshkina, Tamara; Sylvester, Andrew; Sadiq, Saud; Bonilla, Eduardo; Canter, Jeff A.; Perl, Andras; Kalman, Bernadette

2008-01-01

Mitochondrial dysfunction has been implicated in the pathogenesis of multiple sclerosis (MS) and systemic lupus erythematosus (SLE). This study re-investigates the roles of previously suggested candidate genes of energy metabolism (Complex I genes located in the nucleus and in the mitochondria) in patients with MS relative to ethnically matched SLE patients and healthy controls. After stringent correction for multiple testing, we reproduce the association of the mitochondrial (mt)DNA haplotype K* with MS, but reject the importance of previously suggested borderline associations with nuclear genes of Complex I. In addition, we detect the association of common variants of the mitochondrial ND2 and ATP6 genes with both MS and SLE, which raises the possibility of a shared mitochondrial genetic background of these two autoimmune diseases. PMID:18708297

Quantification of blood-to-brain transfer rate in multiple sclerosis

PubMed Central

Taheri, Saeid; Rosenberg, Gary A.; Ford, Corey

2016-01-01

Blood–brain barrier (BBB) disruption visualized in lesions by MRI is a major biomarker of disease activity in multiple sclerosis (MS). However, in MS, destruction occurs to a variable extent in lesions as well as in gray matter (GM) and in the normal appearing white matter (NAWM). A method to quantify the BBB disruption in lesions as well as in non-lesion areas would be useful for assessment of MS progression and treatments. The objective of this study was to quantify the BBB transfer rate (Ki) in WM lesions, in the NAWM, and in the full-brain of MS patients. Thirteen MS patients with active lesions and 10 healthy controls with age and gender matching were recruited for full-brain and WM Ki studies. Dynamic contrast-enhanced MRI (DCEMRI) scans were conducted using T1 mapping with partial inversion recovery (TAPIR), a fast T1 mapping technique, following administration of a quarter-dose of the contrast agent Gadolinium-DTPA (Gd-DTPA). The Patlak modeling technique was used to derive a voxel-based map of Ki. In all patients contrast-enhanced lesions, quantified by Ki maps, were observed. Compared with controls, patients with MS exhibited an increase in mean Ki of the full-brain (P-value<0.05) but no significant difference in mean Ki of NAWM. The identified increase in full-brain Ki of MS patients suggests a global vascular involvement associated with MS disease. The lack of observed significant decrease in Ki in NAWM suggests lower involvement of WM vasculature than full-brain vasculature in MS. Ki maps constructed from time series data acquired by DCEMRI provide additional information about BBB that could be used for evaluation of vascular involvement in MS and monitoring treatment effectiveness. PMID:25877634

Comparisons between youth of a parent with MS and a control group on adjustment, caregiving, attachment and family functioning.

PubMed

Pakenham, K I; Cox, S

2013-01-01

Few studies have examined the effects of parental MS on children, and those that have suffered from numerous methodological weaknesses, some of which are addressed in this study. This study investigated the effects of parental MS on children by comparing youth of a parent with MS to youth who have no family member with a serious health condition on adjustment outcomes, caregiving, attachment and family functioning. A questionnaire survey methodology was used. Measures included youth somatisation, health, pro-social behaviour, behavioural-social difficulties, caregiving, attachment and family functioning. A total of 126 youth of a parent with MS were recruited from MS Societies in Australia and, were matched one-to-one with youth who had no family member with a health condition drawn from a large community sample. Comparisons showed that youth of a parent with MS did not differ on any of the outcomes except for peer relationship problems: adolescent youth of a parent with MS reported lower peer relationship problems than control adolescents. Overall, results did not support prior research findings suggesting adverse impacts of parental MS on youth.

The Role of Fungi in the Etiology of Multiple Sclerosis

PubMed Central

Benito-León, Julián; Laurence, Martin

2017-01-01

Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system. Infectious triggers of MS are being actively investigated. Substantial evidence supports the involvement of the Epstein-Barr virus (EBV), though other viruses, bacteria, protists, and fungi are also being considered. Many links between fungi and diseases involving chronic inflammation have been found recently. Evidence linking MS and fungi is reviewed here. The HLA-DRB1*15 allele group is the most important genetic risk factor of MS, and is a risk factor in several other conditions linked to fungal infections. Many biomarkers of MS are consistent with fungal infections, such as IL-17, chitotriosidase, and antibodies against fungi. Dimethyl fumarate (DMF), first used as an industrial fungicide, was recently repurposed to reduce MS symptoms. Its mechanisms of action in MS have not been firmly established. The low risk of MS during childhood and its moderate association with herpes simplex virus type 2 suggest genital exposure to microbes (including fungi) should be investigated as a possible trigger. Molecular and epidemiological evidence support a role for infections such as EBV in MS. Though fungal infections have not been widely studied in MS, many lines of evidence are consistent with a fungal etiology. Future microbiome and serological studies should consider fungi as a possible risk factor for MS, and future clinical studies should consider the effect of fungicides other than DMF on MS symptoms. PMID:29085329

Histone Deacetylase Inhibitor MS-275 Exhibits Poor Brain Penetration: Pharmacokinetic Studies of [11C]MS-275 using Positron Emission Tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hooker, J.M.; Hooker, J.M.; Kim, S.W.

2009-10-01

MS-275 (entinostat) is a histone deacetylase (HDAC) inhibitor currently in clinical trials for the treatment of several types of cancer. Recent reports have noted that MS-275 can cross the blood-brain barrier (BBB) and cause region-specific changes in rodent brain histone acetylation. To characterize the pharmacokinetics and distribution of MS-275 in the brain using positron emission tomography (PET), we labeled the carbamate carbon of MS-275 with carbon-11. Using PET, we determined that [{sup 11}C]MS-275 has low uptake in brain tissue when administered intravenously to nonhuman primates. In rodent studies, we observed that pharmacokinetics and brain accumulation of [{sup 11}C]MS-275 were notmore » changed by the coadministration of large doses of unlabeled MS-275. These results, which both highlight the poor brain penetration of MS-275, clearly suggest its limitation as a therapeutic agent for the central nervous system (CNS). Moreover, our study demonstrates the effectiveness of PET at providing brain pharmacokinetic data for HDAC inhibitors. These data are important not only for the development of new compounds for peripheral cancer treatment (where CNS exclusion is often advantageous) but also for the treatment of neurological disorders (where CNS penetration is critical).« less

Type II flavohemoglobin of Mycobacterium smegmatis oxidizes d-lactate and mediate electron transfer.

PubMed

Thakur, Naveen; Kumar, Ashwani; Dikshit, Kanak L

2018-06-01

Two distantly related flavohemoglobins (FHbs), MsFHbI and MsFHbII, having crucial differences in their heme and reductase domains, co-exist in Mycobacterium smegmatis. Function of MsFHbI is associated with nitric-oxide detoxification but physiological relevance of MsFHbII remains unknown. This study unravels some unique spectral and functional characteristics of MsFHbII. Unlike conventional type I FHbs, MsFHbII lacks nitric-oxide dioxygenase and NADH oxidase activities but utilizes d-lactate as an electron donor to mediate electron transfer. MsFHbII carries a d-lactate dehydrogenase type FAD binding motif in its reductase domain and oxidizes d-lactate in a FAD dependent manner to reduce the heme iron, suggesting that the globin is acting as an electron acceptor. Importantly, expression of MsFHbII in Escherichia coli imparted protection under oxidative stress, suggesting its important role in stress management of its host. Since M. smegmatis lacks the gene encoding for d-lactate dehydrogenase and d-lactate is produced during aerobic metabolism and also as a by-product of lipid peroxidation, the ability of MsFHbII to metabolize d-lactate may provide it a unique ability to balance the oxidative stress generated due to accumulation of d-lactate in the cell and at the same time sequester electrons and pass it to the respiratory apparatus. Copyright © 2018 Elsevier B.V. All rights reserved.

Oligoclonal Band Status in Scandinavian Multiple Sclerosis Patients Is Associated with Specific Genetic Risk Alleles

PubMed Central

Sæther, Hanne S.; Flåm, Siri T.; Berg-Hansen, Pål; Søndergaard, Helle B.; Jensen, Poul Erik H.; Berge, Tone; Bjølgerud, Anja; Muggerud, Aslaug; Aarseth, Jan H.; Myhr, Kjell-Morten; Celius, Elisabeth G.; Sellebjerg, Finn; Hillert, Jan; Alfredsson, Lars; Olsson, Tomas; Oturai, Annette Bang; Kockum, Ingrid; Lie, Benedicte A.; Andreassen, Bettina Kulle; Harbo, Hanne F.

2013-01-01

The presence of oligoclonal bands (OCB) in cerebrospinal fluid (CSF) is a typical finding in multiple sclerosis (MS). We applied data from Norwegian, Swedish and Danish (i.e. Scandinavian) MS patients from a genome-wide association study (GWAS) to search for genetic differences in MS relating to OCB status. GWAS data was compared in 1367 OCB positive and 161 OCB negative Scandinavian MS patients, and nine of the most associated SNPs were genotyped for replication in 3403 Scandinavian MS patients. HLA-DRB1 genotypes were analyzed in a subset of the OCB positive (n = 2781) and OCB negative (n = 292) MS patients and compared to 890 healthy controls. Results from the genome-wide analyses showed that single nucleotide polymorphisms (SNPs) from the HLA complex and six other loci were associated to OCB status. In SNPs selected for replication, combined analyses showed genome-wide significant association for two SNPs in the HLA complex; rs3129871 (p = 5.7×10−15) and rs3817963 (p = 5.7×10−10) correlating with the HLA-DRB1*15 and the HLA-DRB1*04 alleles, respectively. We also found suggestive association to one SNP in the Calsyntenin-2 gene (p = 8.83×10−7). In HLA-DRB1 analyses HLA-DRB1*15∶01 was a stronger risk factor for OCB positive than OCB negative MS, whereas HLA-DRB1*04∶04 was associated with increased risk of OCB negative MS and reduced risk of OCB positive MS. Protective effects of HLA-DRB1*01∶01 and HLA-DRB1*07∶01 were detected in both groups. The groups were different with regard to age at onset (AAO), MS outcome measures and gender. This study confirms both shared and distinct genetic risk for MS subtypes in the Scandinavian population defined by OCB status and indicates different clinical characteristics between the groups. This suggests differences in disease mechanisms between OCB negative and OCB positive MS with implications for patient management, which need to be further studied. PMID:23472185

Gray Matter Is Targeted in First-Attack Multiple Sclerosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schutzer, Steven E.; Angel, Thomas E.; Liu, Tao

The cause of multiple sclerosis (MS), its driving pathogenesis at the earliest stages, and what factors allow the first clinical attack to manifest remain unknown. Some imaging studies suggest gray rather than white matter may be involved early, and some postulate this may be predictive of developing MS. Other imaging studies are in conflict. To determine if there was objective molecular evidence of gray matter involvement in early MS we used high-resolution mass spectrometry to identify proteins in the cerebrospinal fluid (CSF) of first-attack MS patients (two independent groups) compared to established relapsing remitting (RR) MS and controls. We foundmore » that the CSF proteins in first-attack patients were differentially enriched for gray matter components (axon, neuron, synapse). Myelin components did not distinguish these groups. The results support that gray matter dysfunction is involved early in MS, and also may be integral for the initial clinical presentation.« less

UPLC-QTOF-MS/MS-guided isolation and purification of sulfur-containing derivatives from sulfur-fumigated edible herbs, a case study on ginseng.

PubMed

Zhang, Li; Shen, Hong; Xu, Jun; Xu, Jin-Di; Li, Zhen-Ling; Wu, Jie; Zou, Ye-Ting; Liu, Li-Fang; Li, Song-Lin

2018-04-25

In this study, a novel ultra-performance liquid chromatography coupled with quadrupole/time-of-flight mass spectrometry (UPLC-QTOF-MS/MS)-guidance strategy was proposed for preparation of sulfur-containing derivatives in sulfur-fumigated edible herbs. Being versatile in both chromatographic separation and mass spectrometric detection, UPLC-QTOF-MS/MS was inducted into each experimental step for multifaceted purposes including finding, tracking, purity determination and structural elucidation of targeted compounds as well as UPLC-HPLC chromatographic conditions transplantation, whereby the isolation and purification procedures were greatly facilitated. Using this strategy, a new sulfur-containing ginsenoside Rg 1 derivative (named compound I) was obtained from sulfur-fumigated ginseng. The chemical structure of compound I was elucidated to be (3β, 6α, 12β)-3, 12-dihydroxydammar-25-ene-6, 20-diylbis-β-d-glucopyranoside, 24-sulfonic acid by QTOF-MS/MS, 1 H-NMR and 13 C-NMR analysis, and its generation mechanisms by sulfur-fumigation were accordingly discussed. The research deliverable suggests that the UPLC-QTOF-MS/MS-guidance strategy is promising for targeted preparation of sulfur-containing derivatives from sulfur-fumigated edible herbs. Copyright © 2017 Elsevier Ltd. All rights reserved.

The effects of noncontingent music and response interruption and redirection on vocal stereotypy.

PubMed

Gibbs, Ashley R; Tullis, Christopher A; Thomas, Raven; Elkins, Brittany

2018-06-17

Vocal stereotypy is a commonly occurring challenging behavior in children with autism spectrum disorder (ASD) that is frequently maintained by automatic reinforcement and often interferes with skill acquisition. Matched stimulation (MS), and response interruption and redirection (RIRD) are two interventions that have been demonstrated to be effective in reducing the occurrence of vocal stereotypy with participants with ASD. The current study sought to determine if the combination of MS (noncontingent music) and RIRD was more effective at reducing vocal stereotypy than RIRD alone and if the parents of children with ASD found the combination of MS and RIRD more socially valid than RIRD alone. The results suggested that the combined intervention resulted in greater suppression of vocal stereotypy and increased occurrences of on-task behavior in both participants. Additionally, RIRD required fewer implementations and had a shorter duration when combined with MS. Results suggest that the combination of MS and RIRD may be an effective intervention outside of highly controlled settings. © 2018 Society for the Experimental Analysis of Behavior.

Metabolic syndrome in patients with psoriasis: A comparative study.

PubMed

Lakshmi, Sristi; Nath, Amiya Kumar; Udayashankar, Carounanidy

2014-04-01

Psoriasis patients are at increased risk of developing the metabolic syndrome (MS). Proinflammatory cytokines such as tumor necrosis factor-α, interleukin-6 that are increased in the psoriatic plaques are known to contribute to features of MS such as hypertension, dyslipidemia and insulin resistance. (1) To establish the frequency of MS in patients with psoriasis. (2) To study the risk factors associated with MS in psoriasis. A hospital based comparative study was conducted involving 40 adult patients with psoriasis and 40 age- and sex-matched controls. All participants were evaluated for components of MS. Both groups included 31 males and 9 females. The mean age of the cases and controls were 49.95 years and 49.35 years, respectively. Psoriasis patients with MS had a statistically significant higher mean age (56.31 ± 11.36 years) compared with those without MS (46.89 ± 11.51 years). MS was present in 13 out of 40 (32.5%) patients with psoriasis and 12 out of 40 (30%) controls; this difference was not statistically significant. Higher age and female gender correlated with the presence of MS in psoriasis patients. The presence of MS in psoriasis patients was statistically independent of psoriasis area severity index score, body surface area involvement or psoriatic arthropathy. Our results suggest that there is no close correlation between psoriasis and MS in South Indian patients.

Circulating dendritic cells of multiple sclerosis patients are proinflammatory and their frequency is correlated with MS-associated genetic risk factors.

PubMed

Thewissen, Kristof; Nuyts, Amber H; Deckx, Nathalie; Van Wijmeersch, Bart; Nagels, Guy; D'hooghe, Marie; Willekens, Barbara; Cras, Patrick; Eijnde, Bert O; Goossens, Herman; Van Tendeloo, Viggo F I; Stinissen, Piet; Berneman, Zwi N; Hellings, Niels; Cools, Nathalie

2014-04-01

The role of the adaptive immune system and more specifically T cells in the pathogenesis of multiple sclerosis (MS) has been studied extensively. Emerging evidence suggests that dendritic cells (DCs), which are innate immune cells, also contribute to MS. This study aimed to characterize circulating DC populations in MS and to investigate the contribution of MS-associated genetic risk factors to DCs. Ex vivo analysis of conventional (cDCs) and plasmacytoid DCs (pDCs) was carried out on peripheral blood of MS patients (n = 110) and age- and gender-matched healthy controls (n = 112). Circulating pDCs were significantly decreased in patients with chronic progressive MS compared to relapsing-remitting MS and healthy controls. While no differences in cDCs frequency were found between the different study groups, HLA-DRB1*1501(+) MS patients and patients not carrying the protective IL-7Rα haplotype 2 have reduced frequencies of circulating cDCs and pDCs, respectively. MS-derived DCs showed enhanced IL-12p70 production upon TLR ligation and had an increased expression of the migratory molecules CCR5 and CCR7 as well as an enhanced in vitro chemotaxis. DCs in MS are in a pro-inflammatory state, have a migratory phenotype and are affected by genetic risk factors, thereby contributing to pathogenic responses.

Radioimmunoassay of CSF for encephalitogenic basic protein: a diagnostic test for MS?

PubMed Central

McPherson, T. A.; Gilpin, Annabel; Seland, T. P.

1972-01-01

Competitive inhibition of binding between radioiodine-labelled encephalitogenic basic protein from human myelin (125I-HEProt) and normal human alpha-2 macroglobulin and between 125I-HEProt and rabbit antiHEProt serum was used to study concentrated cerebrospinal fluid (CSF) under “blind” control for cross-reactivity with HEProt. Samples of CSF from patients meeting the standard criteria for definite MS and possible MS, and from patients with optic neuritis and “other” diagnoses were studied. CSF from patients in all four groups was shown to have an inhibitor cross-reactive with HEProt when studied by the 125I-HEProt/alpha-2 macroglobulin test, but the amount was significantly greater in the definite MS group than in the “other” group. Results of the two tests on CSF from MS patients correlated, suggesting that the tests were identifying the same inhibitor. It was concluded that CSF contains an inhibitor similar to HEProt and that the amount present in CSF could be a useful diagnostic marker of MS. PMID:4120149

Polymorphisms in CD14 Gene May Modify Soluble CD14 Levels and Represent Risk Factors for Multiple Sclerosis.

PubMed

Farrokhi, Mehrdad; Moeini, Pedram; Fazilati, Mohammad; Nazem, Habibollah; Faraji, Shahla; Saadatpour, Zahra; Fadaei, Elyas; Saadatpour, Leila; Rezaei, Ali; Ansaripour, Sadra; Amani-Beni, Ali

2016-11-07

Besides the central role of the adaptive immune system, a disturbance of innate immune system is also suggested to be involved in the pathogenesis of multiple sclerosis (MS). CD14, a receptor upregulated in activated microglia, is known to be an essential mediator of inflammation in innate immune responses. Therefore, in this study we aimed to assess possible roles of CD14-159 and -260 gene polymorphisms in MS susceptibility and the effects of those polymorphisms to its protein producing capacity in Iranian population. In this case control study, CD14-159 and -260 polymorphisms were genotyped using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) in 200 MS patients and 200 healthy controls matched in age and gender. Serum levels of soluble CD14 (sCD14) was determined by enzyme-linked immunosorbent assay (ELISA). There were significant differences in genotype distribution of CD14-159 and -260 polymorphisms between patients and controls (P = 0.01, for-both). Mean serum level of sCD14 was significantly higher in MS patients than in control subjects (3340.30 ± 612.50 ng/ml vs 2353.73 ± 539.07 ng/ml; P < 0.01). In summary, we conclude that CD14-159 and -260 polymorphisms are associated with the risk of MS in Iranian population and affects CD14 promoter activity, thereby regulating CD14 expression. Furthermore, our study provides preliminary evidence for the activation of innate immunity in the pathogenesis of MS. In addition, the findings of the present study suggest serum level of sCD14 as candidate biomarker of MS severity.

Intimate relationship quality, self-concept and illness acceptance in those with multiple sclerosis.

PubMed

Wright, Thomas M; Kiropoulos, Litza A

2017-02-01

Lower levels of Intimate Relationship Quality (IRQ) have been found in those with Multiple Sclerosis (MS) compared to the general population. This study examined an MS sample to see whether IRQ was positively associated with self-concept, whether IRQ was positively associated with MS illness acceptance and whether IRQ was predicted by self-concept and illness acceptance. In this cross-sectional study, 115 participants with MS who were in an intimate relationship completed an online survey advertised on MS related websites. The survey assessed demographic variables, MS illness variables and levels of IRQ, self-concept and illness acceptance. Results revealed that IRQ was significantly positively associated with self-concept and with illness acceptance. Multiple hierarchical linear regression analysis revealed that, after controlling for illness duration and level of disability, self-concept significantly predicted IRQ but illness acceptance did not significantly predict IRQ. This study addressed several gaps and methodological flaws in the literature and was the first known to assess predictors of IRQ in those with MS. The results suggest that self-concept could be a potential target for individual and couple psychological interventions to improve IRQ and contribute to improved outcomes for those with MS.

Microarray gene expression profiling analysis combined with bioinformatics in multiple sclerosis.

PubMed

Liu, Mingyuan; Hou, Xiaojun; Zhang, Ping; Hao, Yong; Yang, Yiting; Wu, Xiongfeng; Zhu, Desheng; Guan, Yangtai

2013-05-01

Multiple sclerosis (MS) is the most prevalent demyelinating disease and the principal cause of neurological disability in young adults. Recent microarray gene expression profiling studies have identified several genetic variants contributing to the complex pathogenesis of MS, however, expressional and functional studies are still required to further understand its molecular mechanism. The present study aimed to analyze the molecular mechanism of MS using microarray analysis combined with bioinformatics techniques. We downloaded the gene expression profile of MS from Gene Expression Omnibus (GEO) and analysed the microarray data using the differentially coexpressed genes (DCGs) and links package in R and Database for Annotation, Visualization and Integrated Discovery. The regulatory impact factor (RIF) algorithm was used to measure the impact factor of transcription factor. A total of 1,297 DCGs between MS patients and healthy controls were identified. Functional annotation indicated that these DCGs were associated with immune and neurological functions. Furthermore, the RIF result suggested that IKZF1, BACH1, CEBPB, EGR1, FOS may play central regulatory roles in controlling gene expression in the pathogenesis of MS. Our findings confirm the presence of multiple molecular alterations in MS and indicate the possibility for identifying prognostic factors associated with MS pathogenesis.

Lexical access changes in patients with multiple sclerosis: a two-year follow-up study.

PubMed

Sepulcre, Jorge; Peraita, Herminia; Goni, Joaquin; Arrondo, Gonzalo; Martincorena, Inigo; Duque, Beatriz; Velez de Mendizabal, Nieves; Masdeu, Joseph C; Villoslada, Pablo

2011-02-01

The aim of the study was to analyze lexical access strategies in patients with multiple sclerosis (MS) and their changes over time. We studied lexical access strategies during semantic and phonemic verbal fluency tests and also confrontation naming in a 2-year prospective cohort of 45 MS patients and 20 healthy controls. At baseline, switching lexical access strategy (both in semantic and in phonemic verbal fluency tests) and confrontation naming were significantly impaired in MS patients compared with controls. After 2 years follow-up, switching score decreased, and cluster size increased over time in semantic verbal fluency tasks, suggesting a failure in the retrieval of lexical information rather than an impairment of the lexical pool. In conclusion, these findings underline the significant presence of lexical access problems in patients with MS and could point out their key role in the alterations of high-level communications abilities in MS.

Prevalence of metabolic syndrome in Brazilian adults: a systematic review

PubMed Central

2013-01-01

Background The metabolic syndrome (MS) is a complex of risk factors for cardiovascular disease. This syndrome increases the risk of diabetes, cardiovascular disease and all-cause mortality. It has been demonstrated that the prevalence of MS is increasing worldwide. Despite the importance of MS in the context of metabolic and cardiovascular disease, few studies have described the prevalence of MS and its determinants in Latin America. The present study aims to assess studies describing the prevalence of MS in Brazil in order to determine the global prevalence of the syndrome and its components. Methods Systematic review. Searches were carried out in PubMed and Scielo from the earliest available online indexing year through May 2013. There were no restrictions on language. The search terms used to describe MS were taken from the PubMed (MeSH) dictionary: “metabolic syndrome x”, “prevalence” and “Brazil”. Studies were included if they were cross-sectional, described the prevalence of MS and were conducted in apparently healthy subjects, from the general population, 19-64 years old (adult and middle aged) of both genders. The titles and abstracts of all the articles identified were screened for eligibility. Results Ten cross-sectional studies were selected. The weighted mean for general prevalence of MS in Brazil was 29.6% (range: 14.9%-65.3%). Half of the studies used the criteria for clinical diagnosis of MS proposed by the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) (2001). The highest prevalence of MS (65.3%) was found in a study conducted in an indigenous population, whereas the lowest prevalence of MS (14.9%) was reported in a rural area. The most frequent MS components were low HDL-cholesterol (59.3%) and hypertension (52.5%). Conclusions Despite methodological differences among the studies selected, our findings suggested a high prevalence of MS in the Brazilian adult population. PMID:24350922

Viruses and Multiple Sclerosis

PubMed Central

Virtanen, Jussi Oskari; Jacobson, Steve

2016-01-01

Multiple sclerosis (MS) is a heterogeneous disease that develops as an interplay between the immune system and environmental stimuli in genetically susceptible individuals. There is increasing evidence that viruses may play a role in MS pathogenesis acting as these environmental triggers. However, it is not known if any single virus is causal, or rather several viruses can act as triggers in disease development. Here, we review the association of different viruses to MS with an emphasis on two herpesviruses, Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6). These two agents have generated the most impact during recent years as possible co-factors in MS disease development. The strongest argument for association of EBV with MS comes from the link between symptomatic infectious mononucleosis and MS and from seroepidemiological studies. In contrast to EBV, HHV-6 has been found significantly more often in MS plaques than in MS normal appearing white matter or non-MS brains and HHV-6 re-activation has been reported during MS clinical relapses. In this review we also suggest new strategies, including the development of new infectious animal models of MS and antiviral MS clinical trials, to elucidate roles of different viruses in the pathogenesis of this disease. Furthermore, we introduce the idea of using unbiased sequence-independent pathogen discovery methodologies, such as next generation sequencing, to study MS brain tissue or body fluids for detection of known viral sequences or potential novel viral agents. PMID:22583435

Effect of Cytokine Signaling 3 Gene Polymorphisms in Childhood Obesity.

PubMed

Boyraz, Mehmet; Yeşilkaya, Ediz; Ezgü, Fatih; Bideci, Aysun; Doğan, Haldun; Ulucan, Korkut; Cinaz, Peyami

2016-12-01

Although polymorphisms in suppressor of cytokine signaling 3 (SOCS3) was reported to be related to obesity, Metabolic syndrome (MS), and type 2 diabetes mellitus in various adult studies, there is a lack of data in children. In this study, we examined eight reported polymorphisms of SOCS3 in obese Turkish children and adolescent with and without MS and compared the results with that of controls. One hundred and forty eight obese and 63 age- and sex-matched control subjects were enrolled in the study. Obesity classification was carried out according to body mass index. World Health Organization and National Cholesterol Education Program criteria were used for the diagnosis of MS. Genotyping procedure was carried out by polymerase chain reaction and Sanger sequencing protocol. The frequency of rs2280148 polymorphism was significantly higher in obese subjects with MS than in the control group, whereas the frequency of rs8064821 polymorphism was significantly higher in obese subjects with MS than in obese children without MS. The significant associations of certain SOCS3 polymorphisms with obesity parameters in both MS and MS -related insulin resistance, hypertension, and fatty liver suggest that polymorphisms in this gene may play a role in the pathogenesis of MS and also that they can be potentially used as a marker for attenuated or aggressive disease.

The Geomagnetic Field and Correlations with Multiple Sclerosis: A Possible Etiology of Disease

NASA Astrophysics Data System (ADS)

Wade, Brett

Multiple sclerosis (MS) is a complex autoimmune disease that results in a demyelinating process of the central nervous system. It is the most common, progressive, neurological disease affecting young adults, and there is no cure. A curious feature of MS is its distinct global prevalence with high rates of occurrence between 40 and 60 degrees latitude. While genetics may partially explain this phenomenon, studies have shown that the influence of genetics is modest. Many non-genetic variables, such as viruses, vitamin D, smoking, diet, hormones, etc., have been shown to be related to the expression of MS but none of these variables have been determined to be necessarily strong enough to exclude other factors. The geomagnetic field, which is a non-uniform, three dimensional entity which protects all living things from ionizing radiation, is suggested in this research to be related to global MS prevalence. This study hypothesized that either the total field, the vertical field, or the horizontal field strength of the geomagnetic field will be correlated with MS. Using secondary sources of prevalence studies (N=131) and geomagnetic data, the results supported all three hypotheses with the strongest correlation being an inverse relationship between the horizontal field and MS (r = -.607). The explanation for the inverse relationship being most strongly correlated with MS prevalence is explained by the fact that the horizontal aspect of the geomagnetic field has a protective effect from incoming cosmic radiation. Chronic exposure to high levels of background radiation can have deleterious health effects. This research suggests that living in areas of a weak horizontal field increases a person's exposure to ionizing radiation and therefore increases the risk for developing MS. While it was not the intention of this research, it became clear that an explanation which explained the results of this research and also attempted to unify the mechanisms of all non-genetic variables was prudent. A Unified Theory of MS Disease Expression is presented in this research.

Terror management and aggression: evidence that mortality salience motivates aggression against worldview-threatening others.

PubMed

McGregor, H A; Lieberman, J D; Greenberg, J; Solomon, S; Arndt, J; Simon, L; Pyszczynski, T

1998-03-01

The hypothesis that mortality salience (MS) motivates aggression against worldview-threatening others was tested in 4 studies. In Study 1, the experimenters induced participants to write about either their own death or a control topic, presented them with a target who either disparaged their political views or did not, and gave them the opportunity to choose the amount of hot sauce the target would have to consume. As predicted, MS participants allocated a particularly large amount of hot sauce to the worldview-threatening target. In Studies 2 and 3, the authors found that following MS induction, the opportunity to express a negative attitude toward the critical target eliminated aggression and the opportunity to aggress against the target eliminated derogation. This suggests that derogation and aggression are two alternative modes of responding to MS that serve the same psychological function. Finally, Study 4 showed that MS did not encourage aggression against a person who allocated unpleasant juice to the participant, supporting the specificity of MS-induced aggression to worldview-threatening others.

Characterization of RbmD (glycosyltransferase in ribostamycin gene cluster) through neomycin production reconstituted from the engineered Streptomyces fradiae BS1.

PubMed

Nepal, Keshav Kumar; Oh, Tae-Jin; Subba, Bimala; Yoo, Jin Cheol; Sohng, Jae Kyung

2009-01-31

Amino acid homology analysis predicted that rbmD, a putative glycosyltransferase from Streptomyces ribosidificus ATCC 21294, has the highest homology with neoD in neomycin biosynthesis. S. fradiae BS1, in which the production of neomycin was abolished, was generated by disruption of the neoD gene in the neomycin producer S. fradiae. The restoration of neomycin by self complementation suggested that there was no polar effect in the mutant. In addition, S. fradiae BS6 was created with complementation by rbmD in S. fradiae BS1, and secondary metabolite analysis by ESI/MS, LC/MS and MS/MS showed the restoration of neomycin production in S. fradiae BS6. These gene inactivation and complementation studies suggested that, like neoD, rbmD functions as a 2-N-acetlyglucosaminyltransferase and demonstrated the potential for the generation of novel aminoglycoside antibiotics using glycosyltransferases in vivo.

Is the hygiene hypothesis relevant for the risk of multiple sclerosis?

PubMed

Wendel-Haga, M; Celius, E G

2017-11-01

The hygiene hypothesis, suggesting that low exposure to pathogens early in life can increase the risk for immune-mediated diseases, has been proposed as an explanation for the increase in incidence of allergy and autoimmune diseases in industrialized countries during the last decades. Several aspects of the hygiene hypothesis have been related to MS. Already in 1966, the risk of MS was suggested to be higher in individuals with high hygienic standard during childhood. Further, an episode of infectious mononucleosis is an independent risk factor for MS and can be regarded as an indicator of low exposure to pathogens early in life, as infection with Epstein-Barr virus often is asymptomatic when it occurs in young children. Conflicting results have been reported regarding number of siblings, attendance in a day care center and exposure to animals during childhood in relation to MS risk, but common childhood infections and vaccinations do not seem to influence the risk of MS. In line with the hygiene hypothesis, two large meta-analyses have recently shown that infection with Helicobacter pylori is negatively correlated with MS. Moreover, a protective influence of helminth infection on MS has been observed in several, small clinical studies, but more knowledge is needed before a potential role of helminth-derived therapy in MS is determined. Also, it has been hypothesized that infection with the parasite Toxoplasma gondii could be protective against MS. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Genome-Wide Analyses of Calcium Sensors Reveal Their Involvement in Drought Stress Response and Storage Roots Deterioration after Harvest in Cassava.

PubMed

Hu, Wei; Yan, Yan; Tie, Weiwei; Ding, Zehong; Wu, Chunlai; Ding, Xupo; Wang, Wenquan; Xia, Zhiqiang; Guo, Jianchun; Peng, Ming

2018-04-19

Calcium (Ca 2+ ) plays a crucial role in plant development and responses to environmental stimuli. Currently, calmodulins (CaMs), calmodulin-like proteins (CMLs), and calcineurin B-like proteins (CBLs), such as Ca 2+ sensors, are not well understood in cassava ( Manihot esculenta Crantz), an important tropical crop. In the present study, 8 CaMs, 48 CMLs, and 9 CBLs were genome-wide identified in cassava, which were divided into two, four, and four groups, respectively, based on evolutionary relationship, protein motif, and gene structure analyses. Transcriptomic analysis revealed the expression diversity of cassava CaMs-CMLs-CBLs in distinct tissues and in response to drought stress in different genotypes. Generally, cassava CaMs-CMLs-CBLs showed different expression profiles between cultivated varieties (Arg7 and SC124) and wild ancestor (W14) after drought treatment. In addition, numerous CaMs-CMLs-CBLs were significantly upregulated at 6 h, 12 h, and 48 h after harvest, suggesting their possible role during storage roots (SR) deterioration. Further interaction network and co-expression analyses suggested that a CBL-mediated interaction network was widely involved in SR deterioration. Taken together, this study provides new insights into CaMs-CMLs-CBLs-mediated drought adaption and SR deterioration at the transcription level in cassava, and identifies some candidates for the genetic improvement of cassava.

A retrospective study of murder-suicide at the Forensic Institute of Ghent University, Belgium: 1935-2010.

PubMed

De Koning, Eva; Piette, Michel H A

2014-04-01

Murder followed by suicide (M-S) is a rare phenomenon that has been studied in several countries. Previous studies show that offenders of M-S are predominately men who live in an intimate relationship. Amorous jealousy is often the trigger to commit M-S. Shooting is the most common way to kill a partner and/or children. In general, women are likely to become victims. The aim of this study was to identify M-S and detect patterns of M-S in the district of Ghent and the surrounding areas, since no research on this event was conducted in Belgium. Over a period of 75 years, a total of 80 M-S incidents was recorded involving 176 individuals. Eighty-six percent of the offenders were males and 14% were females. Murder-suicides were mostly completed with firearms. The main motive for offenders to execute M-S is amorous jealousy (56%), followed by familial, financial, or social stressors (27%). In addition, three types of M-S were selected (e.g., spousal murder-suicides, filicide-suicides, and familicides-suicides). Our results suggest differences in these types of M-S in which younger couples' intentions were amorous jealousy; as for older couples the prominent motive was mercy killing; most likely women killed their children and only men committed familicides. Finally a study of the evolution during this period was carried out.

Comparison of different real time VOC measurement techniques in a ponderosa pine forest

NASA Astrophysics Data System (ADS)

Kaser, L.; Karl, T.; Schnitzhofer, R.; Graus, M.; Herdlinger-Blatt, I. S.; DiGangi, J. P.; Sive, B.; Turnipseed, A.; Hornbrook, R. S.; Zheng, W.; Flocke, F. M.; Guenther, A.; Keutsch, F. N.; Apel, E.; Hansel, A.

2013-03-01

Volatile organic compound (VOC) mixing ratios measured by five independent instruments are compared at a forested site dominated by ponderosa pine (Pinus Ponderosa) during the BEACHON-ROCS field study in summer 2010. The instruments included a Proton Transfer Reaction Time of Flight Mass Spectrometer (PTR-TOF-MS), a Proton Transfer Reaction Quadrupole Mass Spectrometer (PTR-MS), a Fast Online Gas-Chromatograph coupled to a Mass Spectrometer (GC/MS; TOGA), a Thermal Dissociation Chemical Ionization Mass Spectrometer (PAN-CIMS) and a Fiber Laser-Induced Fluorescence Instrument (FILIF). The species discussed in this comparison include the most important biogenic VOCs and a selected suite of oxygenated VOCs that are thought to dominate the VOC reactivity at this particular site as well as typical anthropogenic VOCs that showed low mixing ratios at this site. Good agreement was observed for methanol, the sum of the oxygenated hemiterpene 2-methyl-3-buten-2-ol (MBO) and the hemiterpene isoprene, acetaldehyde, the sum of acetone and propanal, benzene and the sum of methyl ethyl ketone (MEK) and butanal. Measurements of the above VOCs conducted by different instruments agree within 20%. The ability to differentiate the presence of toluene and cymene by PTR-TOF-MS is tested based on a comparison with GC-MS measurements, suggesting a study-average relative contribution of 74% for toluene and 26% for cymene. Similarly, 2-hydroxy-2-methylpropanal (HMPR) is found to interfere with the sum of methyl vinyl ketone and methacrolein (MVK + MAC) using PTR-(TOF)-MS at this site. A study-average relative contribution of 85% for MVK + MAC and 15% for HMPR was determined. The sum of monoterpenes measured by PTR-MS and PTR-TOF-MS was generally 20-25% higher than the sum of speciated monoterpenes measured by TOGA, which included α-pinene, β-pinene, camphene, carene, myrcene, limonene, cineole as well as other terpenes. However, this difference is consistent throughout the study, and likely points to an offset in calibration, rather than a difference in the ability to measure the sum of terpenes. The contribution of isoprene relative to MBO inferred from PTR-MS and PTR-TOF-MS was smaller than 12% while GC-MS data suggested an average of 21% of isoprene relative to MBO. This comparison demonstrates that the current capability of VOC measurements to account for OH reactivity associated with the measured VOCs is within 20%.

Comparison of different real time VOC measurement techniques in a ponderosa pine forest

NASA Astrophysics Data System (ADS)

Kaser, L.; Karl, T.; Schnitzhofer, R.; Graus, M.; Herdlinger-Blatt, I. S.; DiGangi, J. P.; Sive, B.; Turnipseed, A.; Hornbrook, R. S.; Zheng, W.; Flocke, F. M.; Guenther, A.; Keutsch, F. N.; Apel, E.; Hansel, A.

2012-10-01

Volatile organic compound (VOC) mixing ratios measured by five independent instruments are compared at a forested site dominated by ponderosa pine (Pinus Ponderosa) during the BEACHON-ROCS field study in summer 2010. The instruments included a Proton Transfer Reaction Time of Flight Mass Spectrometer (PTR-TOF-MS), a Proton Transfer Reaction Quadrupole Mass Spectrometer (PTR-MS), a Fast Online Gas-Chromatograph coupled to a Mass Spectrometer (GC/MS; TOGA), a Thermal Dissociation Chemical Ionization Mass Spectrometer (PAN-CIMS) and a Fiber Laser-Induced Fluorescence Instrument (FILIF). The species discussed in this comparison include the most important biogenic VOCs and a selected suite of oxygenated VOCs that are thought to dominate the VOC reactivity at this particular site as well as typical anthropogenic VOCs that showed low mixing ratios at this site. Good agreement was observed for methanol, the sum of the oxygenated hemiterpene 2-methyl-3-buten-2-ol (MBO) and the hemiterpene isoprene, acetaldehyde, the sum of acetone and propanal, benzene and the sum of methyl ethyl ketone (MEK) and butanal. Measurements of the above VOCs conducted by different instruments agree within 20%. The ability to differentiate the presence of toluene and cymene by PTR-TOF-MS is tested based on a comparison with GC-MS measurements, suggesting a study-average relative contribution of 74% for toluene and 26% for cymene. Similarly, 2-hydroxy-2-methylpropanal (HMPR) is found to interfere with the sum of methyl vinyl ketone and methacrolein (MVK+MAC) using PTR-(TOF)-MS at this site. A study-average relative contribution of 85% for MVK+MAC and 15% for HMPR was determined. The sum of monoterpenes measured by PTR-MS and PTR-TOF-MS was generally 20-25% higher than the sum of speciated monoterpenes measured by TOGA, which included α-pinene, β-pinene, camphene, carene, myrcene, limonene, cineole as well as other terpenes. However, this difference is consistent throughout the study, and likely points to an offset in calibration, rather than a difference in the ability to measure the sum of terpenes. The contribution of isoprene relative to MBO inferred from PTR-MS and PTR-TOF-MS was smaller than 12% while GC-MS data suggested an average of 21% of isoprene relative to MBO. This comparison demonstrates that the current capability of VOC measurements to account for OH reactivity associated with the measured VOCs is within 20%.

Resting State Brain Entropy Alterations in Relapsing Remitting Multiple Sclerosis.

PubMed

Zhou, Fuqing; Zhuang, Ying; Gong, Honghan; Zhan, Jie; Grossman, Murray; Wang, Ze

2016-01-01

Brain entropy (BEN) mapping provides a novel approach to characterize brain temporal dynamics, a key feature of human brain. Using resting state functional magnetic resonance imaging (rsfMRI), reliable and spatially distributed BEN patterns have been identified in normal brain, suggesting a potential use in clinical populations since temporal brain dynamics and entropy may be altered in disease conditions. The purpose of this study was to characterize BEN in multiple sclerosis (MS), a neurodegenerative disease that affects millions of people. Since currently there is no cure for MS, developing treatment or medication that can slow down its progression represents a high research priority, for which validating a brain marker sensitive to disease and the related functional impairments is essential. Because MS can start long time before any measurable symptoms and structural deficits, assessing the dynamic brain activity and correspondingly BEN may provide a critical way to study MS and its progression. Because BEN is new to MS, we aimed to assess BEN alterations in the relapsing-remitting MS (RRMS) patients using a patient versus control design, to examine the correlation of BEN to clinical measurements, and to check the correlation of BEN to structural brain measures which have been more often used in MS studies. As compared to controls, RRMS patients showed increased BEN in motor areas, executive control area, spatial coordinating area, and memory system. Increased BEN was related to greater disease severity as measured by the expanded disability status scale (EDSS) and greater tissue damage as indicated by the mean diffusivity. Patients also showed decreased BEN in other places, which was associated with less disability or fatigue, indicating a disease-related BEN re-distribution. Our results suggest BEN as a novel and useful tool for characterizing RRMS.

Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota

PubMed Central

van den Hoogen, Ward J.; Laman, Jon D.; ’t Hart, Bert A.

2017-01-01

Multiple sclerosis (MS) is an autoimmune neurological disease characterized by chronic inflammation of the central nervous system (CNS), leading to demyelination, axonal damage, and symptoms such as fatigue and disability. Although the cause of MS is not known, the infiltration of peripherally activated immune cells into the CNS has a key pathogenic role. Accumulating evidence supports an important role of diet and gut microbiota in immune-mediated diseases. Preclinical as well as clinical studies suggest a role for gut microbiota and dietary components in MS. Here, we review these recent studies on gut microbiota and dietary interventions in MS and its animal model experimental autoimmune encephalomyelitis. We also propose directions for future research. PMID:28928747

The meaning of women's experiences of living with multiple sclerosis.

PubMed

Olsson, Malin; Lexell, Jan; Söderberg, Siv

2008-04-01

We conducted a qualitative inquiry in order to describe the meaning of women's experiences of living with multiple sclerosis (MS). Multiple sclerosis is a chronic autoimmune disease of the central nervous system. The majority of persons living with MS are women. Living with MS has been described as difficult because of the uncertainty of the illness. Ten women with MS were interviewed and the interviews were analyzed with a phenomenological hermeneutic interpretation. In this study, we suggest that the meaning of living with MS for women can be understood as trying to maintain power and living with an unrecognizable body. The bodies of women with MS serve as hindrances in everyday life. Bodily changes evident to others impose feelings of being met in a different way, which can be understood as an expression of a violated dignity. At the same time, the women with MS struggle to protect their dignity.

LINGO1 rs9652490 and rs11856808 polymorphisms are not associated with risk for multiple sclerosis

PubMed Central

2013-01-01

Background Some recent experimental data suggest a possible role of LINGO-1 in the pathogenesis of multiple sclerosis (MS). In an attempt to identify genetic biomarkers related to MS susceptibility, we genotyped two common SNPs in the LINGO1 gene which have been associated to other neurological conditions, in patients with MS and in healthy subjects. These SNPs are linked to several SNPs within the LINGO1 gene, especially in individuals of Oriental or Caucasian descent. Methods We analyzed the allelic and genotype frequency of two LINGO1 variants (rs9652490 and rs11856808) in 293 patients with MS and 318 healthy controls, using KASPar assays. Results LINGO1 rs9652490 and rs11856808 allelic and genotype frequencies did not differ significantly between MS patients and controls. The minor allele frequencies for rs9652490 were 0.171 (95% CI = 0.140-0.201) and 0.167 (95% CI = 0.138-0.196 for cases and controls respectively (p = 0.853). For rs11856808 the minor allele frequencies were 0.317 (95% CI = 0.280-0.355) and 0.310 (95% CI = 0.274-0.346) for cases and controls, respectively (p = 0.773). Allele and genotype frequencies were unrelated with the age of onset of MS, gender, and clinical course of MS. In addition, haplotype analyses did not reveal any putative risk related to haplotypes. Conclusions These results suggest that LINGO1 rs9652490 and rs11856808 polymorphisms are not related with risk for MS. This study adds to other published evidence indicating that, to date, the LINGO1 SNPs studied here could be useful risk biomarkers of developing essential tremor, but not other movement disorders. PMID:23574883

Protective Role of Flaxseed Oil and Flaxseed Lignan Secoisolariciresinol Diglucoside Against Oxidative Stress in Rats with Metabolic Syndrome.

PubMed

Pilar, Bruna; Güllich, Angélica; Oliveira, Patrícia; Ströher, Deise; Piccoli, Jacqueline; Manfredini, Vanusa

2017-12-01

This study evaluated the protective effect of flaxseed oil (FO) and flaxseed lignan secoisolariciresinol diglucoside (SDG) against oxidative stress in rats with metabolic syndrome (MS). 48 rats were allocated into the following 6 groups: Groups 1 (control), 5 (FO), and 6 (SDG) received water and were treated daily orally with saline, FO, and SDG, respectively. Groups 2 (MS), 3 (MS+FO), and 4 (MS+SDG) received 30% fructose in drinking water for MS induction and were treated daily orally with saline, FO, and SDG, respectively. After 30 d, animals were sacrificed, and blood was collected for biochemical and oxidative analysis. Body weight was recorded weekly. Systolic blood pressure (SBP) was measured before and after treatment. Fructose could produce MS and oxidative stress. FO and SDG prevented changes in SBP, lipids, and glucose. FO and SDG prevented oxidative damage to lipids, and only FO prevented oxidative damage to proteins associated to MS. FO and SDG improved enzymatic antioxidants defenses and reduced glutathione levels, which was greater with SDG. Total polyphenol levels were enhanced in groups that received SDG. Thus, the results of this study demonstrated that treatment with a 30% fructose solution for 30 d is effective for MS induction and the oxidative stress is involved in the pathophysiology of MS induced by fructose-rich diets. Furthermore, we demonstrated that the antioxidant effects attributed to flaxseed are mainly due to its high lignan content especially that of SDG, suggesting that this compound can be used in isolation to prevent oxidative stress associated with MS. We report that the antioxidant effects attributed to flaxseed are mainly due to its high lignan content, especially that of secoisolariciresinol diglucoside. This is significant because suggests that this compound can be used in isolation to prevent oxidative stress associated with MS. Furthermore, this study was the only one to perform a comparison of the abilities of 2 components of flaxseed to protect against oxidative stress in an MS model, which brings a great advance in the medicine's field, since it indicates another alternative for improve the health and the quality of life of patients with this disorder. © 2017 Institute of Food Technologists®.

The Role of the Gut Microbiome in Multiple Sclerosis Risk and Progression: Towards Characterization of the "MS Microbiome".

PubMed

Pröbstel, Anne-Katrin; Baranzini, Sergio E

2018-01-01

Multiple sclerosis (MS) is the prototypic complex disease, in which both genes and the environment contribute to its pathogenesis. To date, > 200 independent loci across the genome have been associated with MS risk. However, these only explain a fraction of the total phenotypic variance, suggesting the possible presence of additional genetic factors, and, most likely, also environmental factors. New DNA sequencing technologies have enabled the sequencing of all kinds of microorganisms, including those living in and around humans (i.e., microbiomes). The study of bacterial populations inhabiting the gut is of particular interest in autoimmune diseases owing to their key role in shaping immune responses. In this review, we address the potential crosstalk between B cells and the gut microbiota, a relevant scenario in light of recently approved anti-B-cell therapies for MS. In addition, we review recent efforts to characterize the gut microbiome in patients with MS and discuss potential challenges and future opportunities. Finally, we describe the international MS microbiome study, a multicenter effort to study a large population of patients with MS and their healthy household partners to define the core MS microbiome, how it is shaped by disease-modifying therapies, and to explore potential therapeutic interventions.

On the horizon: possible neuroprotective role for glatiramer acetate.

PubMed

Kreitman, Rivka Riven; Blanchette, François

2004-06-01

Inflammation and neurodegeneration characterize the pathogenesis of multiple sclerosis (MS). Slow axonal degeneration, rather than acute inflammation, is considered the cause of chronic disability in MS. The signs of acute axonal damage and loss have been shown to occur early in the lesion development of patients with chronic MS and often correlate with demyelination and inflammation. While immune activity in the central nervous system has traditionally been considered to be a detrimental event in MS, recent studies have found that autoimmune T cells may play an important role in protecting neurons from the ongoing spreading damage. Neuroprotection in MS is a new and evolving concept, and many questions remain with regard to potential targets for therapeutic intervention. Preliminary studies, both in animals and in humans, have suggested that glatiramer acetate (GA) may confer neuroprotective activity in addition to bystander suppression. Additional research is needed to determine if these promising neuroprotective effects correlated with the long-term effect of GA in MS.

Driving competences and neuropsychological factors associated to driving counseling in multiple sclerosis.

PubMed

Badenes, Dolors; Garolera, Maite; Casas, Laura; Cejudo-Bolivar, Juan Carlos; de Francisco, Jorge; Zaragoza, Silvia; Calzado, Noemi; Aguilar, Miquel

2014-05-01

Multiple Sclerosis (MS) significantly impacts daily living activities, including car driving. To investigate driving difficulties experienced with MS, we compared 50 MS patients with minor or moderate disability and 50 healthy controls (HC) using computerized driving tests (the ASDE driver test and the Useful Field of View (UFOV) test) and neuropsychological tests. Inclusion criteria included being active drivers. We evaluated whether cognitive deterioration in MS is associated with the results of driving tests by comparing MS patients without cognitive deterioration with HC. The results indicated that the MS patients performed worse than the HCs in attention, information processing, working memory and visuomotor coordination tasks. Furthermore, MS patients with cognitive impairments experienced more difficulties in the driving tests than did the non-impaired MS patients. Motor dysfunction associated with MS also played an important role in this activity. The results of this study suggest that MS should be assessed carefully and that special emphasis should be placed on visuomotor coordination and executive functions because patients with minor motor disability and subtle cognitive impairments can pass measures predictive of driving safety.

Multiple sclerosis in pregnancy: prevalence, sociodemographic features, and obstetrical outcomes.

PubMed

Fong, Alex; Chau, Cindy T; Quant, Cara; Duffy, Jennifer; Pan, Deyu; Ogunyemi, Dotun A

2018-02-01

We sought to describe the prevalence, sociodemographic features, and antenatal/peripartum outcomes of multiple sclerosis (MS) in pregnancy. A retrospective cohort study was performed using deliveries in California from 2001 to 2009. Cases of MS as well as other morbidities were identified via ICD-9-CM code. Logistic regression was performed to adjust for potential confounders. About 1185 out of 4,424,049 deliveries were complicated by MS. MS prevalence increased with maternal age, with Caucasians comprising a higher proportion of MS subjects. MS subjects were older and more likely to have private insurance. Women with MS were more likely to have preexisting medical conditions such as asthma, chronic hypertension, thyroid disease, or cardiac disease. However, no significant antepartum and peripartum morbidities were found to be increased in patients with MS. Urinary tract infection, cesarean delivery, and induction of labor were slightly increased in MS patients. MS is a rare condition which is more likely to affect older Caucasian women of higher socioeconomic status and is associated with several preexisting medical conditions. MS, however, does not appear to pose significant increases in adverse pregnancy outcome. This suggests that pregnant patients with MS may likely experience an uneventful pregnancy.

Attributional Style and Depression in Multiple Sclerosis

PubMed Central

Arnett, Peter A.

2013-01-01

Several etiologic theories have been proposed to explain depression in the general population. Studying these models and modifying them for use in the multiple sclerosis (MS) population may allow us to better understand depression in MS. According to the reformulated learned helplessness (LH) theory, individuals who attribute negative events to internal, stable, and global causes are more vulnerable to depression. This study differentiated attributional style that was or was not related to MS in 52 patients with MS to test the LH theory in this population and to determine possible differences between illness-related and non-illness-related attributions. Patients were administered measures of attributional style, daily stressors, disability, and depressive symptoms. Participants were more likely to list non-MS-related than MS-related causes of negative events on the Attributional Style Questionnaire (ASQ), and more-disabled participants listed significantly more MS-related causes than did less-disabled individuals. Non-MS-related attributional style correlated with stress and depressive symptoms, but MS-related attributional style did not correlate with disability or depressive symptoms. Stress mediated the effect of non-MS-related attributional style on depressive symptoms. These results suggest that, although attributional style appears to be an important construct in MS, it does not seem to be related directly to depressive symptoms; rather, it is related to more perceived stress, which in turn is related to increased depressive symptoms. PMID:24453767

Attributional style and depression in multiple sclerosis: the learned helplessness model.

PubMed

Vargas, Gray A; Arnett, Peter A

2013-01-01

Several etiologic theories have been proposed to explain depression in the general population. Studying these models and modifying them for use in the multiple sclerosis (MS) population may allow us to better understand depression in MS. According to the reformulated learned helplessness (LH) theory, individuals who attribute negative events to internal, stable, and global causes are more vulnerable to depression. This study differentiated attributional style that was or was not related to MS in 52 patients with MS to test the LH theory in this population and to determine possible differences between illness-related and non-illness-related attributions. Patients were administered measures of attributional style, daily stressors, disability, and depressive symptoms. Participants were more likely to list non-MS-related than MS-related causes of negative events on the Attributional Style Questionnaire (ASQ), and more-disabled participants listed significantly more MS-related causes than did less-disabled individuals. Non-MS-related attributional style correlated with stress and depressive symptoms, but MS-related attributional style did not correlate with disability or depressive symptoms. Stress mediated the effect of non-MS-related attributional style on depressive symptoms. These results suggest that, although attributional style appears to be an important construct in MS, it does not seem to be related directly to depressive symptoms; rather, it is related to more perceived stress, which in turn is related to increased depressive symptoms.

Outcome expectations and physical activity in persons with longstanding multiple sclerosis.

PubMed

Morrison, Janet D; Stuifbergen, Alexa K

2014-06-01

Research suggests that persons with multiple sclerosis (MS) are much less physically active than the general population and that increased physical activity in persons with MS is associated with numerous benefits such as improvements in fatigue, mobility, and quality of life (). Potentially modifiable theory-based determinants of physical activity behavior need to be identified so that researchers may study their effectiveness in randomized clinical trials and clinicians may integrate them into practice to promote physical activity in this population. The purpose of this study was to explore the multidimensional (physical, social, and self-evaluative) outcome expectations for physical activity among persons with longstanding MS. A sample of 369 participants diagnosed with MS for more than 15 years completed surveys to measure multidimensional outcome expectations for exercise, MS functional limitations, and physical activity using two different instruments: one measuring physical activity engagement and the other measuring physical activity capability. Results indicated that MS functional limitation was the strongest predictor of both physical activity engagement and physical activity capability. Physical and social outcome expectations contributed to the model explaining 12% of the variation in physical activity engagement, whereas none of the outcome expectancy dimensions (physical, social, or self-evaluative) contributed to the model explaining variation in physical activity capability. Although analyses of cross-sectional data do not infer causation, these findings suggest that positive physical and social outcome expectations for physical activity are associated with engagement in physical activity as well as being potential sources of motivation for increasing physical activity behavior in individuals living with longstanding MS.

Staying on the job: The relationship between work performance and cognition in individuals diagnosed with multiple sclerosis.

PubMed

Baughman, Brandon C; Basso, Michael R; Sinclair, Robert R; Combs, Dennis R; Roper, Brad L

2015-01-01

People with multiple sclerosis (MS) are apt to become unemployed as the disease progresses, and most research implies that this is due to diminishing mobility. Some studies have shown that presence of cognitive impairment also predicts employment status. Yet, no studies have examined how neuropsychological factors predict vocational performance among individuals with MS who remain employed. We assessed employer- and self-rated work performance, mobility status, and neuropsychological function in a sample of 44 individuals diagnosed with MS. Results suggest that cognitive impairment is common in these employed individuals, despite largely intact mobility status. Moreover, a significant interaction emerged, such that cognitively impaired individuals' work performance was rated more poorly by supervisors. In contrast, self-ratings of work performance were higher in cognitively impaired than in unimpaired participants. These novel findings suggest that cognitive impairment may influence work performance, even in patients whose physical disability status is relatively intact.

Chronic Cerebrospinal Vascular Insufficiency Is Not Associated with HLA DRB1*1501 Status in Multiple Sclerosis Patients

PubMed Central

Weinstock-Guttman, Bianca; Zivadinov, Robert; Cutter, Gary; Tamaño-Blanco, Miriam; Marr, Karen; Badgett, Darlene; Carl, Ellen; Elfadil, Makki; Kennedy, Cheryl; Benedict, Ralph H. B.; Ramanathan, Murali

2011-01-01

Background Chronic cerebrospinal venous insufficiency (CCSVI) was described as a vascular condition characterized by anomalies of veins outside the skull was reported to be associated with multiple sclerosis (MS). The objective was to assess the associations between HLA DRB1*1501 status and the occurrence of CCSVI in MS patients. Methodology/Principal Findings This study included 423 of 499 subjects enrolled in the Combined Transcranial and Extracranial Venous Doppler Evaluation (CTEVD) study. The HLA DRB1*1501 status was obtained in 268 MS patients and 155 controls by genotyping rs3135005, a SNP associated with DRB1*1501 status. All subjects underwent a clinical examination and Doppler scan of the head and neck. The frequency of CCSVI was higher (OR = 4.52, p<0.001) in the MS group 56.0% vs. 21.9% in the controls group and also higher in the progressive MS group 69.8% vs. 49.5% in the non-progressive MS group. The 51.9% frequency of HLA DRB1*1501 positivity (HLA+) in MS was higher compared (OR = 2.33, p<0.001) to 31.6% to controls. The HLA+ frequency in the non-progressive (51.6%) and progressive MS groups (52.3%) was similar. The frequency of HLA+ CCSVI+ was 40.7% in progressive MS, 27.5% in non-progressive MS and 8.4% in controls. The presence of CCSVI was independent of HLA DRB1*1501 status in MS patients. Conclusions/Significance The lack of strong associations of CCSVI with HLA DRB1*1501 suggests that the role of the underlying associations of CCSVI in MS should be interpreted with caution. Further longitudinal studies should determine whether interactions between these factors can contribute to disease progression in MS. PMID:21340025

On the Ionization and Ion Transmission Efficiencies of Different ESI-MS Interfaces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cox, Jonathan T.; Marginean, Ioan; Smith, Richard D.

2014-09-30

It is well known that the achievable sensitivity of electrospray ionization mass spectrometry (ESI-MS) is largely determined by the ionization efficiency in the ESI source and ion transmission efficiency through the ESI-MS interface. In this report we systematically study the ion transmission and ionization efficiencies in different ESI-MS interface configurations. The configurations under investigation include a single emitter/single inlet capillary, single emitter/multi-inlet capillary, and a subambient pressure ionization with nanoelectrospray (SPIN) MS interfaces with a single emitter and an emitter array, respectively. We present an effective method to evaluate the overall ion utilization efficiency of an ESI-MS interface by measuringmore » the total gas phase ion current transmitted through the interface and correlating it to the observed ion abundance measured in the corresponding mass spectrum. Our experimental results suggest that the overall ion utilization efficiency in the SPIN-MS interface configurations is better than that in the inlet capillary based ESI-MS interface configurations.« less

Shift work at young age is associated with increased risk of multiple sclerosis in a Danish population.

PubMed

Gustavsen, S; Søndergaard, H B; Oturai, D B; Laursen, B; Laursen, J H; Magyari, M; Ullum, H; Larsen, M H; Sellebjerg, F; Oturai, A B

2016-09-01

Epidemiological studies suggest an important role for environmental factors in developing multiple sclerosis (MS). Furthermore several studies have indicated that the effect of environmental factors may be especially pronounced in adolescents. Recently only one study investigated and found that shift work at young age is associated with an increased risk of developing MS. In this study we focused on the effect of shift work in the vulnerable period between 15-19 years. The aim of this study was to investigate the association between shift work at young age and the risk of developing MS. We performed a large case-control study including 1723 patients diagnosed with MS and 4067 controls. MS patients were recruited from the Danish Multiple Sclerosis Biobank and controls from The Danish Blood Donor Study. Information on working patterns and lifestyle factors was obtained using a comprehensive lifestyle-environmental factor questionnaire with participants enrolled between 2009 and 2014. Logistic regression models were used to investigate the association between shift work at age 15-19 years and the subsequent risk of MS and were controlled for effects due to established MS risk factors. We found a statistically significant association when total numbers of night shifts were compared with non-shift workers. For every additional 100 night shifts the odds ratio (OR) for MS was 1.20 (95% confidence interval (CI), 1.08-1.34, p=0.001). Increasing intensity of shift work also increased MS risk. For every additional night per month the OR was 1.04 (95% CI, 1.01-1.06, p=0.002). Duration of shift work in years was not associated with risk of MS. This study supports a statistically significant association between shift work at age 15-19 years and MS risk. Copyright © 2016 Elsevier B.V. All rights reserved.

BMI levels with MS Bone mineral density levels in adults with multiple sclerosis: a meta-analysis.

PubMed

Huang, Zhongming; Qi, Yiying; Du, Shaohua; Chen, Guangnan; Yan, Weiqi

2015-01-01

Multiple sclerosis (MS) and osteoporosis (OP) affect a substantial proportion of the population. Accumulating evidence suggests that MS patients are at high risk for OP. We performed a meta-analysis to identify risk factors for lowered bone mineral density (BMD) in MS patients. We searched for articles within the Medline, Embase and Cochrane Library databases, published up to March 2014, pertaining to associations between MS and BMD. A total of 11 studies was included in the meta-analysis. The analysis indicated that MS patients have reduced lumbar spine, femur neck, and hip BMD compared with healthy controls (lumbar spine, standardized mean difference (SMD) = -0.76, 95% CI: -1.07, -0.45; femur neck, SMD = -0.56, 95% CI: -0.84, -0.29; and hip, SMD = -0.62, 95% CI: -0.96, -0.29). Further subgroup analysis revealed that a disease duration of >7 years, total steroid dose during the disease of >15 g, and an Expanded Disability Status Scale (EDSS) score of > 3, increased the risk of reduced BMD in the lumbar spine and femoral neck, but not in the hip. Meta-regression analysis did not explain the heterogeneity in the clinical characteristics or outcome definitions. Our meta-analysis suggests that MS patients have reduced overall BMD compared with healthy controls. Furthermore, disease duration (>7 years), total steroid dose (>15 g), and EDSS score (>3) are risk factors for reduced BMD in MS patients.

Backscatter Mossbauer Spectrometer (BaMS) for extraterrestrial applications

NASA Technical Reports Server (NTRS)

Agresti, D. G.; Shelfer, T. D.; Pimperl, M. M.; Wills, E. L.; Shen, M. H.; Morris, R. V.

1993-01-01

Mossbauer spectroscopy is a nuclear gamma resonance technique particularly well suited to the study of materials that contain iron (Fe-57). It can provide information on the oxidation state of iron as well as the type and proportion of iron-containing mineral species in a sample of interest. Iron Mossbauer spectroscopy (FeMS) has been applied to samples believed to have come from Mars (SNC meteorites) and has been helpful in refining the choice among putative Martian surface materials by suggesting a likely nanophase component of the Martian regolity. FeMS spectrum of a Martial analogue material (Hawaiian palagonite) is shown; it is dominated by ferric-bearing phases and shows evidence of a nanophase component. FeMS has also been applied to lunar materials. It can be used to measure the maturity of lunar surface material and has been proposed as a prospector for lunar ilmenite, an oxygen resource mineral. Several years ago we suggested a backscatter Mossbauer spectrometer (BaMS) for a Mars rover mission. Backscatter design was selected as most appropriate for in-situ application because no sample preparation is required. Since that time, we have continued to develop the BaMS instrument in anticipation that it would eventually find a home on a NASA planetary mission. Gooding proposed BaMS as a geochemistry instrument on MESUR. More recently, an LPI workshop has recommended that BaMS be included in a three-instrument payload on the next (1996?) lunar lander.

Can vitamin d suppress endothelial cells apoptosis in multiple sclerosis patients?

PubMed

Dehghani, Leila; Meamar, Rokhsareh; Etemadifar, Masoud; Sheshde, Zahra Dehghani; Shaygannejad, Vahid; Sharifkhah, Mostafa; Tahani, Soheil

2013-05-01

Multiple sclerosis (MS) is an autoimmune disease of central nerves system, in which neurological disabilities occur in young adults. Despite increasing number of studies on MS, some aspects of this disorder are still unclear. In the previous studies, it has been proven that there is direct relation between MS incidence and vitamin D deficiency. Thereby, strong evidence in MS pathogenesis suggests that endothelial cells (EC) could be harmed in MS. In addition, functional changes in EC and macrovascular injuries lead blood-brain barrier disruption in MS. Current study is the first investigation to elucidate positive influences of vitamin D against EC apoptosis in MS. Human umbilical vein endothelial cells (HUVECs) were cultured and then treated with sera from patients with active MS (in relapse) and sera from healthy volunteer participants as control group (each group n=15). 3-(4,5-dimethylthiazol-2-yl)-5- (3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay for cell surveillance and cell-death detection kit for evaluating apoptosis were used in this study. There was a significant decrease in apoptosis rate by the serum of patients, just when 1,25(OH)2D3 applied before treating HUVECs with sera from active MS (in relapse). Furthermore, the cells surveillance increased markedly with the presence of 1,25(OH)(2)D(3) in culture, too. Withregard to increment in EC apoptosis rate, which treated by the sera from MS patients and decrement in apoptosis rate by the presence of vitamin D in culture media, it could be proposed that vitamin D pre-treatment can be used for MS patients, due to its beneficial effects on protecting EC apoptosis.

Hypothalamic damage in multiple sclerosis correlates with disease activity, disability, depression, and fatigue.

PubMed

Kantorová, E; Poláček, H; Bittšanský, M; Baranovičová, E; Hnilicová, P; Čierny, D; Sivák, Š; Nosáľ, V; Zeleňák, K; Kurča, E

2017-04-01

Disturbances in the hypothalamo-pituitary axis are supposed to modulate activity of multiple sclerosis (MS). We hypothesised that the extent of HYP damage may determine severity of MS and may be associated with the disease evolution. We suggested fatigue and depression may depend on the degree of damage of the area. 33 MS patients with relapsing-remitting and secondary progressive disease, and 24 age and sex-related healthy individuals (CON) underwent 1H-MR spectroscopy (1H-MRS) of the hypothalamus. Concentrations of glutamate + glutamin (Glx), cholin (Cho), myoinositol (mIns), N-acetyl aspartate (NAA) expressed as ratio with creatine (Cr) and NAA were correlated with markers of disease activity (RIO score), Multiple Sclerosis Severity Scale (MSSS), Depressive-Severity Status Scale and Simple Numerical Fatigue Scale. Cho/Cr and NAA/Cr ratios were decreased and Glx/NAA ratio increased in MS patients vs CON. Glx/NAA, Glx/Cr, and mIns/NAA were significantly higher in active (RIO 1-2) vs non-active MS patients (RIO 0). Glx/NAA and Glx/Cr correlated with MSSS and fatigue score, and Glx/Cr with depressive score of MS patients. In CON, relationships between Glx/Cr and age, and Glx/NAA and fatigue score were inverse. Our study provides the first evidence about significant hypothalamic alterations correlating with clinical outcomes of MS, using 1H-MRS. The combination of increased Glu or mIns with reduced NAA in HYP reflects whole-brain activity of MS. In addition, excess of Glu is linked to severe disease course, depressive mood and fatigue in MS patients, suggesting superiority of Glu over other metabolites in determining MS burden.

The Dopamine Imbalance Hypothesis of Fatigue in Multiple Sclerosis and Other Neurological Disorders

PubMed Central

Dobryakova, Ekaterina; Genova, Helen M.; DeLuca, John; Wylie, Glenn R.

2015-01-01

Fatigue is one of the most pervasive symptoms of multiple sclerosis (MS), and has engendered hundreds of investigations on the topic. While there is a growing literature using various methods to study fatigue, a unified theory of fatigue in MS is yet to emerge. In the current review, we synthesize findings from neuroimaging, pharmacological, neuropsychological, and immunological studies of fatigue in MS, which point to a specific hypothesis of fatigue in MS: the dopamine imbalance hypothesis. The communication between the striatum and prefrontal cortex is reliant on dopamine, a modulatory neurotransmitter. Neuroimaging findings suggest that fatigue results from the disruption of communication between these regions. Supporting the dopamine imbalance hypothesis, structural and functional neuroimaging studies show abnormalities in the frontal and striatal regions that are heavily innervated by dopamine neurons. Further, dopaminergic psychostimulant medication has been shown to alleviate fatigue in individuals with traumatic brain injury, chronic fatigue syndrome, and in cancer patients, also indicating that dopamine might play an important role in fatigue perception. This paper reviews the structural and functional neuroimaging evidence as well as pharmacological studies that suggest that dopamine plays a critical role in the phenomenon of fatigue. We conclude with how specific aspects of the dopamine imbalance hypothesis can be tested in future research. PMID:25814977

Fatigue in Multiple Sclerosis: Is it related to cytokines and hypothalamic-pituitary-adrenal axis?

PubMed

Akcali, Aylin; Zengin, Fatma; Aksoy, Sefika Nur; Zengin, Orhan

2017-07-01

Fatigue is a common symptom of Multiple Sclerosis (MS) that diminishes the quality of life of patients, but its exact mechanism remains poorly understood. There is not a generally adopted scale to determine MS fatigue. Studies that investigated physiopathology of fatigue symptom have shown dysregulation of hypothalamic-pituitaryadrenal (HPA) axis. In the current study, we aimed to compare the results obtained with two separate scales, namely the Fatigue Severity Scale (FSS) and the Neurological Fatigue Index-Multiple Sclerosis (NFI-MS), and assess the relationship between fatigue and serum IL-1β, TNF-α, IL-35, IL-2, IL-10, ACTH, cortisol, α-MSH, β-MSH, γ-MSH and CLIP (Corticotropinlike intermediate lobe peptide) in MS patients categorized as fatigued and non-fatigued on the basis of FSS scores. For the study, a total of 54 (29 females, 25 males) patients diagnosed with RRMS including 26 with fatigue symptom (48.1%), and 26 healthy controls (13 females, 13 males) were enrolled. A FSS score ≥36 was considered as cut-off score to separate fatigued patients from nonfatigued patients. A significant positive correlation was determined between FSS score and NFI-MS scale, NFI-MS 1, NFI-MS 2, NFI-MS 3 and NFI-MS 4 scores. IL-1β, IL-10 and TNF-α levels did not differ between patient and control groups. IL-35 and IL-2 levels were significantly higher among MS patients (p<0.01). However, no difference was observed between fatigued and nonfatigued patients in the cytokines and HPA parameters studied. ACTH, cortisol and α-MSH were significantly higher in MS group (p=0.02, p<0.01 and p<0.01, respectively). CLIP level was significantly low in MS patient group (p<0.01). NFI-MS scale is equally sensitive as FSS scale for assessment of MS fatigue; thus, it may also be widely used to evaluate that symptom. Generally HPA axis is hyperactive in MS patients, but it is not correlated with fatigue in our study. For the first time, levels of CLIP (a type of melanocortin) are studied, and determined to be lower among MS patients. Elevated levels of IL-35 and IL-2 suggest that these cytokines may have a prominent role in MS pathophysiology and can be investigated as potential targets for development of novel therapies. Copyright © 2017 Elsevier B.V. All rights reserved.

Sex- and gender-related prevalence, cardiovascular risk and therapeutic approach in metabolic syndrome: A review of the literature.

PubMed

Pucci, Giacomo; Alcidi, Riccardo; Tap, Lisanne; Battista, Francesca; Mattace-Raso, Francesco; Schillaci, Giuseppe

2017-06-01

Metabolic syndrome (MS), a cluster of metabolic abnormalities linked to insulin-resistance and abdominal obesity, is associated with an increased risk of Type II diabetes mellitus (DM) and cardiovascular (CV) disease. Its prevalence is high, affecting 20%-30% of the general population, and increases with age in a sex-specific manner: in fact, while below 50 years it is slightly higher in men, it reverses after 50 years. The pronounced age-related increase in the prevalence of MS in women occurs as the result of several factors, which may be classified into sex- and gender-related factors. Sex-related factors, linked to genetical and biological pathways, are mainly driven by hyperandrogenism, insulin-resistance, and the associated increase in abdominal obesity and HDL-cholesterol reduction occurring after menopause. Gender-related factors are sensitive to social and cultural behaviors, dietary habits and psychosocial factors. Women are more prone than men to develop MS in response to work stress and low socio-economic status. Sex and gender differences in the prevalence of MS may translate in different CV risk associated. Prospective studies suggest that the CV risk in women with MS is not only equal but also superior to the CV risk of men with MS. This difference is mostly attenuated when adjusting for the presence of overt DM. Despite similar odds for CV events, the number of CV events may be higher in elderly women because of the higher prevalence of MS compared to men in this age group. Men and women may also have a differential response to treatments for MS, such as lifestyle measures and weight loss. Recent observations suggest that men are better responders than women to non-pharmaceutical therapeutic strategies aimed at reducing the prevalence of MS, although this should be confirmed in large-scale studies. The present review describes the impact of sex and gender on the prevalence, clinical presentation, prognostic significance and treatment of the MS. Attention to gender specificities should be a mandatory pre-requisite of clinical and epidemiological research on MS and CV disease, for a better knowledge and development of health strategies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Speech and pause characteristics in multiple sclerosis: A preliminary study of speakers with high and low neuropsychological test performance

PubMed Central

FEENAUGHTY, LYNDA; TJADEN, KRIS; BENEDICT, RALPH H.B.; WEINSTOCK-GUTTMAN, BIANCA

2017-01-01

This preliminary study investigated how cognitive-linguistic status in multiple sclerosis (MS) is reflected in two speech tasks (i.e. oral reading, narrative) that differ in cognitive-linguistic demand. Twenty individuals with MS were selected to comprise High and Low performance groups based on clinical tests of executive function and information processing speed and efficiency. Ten healthy controls were included for comparison. Speech samples were audio-recorded and measures of global speech timing were obtained. Results indicated predicted differences in global speech timing (i.e. speech rate and pause characteristics) for speech tasks differing in cognitive-linguistic demand, but the magnitude of these task-related differences was similar for all speaker groups. Findings suggest that assumptions concerning the cognitive-linguistic demands of reading aloud as compared to spontaneous speech may need to be re-considered for individuals with cognitive impairment. Qualitative trends suggest that additional studies investigating the association between cognitive-linguistic and speech motor variables in MS are warranted. PMID:23294227

NQO1 gene rs1800566 variant is not associated with risk for multiple sclerosis

PubMed Central

2014-01-01

Background A possible role of oxidative stress in the pathogenesis of multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis has been suggested. The detoxification enzyme NAD(P)H dehydrogenase, quinone 1 (NQO1) has been found up-regulated in MS lesions. A previous report described an association between the SNP rs1800566 in the NQO1 gene and the risk for MS in the Greek population. The aim of this study was to replicate a possible influence of the. SNP rs1800566 in the NQO1 gene in the risk for MS in the Spanish Caucasian population. Methods We analyzed allelic and genotypic frequency of NQO1 rs1800566 in 290 patients with MS and 310 healthy controls, using TaqMan Assays. Results NQO1 rs1800566 allelic and genotypic frequencies did not differ significantly between MS patients and controls, and were unrelated with age of onset of MS, gender, and clinical type of MS. Conclusions Our results indicate that NQO1 rs1800566 does not have an effect on MS disease risk. PMID:24755231

Peer mentorship in student-run free clinics: the impact on preclinical education.

PubMed

Choudhury, Noura; Khanwalkar, Ashoke; Kraninger, Jennifer; Vohra, Adam; Jones, Kohar; Reddy, Shalini

2014-03-01

Our study examines the perceptions of first-year medical students (MS1s) toward fourth-year colleagues (MS4s) in student-run free clinics to investigate the impact of peer mentorship on augmenting the clinical education received by MS1s in a primary care setting. To our knowledge, this is the first study examining the impact of MS4 mentorship in free clinics. A 55-item online questionnaire was administered to MS1s 9 months after matriculation in April 2012. Questions focused on MS1 perceptions of MS4 impact on comfort with patients, self-reported improvement in clinical skills, and overall satisfaction with mentorship in free clinics. The MS4s referenced in the questionnaire were enrolled in a longitudinal service-learning elective. Results were analyzed using one-sample Wilcoxon sign-ranked median test and ordered logistic regression with STATA software. Fifty-five of 77 (71.4%) eligible students began the online survey, with 48 (62.3%) completing it. Responses reflected experiences at four student-run free clinics. Overall, MS4 presence improved MS1 comfort with patients and enhanced interactions with attendings. MS1s were satisfied with the level of MS4 mentorship and agreed that MS4s had a distinct mentoring role from attendings. Ordered logistic regression showed that presence of MS4s was significantly associated with self-reported improvements to physical exam skills at one clinic. At each clinic, MS1s reported improved comfort with patients and satisfaction with mentorship received from MS4s. MS4s did not merely duplicate the role of attending physicians but enhanced interactions between MS1s and physicians. This suggests that the consistent presence of MS4s is a valuable adjunct to the educational experience of free clinics volunteering for MS1s.

Effect of Antimicrobial Intervention on Oral Microbiota Associated with Early Childhood Caries

PubMed Central

Li, Yihong; Tanner, Anne

2015-01-01

Purpose The aim of this systematic literature review was to identify research-based evidence for an effect of antimicrobial therapeutic approaches on the cariogenic microbiota and early childhood caries (ECC) outcomes. Additionally, we reviewed methods used to perform microbial assessments in clinical studies of ECC. Methods Multiple database searches were conducted; only clinical cohort studies and randomized controlled trials published from 1998 to 2014 were selected for the review. A total of 471 titles and abstracts were identified; 114 studies met the inclusion criteria for a full review, and finally 41 studies were selected for the meta-analyses. Results Moderate reductions in cariogenic bacterial levels, mainly in mutans streptococci (MS), were demonstrated following the use of antimicrobial agents. The results varied depending on the different approaches used. In most of the reviewed studies MS levels were reduced after treatment, but the bacterial regrowth occurred once the treatment had ceased, and new caries lesions developed, particularly in high-risk children. Relatively consistent findings suggested that anti-cariogenic-microbial interventions in mothers significantly reduced MS acquisition by children. However, studies of the long-term benefits of ECC prevention are lacking. Conclusion Based on the meta-analyses, antimicrobial interventions and treatments show temporary reductions in MS colonization levels. However, insufficient evidence suggest that the approaches used produced sustainable effects on cariogenic microbial colonization, caries reduction, and ECC prevention. PMID:26063552

Benefits of Exercise Training in Multiple Sclerosis.

PubMed

Motl, Robert W; Sandroff, Brian M

2015-09-01

Exercise training represents a behavioral approach for safely managing many of the functional, symptomatic, and quality of life consequences of multiple sclerosis (MS). This topical review paper summarizes evidence from literature reviews and meta-analyses, supplemented by recent individual studies, indicating that exercise training can yield small but important improvements in walking, balance, cognition, fatigue, depression, and quality of life in MS. The paper highlights limitations of research on exercise training and its consequences and future research directions and provides an overview for promotion of exercise training in MS based on recent prescriptive guidelines. Collectively, the evidence for the benefits of exercise training in MS suggests that the time is ripe for the promotion of exercise by healthcare providers, particularly neurologists as a central part of the clinical care and management of MS patients.

Human single-neuron responses at the threshold of conscious recognition

PubMed Central

Quiroga, R. Quian; Mukamel, R.; Isham, E. A.; Malach, R.; Fried, I.

2008-01-01

We studied the responses of single neurons in the human medial temporal lobe while subjects viewed familiar faces, animals, and landmarks. By progressively shortening the duration of stimulus presentation, coupled with backward masking, we show two striking properties of these neurons. (i) Their responses are not statistically different for the 33-ms, 66-ms, and 132-ms stimulus durations, and only for the 264-ms presentations there is a significantly higher firing. (ii) These responses follow conscious perception, as indicated by the subjects' recognition report. Remarkably, when recognized, a single snapshot as brief as 33 ms was sufficient to trigger strong single-unit responses far outlasting stimulus presentation. These results suggest that neurons in the medial temporal lobe can reflect conscious recognition by “all-or-none” responses. PMID:18299568

LC-MS/MS based identification of piperine production by endophytic Mycosphaerella sp. PF13 from Piper nigrum.

PubMed

Chithra, S; Jasim, B; Anisha, C; Mathew, Jyothis; Radhakrishnan, E K

2014-05-01

Piper nigrum is very remarkable for its medicinal properties due to the presence of metabolites like piperine. Emerging understanding on the biosynthetic potential of endophytic fungi suggests the possibility to have piperine producing fungi in P. nigrum. In the current study, endophytic fungi isolated from P. nigrum were screened for the presence of piperine by liquid chromatography-tandem mass spectrometry (LC-MS/MS). This resulted in the identification of a Mycosphaerella sp. with the ability to produce piperine extracellularly. The biosynthesis of piperine (C17H19NO3) by the endophytic fungal isolate was confirmed by the presence of m/z 286.1 (M + H(+)) in the LC-MS/MS analysis using positive mode ionization. This was further supported by the presence of specific fragment ions with masses 135, 143, 171 and 201 formed due to the fragmentation of piperine present in the fungal extract.

Supervised resistance training results in changes in postural control in patients with multiple sclerosis.

PubMed

Huisinga, Jessie M; Filipi, Mary L; Stergiou, Nicholas

2012-01-01

Postural disturbances are one of the first reported symptoms in patients with Multiple Sclerosis (MS). The purpose of this study was to investigate the effect of supervised resistance training on postural control in MS patients. Postural control was assessed using amount of sway variability [Root Mean Square (RMS)] and temporal structure of sway variability [Lyapunov Exponent (LyE)] from 15 MS patients. Posture was evaluated before and after completion of three months of resistance training. There were significant differences between MS patients pretraining and healthy controls for both LyE (p = .000) and RMS (p = .002), but no differences between groups after training. There was a significant decrease in RMS (p = .025) and a significant increase in LyE (p = .049) for MS patients pre- to posttraining. The findings suggested that postural control of MS patients could be affected by a supervised resistance training intervention.

Xylitol gum and maternal transmission of mutans streptococci.

PubMed

Nakai, Y; Shinga-Ishihara, C; Kaji, M; Moriya, K; Murakami-Yamanaka, K; Takimura, M

2010-01-01

An important caries prevention strategy for children includes measures to interfere with transmission of mutans streptococci (MS). This study confirmed the effectiveness of maternal early exposure to xylitol chewing gum on mother-child transmission of MS. After screening, 107 pregnant women with high salivary MS were randomized into two groups: xylitol gum (Xylitol; n = 56) and no gum (Control; n = 51) groups. Maternal chewing started at the sixth month of pregnancy and terminated 13 months later in the Xylitol group. Outcome measures were the presence of MS in saliva or plaque of the children until age 24 months. The Xylitol-group children were significantly less likely to show MS colonization than Control-group children aged 9-24 months. The Control-group children acquired MS 8.8 months earlier than those in the Xylitol group, suggesting that maternal xylitol gum chewing in Japan shows beneficial effects similar to those demonstrated in Nordic countries.

Changes of Metabolomic Profile in Helianthus annuus under Exposure to Chromium(VI) Studied by capHPLC-ESI-QTOF-MS and MS/MS

PubMed Central

Gonzalez Ibarra, Alan Alexander; Wrobel, Kazimierz; Yanez Barrientos, Eunice; Corrales Escobosa, Alma Rosa; Gutierrez Corona, J. Felix; Enciso Donis, Israel

2017-01-01

The application of capHPLC-ESI-QTOF-MS and MS/MS to study the impact of Cr(VI) on metabolites profile in Helianthus annuus is reported. Germinated seeds were grown hydroponically in the presence of Cr(VI) (25 mgCr/L) and root extracts of the exposed and control plants were analyzed by untargeted metabolomic approach. The main goal was to detect which metabolite groups were mostly affected by Cr(VI) stress; two data analysis tools (ProfileAnalysis, Bruker, and online XCMS) were used under criteria of intensity threshold 5 · 104 cps, fold change ≥ 5, and p ≤ 0.01, yielding precursor ions. Molecular formulas were assigned based on data processing with two computational tools (SIRIUS and MS-Finder); annotation of candidate structures was performed by database search using CSI:FingerID and MS-Finder. Even though ultimate identification has not been achieved, it was demonstrated that secondary metabolism became activated under Cr(VI) stress. Among 42 candidate compounds returned from database search for seven molecular formulas, ten structures corresponded to isocoumarin derivatives and eleven were sesquiterpenes or sesquiterpene lactones; three benzofurans and four glycoside or pyrane derivatives of phenolic compounds were also suggested. To gain further insight on the effect of Cr(VI) in sunflower, isocoumarins and sesquiterpenes were selected as the target compounds for future study. PMID:29359067

A Proof of Concept to Bridge the Gap between Mass Spectrometry Imaging, Protein Identification and Relative Quantitation: MSI~LC-MS/MS-LF.

PubMed

Théron, Laëtitia; Centeno, Delphine; Coudy-Gandilhon, Cécile; Pujos-Guillot, Estelle; Astruc, Thierry; Rémond, Didier; Barthelemy, Jean-Claude; Roche, Frédéric; Feasson, Léonard; Hébraud, Michel; Béchet, Daniel; Chambon, Christophe

2016-10-26

Mass spectrometry imaging (MSI) is a powerful tool to visualize the spatial distribution of molecules on a tissue section. The main limitation of MALDI-MSI of proteins is the lack of direct identification. Therefore, this study focuses on a MSI~LC-MS/MS-LF workflow to link the results from MALDI-MSI with potential peak identification and label-free quantitation, using only one tissue section. At first, we studied the impact of matrix deposition and laser ablation on protein extraction from the tissue section. Then, we did a back-correlation of the m / z of the proteins detected by MALDI-MSI to those identified by label-free quantitation. This allowed us to compare the label-free quantitation of proteins obtained in LC-MS/MS with the peak intensities observed in MALDI-MSI. We managed to link identification to nine peaks observed by MALDI-MSI. The results showed that the MSI~LC-MS/MS-LF workflow (i) allowed us to study a representative muscle proteome compared to a classical bottom-up workflow; and (ii) was sparsely impacted by matrix deposition and laser ablation. This workflow, performed as a proof-of-concept, suggests that a single tissue section can be used to perform MALDI-MSI and protein extraction, identification, and relative quantitation.

A Proof of Concept to Bridge the Gap between Mass Spectrometry Imaging, Protein Identification and Relative Quantitation: MSI~LC-MS/MS-LF

PubMed Central

Théron, Laëtitia; Centeno, Delphine; Coudy-Gandilhon, Cécile; Pujos-Guillot, Estelle; Astruc, Thierry; Rémond, Didier; Barthelemy, Jean-Claude; Roche, Frédéric; Feasson, Léonard; Hébraud, Michel; Béchet, Daniel; Chambon, Christophe

2016-01-01

Mass spectrometry imaging (MSI) is a powerful tool to visualize the spatial distribution of molecules on a tissue section. The main limitation of MALDI-MSI of proteins is the lack of direct identification. Therefore, this study focuses on a MSI~LC-MS/MS-LF workflow to link the results from MALDI-MSI with potential peak identification and label-free quantitation, using only one tissue section. At first, we studied the impact of matrix deposition and laser ablation on protein extraction from the tissue section. Then, we did a back-correlation of the m/z of the proteins detected by MALDI-MSI to those identified by label-free quantitation. This allowed us to compare the label-free quantitation of proteins obtained in LC-MS/MS with the peak intensities observed in MALDI-MSI. We managed to link identification to nine peaks observed by MALDI-MSI. The results showed that the MSI~LC-MS/MS-LF workflow (i) allowed us to study a representative muscle proteome compared to a classical bottom-up workflow; and (ii) was sparsely impacted by matrix deposition and laser ablation. This workflow, performed as a proof-of-concept, suggests that a single tissue section can be used to perform MALDI-MSI and protein extraction, identification, and relative quantitation. PMID:28248242

Dietary Inflammatory Index and risk of multiple sclerosis in a case-control study from Iran

PubMed Central

Shivappa, Nitin; Hébert, James R.; Behrooz, Maryam; Rashidkhani, Bahram

2016-01-01

Background Diet and inflammation have been suggested to be important risk factors for multiple sclerosis (MS). Objectives In this study, we examined the ability of the dietary inflammatory index (DII) to predict MS in a case-control study conducted in Iran. Methods This study included 68 MS cases and 140 controls hospitalized for acute non-neoplastic diseases. The DII was computed based on dietary intake assessed by a previously validated food frequency questionnaire. Logistic regression models were used to estimate odds ratios (ORs) adjusted for age, energy, sex, BMI, season of birth, rubella history, history of routine exercise before MS, smoking and history of consumption of cow's mile in the first 2 years of life. Results Subjects with higher DII scores (i.e., with a more pro-inflammatory diet) had a higher risk of MS, with the DII being used as both a continuous variable (ORcontinuous 1.66, 95% confidence interval, (CI), 1.19-2.31; one unit increase corresponding to ≈15% of its range in the current study) and a categorical variable (ORdii>1.43 vs ≤ 1.43 2.68, 95%CI 1.15-6.26). Conclusions These results indicate that a pro-inflammatory diet is associated with increased risk of MS. PMID:27362443

Morphostructural MRI abnormalities related to neuropsychiatric disorders associated to multiple sclerosis.

PubMed

Bonavita, Simona; Tedeschi, Gioacchino; Gallo, Antonio

2013-01-01

Multiple Sclerosis associated neuropsychiatric disorders include major depression (MD), obsessive-compulsive disorder (OCD), bipolar affective disorder, euphoria, pseudobulbar affect, psychosis, and personality change. Magnetic Resonance Imaging (MRI) studies focused mainly on identifying morphostructural correlates of MD; only a few anecdotal cases on OCD associated to MS (OCD-MS), euphoria, pseudobulbar affect, psychosis, personality change, and one research article on MRI abnormalities in OCD-MS have been published. Therefore, in the present review we will report mainly on neuroimaging abnormalities found in MS patients with MD and OCD. All together, the studies on MD associated to MS suggest that, in this disease, depression is linked to a damage involving mainly frontotemporal regions either with discrete lesions (with those visible in T1 weighted images playing a more significant role) or subtle normal appearing white matter abnormalities. Hippocampal atrophy, as well, seems to be involved in MS related depression. It is conceivable that grey matter pathology (i.e., global and regional atrophy, cortical lesions), which occurs early in the course of disease, may involve several areas including the dorsolateral prefrontal cortex, the orbitofrontal cortex, and the anterior cingulate cortex whose disruption is currently thought to explain late-life depression. Further MRI studies are necessary to better elucidate OCD pathogenesis in MS.

Morphostructural MRI Abnormalities Related to Neuropsychiatric Disorders Associated to Multiple Sclerosis

PubMed Central

Bonavita, Simona; Tedeschi, Gioacchino; Gallo, Antonio

2013-01-01

Multiple Sclerosis associated neuropsychiatric disorders include major depression (MD), obsessive-compulsive disorder (OCD), bipolar affective disorder, euphoria, pseudobulbar affect, psychosis, and personality change. Magnetic Resonance Imaging (MRI) studies focused mainly on identifying morphostructural correlates of MD; only a few anecdotal cases on OCD associated to MS (OCD-MS), euphoria, pseudobulbar affect, psychosis, personality change, and one research article on MRI abnormalities in OCD-MS have been published. Therefore, in the present review we will report mainly on neuroimaging abnormalities found in MS patients with MD and OCD. All together, the studies on MD associated to MS suggest that, in this disease, depression is linked to a damage involving mainly frontotemporal regions either with discrete lesions (with those visible in T1 weighted images playing a more significant role) or subtle normal appearing white matter abnormalities. Hippocampal atrophy, as well, seems to be involved in MS related depression. It is conceivable that grey matter pathology (i.e., global and regional atrophy, cortical lesions), which occurs early in the course of disease, may involve several areas including the dorsolateral prefrontal cortex, the orbitofrontal cortex, and the anterior cingulate cortex whose disruption is currently thought to explain late-life depression. Further MRI studies are necessary to better elucidate OCD pathogenesis in MS. PMID:23691320

Numeracy of multiple sclerosis patients: A comparison of patients from the PERCEPT study to a German probabilistic sample.

PubMed

Gaissmaier, Wolfgang; Giese, Helge; Galesic, Mirta; Garcia-Retamero, Rocio; Kasper, Juergen; Kleiter, Ingo; Meuth, Sven G; Köpke, Sascha; Heesen, Christoph

2018-01-01

A shared decision-making approach is suggested for multiple sclerosis (MS) patients. To properly evaluate benefits and risks of different treatment options accordingly, MS patients require sufficient numeracy - the ability to understand quantitative information. It is unknown whether MS affects numeracy. Therefore, we investigated whether patients' numeracy was impaired compared to a probabilistic national sample. As part of the larger prospective, observational, multicenter study PERCEPT, we assessed numeracy for a clinical study sample of German MS patients (N=725) with a standard test and compared them to a German probabilistic sample (N=1001), controlling for age, sex, and education. Within patients, we assessed whether disease variables (disease duration, disability, annual relapse rate, cognitive impairment) predicted numeracy beyond these demographics. MS patients showed a comparable level of numeracy as the probabilistic national sample (68.9% vs. 68.5% correct answers, P=0.831). In both samples, numeracy was higher for men and the highly educated. Disease variables did not predict numeracy beyond demographics within patients, and predictability was generally low. This sample of MS patients understood quantitative information on the same level as the general population. There is no reason to withhold quantitative information from MS patients. Copyright © 2017 Elsevier B.V. All rights reserved.

IL2RA/CD25 Gene Polymorphisms: Uneven Association with Multiple Sclerosis (MS) and Type 1 Diabetes (T1D)

PubMed Central

Alcina, Antonio; Fedetz, María; Ndagire, Dorothy; Fernández, Oscar; Leyva, Laura; Guerrero, Miguel; Abad-Grau, María M.; Arnal, Carmen; Delgado, Concepción; Lucas, Miguel; Izquierdo, Guillermo; Matesanz, Fuencisla

2009-01-01

Background IL-2 receptor (IL2R) alpha is the specific component of the high affinity IL2R system involved in the immune response and in the control of autoimmunity. Methods and Results Here we perform a replication and fine mapping of the IL2RA gene region analyzing 3 SNPs previously associated with multiple sclerosis (MS) and 5 SNPs associated with type 1 diabetes (T1D) in a collection of 798 MS patients and 927 matched Caucasian controls from the south of Spain. We observed association with MS in 6 of 8 SNPs. The rs1570538, at the 3′- UTR extreme of the gene, previously reported to have a weak association with MS, is replicated here (P = 0.032). The most associated T1D SNP (rs41295061) was not associated with MS in the present study. However, the rs35285258, belonging to another independent group of SNPs associated with T1D, showed the maximal association in this study but different risk allele. We replicated the association of only one (rs2104286) of the two IL2RA SNPs identified in the recently performed genome-wide association study of MS. Conclusions These findings confirm and extend the association of this gene with MS and reveal a genetic heterogeneity of the associated polymorphisms and risk alleles between MS and T1D suggesting different immunopathological roles of IL2RA in these two diseases. PMID:19125193

PER3 VNTR polymorphism in Multiple Sclerosis: A new insight to impact of sleep disturbances in MS.

PubMed

Golalipour, Masoud; Maleki, Zahra; Farazmandfar, Touraj; Shahbazi, Majid

2017-10-01

Multiple Sclerosis (MS) is a degenerative disease of central nervous system caused by an immune response against the myelin. About half of MS patients suffers from sleep disturbances. The circadian clock genes such as PER3 controls circadian rhythm and sleep. Due to the role of PER3 in sleep disturbances and regulation of immune response, it is possible that PER3 dysregulation increase risk of MS disease. Study groups included 160 MS patients and 160 healthy volunteers. PER3 VNTR polymorphism was evaluated by PCR method. The genotypic and allelic distribution analyzed by chi square test. There was a significant association between genotype PER3 4/4 , and 4-repeat allele with MS disease (p = 0.014 and p < 0.001 respectively). The association analysis of PER3 VNTR polymorphism with gender status among MS group, and MS onset showed that there was a significant correlation between PER3 4/4 genotype with female gender and early onset of MS disease (p = 0.033 and p = 0.028 respectively). Our data suggest that, PER3 4/4 genotype may accelerate the course of disease in MS susceptible individuals. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of Atmospheric Pressure Chemical Ionization and Field Ionization Mass Spectrometry for the Analysis of Large Saturated Hydrocarbons.

PubMed

Jin, Chunfen; Viidanoja, Jyrki; Li, Mingzhe; Zhang, Yuyang; Ikonen, Elias; Root, Andrew; Romanczyk, Mark; Manheim, Jeremy; Dziekonski, Eric; Kenttämaa, Hilkka I

2016-11-01

Direct infusion atmospheric pressure chemical ionization mass spectrometry (APCI-MS) was compared to field ionization mass spectrometry (FI-MS) for the determination of hydrocarbon class distributions in lubricant base oils. When positive ion mode APCI with oxygen as the ion source gas was employed to ionize saturated hydrocarbon model compounds (M) in hexane, only stable [M - H] + ions were produced. Ion-molecule reaction studies performed in a linear quadrupole ion trap suggested that fragment ions of ionized hexane can ionize saturated hydrocarbons via hydride abstraction with minimal fragmentation. Hence, APCI-MS shows potential as an alternative of FI-MS in lubricant base oil analysis. Indeed, the APCI-MS method gave similar average molecular weights and hydrocarbon class distributions as FI-MS for three lubricant base oils. However, the reproducibility of APCI-MS method was found to be substantially better than for FI-MS. The paraffinic content determined using the APCI-MS and FI-MS methods for the base oils was similar. The average number of carbons in paraffinic chains followed the same increasing trend from low viscosity to high viscosity base oils for the two methods.

Immunomodulatory Role of Diet and Adipokines in Multiple Sclerosis and Its Animal Model

DTIC Science & Technology

2015-09-01

beginning to be elucidated. In this regard, MS has been studied very little. Several recent studies showed that obesity during childhood /young adulthood...confers increased risk of developing MS. Obesity in the past 20 years has become an epidemic in western counties. New evidence suggests a link...between obesity and several autoimmune diseases (Procaccini, Carbone et al. 2011). Obesity is characterized by a low-grade chronic inflammatory state

Disruption of medial septum and diagonal bands of Broca cholinergic projections to the ventral hippocampus disrupt auditory fear memory.

PubMed

Staib, Jennifer M; Della Valle, Rebecca; Knox, Dayan K

2018-07-01

In classical fear conditioning, a neutral conditioned stimulus (CS) is paired with an aversive unconditioned stimulus (US), which leads to a fear memory. If the CS is repeatedly presented without the US after fear conditioning, the formation of an extinction memory occurs, which inhibits fear memory expression. A previous study has demonstrated that selective cholinergic lesions in the medial septum and vertical limb of the diagonal bands of Broca (MS/vDBB) prior to fear and extinction learning disrupt contextual fear memory discrimination and acquisition of extinction memory. MS/vDBB cholinergic neurons project to a number of substrates that are critical for fear and extinction memory. However, it is currently unknown which of these efferent projections are critical for contextual fear memory discrimination and extinction memory. To address this, we induced cholinergic lesions in efferent targets of MS/vDBB cholinergic neurons. These included the dorsal hippocampus (dHipp), ventral hippocampus (vHipp), medial prefrontal cortex (mPFC), and in the mPFC and dHipp combined. None of these lesion groups exhibited deficits in contextual fear memory discrimination or extinction memory. However, vHipp cholinergic lesions disrupted auditory fear memory. Because MS/vDBB cholinergic neurons are the sole source of acetylcholine in the vHipp, these results suggest that MS/vDBB cholinergic input to the vHipp is critical for auditory fear memory. Taken together with previous findings, the results of this study suggest that MS/vDBB cholinergic neurons are critical for fear and extinction memory, though further research is needed to elucidate the role of MS/vDBB cholinergic neurons in these types of emotional memory. Copyright © 2018 Elsevier Inc. All rights reserved.

Pharmacological treatments for fatigue in patients with multiple sclerosis: A systematic review and meta-analysis.

PubMed

Yang, Ting-Ting; Wang, Li; Deng, Xiao-Yang; Yu, Gang

2017-09-15

Multiple sclerosis (MS) is a chronic immune-mediated inflammatory disease. Fatigue is the most common symptom of MS patients, affecting >80% subjects. Medical treatment is an important method for managing fatigue. Currently, although many drugs have been tested in treatment of MS fatigue, the efficacy of these drugs remain largely unclear. We researched available literatures in PubMed, Embase, Medline, Google Scholar, Cochrane Library (August 31, 2016). Search terms included multiple sclerosis, fatigue, medication treatments, amantadine, modafinil, aspirin, acetyl-l-carnitine, pemoline, 4-aminopyridine and randomized controlled trial (RCT). Two researchers were required to independently assess the quality of literatures, and finish data extraction. Meta-analysis was conducted using RevMan 5.3 software. A total of 11 RCTs involving 723 patients were included. The therapeutic effects were quantified by different scales, such as Modified Fatigue Impact Scale (MFIS) or Fatigue Severity Scale (FSS). Here, meta-analysis suggested that amantadine, not modafinil, was effective for treating the fatigue in MS. Moreover, two studies implied that l-carnitine might have similar therapeutic effect with amantadine. However, the reliability of this finding was greatly weakened by the limited sample sizes. Additionally, current data could not answer whether treatment of MS fatigue using aspirin or 4-aminopyridine was beneficial. Finally, we found that all drugs except pemoline were relatively safe for treating MS fatigue. Current limited data suggest that amantadine may be the only drug that has relatively sufficient evidences in treatment of fatigue symptoms in MS. Further RCT studies recruiting larger samples sizes are required to validate the therapeutic effect of these candidate drugs. Copyright © 2017. Published by Elsevier B.V.

Multiple sclerosis (MS) in the life cycle of the family: An interpretative phenomenological analysis of the perspective of persons with recently diagnosed MS.

PubMed

de Ceuninck van Capelle, Archie; Visser, Leo H; Vosman, Frans

2016-12-01

In this study the authors explored how people with recently diagnosed multiple sclerosis (MS) experience their disease within their family lives. Ten people in various stages of the cycle of family life (leaving home, finding a partner, raising children, parenting adolescents, launching children) who had been diagnosed with MS were interviewed in half-structured conversational interviews. Transcriptions were analyzed following a phenomenological approach. Five themes were found: (a) dwindling capacity for housekeeping and childcare (b) struggling to ask for or to accept help, (c) countering awkward attitudes toward my illness, (d) suspecting family members of concealing their, and (e) watching family members wrestle with your illness. The participants described that their illness affected their ability to care for their family and home as they used to. Only a couple of studies have addressed the first person perspective of patients on family and MS. The study expands on these studies by exploring not previously examined perspectives on leaving home, finding a partner, parenting adolescents, and launching children. The findings on family and MS, approached as elements of the first person perspective of MS patients, may guide future research. Given the pivotal role of worries on family in patient experience of MS, we argue that acknowledgment of family as a constitutive element of the patient perspective should be integrated in regular MS care. The authors suggest that the clinical handling of MS as a family issue needs to be done thoughtfully and with attention to the specifics of each unique family situation. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Initial studies of submarine groundwater discharge in Mississippi coastal waters

NASA Astrophysics Data System (ADS)

Shiller, A. M.; Moore, W. S.; Joung, D. J.; Box, H.; Ho, P.; Whitmore, L. M.; Gilbert, M.; Anderson, H.

2017-12-01

Submarine groundwater discharge (SGD) is a critical component of coastal ecosystems, affecting biogeochemistry and productivity. The SGD flux and effect on the ecosystem of the Mississippi (MS) Bight has not previously been studied. We have determined Ba, δ18O of water, and Ra-isotopes, together with nutrients, chlorophyll, and dissolved oxygen (DO) during multiple cruises from fall 2015 to summer 2016. Water isotope distributions (δ18O) show that, although the MS River Delta bounds the western side of the Bight, nonetheless, Mobile Bay and other local rivers are the Bight's dominant freshwater sources. But elevated dissolved Ba and Ra isotopes cannot be explained by river input. Spatially, SGD in the MS Bight occurs over a wide area, with hot spots near the barrier islands (e.g., Chandeleurs, Horn and Dauphin Islands) and the mouth of Mobile Bay, probably in association with old buried river channels, or dredged ship channels. Based on their high concentrations in saline groundwaters sampled on the barrier islands, the elevated Ba and Ra in MS Bight water are likely due to SGD. In subsurface waters, long-lived Ra isotopes were negatively correlated with DO during spring and summer 2016, suggesting direct discharge of DO-depleted groundwater and/or accumulation of SGD-derived Ra and microbial DO consumption under strongly stratified conditions. Our ongoing study suggests that seasonal variability in flushing, water stratification, and SGD input play important roles in biological production and bottom water hypoxia in the MS Bight.

Assessing direct analysis in real-time-mass spectrometry (DART-MS) for the rapid identification of additives in food packaging.

PubMed

Ackerman, L K; Noonan, G O; Begley, T H

2009-12-01

The ambient ionization technique direct analysis in real time (DART) was characterized and evaluated for the screening of food packaging for the presence of packaging additives using a benchtop mass spectrometer (MS). Approximate optimum conditions were determined for 13 common food-packaging additives, including plasticizers, anti-oxidants, colorants, grease-proofers, and ultraviolet light stabilizers. Method sensitivity and linearity were evaluated using solutions and characterized polymer samples. Additionally, the response of a model additive (di-ethyl-hexyl-phthalate) was examined across a range of sample positions, DART, and MS conditions (temperature, voltage and helium flow). Under optimal conditions, molecular ion (M+H+) was the major ion for most additives. Additive responses were highly sensitive to sample and DART source orientation, as well as to DART flow rates, temperatures, and MS inlet voltages, respectively. DART-MS response was neither consistently linear nor quantitative in this setting, and sensitivity varied by additive. All additives studied were rapidly identified in multiple food-packaging materials by DART-MS/MS, suggesting this technique can be used to screen food packaging rapidly. However, method sensitivity and quantitation requires further study and improvement.

Decision-Making in Multiple Sclerosis Patients: A Systematic Review.

PubMed

Neuhaus, Mireille; Calabrese, Pasquale; Annoni, Jean-Marie

2018-01-01

Multiple sclerosis (MS) is frequently associated with cognitive and behavioural deficits. A growing number of studies suggest an impact of MS on decision-making abilities. The aim of this systematic review was to assess if (1) performance of MS patients in decision-making tasks was consistently different from controls and (2) whether this modification was associated with cognitive dysfunction and emotional alterations. The search was conducted on Pubmed/Medline database. 12 studies evaluating the difference between MS patients and healthy controls using validated decision-making tasks were included. Outcomes considered were quantitative (net scores) and qualitative measurements (deliberation time and learning from feedback). Quantitative and qualitative decision-making impairment in MS was present in 64.7% of measurements. Patients were equally impaired in tasks for decision-making under risk and ambiguity. A correlation to other cognitive functions was present in 50% of cases, with the highest associations in the domains of processing speed and attentional capacity. In MS patients, qualitative and quantitative modifications may be present in any kind of decision-making task and can appear independently of other cognitive measures. Since decision-making abilities have a significant impact on everyday life, this cognitive aspect has an influential importance in various MS-related treatment settings.

Selective reminding of prospective memory in Multiple Sclerosis.

PubMed

McKeever, Joshua D; Schultheis, Maria T; Sim, Tiffanie; Goykhman, Jessica; Patrick, Kristina; Ehde, Dawn M; Woods, Steven Paul

2017-04-19

Multiple sclerosis (MS) is associated with prospective memory (PM) deficits, which may increase the risk of poor functional/health outcomes such as medication non-adherence. This study examined the potential benefits of selective reminding to enhance PM functioning in persons with MS. Twenty-one participants with MS and 22 healthy adults (HA) underwent a neuropsychological battery including a Selective Reminding PM (SRPM) experimental procedure. Participants were randomly assigned to either: (1) a selective reminding condition in which participants learn (to criterion) eight prospective memory tasks in a Selective Reminding format; or (2) a single trial encoding condition (1T). A significant interaction was demonstrated, with MS participants receiving greater benefit than HAs from the SR procedure in terms of PM performance. Across diagnostic groups, participants in the SR conditions (vs. 1T conditions) demonstrated significantly better PM performance. Individuals with MS were impaired relative to HAs in the 1T condition, but performance was statistically comparable in the SR condition. This preliminary study suggests that selective reminding can be used to enhance PM cue detection and retrieval in MS. The extent to which selective reminding of PM is effective in naturalistic settings and for health-related behaviours in MS remains to be determined.

Higher Carotid Intima-Media Thickness in Subclinical Hypothyroidism Associated with the Metabolic Syndrome.

PubMed

França, Mariana Martins; Nogueira, Célia Regina; Hueb, João Carlos; Mendes, Adriana Lúcia; Padovani, Carlos Roberto; Mazeto, Gláucia Maria Ferreira da Silva

2016-10-01

The subclinical hypothyroidism (SH) and the metabolic syndrome (MS) have been associated with increased risk of atherosclerosis and cardiovascular disease (CVD). The measurement of carotid intima-media thickness (IMT) is capable of detecting early signs of atherosclerotic disease. The goal of the study was to compare the carotid IMT of patients with SH with and without the MS. Twenty-nine SH patients were subdivided into two groups: one with MS (SH + MS) and one without MS (SH - MS). The study also assessed a group of euthyroid patients (n = 31), also subdivided into two groups: one with MS (EU + MS) and one without MS (EU - MS). The clinical and laboratory data and the mean and maximum carotid IMT of the groups were compared. Maximum (P = 0.012) and mean (P = 0.025) IMT were higher in the SH + MS group than in the SH-MS group. Maximum IMT was higher in the SH + MS group than in the EU + MS group (P = 0.048). Maximum IMT was positively correlated with fasting glucose (FG; R = 0.621; P < 0.01) and body mass index (R = 0.258; P = 0.041) and negatively correlated with low-density lipoprotein cholesterol (LDL-C) (R = -0.297; P = 0.017). Mean IMT was positively correlated with FG (R = 0.580; P < 0.01), systolic blood pressure (R = 0.292; P = 0.02), and triglycerides (R = 0.250; P = 0.048) and negatively correlated with LDL-C (R = -0.288; P = 0.022). SH + MS patients have higher IMT than SH - MS or EU + MS patients, suggesting that SH may be one more CVD risk factor in patients with the MS.

Cancer risk among patients with multiple sclerosis: A cohort study in Isfahan, Iran.

PubMed

Etemadifar, Masoud; Jahanbani-Ardakani, Hamidreza; Ghaffari, Sara; Fereidan-Esfahani, Maboobeh; Changaei, Hossein; Aghadoost, Nazila; Jahanbani Ardakani, Ameneh; Moradkhani, Negin

2017-01-01

Multiple sclerosis (MS), a central nervous system (CNS) autoimmune disorder, affects 2.3 million people around the world. Cancer kills around 7.5 million people annually. Both diseases have similar risks and intertwining molecular causes. Most studies focusing on MS and cancer have found an insignificant difference or reduction in the amount of cancer found in the MS community. We performed a cohort study using data from Isfahan Multiple Sclerosis Society (IMSS) and Isfahan cancer society and followed-up for 8 years on average (2006-2014). All of the 1718 MS patients were diagnosed according to McDonald's criteria, then standardized incidence ratio and the numbers of expected cancer case were calculated. While patients had an insignificant change in cancer prevalence, men had fewer cancer cases and women showed an increased prevalence of cancer. Certain types of cancer proved statistically significant. Breast cancer, nervous system cancers, and lymphoma were elevated in the cohort. Our results support the hypothesis that MS significantly affects certain cancers in a protective or associative manner. All cancer rates, except breast cancer, cancers located in the nervous system, and lymphomas were reduced in cohort, suggesting that unregulated immune function may provide protective effects to MS patients against cancer.

Metabolic syndrome and chronic kidney disease in general Chinese adults: results from the 2007-08 China National Diabetes and Metabolic Disorders Study.

PubMed

Ming, Jie; Xu, Shaoyong; Yang, Chao; Gao, Bin; Wan, Yi; Xing, Ying; Zhang, Lei; Yang, Wenying; Ji, Qiuhe

2014-03-20

China is undergoing a rapid transition to an urbanized and Western diet pattern, which worsens the public health burden of metabolic syndrome (MS) and chronic kidney disease (CKD). We aimed to estimate the prevalence of CKD among adults with MS and to evaluate the association between MS and CKD in China. The data were obtained from the China National Diabetes and Metabolic Disorders Study conducted from June 2007 to May 2008. A total of 15,987 individuals aged 20 y or older were included as study participants. Age-standardized prevalence of CKD, which was defined as a glomerular filtration rate <60 ml/min/1.73 m(2), in participants with and without MS was 4.64% and 3.30%, respectively. The multivariate-adjusted odds ratio of CKD associated with MS was 1.495 (95% CI: 1.190-1.879). Elevated blood pressure, elevated fasting glucose, elevated triglycerides, and reduced high-density lipoprotein cholesterol had statistically significant increased odds ratios of 1.218, 1.256, 1.325 and 1.797 for CKD, respectively, while elevated waist circumference was not significantly associated with an increased odds ratio of CKD. Our study suggests an increasing prevalence of CKD among Chinese adults with MS and a strong association between CKD and MS. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

In Vivo Imaging of Cortical Inflammation and Subpial Pathology in Multiple Sclerosis by Combined PET and MRI

DTIC Science & Technology

2014-09-01

and Subpial Pathology in Multiple Sclerosis by Combined PET and MRI PRINCIPAL INVESTIGATOR: Dr. Caterina Mainero...studies in multiple sclerosis (MS) suggested that cortical demyelinating lesions, which are hardly detected in vivo on conventional magnetic resonance...disease progression in many MS cases. 15. SUBJECT TERMS Multiple sclerosis ; cortex; cortical sulci; neuroinflammation; microglia; cortical

Effective Application of Bicelles for Conformational Analysis of G Protein-Coupled Receptors by Hydrogen/Deuterium Exchange Mass Spectrometry

NASA Astrophysics Data System (ADS)

Duc, Nguyen Minh; Du, Yang; Thorsen, Thor S.; Lee, Su Youn; Zhang, Cheng; Kato, Hideaki; Kobilka, Brian K.; Chung, Ka Young

2015-05-01

G protein-coupled receptors (GPCRs) have important roles in physiology and pathology, and 40% of drugs currently on the market target GPCRs for the treatment of various diseases. Because of their therapeutic importance, the structural mechanism of GPCR signaling is of great interest in the field of drug discovery. Hydrogen/deuterium exchange mass spectrometry (HDX-MS) is a useful tool for analyzing ligand binding sites, the protein-protein interaction interface, and conformational changes of proteins. However, its application to GPCRs has been limited for various reasons, including the hydrophobic nature of GPCRs and the use of detergents in their preparation. In the present study, we tested the application of bicelles as a means of solubilizing GPCRs for HDX-MS studies. GPCRs (e.g., β2-adrenergic receptor [β2AR], μ-opioid receptor, and protease-activated receptor 1) solubilized in bicelles produced better sequence coverage (greater than 90%) than GPCRs solubilized in n-dodecyl-β-D-maltopyranoside (DDM), suggesting that bicelles are a more effective method of solubilization for HDX-MS studies. The HDX-MS profile of β2AR in bicelles showed that transmembrane domains (TMs) undergo lower deuterium uptake than intracellular or extracellular regions, which is consistent with the fact that the TMs are highly ordered and embedded in bicelles. The overall HDX-MS profiles of β2AR solubilized in bicelles and in DDM were similar except for intracellular loop 3. Interestingly, we detected EX1 kinetics, an important phenomenon in protein dynamics, at the C-terminus of TM6 in β2AR. In conclusion, we suggest the application of bicelles as a useful method for solubilizing GPCRs for conformational analysis by HDX-MS.

Gut commensalism, cytokines, and central nervous system demyelination.

PubMed

Telesford, Kiel; Ochoa-Repáraz, Javier; Kasper, Lloyd H

2014-08-01

There is increasing support for the importance of risk factors such as genetic makeup, obesity, smoking, vitamin D insufficiency, and antibiotic exposure contributing to the development of autoimmune diseases, including human multiple sclerosis (MS). Perhaps the greatest environmental risk factor associated with the development of immune-mediated conditions is the gut microbiome. Microbial and helminthic agents are active participants in shaping the immune systems of their hosts. This concept is continually reinforced by studies in the burgeoning area of commensal-mediated immunomodulation. The clinical importance of these findings for MS is suggested by both their participation in disease and, perhaps of greater clinical importance, attenuation of disease severity. Observations made in murine models of central nervous system demyelinating disease and a limited number of small studies in human MS suggest that immune homeostasis within the gut microbiome may be of paramount importance in maintaining a disease-free state. This review describes three immunological factors associated with the gut microbiome that are central to cytokine network activities in MS pathogenesis: T helper cell polarization, T regulatory cell function, and B cell activity. Comparisons are drawn between the regulatory mechanisms attributed to first-line therapies and those described in commensal-mediated amelioration of central nervous system demyelination.

Associations between Proprioceptive Neural Pathway Structural Connectivity and Balance in People with Multiple Sclerosis

PubMed Central

Fling, Brett W.; Dutta, Geetanjali Gera; Schlueter, Heather; Cameron, Michelle H.; Horak, Fay B.

2014-01-01

Mobility and balance impairments are a hallmark of multiple sclerosis (MS), affecting nearly half of patients at presentation and resulting in decreased activity and participation, falls, injuries, and reduced quality of life. A growing body of work suggests that balance impairments in people with mild MS are primarily the result of deficits in proprioception, the ability to determine body position in space in the absence of vision. A better understanding of the pathophysiology of balance disturbances in MS is needed to develop evidence-based rehabilitation approaches. The purpose of the current study was to (1) map the cortical proprioceptive pathway in vivo using diffusion-weighted imaging and (2) assess associations between proprioceptive pathway white matter microstructural integrity and performance on clinical and behavioral balance tasks. We hypothesized that people with MS (PwMS) would have reduced integrity of cerebral proprioceptive pathways, and that reduced white matter microstructure within these tracts would be strongly related to proprioceptive-based balance deficits. We found poorer balance control on proprioceptive-based tasks and reduced white matter microstructural integrity of the cortical proprioceptive tracts in PwMS compared with age-matched healthy controls (HC). Microstructural integrity of this pathway in the right hemisphere was also strongly associated with proprioceptive-based balance control in PwMS and controls. Conversely, while white matter integrity of the right hemisphere’s proprioceptive pathway was significantly correlated with overall balance performance in HC, there was no such relationship in PwMS. These results augment existing literature suggesting that balance control in PwMS may become more dependent upon (1) cerebellar-regulated proprioceptive control, (2) the vestibular system, and/or (3) the visual system. PMID:25368564

Prognostic value of high-field proton magnetic resonance spectroscopy in patients presenting with clinically isolated syndromes suggestive of multiple sclerosis.

PubMed

Wattjes, Mike P; Harzheim, Michael; Lutterbey, Götz G; Bogdanow, Manuela; Schmidt, Stephan; Schild, Hans H; Träber, Frank

2008-02-01

The aim of this study was to determine the prognostic value of metabolic alterations in the normal-appearing white matter (NAWM) of patients presenting with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS) with special regard to the prediction of conversion to definite MS. Using a 3T whole-body MR system, a multisequence conventional MRI protocol and single-voxel proton MR spectroscopy (PRESS, repetition time 2000 ms, echo times 38 ms and 140 ms) of the parietal NAWM were performed in 25 patients presenting with CIS at baseline and in 20 controls. Absolute concentrations of N-acetyl-aspartate (tNAA), myo-inositol (Ins), choline (Cho) and creatine (tCr) as well as metabolite ratios were determined. Follow-up including neurological assessment and conventional MRI was performed 3-4 and 6-7 months after the initial event. Nine patients converted to definite MS during the follow-up period. Compared to controls, those patients who converted to MS also showed significantly lower tNAA concentrations in the NAWM (-13.4%, P = 0.002) whereas nonconverters (-6.5%, P = 0.052) did not. The Ins concentration was 20.2% higher in the converter group and 1.9% higher in the nonconverter group, but these differences did not reach significance. No significant differences could be observed for tCr and Cho in either patient group. Axonal damage at baseline in patients presenting with CIS was more prominent in those who subsequently converted to definite MS in the short term follow-up, indicating that tNAA might be a sufficient prognostic marker for patients with a higher risk of conversion to early definite MS.

Associations between Proprioceptive Neural Pathway Structural Connectivity and Balance in People with Multiple Sclerosis.

PubMed

Fling, Brett W; Dutta, Geetanjali Gera; Schlueter, Heather; Cameron, Michelle H; Horak, Fay B

2014-01-01

Mobility and balance impairments are a hallmark of multiple sclerosis (MS), affecting nearly half of patients at presentation and resulting in decreased activity and participation, falls, injuries, and reduced quality of life. A growing body of work suggests that balance impairments in people with mild MS are primarily the result of deficits in proprioception, the ability to determine body position in space in the absence of vision. A better understanding of the pathophysiology of balance disturbances in MS is needed to develop evidence-based rehabilitation approaches. The purpose of the current study was to (1) map the cortical proprioceptive pathway in vivo using diffusion-weighted imaging and (2) assess associations between proprioceptive pathway white matter microstructural integrity and performance on clinical and behavioral balance tasks. We hypothesized that people with MS (PwMS) would have reduced integrity of cerebral proprioceptive pathways, and that reduced white matter microstructure within these tracts would be strongly related to proprioceptive-based balance deficits. We found poorer balance control on proprioceptive-based tasks and reduced white matter microstructural integrity of the cortical proprioceptive tracts in PwMS compared with age-matched healthy controls (HC). Microstructural integrity of this pathway in the right hemisphere was also strongly associated with proprioceptive-based balance control in PwMS and controls. Conversely, while white matter integrity of the right hemisphere's proprioceptive pathway was significantly correlated with overall balance performance in HC, there was no such relationship in PwMS. These results augment existing literature suggesting that balance control in PwMS may become more dependent upon (1) cerebellar-regulated proprioceptive control, (2) the vestibular system, and/or (3) the visual system.

Visual Occlusion Decreases Motion Sickness in a Flight Simulator.

PubMed

Ishak, Shaziela; Bubka, Andrea; Bonato, Frederick

2018-05-01

Sensory conflict theories of motion sickness (MS) assert that symptoms may result when incoming sensory inputs (e.g., visual and vestibular) contradict each other. Logic suggests that attenuating input from one sense may reduce conflict and hence lessen MS symptoms. In the current study, it was hypothesized that attenuating visual input by blocking light entering the eye would reduce MS symptoms in a motion provocative environment. Participants sat inside an aircraft cockpit mounted onto a motion platform that simultaneously pitched, rolled, and heaved in two conditions. In the occluded condition, participants wore "blackout" goggles and closed their eyes to block light. In the control condition, participants opened their eyes and had full view of the cockpit's interior. Participants completed separate Simulator Sickness Questionnaires before and after each condition. The posttreatment total Simulator Sickness Questionnaires and subscores for nausea, oculomotor, and disorientation in the control condition were significantly higher than those in the occluded condition. These results suggest that under some conditions attenuating visual input may delay the onset of MS or weaken the severity of symptoms. Eliminating visual input may reduce visual/nonvisual sensory conflict by weakening the influence of the visual channel, which is consistent with the sensory conflict theory of MS.

Histaminergic and cholinergic neuron systems in the impairment of human thermoregulation during motion sickness.

PubMed

Nobel, Gerard; Tribukait, Arne; Mekjavic, Igor B; Eiken, Ola

2010-05-31

Motion sickness (MS) exaggerates body cooling during cold-water immersion. The aim of the present study was to investigate whether such MS-induced predisposition to hypothermia is influenced by two anti-MS drugs: the histamine-receptor blocker dimenhydrinate (DMH) and the muscarine-receptor blocker scopolamine (Scop). Nine healthy male subjects were immersed in 15 degrees C water for a maximum of 90min in five conditions: (1) control (CN): no medication, no MS provocation; (2) MS-control (MS-CN): no medication, MS provocation; (3) MS-placebo (MS-P): placebo DMH and placebo Scop, MS provocation; (4) MS-DMH: DMH and placebo Scop, MS provocation; (5) MS-Scop: Scop and placebo DMH, MS provocation. MS was induced by use of a rotating chair. Throughout the experiments rectal temperature (T(re)), the difference in temperature between the non-immersed right forearm and third finger (T(ff)) as an index of peripheral vasoconstriction, and oxygen uptake (VO(2)) as a measure of shivering thermogenesis, were recorded. DMH and Scop were similarly efficacious in ameliorating nausea. The fall in T(re) was greater in the MS-CN and MS-P conditions than in the CN condition. DMH, but not Scop, prevented the MS-induced increase in body-core cooling. MS attenuated the cold-induced vasoconstriction, an effect which was fully prevented by DMH but only partially by Scop. MS provocation did not affect VO(2) in any condition. The results suggest that the MS-induced predisposition to hypothermia is predominantly mediated by histaminergic mechanisms and that DMH might be useful in conjunction with maritime accidents or other scenarios where exposure to cold and MS are imminent features. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Modeling Markov switching ARMA-GARCH neural networks models and an application to forecasting stock returns.

PubMed

Bildirici, Melike; Ersin, Özgür

2014-01-01

The study has two aims. The first aim is to propose a family of nonlinear GARCH models that incorporate fractional integration and asymmetric power properties to MS-GARCH processes. The second purpose of the study is to augment the MS-GARCH type models with artificial neural networks to benefit from the universal approximation properties to achieve improved forecasting accuracy. Therefore, the proposed Markov-switching MS-ARMA-FIGARCH, APGARCH, and FIAPGARCH processes are further augmented with MLP, Recurrent NN, and Hybrid NN type neural networks. The MS-ARMA-GARCH family and MS-ARMA-GARCH-NN family are utilized for modeling the daily stock returns in an emerging market, the Istanbul Stock Index (ISE100). Forecast accuracy is evaluated in terms of MAE, MSE, and RMSE error criteria and Diebold-Mariano equal forecast accuracy tests. The results suggest that the fractionally integrated and asymmetric power counterparts of Gray's MS-GARCH model provided promising results, while the best results are obtained for their neural network based counterparts. Further, among the models analyzed, the models based on the Hybrid-MLP and Recurrent-NN, the MS-ARMA-FIAPGARCH-HybridMLP, and MS-ARMA-FIAPGARCH-RNN provided the best forecast performances over the baseline single regime GARCH models and further, over the Gray's MS-GARCH model. Therefore, the models are promising for various economic applications.

Modeling Markov Switching ARMA-GARCH Neural Networks Models and an Application to Forecasting Stock Returns

PubMed Central

Bildirici, Melike; Ersin, Özgür

2014-01-01

The study has two aims. The first aim is to propose a family of nonlinear GARCH models that incorporate fractional integration and asymmetric power properties to MS-GARCH processes. The second purpose of the study is to augment the MS-GARCH type models with artificial neural networks to benefit from the universal approximation properties to achieve improved forecasting accuracy. Therefore, the proposed Markov-switching MS-ARMA-FIGARCH, APGARCH, and FIAPGARCH processes are further augmented with MLP, Recurrent NN, and Hybrid NN type neural networks. The MS-ARMA-GARCH family and MS-ARMA-GARCH-NN family are utilized for modeling the daily stock returns in an emerging market, the Istanbul Stock Index (ISE100). Forecast accuracy is evaluated in terms of MAE, MSE, and RMSE error criteria and Diebold-Mariano equal forecast accuracy tests. The results suggest that the fractionally integrated and asymmetric power counterparts of Gray's MS-GARCH model provided promising results, while the best results are obtained for their neural network based counterparts. Further, among the models analyzed, the models based on the Hybrid-MLP and Recurrent-NN, the MS-ARMA-FIAPGARCH-HybridMLP, and MS-ARMA-FIAPGARCH-RNN provided the best forecast performances over the baseline single regime GARCH models and further, over the Gray's MS-GARCH model. Therefore, the models are promising for various economic applications. PMID:24977200

Sedentary behaviour in people with multiple sclerosis: Is it time to stand up against MS?

PubMed

Veldhuijzen van Zanten, Jet Jcs; Pilutti, Lara A; Duda, Joan L; Motl, Robert W

2016-09-01

Historically, people with multiple sclerosis (MS) have been considered sedentary, although the actual scientific study of sedentary behaviour in MS did not originate until 2011. Sedentary behaviour, which is conceptually distinct from physical inactivity, is defined as any waking activity characterised by an energy expenditure ⩽ 1.5 metabolic equivalents and in a sitting or reclining posture. In the general population, the volume of sitting time is associated with increased risks of morbidity and mortality, independent of physical activity, and has been suggested to carry a greater risk of mortality than smoking behaviour. There are many symptoms of MS (e.g. mobility disability and fatigue) that could increase the prevalence of sedentary behaviour, and sedentary behaviour may have considerable implications for the development of comorbid conditions prevalent in MS. This review provides a summary of the rates, correlates, consequences and interventions attempting to reduce sedentary behaviour in MS. We provide a research agenda that guides future research on sedentary behaviour in MS. This paper provides a clarion call that it is time to 'stand up against MS'. © The Author(s), 2016.

Effects of a 4-month Ananda Yoga program on physical and mental health outcomes for persons with multiple sclerosis.

PubMed

Salgado, Bryan Coleman; Jones, Maitri; Ilgun, Suzanne; McCord, Gyandev; Loper-Powers, Mangala; van Houten, Peter

2013-01-01

Yoga has been found to be effective for addressing problems with strength, flexibility, balance, gait, anxiety, depression, and concentration. Varying degrees of these problems occur in individuals with multiple sclerosis (MS). This study examined the effects of a comprehensive, 4-month yoga program on strength, mobility, balance, respiratory function, and quality of life for individuals with MS. Twenty four individuals with MS participated in an intensive Ananda Yoga training followed by 17 weeks of home practice. Significant improvements in functional strength, balance, and peak expiratory flow and a trend toward improvements in mental health and quality of life outcomes were detected following the intervention. The results of this exploratory study suggest that yoga can have a positive impact on physical functioning and quality of life for persons with mild to moderate MS.

Late-onset multiple sclerosis presenting with cognitive dysfunction and severe cortical/infratentorial atrophy.

PubMed

Calabrese, Massimiliano; Gajofatto, Alberto; Gobbin, Francesca; Turri, Giulia; Richelli, Silvia; Matinella, Angela; Oliboni, Eugenio Simone; Benedetti, Maria Donata; Monaco, Salvatore

2015-04-01

Although cognitive dysfunction is a relevant aspect of multiple sclerosis (MS) from the earliest disease phase, cognitive onset is unusual thus jeopardizing early and accurate diagnosis. Here we describe 12 patients presenting with cognitive dysfunction as primary manifestation of MS with either mild or no impairment in non-cognitive neurological domains. Twelve patients with cognitive onset who were subsequently diagnosed with MS (CI-MS) were included in this retrospective study. Twelve cognitively normal MS patients (CN-MS), 12 healthy controls and four patients having progressive supranuclear palsy (PSP) served as the reference population. Ten CI-MS patients had progressive clinical course and all patients had late disease onset (median age = 49 years; range = 40-58 years). Among cognitive functions, frontal domains were the most involved. Compared to CN-MS and healthy controls, significant cortical and infratentorial atrophy characterized CI-MS patients. Selective atrophy of midbrain tegmentum with relative sparing of pons, known as "The Hummingbird sign," was observed in eight CI-MS and in three PSP patients. Our observation suggests that MS diagnosis should be taken into consideration in case of cognitive dysfunction, particularly when associated with slowly progressive disease course and severe cortical, cerebellar and brainstem atrophy even in the absence of other major neurological symptoms and signs. © The Author(s), 2014.

"Putting one foot in front of the other": a qualitative study of emotional experiences and help-seeking in women with multiple sclerosis.

PubMed

Blundell Jones, Joanna; Walsh, Sue; Isaac, Claire

2014-12-01

Treatments for depression and anxiety in multiple sclerosis (MS) are effective but evidence suggests that individuals do not always seek help for emotional difficulties. This study explored how ten women with MS (aged 30-64), recruited via a hospital based MS clinic, coped with and understood their emotions. The semi-structured interviews were analysed using interpretative phenomenological analysis. Eight participants discussed the analytic process and themes. Four overarching themes emerged: Disclosure stress, Uncomfortable dependence, Facing deterioration and One step at a time. The women struggled emotionally with many aspects of living with MS yet coping alone provided a way of defying MS and maintaining independence and control. The women needed emotional support but reported thinking others either did not notice or understand; their emotions often felt invisible. More holistic care from services was desired. Non help-seeking for distress was partially influenced by a desire to keep things "normal" and a lack of knowledge regarding service provision.

Evaluation of SDS depletion using an affinity spin column and IMS-MS detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hengel, Shawna M.; Floyd, Erica A.; Baker, Erin Shammel

2012-11-01

While the use of detergents is necessary for a variety of protein isolation preparation protocols, often prior to mass spectral (MS) analysis, they are not compatible with MS analysis due to ion suppression and adduct formation. This manuscript describes optimization of detergent removal, using commercially available SDS depletion spin columns containing an affinity resin, providing for both increased protein recovery and thorough SDS removal. Ion mobility spectrometry coupled with mass spectrometry (IMS-MS) allowed for a concurrent analysis of both analyte and detergent. In the case of both proteins and peptides, higher detergent concentrations than previously reported provided an increase ofmore » sample recovery; however there was a limit as SDS was detected by IMS-MS at higher levels of SDS indicating incomplete detergent depletion. The results also suggest optimal conditions for SDS removal are dependent on the sample concentration. Overall, this study provides a useful guide for proteomic studies where SDS is required for efficient sample preparation.« less

The Pathophysiology of HIV-/HAART-Related Metabolic Syndrome Leading to Cardiovascular Disorders: The Emerging Role of Adipokines

PubMed Central

Palios, John; Kadoglou, Nikolaos P. E.; Lampropoulos, Stylianos

2012-01-01

Individuals infected with human immunodeficiency virus (HIV) frequently demonstrate metabolic syndrome (MS) associated with increased incidence of cardiovascular disorders. Characteristics of HIV infection, such as immunodeficiency, viral load, and duration of the disease, in addition to the highly active antiretroviral therapy (HAART) have been suggested to induce MS in these patients. It is well documented that MS involves a number of traditional cardiovascular risk factors, like glucose, lipids, and arterial blood pressure abnormalities, leading to extensive atherogenic arterial wall changes. Nevertheless, the above traditional cardiovascular risk factors merely explain the exacerbated cardiovascular risk in MS. Nowadays, the adipose-tissue derivatives, known as adipokines, have been suggested to contribute to chronic inflammation and the MS-related cardiovascular disease. In view of a novel understanding on how adipokines affect the pathogenesis of HIV/HAART-related MS and cardiovascular complications, this paper focuses on the interaction of the metabolic pathways and the potential cardiovascular consequences. Based on the current literature, we suggest adipokines to have a role in the pathogenesis of the HIV/HAART-related MS. It is crucial to understand the pathophysiology of the HIV/HAART-related MS and apply therapeutic strategies in order to reduce cardiovascular risk in HIV patients. PMID:22203832

A relationship between bruxism and orofacial-dystonia? A trigeminal electrophysiological approach in a case report of pineal cavernoma.

PubMed

Frisardi, Gianni; Iani, Cesare; Sau, Gianfranco; Frisardi, Flavio; Leornadis, Carlo; Lumbau, Aurea; Enrico, Paolo; Sirca, Donatella; Staderini, Enrico Maria; Chessa, Giacomo

2013-10-28

In some clinical cases, bruxism may be correlated to central nervous system hyperexcitability, suggesting that bruxism may represent a subclinical form of dystonia. To examine this hypothesis, we performed an electrophysiological evaluation of the excitability of the trigeminal nervous system in a patient affected by pineal cavernoma with pain symptoms in the orofacial region and pronounced bruxism. Electrophysiological studies included bilateral electrical transcranial stimulation of the trigeminal roots, analysis of the jaw jerk reflex, recovery cycle of masseter inhibitory reflex, and a magnetic resonance imaging study of the brain. The neuromuscular responses of the left- and right-side bilateral trigeminal motor potentials showed a high degree of symmetry in latency (1.92 ms and 1.96 ms, respectively) and amplitude (11 mV and 11.4 mV, respectively), whereas the jaw jerk reflex amplitude of the right and left masseters was 5.1 mV and 8.9 mV, respectively. The test stimulus for the recovery cycle of masseter inhibitory reflex evoked both silent periods at an interstimulus interval of 150 ms. The duration of the second silent period evoked by the test stimulus was 61 ms and 54 ms on the right and left masseters, respectively, which was greater than that evoked by the conditioning stimulus (39 ms and 35 ms, respectively). We found evidence of activation and peripheral sensitization of the nociceptive fibers, the primary and secondary nociceptive neurons in the central nervous system, and the endogenous pain control systems (including both the inhibitory and facilitatory processes), in the tested subject. These data suggest that bruxism and central orofacial pain can coexist, but are two independent symptoms, which may explain why numerous experimental and clinical studies fail to reach unequivocal conclusions.

A relationship between bruxism and orofacial-dystonia? A trigeminal electrophysiological approach in a case report of pineal cavernoma

PubMed Central

2013-01-01

Background In some clinical cases, bruxism may be correlated to central nervous system hyperexcitability, suggesting that bruxism may represent a subclinical form of dystonia. To examine this hypothesis, we performed an electrophysiological evaluation of the excitability of the trigeminal nervous system in a patient affected by pineal cavernoma with pain symptoms in the orofacial region and pronounced bruxism. Methods Electrophysiological studies included bilateral electrical transcranial stimulation of the trigeminal roots, analysis of the jaw jerk reflex, recovery cycle of masseter inhibitory reflex, and a magnetic resonance imaging study of the brain. Results The neuromuscular responses of the left- and right-side bilateral trigeminal motor potentials showed a high degree of symmetry in latency (1.92 ms and 1.96 ms, respectively) and amplitude (11 mV and 11.4 mV, respectively), whereas the jaw jerk reflex amplitude of the right and left masseters was 5.1 mV and 8.9 mV, respectively. The test stimulus for the recovery cycle of masseter inhibitory reflex evoked both silent periods at an interstimulus interval of 150 ms. The duration of the second silent period evoked by the test stimulus was 61 ms and 54 ms on the right and left masseters, respectively, which was greater than that evoked by the conditioning stimulus (39 ms and 35 ms, respectively). Conclusions We found evidence of activation and peripheral sensitization of the nociceptive fibers, the primary and secondary nociceptive neurons in the central nervous system, and the endogenous pain control systems (including both the inhibitory and facilitatory processes), in the tested subject. These data suggest that bruxism and central orofacial pain can coexist, but are two independent symptoms, which may explain why numerous experimental and clinical studies fail to reach unequivocal conclusions. PMID:24165294

HDAC Inhibitors Restore the Capacity of Aged Mice to Respond to Haloperidol through Modulation of Histone Acetylation

PubMed Central

Montalvo-Ortiz, Janitza L; Keegan, Jack; Gallardo, Christopher; Gerst, Nicolas; Tetsuka, Kazuhiro; Tucker, Chris; Matsumoto, Mitsuyuki; Fang, Deyu; Csernansky, John G; Dong, Hongxin

2014-01-01

Antipsychotic drugs are widely prescribed to elderly patients for the treatment of a variety of psychopathological conditions, including psychosis and the behavioral disturbances associated with dementia. However, clinical experience suggests that these drugs may be less efficacious in the elderly individuals than in the young. Recent studies suggest that aging may be associated with epigenetic changes and that valproic acid (VPA), a histone deacetylase inhibitor, may reverse such changes. However, it is not yet known whether HDAC inhibitors can modulate age-related epigenetic changes that may impact antipsychotic drug action. In this study, we analyzed conditioned avoidance response (CAR) and c-Fos expression patterns to elucidate the effect of HDAC inhibitors VPA and entinostat (MS-275) on behavioral and molecular markers of the effects of haloperidol (HAL) in aged mice. Our results showed that HAL administration failed to suppress the avoidance response during the CAR test, suggesting an age-related decrease in drug efficacy. In addition, HAL-induced c-Fos expression in the nucleus accumbens shell and prefrontal cortex was significantly lower in aged mice as compared with young mice. Pretreatment with VPA and MS-275 significantly improved HAL effects on the CAR test in aged mice. Also, VPA and MS-275 pretreatment restored HAL-induced increases in c-Fos expression in the nucleus accumbens shell and prefrontal cortex of aged mice to levels comparable with those observed in young mice. Lastly, but most importantly, increases in c-Fos expression and HAL efficacy in the CAR test of the HAL+VPA and HAL+MS-275 groups were correlated with elevated histone acetylation at the c-fos promoter region in aged mice. These findings suggest that pretreatment with VPA or MS-275 increases the behavioral and molecular effects of HAL in aged mice and that these effects occur via modulation of age-related histone hypoacetylation in the nucleus accumbens shell and prefrontal cortex. PMID:24366052

Pharmacokinetic Evaluation of Empagliflozin in Healthy Egyptian Volunteers Using LC-MS/MS and Comparison with Other Ethnic Populations.

PubMed

Ayoub, Bassam M; Mowaka, Shereen; Elzanfaly, Eman S; Ashoush, Nermeen; Elmazar, Mohamed M; Mousa, Shaker A

2017-05-31

The present study considered the pharmacokinetic evaluation of empagliflozin after administration to Egyptian volunteers, and the results were compared with other ethnic populations. The FDA recognizes that standard methods of defining racial subgroups are necessary to compare results across pharmacokinetic studies and to assess potential subgroup differences. The design of the study was as an open labeled, randomized, one treatment, one period, single dose pharmacokinetic study. The main pharmacokinetic parameters estimated were C max , T max , t 1/2 , elimination rate constant, AUC 0-t and AUC 0-inf . The insignificant difference in pharmacokinetic parameters between Egyptians and white German subjects suggests that no dose adjustment should be considered with administration of 25 mg empagliflozin to Egyptian population. A new LC-MS/MS method was developed and validated, allowing sensitive estimation of empagliflozin (25-600 ng mL -1 ) in human plasma using dapagliflozin as an internal standard (IS). The method was applied successfully on the underlying pharmacokinetic study with enhanced sample preparation that involved liquid-liquid extraction. Multiple Reaction Monitoring (MRM) of the transition pairs of m/z 449.01 to 371.21 for empagliflozin and m/z 407.00 to 328.81 for dapagliflozin (IS) was employed utilizing negative mode Electro Spray Ionization (ESI). The validated LC-MS/MS method is suitable for further toxicodynamic and bioequivalence studies.

Human endogenous retrovirus W in brain lesions: Rationale for targeted therapy in multiple sclerosis.

PubMed

van Horssen, Jack; van der Pol, Susanne; Nijland, Philip; Amor, Sandra; Perron, Hervé

2016-07-01

Attempts to identify a causative agent of Multiple Sclerosis (MS) among environmental viruses have consistently failed suggesting that development of MS is a result from gene-environment interactions. A new pathogenic player within human genes, a human endogenous retrovirus (HERV) was identified from MS cells, named MS-associated retrovirus element (MSRV) and unveiled homologous multicopy HERVs (HERV-W). As independent studies revealed biological features of HERV-W on immune-mediated inflammation and on remyelinating cells, the present study characterized the presence of HERV-W envelope protein (MSRV-Env) at the cellular level, in different MS lesion stages to extend and validate previous studies. Immunohistological analysis of HERV-W envelope cellular expression in different lesion stages from a cohort of MS brains versus controls, using well-characterized and highly specific monoclonal antibodies. HERV-W envelope protein was detected in all MS brains and quite essentially in lesions. Immunohistochemistry showed dominant expression in macrophages and microglia, coinciding with areas of active demyelination, spread over the active lesions, or limited to the rim of active microglia in chronic active lesions or in few surviving astrocytes of inactive plaques. Weak expression was seen in MS normal appearing white matter. In active plaques, few lymphoid cells and astrocytes were also stained. This HERV-W expression was not observed in control brains. HERV-W was expressed in demyelinated lesions from MS brains, which were all positive for this endogenous pathogenic protein. Pronounced HERV-W immunoreactivity in active MS lesions was intimately associated with areas of active demyelination throughout the successive stages of lesion evolution in MS brains. Based on its pathogenic potential, this HERV-W (MSRV) endogenous toxin thus appears to be a novel therapeutic target in MS. It also has a unique positioning as an early and lifelong expressed pathogenic agonist, acting upstream the pathways in which dysregulated physiological effectors are usually targeted by present therapeutic strategies for MS. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Lower Aerobic Endurance Linked to History of Depression in Multiple Sclerosis: Preliminary Observations.

PubMed

Chapman, Kimberly R; Anderson, Jason R; Calvo, Dayana; Pollock, Brandon S; Petersen, Jennifer; Gerhart, Hayden; Ridgel, Angela; Spitznagel, Mary Beth

2018-06-01

Despite the demonstrated benefits of exercise in multiple sclerosis (MS), this population shows low rates of physical activity. Understanding barriers to exercise in persons with MS is important. The current study examined the relationship between lifetime history of depression, current depressive symptoms, and aerobic endurance in persons with relapsing-remitting MS to determine whether depression might be one such barrier. Thirty-one participants with relapsing-remitting MS self-reported current depressive symptoms and history of depression. Aerobic endurance was assessed via 2-Minute Step Test. Linear regression demonstrated that lifetime history of depression predicted lower aerobic fitness whereas current depressive symptoms did not. Findings suggest a possible role of lifetime depression as a barrier to exercise in MS and highlight the importance of effective treatment of depression in this population to reduce its potential impact on exercise adherence.

Identification of a new sulfonic acid metabolite of metolachlor in soil

USGS Publications Warehouse

Aga, D.S.; Thurman, E.M.; Yockel, M.E.; Zimmerman, L.R.; Williams, T.D.

1996-01-01

An ethanesulfonic acid metabolite of metolachlor (metolachlor ESA) was identified in soil-sample extracts by negative-ion, fast-atom bombardment mass spectrometry (FAB-MS) and FAB tandem mass spectrometry (FAB-MS/MS). Production fragments from MS/MS analysis of the deprotonated molecular ion of metolachlor ESA in the soil extract can be reconciled with the structure of the synthesized standard. The elemental compositions of the (M - H)- ions of the metolachlor ESA standard and the soil-sample extracts were confirmed by high-resolution mass spectrometry. A dissipation study revealed that metolachlor ESA is formed in soil under field conditions corresponding to a decrease in the concentration of the parent herbicide, metolachlor. The identification of the sulfonated metabolite of metolachlor suggests that the glutathione conjugation pathway is a common detoxification pathway shared by chloroacetanilide herbicides.

Simultaneous assessment of myocardial perfusion and function during mental stress in patients with chronic coronary artery disease.

PubMed

Arrighi, James A; Burg, Matthew; Cohen, Ira S; Soufer, Robert

2003-01-01

Mental stress (MS) is an important provocateur of myocardial ischemia in many patients with chronic coronary artery disease. The majority of laboratory assessments of ischemia in response to MS have included measurements of either myocardial perfusion or function alone. We performed this study to determine the relationship between alterations in perfusion and ventricular function during MS. Methods and results Twenty-eight patients with reversible perfusion defects on exercise or pharmacologic stress myocardial perfusion imaging (MPI) underwent simultaneous technetium 99m sestamibi single photon emission computed tomography (SPECT) MPI and transthoracic echocardiography at rest and during MS according to a mental arithmetic protocol. In all cases the MS study was performed within 4 weeks of the initial exercise or pharmacologic MPI that demonstrated ischemia. SPECT studies were analyzed visually with the use of a 13-segment model and quantitatively by semiautomated circumferential profile analysis. Echocardiograms were graded on a segmental model for regional wall motion on a 4-point scale. Of 28 patients, 18 (64%) had perfusion defects and/or left ventricular dysfunction develop during MS: 9 (32%) had myocardial perfusion defects develop, 6 (21%) had regional or global left ventricular dysfunction develop, and 3 (11%) had both perfusion defects and left ventricular dysfunction develop. The overall concordance between perfusion and function criteria for ischemia during MS was only 46%. Among 9 patients with MS-induced left ventricular dysfunction, 5 had new regional wall motion abnormalities and 4 had a global decrement in function. In patients with MS-induced ischemia by SPECT, the number of reversible perfusion defects was similar during both MS and exercise/pharmacologic stress (2.8 +/- 2.0 vs 3.5 +/- 1.8, P =.41). Hemodynamic changes during MS were similar whether patients were divided on the basis of perfusion defects or left ventricular dysfunction during MS. These data indicate the feasibility of simultaneous assessment of perfusion and function responses during MS. Flow and function responses to MS are frequently not concordant. These data suggest that MS-induced changes in perfusion may represent a different phenomenon than MS-induced changes in left ventricular function (either globally or regionally).

Suppression, accessibility of death-related thoughts, and cultural worldview defense: exploring the psychodynamics of terror management.

PubMed

Arndt, J; Greenberg, J; Solomon, S; Pyszczynski, T; Simon, L

1997-07-01

Previous research has shown that after a mortality-salience (MS) treatment, death thought accessibility and worldview defense are initially low and then increase after a delay, suggesting that a person's initial response to conscious thoughts of mortality is to actively suppress death thoughts. If so, then high cognitive load, by disrupting suppression efforts, should lead to immediate increases in death thought accessibility and cultural worldview defense. Studies 1 and 2 supported this reasoning. Specifically, Study 1 replicated the delayed increase in death accessibility after MS among low cognitive load participants but showed a reversed pattern among participants under high cognitive load. Study 2 showed that, unlike low cognitive load participants, high cognitive load participants exhibited immediate increase in pro-American bias after MS. Study 3 demonstrated that worldview defense in response to MS reduces the delayed increase in death accessibility. Implications of these findings for understanding both terror management processes and psychological defense in general are discussed.

Systemic Inflammation in Progressive Multiple Sclerosis Involves Follicular T-Helper, Th17- and Activated B-Cells and Correlates with Progression

PubMed Central

Christensen, Jeppe Romme; Börnsen, Lars; Ratzer, Rikke; Piehl, Fredrik; Khademi, Mohsen; Olsson, Tomas; Sørensen, Per Soelberg; Sellebjerg, Finn

2013-01-01

Pathology studies of progressive multiple sclerosis (MS) indicate a major role of inflammation including Th17-cells and meningeal inflammation with ectopic lymphoid follicles, B-cells and plasma cells, the latter indicating a possible role of the newly identified subset of follicular T-helper (TFH) cells. Although previous studies reported increased systemic inflammation in progressive MS it remains unclear whether systemic inflammation contributes to disease progression and intrathecal inflammation. This study aimed to investigate systemic inflammation in progressive MS and its relationship with disease progression, using flow cytometry and gene expression analysis of CD4+ and CD8+T-cells, B-cells, monocytes and dendritic cells. Furthermore, gene expression of cerebrospinal fluid cells was studied. Flow cytometry studies revealed increased frequencies of ICOS+TFH-cells in peripheral blood from relapsing-remitting (RRMS) and secondary progressive (SPMS) MS patients. All MS subtypes had decreased frequencies of Th1 TFH-cells, while primary progressive (PPMS) MS patients had increased frequency of Th17 TFH-cells. The Th17-subset, interleukin-23-receptor+CD4+T-cells, was significantly increased in PPMS and SPMS. In the analysis of B-cells, we found a significant increase of plasmablasts and DC-SIGN+ and CD83+B-cells in SPMS. ICOS+TFH-cells and DC-SIGN+B-cells correlated with disease progression in SPMS patients. Gene expression analysis of peripheral blood cell subsets substantiated the flow cytometry findings by demonstrating increased expression of IL21, IL21R and ICOS in CD4+T-cells in progressive MS. Cerebrospinal fluid cells from RRMS and progressive MS (pooled SPMS and PPMS patients) had increased expression of TFH-cell and plasmablast markers. In conclusion, this study is the first to demonstrate the potential involvement of activated TFH-cells in MS. The increased frequencies of Th17-cells, activated TFH- and B-cells parallel findings from pathology studies which, along with the correlation between activated TFH- and B-cells and disease progression, suggest a pathogenic role of systemic inflammation in progressive MS. These observations may have implications for the treatment of progressive MS. PMID:23469245

The effect of control and display lag on unmanned air system internal pilot manual landing performance

NASA Astrophysics Data System (ADS)

Lloyd, Marshall Everett

An important characteristic of UASs is lag because it can become a considerable challenge to successful human-in-the-loop control. As such, UASs are designed and configured to minimize system lag, though this can increase acquisition and operation costs considerably. In an effort to cut costs, an organization may choose to accept greater risk and deploy a UAS with high system lag. Before this risk can be responsibly accepted, it must be quantified. While many studies have examined system lag, very few have been able to quantify the risk that various levels of lag pose to an internally piloted, manually landed UAS. This study attempted to do so by evaluating pilot landing performance in a simulator with 0 ms, 240 ms, and 1000 ms of additional lag. Various measures were used, including a novel coding technique. Results indicated that 1000 ms of lag was unsafe by all measures. They also indicate that 240 ms of lag degrades performance, but participants were able to successfully land the simulated aircraft. This study showed the utility of using several measures to evaluate the effect of lag on landing performance and it helped demonstrate that while 1000 ms poses a high risk, 240 ms of lag may be a much more manageable risk. Future research suggested by this research includes: investigating lag between 240 ms and 1000 ms, introducing different weather phenomena, developing system lag training techniques for operators, and investigating the effect of aides such as predictive displays and autopilot-assisted recovery.

Chemical characterization of Azadirachta indica grafted on Melia azedarach and analyses of azadirachtin by HPLC-MS-MS (SRM) and meliatoxins by MALDI-MS.

PubMed

Forim, Moacir Rossi; Cornélio, Vivian Estevam; da Silva, M Fátima das G F; Rodrigues-Filho, Edson; Fernandes, João B; Vieira, Paulo C; Matinez, Sueli Souza; Napolitano, Michael P; Yost, Richard A

2010-01-01

Melia azedarach adapted to cool climates was selected as rootstocks for vegetative propagation of Azadirachta indica. Cleft grafting of A. indica on M. azedarach rootstock showed excellent survival. Little is known about the chemistry of grafting. The roots, stems, leaves and seeds of this graft were examined in order to verify if grafted A. indica would produce limonoids different from those found in non-grafted plants. Intact matured fruits were also studied to verify if they were free of meliatoxins. After successive chromatographic separations the extracts afforded several limonoids. HPLC-MS/MS and MALDI-MS were used to develop sensitive methods for detecting azadirachtin on all aerial parts of this graft and meliatoxins in fruits, respectively. The stem afforded the limonoid salannin, which was previously found in the oil seeds of A. indica. Salannin is also found in the root bark of M. azedarach. Thus, the finding of salannin in this study suggests that it could have been translocated from the M. azedarach rootstock to the A. indica graft. HPLC-MS/MS analyses showed that azadirachtin was present in all parts of the fruits, stem, flowers and root, but absent in the leaves. The results of MALDI-MS analyses confirmed the absence of meliatoxins in graft fruits. This study showed that A. indica grafted onto M. azedarach rootstock produces azadirachtin, and also that its fruits are free of meliatoxins from rootstocks, confirming that this graft forms an excellent basis for breeding vigorous Neem trees in cooler regions.

Reduced cellularity of bone marrow in multiple sclerosis with decreased MSC expansion potential and premature ageing in vitro.

PubMed

Redondo, Juliana; Sarkar, Pamela; Kemp, Kevin; Virgo, Paul F; Pawade, Joya; Norton, Aimie; Emery, David C; Guttridge, Martin G; Marks, David I; Wilkins, Alastair; Scolding, Neil J; Rice, Claire M

2017-05-01

Autologous bone-marrow-derived cells are currently employed in clinical studies of cell-based therapy in multiple sclerosis (MS) although the bone marrow microenvironment and marrow-derived cells isolated from patients with MS have not been extensively characterised. To examine the bone marrow microenvironment and assess the proliferative potential of multipotent mesenchymal stromal cells (MSCs) in progressive MS. Comparative phenotypic analysis of bone marrow and marrow-derived MSCs isolated from patients with progressive MS and control subjects was undertaken. In MS marrow, there was an interstitial infiltrate of inflammatory cells with lymphoid (predominantly T-cell) nodules although total cellularity was reduced. Controlling for age, MSCs isolated from patients with MS had reduced in vitro expansion potential as determined by population doubling time, colony-forming unit assay, and expression of β-galactosidase. MS MSCs expressed reduced levels of Stro-1 and displayed accelerated shortening of telomere terminal restriction fragments (TRF) in vitro. Our results are consistent with reduced proliferative capacity and ex vivo premature ageing of bone-marrow-derived cells, particularly MSCs, in MS. They have significant implication for MSC-based therapies for MS and suggest that accelerated cellular ageing and senescence may contribute to the pathophysiology of progressive MS. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Funding for this study was provided by the Medical Research Council, UK (grant no. MR/K004166/1). The ACTiMuS study is sup-ported by the Silverman Family Foundation, Multiple Sclerosis Trust, Rosetree’s Trust, Catholic Bishops of England and Wales and Friends of Frenchay and SIAMMS-II by the Sir Halley Stewart Trust. C.M.R., P.S., and K.K. received support from the Burden Neurological Institute.

Evaluation of lithium serum level in multiple sclerosis patients: A neuroprotective element.

PubMed

Karimi, Atieh; Bahrampour, Kobra; Momeni Moghaddam, Mohammad Amin; Asadikaram, Gholamreza; Ebrahimi, Ghasem; Torkzadeh-Mahani, Masoud; Esmaeili Tarzi, Mojdeh; Nematollahi, Mohammad Hadi

2017-10-01

It has been claimed that continuous and high production of nitric oxide (NO) and its metabolites may be involved in the pathogenesis of several neurological disorders such as multiple sclerosis. A number of studies have demonstrated that lithium regulates NO levels in disorders of the central nervous system. The aim of this study was to investigate whether NO as a marker of disease activity is correlated with lithium deficiency in relapsing remitting multiple sclerosis (RR-MS). This case-controlled study comprised 44 patients with RR-MS and 43 healthy subjects matched by age, gender, smoking status, and body mass index. The Griess reaction was used to measure the NO metabolites, nitrite and nitrate in serum. In addition serum lithium levels were measured using atomic absorption spectrometry method. The mean serum NO concentrations in the groups RR-MS and the control were 18.5 ± 3.1µM and 15.5 ± 2.9µM, respectively. Data analysis showed a statistically significant difference between subjects with RR-MS and the control group (p < 0.05). Furthermore, serum lithium concentrations in RR-MS (0.57 ± 0.2) were remarkably lower in RR-MS patients than the controls (2.29 ± 0.7) (p < 0.05). The present findings suggest that lithium deficiency may upregulates NO production in RR-MS. Further studies with larger samples are needed to confirm the effects of lithium treatment on NO pathway and its association with synaptic plasticity in RR-MS patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Population genetics of Enterocytozoon bieneusi in captive giant pandas of China.

PubMed

Li, Wei; Song, Yuan; Zhong, Zhijun; Huang, Xiangming; Wang, Chengdong; Li, Caiwu; Yang, Haidi; Liu, Haifeng; Ren, Zhihua; Lan, Jingchao; Wu, Kongju; Peng, Guangneng

2017-10-18

Most studies on Enterocytozoon bieneusi are conducted based on the internal transcribed spacer (ITS) region of the rRNA gene, whereas some have examined E. bieneusi population structures. Currently, the population genetics of this pathogen in giant panda remains unknown. The objective of this study was to determine the E. bieneusi population in captive giant pandas in China. We examined 69 E. bieneusi-positive specimens from captive giant pandas in China using five loci (ITS, MS1, MS3, MS4 and MS7) to infer E. bieneusi population genetics. For multilocus genotype (MLG) analysis of E. bieneusi-positive isolates, the MS1, MS3, MS4, and MS7 microsatellite and minisatellite loci were amplified and sequenced in 48, 45, 50 and 47 specimens, respectively, generating ten, eight, nine and five types. We successfully amplified 36 specimens and sequenced all five loci, forming 24 MLGs. Multilocus sequence analysis revealed a strong and significant linkage disequilibrium (LD), indicating a clonal population. This result was further supported by measurements of pairwise intergenic LD and a standardized index of association (I S A ) from allelic profile data. The analysis in STRUCTURE suggested three subpopulations in E. bieneusi, further confirmed using right's fixation index (F ST ). Subpopulations 1 and 2 exhibited an epidemic structure, whereas subpopulation 3 had a clonal structure. Our results describe E. bieneusi population genetics in giant pandas for the first time, improving the current understanding E. bieneusi epidemiology in the studied region. These data also benefit future studies exploring potential transmission risks from pandas to other animals, including humans.

Brain activation changes during locomotion in middle-aged to older adults with multiple sclerosis.

PubMed

Hernandez, Manuel E; Holtzer, Roee; Chaparro, Gioella; Jean, Kharine; Balto, Julia M; Sandroff, Brian M; Izzetoglu, Meltem; Motl, Robert W

2016-11-15

Mobility and cognitive impairments are common in persons with multiple sclerosis (MS), and are expected to worsen with increasing age. However, no studies, to date, in part due to limitations of conventional neuroimaging methods, have examined changes in brain activation patterns during active locomotion in older patients with MS. This study used functional Near Infrared Spectroscopy (fNIRS) to evaluate real-time neural activation differences in the pre-frontal cortex (PFC) between middle-aged to older adults with MS and healthy controls during single (Normal Walk; NW) and dual-task (Walking While Talking; WWT) locomotion tasks. Eight middle-aged to older adults with MS and eight healthy controls underwent fNIRS recording while performing the NW and WWT tasks with an fNIRS cap consisting of 16 optodes positioned over the forehead. The MS group had greater elevations in PFC oxygenation levels during WWT compared to NW than healthy controls. There was no walking performance difference between groups during locomotion. These findings suggest that middle-aged to older individuals with MS might be able to achieve similar levels of performance through the use of increased brain activation. This study is the first to investigate brain activation changes during the performance of simple and divided-attention locomotion tasks in MS using fNIRS. Copyright © 2016 Elsevier B.V. All rights reserved.

Health-Related Coping and Social Interaction in People with Multiple Sclerosis Supported by a Social Network: Pilot Study With a New Methodological Approach

PubMed Central

De Stefano, Manuela; Lanzillo, Roberta; Esposito, Sabrina; Moshtari, Fatemeh; Rullani, Francesco; Piscopo, Kyrie; Buonanno, Daniela; Brescia Morra, Vincenzo; Gallo, Antonio; Tedeschi, Gioacchino; Bonavita, Simona

2017-01-01

Background Social media are a vital link for people with health concerns who find in Web communities a valid and comforting source for information exchange, debate, and knowledge enrichment. This aspect is important for people affected by chronic diseases like multiple sclerosis (MS), who are very well informed about the disease but are vulnerable to hopes of being cured or saved by therapies whose efficacy is not always scientifically proven. To improve health-related coping and social interaction for people with MS, we created an MS social network (SMsocialnetwork.com) with a medical team constantly online to intervene promptly when false or inappropriate medical information are shared. Objective The goal of this study was to assess the impact of SMsocialnetwork.com on the health-related coping and social interaction of people with MS by analyzing areas of interest through a Web-based survey. Methods Referring to previous marketing studies analyzing the online platform’s role in targeted health care, we conducted a 39-item Web-based survey. We then performed a construct validation procedure using a factorial analysis, gathering together like items of the survey related to different areas of interest such as utility, proximity, sharing, interaction, solving uncertainty, suggestion attitude, and exploration. Results We collected 130 Web-based surveys. The areas of interest analysis demonstrated that the users positively evaluated SMsocialnetwork.com to obtain information, approach and solve problems, and to make decisions (utility: median 4.2); improve feeling of closeness (proximity: median 5); catalyze relationships and text general personal opinions (sharing: median 5.6); get in touch with other users to receive innovative, effective, and practical solutions (interaction, solving uncertainty, and suggestion attitude medians were respectively: 4.1, 3, and 3); and share information about innovative therapeutic approaches and treatment options (suggestion attitude: median: 3.3). Conclusions SMsocialnetwork.com was perceived by users to be a useful tool to support health-related coping and social interaction, and may suggest a new kind of therapeutic alliance between physicians and people with MS. PMID:28710056

Decreased IL-10 production mediated by Toll-like receptor 9 in B cells in multiple sclerosis.

PubMed

Hirotani, Makoto; Niino, Masaaki; Fukazawa, Toshiyuki; Kikuchi, Seiji; Yabe, Ichiro; Hamada, Shinsuke; Tajima, Yasutaka; Sasaki, Hidenao

2010-04-15

The complexity of the roles of Toll-like receptors (TLRs) is attributable to their ability to promote or suppress autoimmune diseases. Recent studies have demonstrated that B cells regulate autoimmune diseases, including multiple sclerosis (MS), by producing interleukin (IL)-10. By using CpG DNA as a TLR9 agonist, we investigated the immunoregulatory functions of B cell via TLR9 in MS. Our results indicate that TLR9-mediated IL-10 production by B cells was significantly decreased in MS, and this decrease is likely due to decreased TLR9 expression in memory B cells, suggesting a role of TLR9 in immunoregulation in MS. Copyright 2010 Elsevier B.V. All rights reserved.

[Increased risk of relapse in multiple sclerosis patients after ovarian stimulation for in vitro fertilization].

PubMed

Laplaud, D-A; Lefrère, F; Leray, E; Barrière, P; Wiertlewski, S

2007-10-01

In this preliminary study we analysed the impact of ovarian stimulations and the different protocols used for in vitro fertilizations (IVF) on the clinical activity of multiple sclerosis (MS). By matching the databases on MS and IVF of the past 10 years at the university hospital of Nantes, six patients have been found and, for five of them MS relapse rate seemed to be increased in the three-month period following IVF as compared to the previous three months and to two other control periods of three months (P<0.05, Friedman test). The increased relapse rate mainly concerned patients treated by GnRH agonists but not the patients treated by GnRH antagonists. This preliminary work suggests a possible impact of the treatments used for IVF on MS relapse rate. Further studies are now underway to validate these results on a larger scale, by including all cases reported in France.

Digital memory encoding in Chinese dyscalculia: An event-related potential study.

PubMed

Wang, Enguo; Qin, Shutao; Chang, MengYan; Zhu, Xiangru

2014-10-22

This study reports the neurophysiological and behavioral correlates of digital memory encoding features in Chinese individuals with and without dyscalculia. Eighteen children with dyscalculia (ages 11.5-13.5) and 18 matched controls were tested, and their event-related potentials (ERPs) were digitally recorded simultaneously with behavioral measures. The results showed that both groups had a significant Dm effect, and this effect was greater in the control group. In the 300-400-ms, 400-500-ms, and 600-700-ms processing stages, both groups showed significant differences of digital memory encoding in the frontal, central, and parietal regions. In the 500-600-ms period, the Dm effect in the control group was significantly greater than that in the dyscalculia group only in the parietal region. These results suggest that individuals with dyscalculia exhibit impaired digital memory encoding and deficits in psychological resource allocation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Time-course of attention for threatening pictures in high and low trait anxiety.

PubMed

Koster, Ernst H W; Verschuere, Bruno; Crombez, Geert; Van Damme, Stefaan

2005-08-01

Cognitive studies about anxiety suggest that the interplay between automatic and strategic biases in attention to threat is related to the persistence of fear. In the present study, the time-course of attention to pictures with varying threat levels was investigated in high trait anxious (HTA, n=21) and low trait anxious (LTA, n=22) students. In a visual probe detection task, high and mild threat pictures were presented at three durations: 100, 500, and 1250 ms. Results indicated that all individuals attended to the high threat pictures for the 100 ms condition. Differential responding between HTA and LTA individuals was found for the 500 ms condition: only HTA individuals showed an attentional bias for mild threatening stimuli. For the 1250 ms condition, the HTA individuals attended away from high and mild threat pictures. The observed pattern of differential attention to threatening pictures may explain the persistence of fear in HTA individuals.

Chromatographic separation of piracetam and its metabolite in a mixture of microsomal preparations, followed by an MS/MS analysis.

PubMed

Sahu, Kapendra; Siddiqui, Anees A; Shaharyar, Mohammad; Ahmad, Niyaz; Anwar, Mohammad; Ahmad, Farhan J

2013-07-01

A rapid bioanalytical method was evaluated for the simultaneous determination of piracetam and its metabolite (M1) in human microsomal preparations by fast ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS). In addition, a validated method of M1 in rat plasma was developed and successfully applied on pharmacokinetic studies. The present study was carried out to determine the metabolic pathways of piracetam for phase I metabolism and used cytochrome P450 isoforms responsible for the piracetam metabolism in human liver microsomes (HLMs). While additional potential metabolites of piracetam were suggested by computer-modeling. The resulting 2-(2-oxopyrrolidin-1-yl) acetic acid was the sole metabolite detected after the microsomal treatment. The amide hydrolysis mainly underwent to form a metabolite i.e., 2-(2-oxopyrrolidin-1-yl) acetic acid (M1). Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Quantification of chemical elements in blood of patients affected by multiple sclerosis.

PubMed

Forte, Giovanni; Visconti, Andrea; Santucci, Simone; Ghazaryan, Anna; Figà-Talamanca, Lorenzo; Cannoni, Stefania; Bocca, Beatrice; Pino, Anna; Violante, Nicola; Alimonti, Alessandro; Salvetti, Marco; Ristori, Giovanni

2005-01-01

Although some studies suggested a link between exposure to trace elements and development of multiple sclerosis (MS), clear information on their role in the aetiology of MS is still lacking. In this study the concentrations of Al, Ba, Be, Bi, Ca, Cd, Co, Cr, Cu, Fe, Hg, Li, Mg, Mn, Mo, Ni, Pb, Sb, Si, Sn, Sr, Tl, V, W, Zn and Zr were determined in the blood of 60 patients with MS and 60 controls. Quantifications were performed by inductively coupled plasma (ICP) atomic emission spectrometry and sector field ICP mass spectrometry. When the two groups were compared, an increased level of Co, Cu and Ni and a decrement of Be, Fe, Hg, Mg, Mo, Pb and Zn in blood of patients were observed. In addition, the discriminant analysis pointed out that Cu, Be, Hg, Co and Mo were able to discriminate between MS patients and controls (92.5% of cases correctly classified).

Trace element analysis of rough diamond by LA-ICP-MS: a case of source discrimination?

PubMed

Dalpé, Claude; Hudon, Pierre; Ballantyne, David J; Williams, Darrell; Marcotte, Denis

2010-11-01

Current profiling of rough diamond source is performed using different physical and/or morphological techniques that require strong knowledge and experience in the field. More recently, chemical impurities have been used to discriminate diamond source and with the advance of laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) empirical profiling of rough diamonds is possible to some extent. In this study, we present a LA-ICP-MS methodology that we developed for analyzing ultra-trace element impurities in rough diamond for origin determination ("profiling"). Diamonds from two sources were analyzed by LA-ICP-MS and were statistically classified by accepted methods. For the two diamond populations analyzed in this study, binomial logistic regression produced a better overall correct classification than linear discriminant analysis. The results suggest that an anticipated matrix match reference material would improve the robustness of our methodology for forensic applications. © 2010 American Academy of Forensic Sciences.

Using channelized Hotelling observers to quantify temporal effects of medical liquid crystal displays on detection performance

NASA Astrophysics Data System (ADS)

Platiša, Ljiljana; Goossens, Bart; Vansteenkiste, Ewout; Badano, Aldo; Philips, Wilfried

2010-02-01

Clinical practice is rapidly moving in the direction of volumetric imaging. Often, radiologists interpret these images in liquid crystal displays at browsing rates of 30 frames per second or higher. However, recent studies suggest that the slow response of the display can compromise image quality. In order to quantify the temporal effect of medical displays on detection performance, we investigate two designs of a multi-slice channelized Hotelling observer (msCHO) model in the task of detecting a single-slice signal in multi-slice simulated images. The design of msCHO models is inspired by simplifying assumptions about how humans observe while viewing in the stack-browsing mode. For comparison, we consider a standard CHO applied only on the slice where the signal is located, recently used in a similar study. We refer to it as a single-slice CHO (ssCHO). Overall, our results confirm previous findings that the slow response of displays degrades the detection performance of the observers. More specifically, the observed performance range of msCHO designs is higher compared to the ssCHO suggesting that the extent and rate of degradation, though significant, may be less drastic than previously estimated by the ssCHO. Especially, the difference between msCHO and ssCHO is more significant for higher browsing speeds than for slow image sequences or static images. This, together with their design criteria driven by the assumptions about humans, makes the msCHO models promising candidates for further studies aimed at building anthropomorphic observer models for the stack-mode image presentation.

Magnetic Susceptibility Measurements as a Proxy for Hydrocarbon Biodegradation

NASA Astrophysics Data System (ADS)

Mewafy, F.; Atekwana, E. A.; Slater, L. D.; Werkema, D.; Revil, A.; Ntarlagiannis, D.; Skold, M.

2011-12-01

Magnetic susceptibility (MS) measurements have been commonly used in paleoclimate studies, as a proxy for environmental pollution such as heavy metal contamination, and for delineating zones of oil seeps related to hydrocarbon exploration. Few studies have assessed the use of MS measurements for mapping zones of oil pollution. In this study, we investigated the variation in magnetic susceptibility across a hydrocarbon contaminated site undergoing biodegradation. Our objective was to investigate if MS measurements could be used as a proxy indicator of intrinsic bioremediation linked to the activity of iron reducing bacteria. An improved understanding of the mechanisms generating geophysical signatures associated with microbial enzymatic activity could permit the development of geophysical imaging technologies for long-term, minimally invasive and sustainable monitoring of natural biodegradation at oil spill sites. We used a Bartington MS probe to measure MS data along fifteen boreholes within contaminated (both free phase and dissolved phase hydrocarbon plumes) and clean areas. Our results show the following: (1) an enhanced zone of MS straddling the water table at the contaminated locations, not observed at the clean locations; (2) MS values within the free product plume are higher compared to values within the dissolved product plume; (3) the MS values within the vadoze zone above the free product plume are higher compared to values within the dissolved product plume; 4) the zone of high MS is thicker within the free product plume compared to the dissolved product plume. We suggest that the zone of enhanced MS results from the precipitation of magnetite related to the oxidation of the hydrocarbons coupled to iron reduction. Our data documents a strong correlation between MS and hydrocarbon concentration. We conclude that recognition of these zones of enhanced magnetite formation allows for the application of MS measurements as a: (1) low cost, rapid monitoring tool for assessing the extent of hydrocarbon contamination and (2) proxy for the presence of intrinsic bioremediation due to the activity of iron reducing bacteria.

Correlation of Serum and Salivary Cytokines Level With Clinical Parameters in Metabolic Syndrome With Periodontitis.

PubMed

Chauhan, Abhishek; Yadav, Suraj Singh; Dwivedi, Pradeep; Lal, Nand; Usman, Kauser; Khattri, Sanjay

2016-09-01

Metabolic Syndrome (MS) and chronic oral condition (periodontitis [PD]) are state of inflammation. The study was conducted to determine alterations in serum and salivary cytokines level in MS and/or chronic PD in the North Indian population. This cross-sectional study carried out in northern part of India. The study subjects of similar ethnicity were recruited according to International Diabetes Federation (IDF) criteria for MS, while chronic PD was diagnosed on the basis of packet depth and clinical attachment level. ELISA method was employed to assess cytokine level. All subjects were divided in four groups Gr A (MS + PD), B (MS), C (PD), and a control Gr D. The serum and salivary tumor necrosis factor alpha (TNF-α) level in Gr A, B, and C was significantly higher than Gr D (P < 0.05). Serum interleukin-10 (IL-10) level in Gr A, B, and C was lower than Gr D (P < 0.05), but this difference was not significant between Gr C and Gr D. Serum IL-10 level in Gr A was significantly lower than Gr C (P < 0.05). Salivary IL-10 level was not significantly altered in any group. Proinflammatory marker TNF-α has correlation with clinical parameters in patients of MS having PD. The study suggests level of salivary TNF-α may be utilized as a surrogate marker of MS and PD. © 2016 Wiley Periodicals, Inc.

Measurement of hydrogen sulfide from oil and natural gas production in the Uintah Basin, Utah using PTR-MS

NASA Astrophysics Data System (ADS)

Li, R.; Warneke, C.; Graus, M.; Field, R. A.; Veres, P. R.; Geiger, F.; Soltis, J.; Li, S.; Murphy, S. M.; De Gouw, J. A.

2013-12-01

Natural gas production is associated with emissions of a variety of toxic trace gases. While volatile organic compounds (VOCs) have received considerable attention, H2S is also of concern due to the known health impacts of exposure to this hazardous air pollutant. Here, we present quantitative, fast time-response measurements of hydrogen sulfide (H2S) using Proton-Transfer-Reaction Mass-Spectrometry (PTR-MS) instruments. The PTR-MS was operated for measurements of VOCs including H2S at the Horsepool ground site in the Uintah Basin during the Uintah Basin Winter Ozone Study (UBWOS) 2013 campaign. Measurements of H2S from a mobile laboratory in the gas and oil fields were also made by Ultra-Light-Weight PTR-MS (ULW-PTR-MS) during UBWOS 2012. The H2S measurement by PTR-MS is strongly humidity dependent. We compare the humidity dependence determined in the laboratory with in-field calibrations of H2S and determine the H2S mixing ratios for the mobile and ground measurements. The PTR-MS measurements at Horsepool are compared with simultaneous H2S measurements using a Proton-Transfer-Reaction Time-of-Flight (PTR-ToF) and an H2S/CH4 Picarro instrument. The H2S measurements by PTR-MS agree with both instruments within 30% uncertainties. The combination of the two campaigns (UBWOS 2012 & 2013) has shown that on average 1 - 2 ppbv of H2S is present in the Uintah Basin. The correlation between H2S and methane suggests that the source of H2S is associated with the oil and gas extraction in the basin. Significant H2S emissions with mixing ratios of up to 3 ppmv from storage tanks and wells were observed during the mobile lab measurements. This study suggests that H2S emissions associated with oil and gas production can lead to short-term high levels close to point sources, and elevated background levels away from those sources. Our work has also shown that PTR-MS can make reliable measurements of H2S at levels below 1 ppbv.

Meta-Analysis of Multiple Sclerosis Microarray Data Reveals Dysregulation in RNA Splicing Regulatory Genes.

PubMed

Paraboschi, Elvezia Maria; Cardamone, Giulia; Rimoldi, Valeria; Gemmati, Donato; Spreafico, Marta; Duga, Stefano; Soldà, Giulia; Asselta, Rosanna

2015-09-30

Abnormalities in RNA metabolism and alternative splicing (AS) are emerging as important players in complex disease phenotypes. In particular, accumulating evidence suggests the existence of pathogenic links between multiple sclerosis (MS) and altered AS, including functional studies showing that an imbalance in alternatively-spliced isoforms may contribute to disease etiology. Here, we tested whether the altered expression of AS-related genes represents a MS-specific signature. A comprehensive comparative analysis of gene expression profiles of publicly-available microarray datasets (190 MS cases, 182 controls), followed by gene-ontology enrichment analysis, highlighted a significant enrichment for differentially-expressed genes involved in RNA metabolism/AS. In detail, a total of 17 genes were found to be differentially expressed in MS in multiple datasets, with CELF1 being dysregulated in five out of seven studies. We confirmed CELF1 downregulation in MS (p=0.0015) by real-time RT-PCRs on RNA extracted from blood cells of 30 cases and 30 controls. As a proof of concept, we experimentally verified the unbalance in alternatively-spliced isoforms in MS of the NFAT5 gene, a putative CELF1 target. In conclusion, for the first time we provide evidence of a consistent dysregulation of splicing-related genes in MS and we discuss its possible implications in modulating specific AS events in MS susceptibility genes.

Effects of attention bias modification with short and long stimulus-duration: A randomized experiment with individuals with subclinical social anxiety.

PubMed

Liang, Chi-Wen; Hsu, Wen-Yau

2016-06-30

This study investigated the differential effects of two attention bias modification (ABM) with different stimulus durations. Seventy-two undergraduates with subclinical social anxiety were randomly assigned to one of four conditions: an ABM condition with either a 100-ms or a 500-ms stimulus duration (ABM-100/ ABM-500) or an attention placebo (AP) condition with either a 100-ms or a 500-ms stimulus duration (AP-100/ AP-500). Participants completed the pre-assessments, eight attentional training sessions, and post-assessments. A modified Posner paradigm was used to assess changes in attentional processing. After completion of attentional training, the ABM-100 group significantly speeded up their responses to 100-ms invalid trials, regardless of the word type. The ABM-100 group also exhibited significant reduced latencies to 500-ms invalid social threat trials and a marginally significant reduced latencies to 500-ms invalid neutral trials. The ABM-500 group showed significant reduced latencies to 500-ms invalid social threat trials. Both ABMs significantly reduced participants' fear of negative evaluations and interactional anxiousness relative to their comparative AP. The effects on social anxiety did not differ between the two ABMs. This study suggests that although both ABMs using short and long stimulus durations reduce some aspects of social anxiety, they influence participants' attentional disengagement in different ways. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Vertebral hemangiomas in the thoracic spine of multiple sclerosis patients are connected with fewer demyelinating lesions at the same level. Possible impact on pathophysiology and clinical course.

PubMed

Anagnostouli, Maria; Katsavos, Serafeim; Kyrozis, Andreas; Gontika, Maria; Voumvourakis, Konstantinos I; Kapaki, Elisabeth

2016-08-01

Mechanisms of angiogenesis regulate multiple sclerosis (MS) lesions' evolution, displaying both neuroprotective and harmful effects. Factors traditionally considered as purely angiogenic, like vascular endothelial growth factor (VEGF), exert complex heterogenous actions on both neural and vascular malformation-derived tissues. Aim of this retrospective study was to examine, for the first time, potential associations between the presence of common vascular malformations, like vertebral hemangiomas (VHs), and several clinico-radiological MS parameters. 236 MS patients who were followed in our Outpatient Clinic were recruited in this study. Outcome measures concerned demographics, disease-derived variables, and MS-lesions' distribution in VHs - positive and negative patients. All data were collected retrospectively. Potential correlations were assessed with univariate statistical analyses (p = 0.05), followed by multivariate regression models, for purposes of confounder-effects elimination. VH presence showed significant negative correlations with presence of MS lesions in the thoracic (p = 0.005 for thoracic VHs), but not the cervical cord. Trends towards negative associations of VH presence with subtentorial MS lesions and positive family history for MS were also observed. Our observations suggest that VH presence may reduce the risk of thoracic demyelinating lesions in MS patients. They could be explained as part of a multifaceted angiogenic process, concomitantly enhancing neural repair and abnormal hemangioma vascularization.

Indentification and Analysis of Occludin Phosphosites: A Combined Mass Spectroscoy and Bioinformatics Approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sundstrom, J.; Tash, B; Murakami, T

2009-01-01

The molecular function of occludin, an integral membrane component of tight junctions, remains unclear. VEGF-induced phosphorylation sites were mapped on occludin by combining MS data analysis with bioinformatics. In vivo phosphorylation of Ser490 was validated and protein interaction studies combined with crystal structure analysis suggest that Ser490 phosphorylation attenuates the interaction between occludin and ZO-1. This study demonstrates that combining MS data and bioinformatics can successfully identify novel phosphorylation sites from limiting samples.

Effects of a pulsed electromagnetic therapy on multiple sclerosis fatigue and quality of life: a double-blind, placebo controlled trial.

PubMed

Lappin, Martha S; Lawrie, Fraser Wilson; Richards, Todd L; Kramer, Eric D

2003-01-01

There is a growing literature on the biological and clinical effects of pulsed electromagnetic fields. Some studies suggest that electromagnetic therapies may be useful in the treatment of chronic illnesses. This study is a follow-up to a placebo controlled pilot study in which multiple sclerosis (MS) patients exposed to weak, extremely low frequency pulsed electromagnetic fields showed significant improvements on a composite symptom measure. To evaluate the effects of a pulsed electromagnetic therapy on MS related fatigue, spasticity, bladder control, and overall quality of life. A multi-site, double-blind, placebo controlled, crossover trial. Each subject received 4 weeks of the active and placebo treatments separated by a 2-week washout period. The University of Washington Medical Center in Seattle Wash, the Neurology Center of Fairfax in Fairfax, Va, and the headquarters of the Multiple Sclerosis Association of America in Cherry Hill, NJ. 117 patients with clinically definite MS. Daily exposure to a small, portable pulsing electromagnetic field generator. The MS Quality of Life Inventory (MSQLI) was used to assess changes in fatigue, bladder control, spasticity, and a quality of life composite. Paired t-tests were used to assess treatment differences in the 117 subjects (81% of the initial sample) who completed both treatment sessions. Improvements in fatigue and overall quality of life were significantly greater on the active device. There were no treatment effects for bladder control and a disability composite, and mixed results for spasticity. Evidence from this randomized, double-bind, placebo controlled trial is consistent with results from smaller studies suggesting that exposure to pulsing, weak electromagnetic fields can alleviate symptoms of MS. The clinical effects were small, however, and need to be replicated. Additional research is also needed to examine the possibility that ambulatory patients and patients taking interferons for their MS may be most responsive to this kind of treatment.

Decision-Making in Multiple Sclerosis Patients: A Systematic Review

PubMed Central

2018-01-01

Background Multiple sclerosis (MS) is frequently associated with cognitive and behavioural deficits. A growing number of studies suggest an impact of MS on decision-making abilities. The aim of this systematic review was to assess if (1) performance of MS patients in decision-making tasks was consistently different from controls and (2) whether this modification was associated with cognitive dysfunction and emotional alterations. Methods The search was conducted on Pubmed/Medline database. 12 studies evaluating the difference between MS patients and healthy controls using validated decision-making tasks were included. Outcomes considered were quantitative (net scores) and qualitative measurements (deliberation time and learning from feedback). Results Quantitative and qualitative decision-making impairment in MS was present in 64.7% of measurements. Patients were equally impaired in tasks for decision-making under risk and ambiguity. A correlation to other cognitive functions was present in 50% of cases, with the highest associations in the domains of processing speed and attentional capacity. Conclusions In MS patients, qualitative and quantitative modifications may be present in any kind of decision-making task and can appear independently of other cognitive measures. Since decision-making abilities have a significant impact on everyday life, this cognitive aspect has an influential importance in various MS-related treatment settings. PMID:29721338

Mildly disabled persons with multiple sclerosis use similar net joint power strategies as healthy controls when walking speed increases.

PubMed

Brincks, John; Christensen, Lars Ejsing; Rehnquist, Mette Voigt; Petersen, Jesper; Sørensen, Henrik; Dalgas, Ulrik

2018-01-01

To improve walking in persons with multiple sclerosis (MS), it is essential to understand the underlying mechanisms of walking. This study examined strategies in net joint power generated or absorbed by hip flexors, hip extensors, hip abductors, knee extensors, and plantar flexors in mildly disabled persons with MS and healthy controls at different walking speeds. Thirteen persons with MS and thirteen healthy controls participated and peak net joint power was calculated using 3D motion analysis. In general, no differences were found between speed-matched healthy controls and persons with MS, but the fastest walking speed was significantly higher in healthy controls (2.42 m/s vs. 1.70 m/s). The net joint power increased in hip flexors, hip extensors, hip abductors, knee extensors and plantar flexors in both groups, when walking speed increased. Significant correlations between changes in walking speed and changes in net joint power of plantar flexors, hip extensors and hip flexors existed in healthy controls and persons with MS, and in net knee extensor absorption power of persons with MS only. In contrast to previous studies, these findings suggest that mildly disabled persons with MS used similar kinetic strategies as healthy controls to increase walking speed.

Discriminating male and female voices: differentiating pitch and gender.

PubMed

Latinus, Marianne; Taylor, Margot J

2012-04-01

Gender is salient, socially critical information obtained from faces and voices, yet the brain processes underlying gender discrimination have not been well studied. We investigated neural correlates of gender processing of voices in two ERP studies. In the first, ERP differences were seen between female and male voices starting at 87 ms, in both spatial-temporal and peak analyses, particularly the fronto-central N1 and P2. As pitch differences may drive gender differences, the second study used normal, high- and low-pitch voices. The results of these studies suggested that differences in pitch produced early effects (27-63 ms). Gender effects were seen on N1 (120 ms) with implicit pitch processing (study 1), but were not seen with manipulations of pitch (study 2), demonstrating that N1 was modulated by attention. P2 (between 170 and 230 ms) discriminated male from female voices, independent of pitch. Thus, these data show that there are two stages in voice gender processing; a very early pitch or frequency discrimination and a later more accurate determination of gender at the P2 latency.

Increased Circulating Levels of Vitamin D Binding Protein in MS Patients

PubMed Central

Rinaldi, Arturo Ottavio; Sanseverino, Isabella; Purificato, Cristina; Cortese, Antonio; Mechelli, Rosella; Francisci, Silvia; Salvetti, Marco; Millefiorini, Enrico; Gessani, Sandra; Gauzzi, Maria Cristina

2015-01-01

Vitamin D (vitD) low status is currently considered a main environmental factor in multiple sclerosis (MS) etiology and pathogenesis. VitD and its metabolites are highly hydrophobic and circulate mostly bound to the vitamin D binding protein (DBP) and with lower affinity to albumin, while less than 1% are in a free form. The aim of this study was to investigate whether the circulating levels of either of the two vitD plasma carriers and/or their relationship are altered in MS. We measured DBP and albumin plasma levels in 28 MS patients and 24 healthy controls. MS patients were found to have higher DBP levels than healthy subjects. Concomitant interferon beta therapy did not influence DBP concentration, and the difference with the control group was significant in both females and males. No significant correlation between DBP and albumin levels was observed either in healthy controls or in patients. These observations suggest the involvement of DBP in the patho-physiology of MS. PMID:25590278

Potential Health Benefits and Metabolomics of Camel Milk by GC-MS and ICP-MS.

PubMed

Ahamad, Syed Rizwan; Raish, Mohammad; Ahmad, Ajaz; Shakeel, Faiyaz

2017-02-01

None of the research reports reveals the metabolomics and elemental studies on camel milk. Recent studies showed that camel milk possesses anticancer and anti-inflammatory activity. Metabolomics and elemental studies were carried out in camel milk which showed us the pathways and composition that are responsible for the key biological role of camel milk. Camel milk was dissolved in methanol and chloroform fraction and then vortexed and centrifuged. Both the fractions were derivatized by N,O-bis-(trimethylsilyl)trifluoroacetamide (BSTFA) and TMCS after nitrogen purging and analyzed by GC-MS. Camel milk was also analyzed by ICP-MS after microwave digestion. We found that higher alkanes and fatty acids are present in the chloroform fraction and amino acids, sugars and fatty acid derivatives are present in aqueous fractions. All the heavy metals like As, Pb, Cd, Co, Cu, and Ni were in the safe limits in terms of maximum daily intake of these elements. Na, K, Mg, and Ca were also present in the safe limits in terms of maximum daily intake of these elements. These results suggested that the camel milk drinking is safe and there is no health hazard. The present data of GC-MS and ICP-MS correlate the activities related to camel milk.

Cancer risk among patients with multiple sclerosis: A cohort study in Isfahan, Iran

PubMed Central

Etemadifar, Masoud; Jahanbani-Ardakani, Hamidreza; Ghaffari, Sara; Fereidan-Esfahani, Maboobeh; Changaei, Hossein; Aghadoost, Nazila; Jahanbani Ardakani, Ameneh; Moradkhani, Negin

2017-01-01

Background: Multiple sclerosis (MS), a central nervous system (CNS) autoimmune disorder, affects 2.3 million people around the world. Cancer kills around 7.5 million people annually. Both diseases have similar risks and intertwining molecular causes. Most studies focusing on MS and cancer have found an insignificant difference or reduction in the amount of cancer found in the MS community. Methods: We performed a cohort study using data from Isfahan Multiple Sclerosis Society (IMSS) and Isfahan cancer society and followed-up for 8 years on average (2006-2014). All of the 1718 MS patients were diagnosed according to McDonald’s criteria, then standardized incidence ratio and the numbers of expected cancer case were calculated. Results: While patients had an insignificant change in cancer prevalence, men had fewer cancer cases and women showed an increased prevalence of cancer. Certain types of cancer proved statistically significant. Breast cancer, nervous system cancers, and lymphoma were elevated in the cohort. Conclusion: Our results support the hypothesis that MS significantly affects certain cancers in a protective or associative manner. All cancer rates, except breast cancer, cancers located in the nervous system, and lymphomas were reduced in cohort, suggesting that unregulated immune function may provide protective effects to MS patients against cancer. PMID:28932368

Comparing depression screening tools in persons with multiple sclerosis (MS).

PubMed

Hanna, Joshua; Santo, Jonathan B; Blair, Mervin; Smolewska, Kathy; Warriner, Erin; Morrow, Sarah A

2017-02-01

Depression is more common among persons with multiple sclerosis (MS) than the general population. Depression in MS is associated with reduced quality of life, transition to unemployment, and cognitive impairment. Two proposed screening measures for depression in MS populations are the Hospital Anxiety and Depression Scale (HADS) and the Beck Depression Inventory-Fast Screen (BDI-FS). Our objective was to compared the associations of the BDI-FS and the HADS-D scores with history of depressive symptoms, fatigue, and functional outcomes to determine the differential clinical utility of these screening measures among persons with MS. We reviewed charts of 133 persons with MS for demographic information; scores on the HADS, BDI-FS, a fatigue measure, and a processing speed measure; and employment status. Structural equation modeling results indicated the HADS-D predicted employment status, disability status, and processing speed more effectively than did the BDI-FS, whereas both measures predicted fatigue. This study suggests the HADS-D is more effective than the BDI-FS in predicting functional outcomes known to be associated with depression among persons with MS. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Exhaled Breath Markers for Nonimaging and Noninvasive Measures for Detection of Multiple Sclerosis.

PubMed

Broza, Yoav Y; Har-Shai, Lior; Jeries, Raneen; Cancilla, John C; Glass-Marmor, Lea; Lejbkowicz, Izabella; Torrecilla, José S; Yao, Xuelin; Feng, Xinliang; Narita, Akimitsu; Müllen, Klaus; Miller, Ariel; Haick, Hossam

2017-11-15

Multiple sclerosis (MS) is the most common chronic neurological disease affecting young adults. MS diagnosis is based on clinical characteristics and confirmed by examination of the cerebrospinal fluids (CSF) or by magnetic resonance imaging (MRI) of the brain or spinal cord or both. However, neither of the current diagnostic procedures are adequate as a routine tool to determine disease state. Thus, diagnostic biomarkers are needed. In the current study, a novel approach that could meet these expectations is presented. The approach is based on noninvasive analysis of volatile organic compounds (VOCs) in breath. Exhaled breath was collected from 204 participants, 146 MS and 58 healthy control individuals. Analysis was performed by gas-chromatography mass-spectrometry (GC-MS) and nanomaterial-based sensor array. Predictive models were derived from the sensors, using artificial neural networks (ANNs). GC-MS analysis revealed significant differences in VOC abundance between MS patients and controls. Sensor data analysis on training sets was able to discriminate in binary comparisons between MS patients and controls with accuracies up to 90%. Blinded sets showed 95% positive predictive value (PPV) between MS-remission and control, 100% sensitivity with 100% negative predictive value (NPV) between MS not-treated (NT) and control, and 86% NPV between relapse and control. Possible links between VOC biomarkers and the MS pathogenesis were established. Preliminary results suggest the applicability of a new nanotechnology-based method for MS diagnostics.

Evaluation of Hydrodynamic Chromatography Coupled with UV-Visible, Fluorescence and Inductively Coupled Plasma Mass Spectrometry Detectors for Sizing and Quantifying Colloids in Environmental Media

PubMed Central

Philippe, Allan; Schaumann, Gabriele E.

2014-01-01

In this study, we evaluated hydrodynamic chromatography (HDC) coupled with inductively coupled plasma mass spectrometry (ICP-MS) for the analysis of nanoparticles in environmental samples. Using two commercially available columns (Polymer Labs-PDSA type 1 and 2), a set of well characterised calibrants and a new external time marking method, we showed that flow rate and eluent composition have few influence on the size resolution and, therefore, can be adapted to the sample particularity. Monitoring the agglomeration of polystyrene nanoparticles over time succeeded without observable disagglomeration suggesting that even weak agglomerates can be measured using HDC. Simultaneous determination of gold colloid concentration and size using ICP-MS detection was validated for elemental concentrations in the ppb range. HDC-ICP-MS was successfully applied to samples containing a high organic and ionic background. Indeed, online combination of UV-visible, fluorescence and ICP-MS detectors allowed distinguishing between organic molecules and inorganic colloids during the analysis of Ag nanoparticles in synthetic surface waters and TiO2 and ZnO nanoparticles in commercial sunscreens. Taken together, our results demonstrate that HDC-ICP-MS is a flexible, sensitive and reliable method to measure the size and the concentration of inorganic colloids in complex media and suggest that there may be a promising future for the application of HDC in environmental science. Nonetheless the rigorous measurements of agglomerates and of matrices containing natural colloids still need to be studied in detail. PMID:24587393

Evaluation of hydrodynamic chromatography coupled with UV-visible, fluorescence and inductively coupled plasma mass spectrometry detectors for sizing and quantifying colloids in environmental media.

PubMed

Philippe, Allan; Schaumann, Gabriele E

2014-01-01

In this study, we evaluated hydrodynamic chromatography (HDC) coupled with inductively coupled plasma mass spectrometry (ICP-MS) for the analysis of nanoparticles in environmental samples. Using two commercially available columns (Polymer Labs-PDSA type 1 and 2), a set of well characterised calibrants and a new external time marking method, we showed that flow rate and eluent composition have few influence on the size resolution and, therefore, can be adapted to the sample particularity. Monitoring the agglomeration of polystyrene nanoparticles over time succeeded without observable disagglomeration suggesting that even weak agglomerates can be measured using HDC. Simultaneous determination of gold colloid concentration and size using ICP-MS detection was validated for elemental concentrations in the ppb range. HDC-ICP-MS was successfully applied to samples containing a high organic and ionic background. Indeed, online combination of UV-visible, fluorescence and ICP-MS detectors allowed distinguishing between organic molecules and inorganic colloids during the analysis of Ag nanoparticles in synthetic surface waters and TiO₂ and ZnO nanoparticles in commercial sunscreens. Taken together, our results demonstrate that HDC-ICP-MS is a flexible, sensitive and reliable method to measure the size and the concentration of inorganic colloids in complex media and suggest that there may be a promising future for the application of HDC in environmental science. Nonetheless the rigorous measurements of agglomerates and of matrices containing natural colloids still need to be studied in detail.

The pupil as an indicator of unconscious memory: Introducing the pupil priming effect.

PubMed

Gomes, Carlos Alexandre; Montaldi, Daniela; Mayes, Andrew

2015-06-01

We explored whether object behavioral priming and pupil changes occur in the absence of recognition memory. Experiment 1 found behavioral priming for unrecognized objects (Ms) regardless of whether they had been encoded perceptually or conceptually. Using the same perceptual encoding task, Experiment 2 showed greater pupil dilation for Ms than for correct rejections of unstudied objects (CRs) when reaction times were matched. In Experiment 3, there was relatively less pupil dilation for Ms than for similarly matched CRs when objects had been encoded conceptually. Mean/peak pupil dilation for CRs, but not Ms, increased in Experiment 3, in which novelty expectation was also reduced, and the pupillary time course for both Ms and CRs was distinct in the two experiments. These findings indicate that both behavioral and pupil memory occur for studied, but unrecognized stimuli, and suggest that encoding and novelty expectation modulate pupillary memory responses. © 2015 Society for Psychophysiological Research.

Magnetic susceptibility as a proxy for investigating microbially mediated iron reduction

USGS Publications Warehouse

Mewafy, F.M.; Atekwana, E.A.; Werkema, D.D.; Slater, L.D.; Ntarlagiannis, D.; Revil, A.; Skold, M.; Delin, G.N.

2011-01-01

We investigated magnetic susceptibility (MS) variations in hydrocarbon contaminated sediments. Our objective was to determine if MS can be used as an intrinsic bioremediation indicator due to the activity of iron-reducing bacteria. A contaminated and an uncontaminated core were retrieved from a site contaminated with crude oil near Bemidji, Minnesota and subsampled for MS measurements. The contaminated core revealed enriched MS zones within the hydrocarbon smear zone, which is related to iron-reduction coupled to oxidation of hydrocarbon compounds and the vadose zone, which is coincident with a zone of methane depletion suggesting aerobic or anaerobic oxidation of methane is coupled to iron-reduction. The latter has significant implications for methane cycling. We conclude that MS can serve as a proxy for intrinsic bioremediation due to the activity of iron-reducing bacteria iron-reducing bacteria and for the application of geophysics to iron cycling studies. ?? 2011 by the American Geophysical Union.

β-Decay Half-Lives of Co76,77, Ni79,80, and Cu81: Experimental Indication of a Doubly Magic Ni78

NASA Astrophysics Data System (ADS)

Xu, Z. Y.; Nishimura, S.; Lorusso, G.; Browne, F.; Doornenbal, P.; Gey, G.; Jung, H.-S.; Li, Z.; Niikura, M.; Söderström, P.-A.; Sumikama, T.; Taprogge, J.; Vajta, Zs.; Watanabe, H.; Wu, J.; Yagi, A.; Yoshinaga, K.; Baba, H.; Franchoo, S.; Isobe, T.; John, P. R.; Kojouharov, I.; Kubono, S.; Kurz, N.; Matea, I.; Matsui, K.; Mengoni, D.; Morfouace, P.; Napoli, D. R.; Naqvi, F.; Nishibata, H.; Odahara, A.; Şahin, E.; Sakurai, H.; Schaffner, H.; Stefan, I. G.; Suzuki, D.; Taniuchi, R.; Werner, V.

2014-07-01

The half-lives of 20 neutron-rich nuclei with Z =27-30 have been measured at the RIBF, including five new half-lives of Co76(21.7-4.9+6.5 ms), Co77(13.0-4.3+7.2 ms), Ni79(43.0-7.5+8.6 ms), Ni80(23.9-17.2+26.0 ms), and Cu81(73.2±6.8 ms). In addition, the half-lives of Co73-75, Ni74-78, Cu78-80, and Zn80-82 were determined with higher precision than previous works. Based on these new results, a systematic study of the β-decay half-lives has been carried out, which suggests a sizable magicity for both the proton number Z =28 and the neutron number N=50 in Ni78.

MS2 inactivation by TiO2 nanoparticles in the presence of quartz sand

NASA Astrophysics Data System (ADS)

Syngouna, Vasiliki I.; Chrysikopoulos, Constantinos V.

2017-04-01

Virus inactivation by nanoparticles (NPs) is hypothesized to affect virus fate and transport in the subsurface. This study examines the interactions of viruses with titanium dioxide (TiO2) anatase NPs, which is a good disinfectant with unique physiochemical properties, using three different virus concentrations. The bacteriophage MS2 was used as a model virus. A series of batch experiments of MS2 inactivation by TiO2 NPs were conducted at room temperature (25 °C), in the presence of quartz sand, with and without ambient light. The virus inactivation experimental data were satisfactorily fitted with a pseudo-first order expression with a time dependent rate coefficient. Quartz sand was shown to affect MS2 inactivation by TiO2 NPs both in the presence and absence of ambient light, because, under the experimental conditions of this study, the quartz sand offers a protection to the attached MS2 against inactivation. Moreover, in most cases similar inactivation rates were observed in reactor and control tubes (absence of TiO2 NPs) suggesting that low TiO2 concentration (10 mg/L) affects only slightly MS2 inactivation with and without ambient light.

Near-infrared signals associated with electrical stimulation of peripheral nerves

NASA Astrophysics Data System (ADS)

Fantini, Sergio; Chen, Debbie K.; Martin, Jeffrey M.; Sassaroli, Angelo; Bergethon, Peter R.

2009-02-01

We report our studies on the optical signals measured non-invasively on electrically stimulated peripheral nerves. The stimulation consists of the delivery of 0.1 ms current pulses, below the threshold for triggering any visible motion, to a peripheral nerve in human subjects (we have studied the sural nerve and the median nerve). In response to electrical stimulation, we observe an optical signal that peaks at about 100 ms post-stimulus, on a much longer time scale than the few milliseconds duration of the electrical response, or sensory nerve action potential (SNAP). While the 100 ms optical signal we measured is not a direct optical signature of neural activation, it is nevertheless indicative of a mediated response to neural activation. We argue that this may provide information useful for understanding the origin of the fast optical signal (also on a 100 ms time scale) that has been measured non-invasively in the brain in response to cerebral activation. Furthermore, the optical response to peripheral nerve activation may be developed into a diagnostic tool for peripheral neuropathies, as suggested by the delayed optical signals (average peak time: 230 ms) measured in patients with diabetic neuropathy with respect to normal subjects (average peak time: 160 ms).

Meditation as an Adjunct to the Management of Multiple Sclerosis

PubMed Central

Levin, Adam B.; Hadgkiss, Emily J.; Weiland, Tracey J.; Jelinek, George A.

2014-01-01

Background. Multiple sclerosis (MS) disease course is known to be adversely affected by several factors including stress. A proposed mechanism for decreasing stress and therefore decreasing MS morbidity and improving quality of life is meditation. This review aims to critically analyse the current literature regarding meditation and MS. Methods. Four major databases were used to search for English language papers published before March 2014 with the terms MS, multiple sclerosis, meditation, and mindfulness. Results. 12 pieces of primary literature fitting the selection criteria were selected: two were randomised controlled studies, four were cohort studies, and six were surveys. The current literature varies in quality; however common positive effects of meditation include improved quality of life (QOL) and improved coping skills. Conclusion. All studies suggest possible benefit to the use of meditation as an adjunct to the management of multiple sclerosis. Additional rigorous clinical trials are required to validate the existing findings and determine if meditation has an impact on disease course over time. PMID:25105026

Epigenetic effects of the pregnancy Mediterranean diet adherence on the offspring metabolic syndrome markers.

PubMed

Lorite Mingot, David; Gesteiro, Eva; Bastida, Sara; Sánchez-Muniz, Francisco J

2017-11-01

Metabolic syndrome (MS) has a multifactorial and not yet fully clarified origin. Insulin resistance is a key element that connects all the accepted components of MS (obesity, dyslipemia, high blood pressure, and hyperglycemia). There is strong evidence that epigenetic changes during fetal development are key factors in the development of MS. These changes are induced by maternal nutrition, among different factors, affecting the intrauterine environment. The Mediterranean diet has been shown to be a healthy eating pattern that protects against the development of MS in adults. Similarly, the Mediterranean diet could have a similar action during pregnancy, protecting the fetus against the development of MS throughout life. This review assembles studies carried out, both in animals and humans, on the epigenetic modifications associated with the consumption, during pregnancy, of Mediterranean diet main components. The relationship between these modifications and the occurrence of factors involved in development of MS is also explained. In addition, the results of our group relating adherence to the Mediterranean diet with MS markers are discussed. The paper ends suggesting future actuation lines in order to increase knowledge on Mediterranean diet adherence as a prevention tool of MS development.

Preclinical evaluation of the PI3K/Akt/mTOR pathway in animal models of multiple sclerosis

PubMed Central

Mammana, Santa; Bramanti, Placido; Mazzon, Emanuela; Cavalli, Eugenio; Basile, Maria Sofia; Fagone, Paolo; Petralia, Maria Cristina; McCubrey, James Andrew; Nicoletti, Ferdinando; Mangano, Katia

2018-01-01

The PI3K/AKT/mTOR pathway is an intracellular signalling pathway that regulates cell activation. proliferation, metabolism and apoptosis. Increasing body of data suggests that alterations in the PI3K/AKT/mTOR pathway may result in an enhanced susceptibility to autoimmunity. Multiple Sclerosis (MS) is one of the most common chronic inflammatory diseases of the central nervous system leading to demyelination and neurodegeneration. In the current study, we have firstly evaluated in silico the involvement of the mTOR network on the generation and progression of MS and on oligodendrocyte function, making use of currently available whole-genome transcriptomic data. Then, the data generated in silico were subjected to an ex-vivo evaluation. To this aim, the involvement of mTOR was validated on a well-known animal model of MS and in vitro on Th17 cells. Our data indicate that there is a significant involvement of the mTOR network in the etiopathogenesis of MS and that Rapamycin treatment may represent a useful therapeutic approach in this clinical setting. On the other hand, our data showed that a significant involvement of the mTOR network could be observed only in the early phases of oligodendrocyte maturation, but not in the maturation process of adult oligodendrocytes and in the process of remyelination following demyelinating injury. Overall, our study suggests that targeting the PI3K/mTOR pathway, although it may not be a useful therapeutic approach to promote remyelination in MS patients, it can be exploited to exert immunomodulation, preventing/delaying relapses, and to treat MS patients in order to slow down the progression of disability. PMID:29492193

Assessing the Value of Treatment to Address Various Symptoms Associated with Multiple Sclerosis: Results from a Contingent Valuation Study.

PubMed

Lin, Pei-Jung; Saret, Cayla J; Neumann, Peter J; Sandberg, Eileen A; Cohen, Joshua T

2016-12-01

Although it is well recognized that people with multiple sclerosis (MS) may experience impairments in addition to limited mobility, there has been little effort to study their relative importance to patients with the condition. The objective of this study was to assess patient preferences for addressing various MS symptoms. This study was conducted at Tufts Medical Center, Boston, Massachusetts. We developed a national online survey of MS patients and neurologists to estimate the value each group places on treating specific MS symptoms. Each respondent was presented with two randomly selected scenarios with different symptoms and treatments. MS patients were asked about their own preferences, whereas neurologists were asked to consider what a patient of theirs would do or think in each scenario. We used a bidding game approach to elicit respondents' willingness to pay (WTP) for the treatments. To treat mobility alone, WTP for MS patients averaged US$410-US$520 per month, depending on the scenario. For paired symptoms, MS patients would pay most to treat mobility and upper limb function (US$525/month) or mobility and cognition (US$514/month), somewhat less to treat mobility and eyesight (US$445/month), and least to treat mobility and fatigue (US$371/month). Patient WTP values increased with income and education. Neurologists believed their patients would be willing to pay US$216-US$249 per month to treat mobility alone, depending on the scenario. For paired symptoms, neurologists believed patients would pay most to treat mobility and fatigue (US$263/month) and least to treat mobility and upper limb function (US$177/month). Our findings suggest MS patients may value one outcome (e.g., improved arm and hand coordination) over another (e.g., less fatigue). Further, MS patients and neurologists may rank the importance of treating various symptoms differently. Given this potential mismatch, it is crucial for MS patients and their clinicians to discuss treatment priorities that take into account patient preferences.

P-wave dispersion and maximum duration are independently associated with insulin resistance in metabolic syndrome.

PubMed

Wang, Weiwei; Zhang, Feilong; Xhen, Jianhua; Chen, Xuehai; Fu, Fayuan; Tang, Mirong; Chen, Lianglong

2014-07-01

Metabolic syndrome (MS) is an important risk factor for atrial fibrillation. P-wave indices, including P-wave dispersion (PWD) and P-wave duration, can be used as non-invasive markers of heterogeneous atrial conduction. The aim of our study was to evaluate the relationship between P-wave indices and insulin resistance in patients with MS. Seventy-four patients with MS (44 men, 30 women) and 81 patients without MS (48 men, 33 women) were enrolled in the study. A diagnosis of MS was made as defined by the Adult Treatment Panel III of the National Cholesterol Education Program. Insulin resistance was estimated using the homeostasis model assessment (HOMA) index. P-wave maximum duration (Pmax) and P-wave minimum duration (Pmin) were calculated on a 12-lead electrocardiogram, and the difference between the Pmax and the Pmin was defined as PWD. Patients with MS had a longer PWD and a higher Pmax compared with patients without MS (PWD, 35.65±4.36 vs. 26.27±4.04, P<0.001; Pmax, 117.12±10.77 vs. 105.98±9.02, P<0.001), whereas no difference was found between Pmin values from MS patients and controls (81.47±9.54 vs. 79.70±8.76, P=0.231). Stepwise multivariate analysis revealed only the HOMA index to be an independent predictor of PWD (β=3.115, P<0.001) and Pmax (β=7.175, P<0.001). This study suggests that patients with MS have a prolonged PWD and Pmax. The increase in these parameters may be an indicator for identification of patients at an increased risk for atrial fibrillation. Copyright © 2014. Published by Elsevier Masson SAS.

Triglycerides and glucose index: a useful indicator of insulin resistance.

PubMed

Unger, Gisela; Benozzi, Silvia Fabiana; Perruzza, Fernando; Pennacchiotti, Graciela Laura

2014-12-01

Insulin resistance assessment requires sophisticated methodology of difficult application. Therefore, different estimators for this condition have been suggested. The aim of this study was to evaluate the triglycerides and glucose (TyG) index as a marker of insulin resistance and to compare it to the triglycerides/HDL cholesterol ratio (TG/HDL-C), in subjects with and without metabolic syndrome (MS). An observational, cross-sectional study was conducted on 525 adults of a population from Bahia Blanca, Argentina, who were divided into two groups: with MS (n=89) and without MS (n=436). The discriminating capacities for MS of the TyG index, calculated as Ln (TG [mg/dL] x glucose [mg/dL]/2), and the TG/HDL-C ratio were evaluated. Pre-test probability for MS was 30%. The mean value of the TyG index was higher in the group with MS as compared to the group without MS and its correlation with the TG/HDL-C ratio was good. The cut-off values for MS in the overall population were 8.8 for the TyG index (sensitivity=79%, specificity=86%), and 2.4 for the TG/HDL-C ratio (sensitivity=88%, specificity=72%). The positive likelihood ratios and post-test probabilities for these parameters were 5.8 vs 3.1 and 72% vs 58% respectively. The cut-off point for the TyG index was 8.8 in men and 8.7 in women; the respective values for TG/C-HDL were 3.1 in men and 2.2 in women. The TyG index was a good discriminant of MS. Its simple calculation warrants its further study as an alternative marker of insulin resistance. Copyright © 2014 SEEN. Published by Elsevier Espana. All rights reserved.

Impact of lifestyle habits on the prevalence of the metabolic syndrome among Greek adults from the ATTICA study.

PubMed

Panagiotakos, Demosthenes B; Pitsavos, Christos; Chrysohoou, Christine; Skoumas, John; Tousoulis, Dimitris; Toutouza, Marina; Toutouzas, Pavlos; Stefanadis, Christodoulos

2004-01-01

Individuals with the metabolic syndrome (MS) are at high risk for coronary heart disease and may benefit from aggressive lifestyle modification. In this study, we evaluated the effect of leisure time physical activity (PA) and the Mediterranean diet (MD) on the prevalence of the MS. The ATTICA study is a health and nutritional survey. On the basis of a multistage, random sampling, 1128 men and 1154 women (>18 years old) without any evidence of cardiovascular disease or diabetes mellitus were enrolled from the greater Athens area during 2001 to 2002. The MS was defined according to the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III criteria. PA was determined from a detailed questionnaire and graded according to the kcal/min expanded. MD was assessed through a validated nutrient questionnaire. The overall prevalence of the MS was 453 of 2282 subjects (19.8%). Of these subjects, 284 (25.2%) were men and 169 (14.6%) were women (P <.001). The prevalence of the MS increased accordingly to age (P for trend <.001). With multiple logistic regression analysis, the odds ratio of having the MS when the participant consumed the MD was 0.81 (95% CI, 0.68-0.976), and when even a little to moderate PA (<7 kcal/min)was reported, the odds ratio was 0.75 (95% CI, 0.65-0.86). The higher levels of inflammation and coagulation markers among participants with MS did not explain much of the aforementioned effect of lifestyle modification. MS is common in Greece and is becoming even more common in the middle-aged population. The suggested therapeutic lifestyle approach may contribute to the reduction of the prevalence of the MS, beyond the levels of several lipid, inflammation, and coagulation markers.

Reinforcement of natural rubber hybrid composites based on marble sludge/Silica and marble sludge/rice husk derived silica

PubMed Central

Ahmed, Khalil; Nizami, Shaikh Sirajuddin; Riza, Nudrat Zahid

2013-01-01

A research has been carried out to develop natural rubber (NR) hybrid composites reinforced with marble sludge (MS)/Silica and MS/rice husk derived silica (RHS). The primary aim of this development is to scrutinize the cure characteristics, mechanical and swelling properties of such hybrid composite. The use of both industrial and agricultural waste such as marble sludge and rice husk derived silica has the primary advantage of being eco-friendly, low cost and easily available as compared to other expensive fillers. The results from this study showed that the performance of NR hybrid composites with MS/Silica and MS/RHS as fillers is extremely better in mechanical and swelling properties as compared with the case where MS used as single filler. The study suggests that the use of recently developed silica and marble sludge as industrial and agricultural waste is accomplished to provide a probable cost effective, industrially prospective, and attractive replacement to the in general purpose used fillers like china clay, calcium carbonate, and talc. PMID:25685484

Comparison of preferences of healthcare professionals and MS patients for attributes of disease-modifying drugs: A best-worst scaling.

PubMed

Kremer, Ingrid E H; Evers, Silvia M A A; Jongen, Peter J; Hiligsmann, Mickaël

2018-02-01

The choice between disease-modifying drugs (DMDs) for the treatment of multiple sclerosis (MS) becomes more often a shared decision between the patient and the neurologist and MS nurse. This study aimed to assess which DMD attributes are most important for the healthcare professionals in selecting a DMD for a patient. Subsequently, within this perspective, the neurologists' and nurses' perspectives were compared. Lastly, the healthcare professionals' perspective was compared with the patients' perspective to detect any differences that may need attention in the communication about DMDs. A best-worst scaling (BWS) was conducted among 27 neurologists and 33 MS nurses treating patients with MS to determine the importance of 27 DMD attributes. These attributes were identified through three focus groups with MS patients in a previous study (N=19). Relative importance scores (RISs) were estimated for each attribute. Multivariable linear regression analyses were used to compare the different perspectives. According to the neurologists and nurses, safety of the DMD was the most important DMD attribute in the treatment decision, closely followed by effect on disability progression, quality of life and relapse rate. Patients with MS agreed with the importance of the last three attributes, but valued safety significantly lower (b=-2.59, P<.001). This study suggests that, overall, neurologists and nurses regard the same DMD attributes as important as MS patients with the notable exception of safety. This study provides valuable information for the development of interventions to support shared decision making and highlights which attributes of DMDs may need additional attention. © 2017 The Authors Health Expectations Published by John Wiley & Sons Ltd.

Image Ambiguity and Fluency

PubMed Central

Jakesch, Martina; Leder, Helmut; Forster, Michael

2013-01-01

Ambiguity is often associated with negative affective responses, and enjoying ambiguity seems restricted to only a few situations, such as experiencing art. Nevertheless, theories of judgment formation, especially the “processing fluency account”, suggest that easy-to-process (non-ambiguous) stimuli are processed faster and are therefore preferred to (ambiguous) stimuli, which are hard to process. In a series of six experiments, we investigated these contrasting approaches by manipulating fluency (presentation duration: 10ms, 50ms, 100ms, 500ms, 1000ms) and testing effects of ambiguity (ambiguous versus non-ambiguous pictures of paintings) on classification performance (Part A; speed and accuracy) and aesthetic appreciation (Part B; liking and interest). As indicated by signal detection analyses, classification accuracy increased with presentation duration (Exp. 1a), but we found no effects of ambiguity on classification speed (Exp. 1b). Fifty percent of the participants were able to successfully classify ambiguous content at a presentation duration of 100 ms, and at 500ms even 75% performed above chance level. Ambiguous artworks were found more interesting (in conditions 50ms to 1000ms) and were preferred over non-ambiguous stimuli at 500ms and 1000ms (Exp. 2a - 2c, 3). Importantly, ambiguous images were nonetheless rated significantly harder to process as non-ambiguous images. These results suggest that ambiguity is an essential ingredient in art appreciation even though or maybe because it is harder to process. PMID:24040172

Tissue Localization of Glycosphingolipid Accumulation in a Gaucher Disease Mouse Brain by LC-ESI-MS/MS and High-Resolution MALDI Imaging Mass Spectrometry.

PubMed

Jones, E Ellen; Zhang, Wujuan; Zhao, Xueheng; Quiason, Cristine; Dale, Stephanie; Shahidi-Latham, Sheerin; Grabowski, Gregory A; Setchell, Kenneth D R; Drake, Richard R; Sun, Ying

2017-12-01

To better understand regional brain glycosphingolipid (GSL) accumulation in Gaucher disease (GD) and its relationship to neuropathology, a feasibility study using mass spectrometry and immunohistochemistry was conducted using brains derived from a GD mouse model (4L/PS/NA) homozygous for a mutant GCase (V394L [4L]) and expressing a prosaposin hypomorphic (PS-NA) transgene. Whole brains from GD and control animals were collected using one hemisphere for MALDI FTICR IMS analysis and the other for quantitation by LC-ESI-MS/MS. MALDI IMS detected several HexCers across the brains. Comparison with the brain hematoxylin and eosin (H&E) revealed differential signal distributions in the midbrain, brain stem, and CB of the GD brain versus the control. Quantitation of serial brain sections with LC-ESI-MS/MS supported the imaging results, finding the overall HexCer levels in the 4L/PS-NA brains to be four times higher than the control. LC-ESI-MS/MS also confirmed that the elevated hexosyl isomers were glucosylceramides rather than galactosylceramides. MALDI imaging also detected differential analyte distributions of lactosylceramide species and gangliosides in the 4L/PS-NA brain, which was validated by LC-ESI-MS/MS. Immunohistochemistry revealed regional inflammation, altered autophagy, and defective protein degradation correlating with regions of GSL accumulation, suggesting that specific GSLs may have distinct neuropathological effects.

A pilot randomised controlled trial of an Internet-based cognitive behavioural therapy self-management programme (MS Invigor8) for multiple sclerosis fatigue.

PubMed

Moss-Morris, Rona; McCrone, Paul; Yardley, Lucy; van Kessel, Kirsten; Wills, Gary; Dennison, Laura

2012-06-01

The majority of people affected by Multiple Sclerosis (paMS) experience severe and disabling fatigue. A recent randomised controlled trial (RCT) showed that cognitive behaviour therapy with a clinical psychologist was an effective treatment for MS fatigue. An Internet-based version of this intervention, MS Invigor8, was developed for the current study using agile design and input from paMS. MS Invigor8 includes eight tailored, interactive sessions. The aim was to test the feasibility and potential efficacy and cost-effectiveness of the programme in a pilot RCT. 40 patients were randomised to MS Invigor8 (n=23) or standard care (n=17). The MS Invigor8 group accessed sessions over 8-10 weeks and received up to three 30-60min telephone support sessions. Participants completed online standardised questionnaires assessing fatigue, mood, quality of life and service use at baseline and 10 weeks follow-up. Large between group treatment effects were found for the primary outcomes of fatigue severity (d=1.19) and impact (d=1.02). The MS Invigor8 group also reported significantly greater improvements in anxiety, depression and quality-adjusted life years. These data suggest that Internet-based CBT may be a clinically and cost-effective treatment for MS fatigue. A larger RCT with longer term follow-up is warranted. Copyright © 2012 Elsevier Ltd. All rights reserved.

Increased Levels of Markers of Oxidative Stress and Inflammation in Patients with Rheumatic Mitral Stenosis Predispose to Left Atrial Thrombus Formation

PubMed Central

Pulimamidi, Vinay Kumar; Murugesan, Vengatesan; Rajappa, Medha; Satheesh, Santhosh; Harichandrakumar, Kottenyen Thazhath

2013-01-01

Background: Rheumatic mitral stenosis (MS) causes stagnation of blood flow, leading to thrombus formation in the left atrium (LA), which may lead to systemic thromboembolic complications. We compared alterations in circulating levels of pro-/anti–oxidants and markers of inflammation in patients of severe rheumatic MS with and without LA thrombus and studied their predictive power to detect the presence of LA thrombus in patients with rheumatic MS. Material and Methods: This is a cross-sectional study of 80 patients with rheumatic MS, evaluated for percutaneous mitral commisurotomy. Group 1 comprised of patients with rheumatic MS with LA thrombus (n=35) and Group 2 included patients with rheumatic MS without LA thrombus (n=45). The following oxidative stress markers-malondialdehyde (MDA), protein carbonyls, total oxidant status and total antioxidant status and inflammation markers-high sensitivity C-reactive protein (hs-CRP), total sialic acid (TSA) and protein-bound sialic acid (PBSA) were estimated in all study subjects. Results: Levels of plasma MDA, protein carbonyl and total oxidant status were significantly elevated, whilst the total antioxidant status levels were significantly lowered, in Group 1, as compared with Group 2. hs-CRP, TSA and PBSA levels showed a significant rise in Group 1 patients, as compared with Group 2. Conclusion: Our results suggest that circulating levels of MDA, protein carbonyl and PBSA were independent predictors of occurrence of LA thrombus in patients with rheumatic MS. PMID:24392368

Different response to hypoxia of adipose-derived multipotent cells from obese subjects with and without metabolic syndrome

PubMed Central

Moreno-Indias, Isabel; Coín-Aragüez, Leticia; Lhamyani, Said; Alcaide Torres, Juan; Fernández-Veledo, Sonia; Vendrell, Joan; Camargo, Antonio; El Bekay, Rajaa; Tinahones, Francisco José

2017-01-01

Background/Objectives Multiple studies suggest that hypoxia, together with inflammation, could be one of the phenomena involved in the onset and progression of obesity-related insulin resistance. In addition, dysfunction of adipose tissue in obese subjects with metabolic syndrome is associated with decreased angiogenesis. However, some subjects with a high body mass index do not develop metabolic abnormalities associated with obesity. The aim of the current study was to examine the neovascular properties of visceral adipose tissue-derived multipotent mesenchymal cells subjected to hypoxia (hypox-visASCs) from normal-weight subjects (Nw) and obese patients with metabolic syndrome (MS) and without metabolic syndrome (NonMS). Methods This was a 2-year study to enroll subjects who underwent bariatric surgery or cholecystectomy. Eight patients who underwent either bariatric surgery or cholecystectomy (27 patients) participated in the study. Visceral adipose tissue samples from Nw, MS and NonMS subjects were processed by enzymatic digestion. VisASCs cultured under hypoxic conditions were characterized by tubule formation assay, ELISA, flow cytometry, migration rate, and qRT-PCR, and the effects of visASCs-conditioned medium on survival and endothelial cell tubule formation were evaluated. Results Hypox-visASCs from NonMS subjects showed a greater capacity for tubule formation than hypox-visASCs from Nw and MS subjects. The lower percentage of CD140b+/CD44+ and CD140b+/CD184+ cells observed in hypox-visASCs from NonMS subjects compared to MS subjects was accompanied not only by a lower migration rate from the chemotactic effects of stromal cell derived factor 1α, but also by lower levels of NOX5 mRNA expression. While the levels of monocyte chemoattractant protein 1 mRNA expressed by hypox-visASCs correlated positively with the body mass index and waist circumference of the subjects, the concentration of vascular endothelial growth factor present in hypox-visASC-conditioned culture medium decreased significantly with increasing plasma glucose. The survival rate and tubules formed by endothelial cells cultured in hypox-visASC-conditioned medium decreased significantly with increasing homeostasis model assessment to quantify insulin resistance. Conclusions Our results suggest that hypox-visASCs from NonMS subjects could promote healthy adipose tissue expansion, while hypox-visASCs from MS subjects appear to contribute to the decreased angiogenic potential and increased inflammation underlying adipose tissue dysfunction in obesity. Our results emphasize the importance of taking into account not only the BMI but also the metabolic profile of the subjects during the implementation of ASCs-based therapy to promote neovascularization. PMID:29166648

Medical chart validation of an algorithm for identifying multiple sclerosis relapse in healthcare claims.

PubMed

Chastek, Benjamin J; Oleen-Burkey, Merrikay; Lopez-Bresnahan, Maria V

2010-01-01

Relapse is a common measure of disease activity in relapsing-remitting multiple sclerosis (MS). The objective of this study was to test the content validity of an operational algorithm for detecting relapse in claims data. A claims-based relapse detection algorithm was tested by comparing its detection rate over a 1-year period with relapses identified based on medical chart review. According to the algorithm, MS patients in a US healthcare claims database who had either (1) a primary claim for MS during hospitalization or (2) a corticosteroid claim following a MS-related outpatient visit were designated as having a relapse. Patient charts were examined for explicit indication of relapse or care suggestive of relapse. Positive and negative predictive values were calculated. Medical charts were reviewed for 300 MS patients, half of whom had a relapse according to the algorithm. The claims-based criteria correctly classified 67.3% of patients with relapses (positive predictive value) and 70.0% of patients without relapses (negative predictive value; kappa 0.373: p < 0.001). Alternative algorithms did not improve on the predictive value of the operational algorithm. Limitations of the algorithm include lack of differentiation between relapsing-remitting MS and other types, and that it does not incorporate measures of function and disability. The claims-based algorithm appeared to successfully detect moderate-to-severe MS relapse. This validated definition can be applied to future claims-based MS studies.

Evaluation of tamoxifen and metabolites by LC-MS/MS and HPLC methods.

PubMed

Heath, D D; Flat, S W; Wu, A H B; Pruitt, M A; Rock, C L

2014-01-01

Epidemiological and laboratory evidence suggests that quantification of serum or plasma levels of tamoxifen and its metabolites, 4-hydroxy-N-desmethyl-tamoxifen (endoxifen), Z-4-hydroxytamoxifen (4HT), N-desmethyl-tamoxifen (ND-tam), is a clinically useful tool in the assessment and monitoring of breast cancer status in patients taking adjuvant tamoxifen. A liquid chromatographic mass spectrometric method (LC-MS/MS) was used to measure the blood levels of tamoxifen and its metabolites. This fully automated analytical method is specific, accurate and sensitive. The LC-MS/MS automated technique has now become a widely accepted reference method. This study analysed a randomly selected batch of blood samples from participants enrolled in a breast cancer study to compare results from this reference method in 40 samples with those obtained from a recently developed high-performance liquid chromatography (HPLC) method with fluorescence detection. The mean (SD) concentrations for the LC-MS/MS method (endoxifen 12.6 [7.5] ng/mL, tamoxifen 105 [44] ng/mL, 4-HT 1.9 [1.0] ng/mL, ND-tam 181 [69] ng/mL) and the HPLC method (endoxifen 13.1 [7.8] ng/mL, tamoxifen 108 [55] ng/mL, 4-HT 1.8 [0.8] ng/mL, ND-tam 184 [81] ng/mL) did not show any significant differences. The results confirm that the HPLC method offers an accurate and comparable alternative for the quantification of tamoxifen and tamoxifen metabolites.

Structural correlates of subjective and objective memory performance in multiple sclerosis.

PubMed

Pardini, Matteo; Bergamino, Maurizio; Bommarito, Giulia; Bonzano, Laura; Luigi Mancardi, Gian; Roccatagliata, Luca

2014-04-01

Subjective and objective memory deficits represent a frequent and ill-understood aspect of multiple sclerosis (MS), and a significant cause of disability and quality of life reduction. The aim of the study is to verify the role of hippocampal and temporal associative fibers' damage in MS-related memory complaints. To reach this aim, 25 patients with low disability relapsing-remitting MS and 19 healthy controls were included in the study. All subjects underwent 3D T1 structural imaging and Diffusion Tensor Imaging. Additionally, MS patients underwent neuropsychological evaluation of objective (Selective Reminding Test and Spatial Recall Test) and of subjective (Perceived Deficit Questionnaire, Retrospective and Prospective Memory Subscales) memory deficits. Normalized hippocampal volume (NHV) and mean Fractional Anisotropy (FA) for the uncinate fasciculus (UF) and for the ventral division of the cingulum bundle (VCB) were calculated for all subjects. We showed that, compared to controls, MS subjects presented with reduced right NHV and with reduced mean FA bilaterally in the UF and the VCB. In the MS group, verbal memory scores correlated with left NHV, spatial memory scores correlated with right NHV, while perceived retrospective and prospective memory deficits correlated with left VCB and left UF mean FA respectively. Our data confirm an early involvement of memory-related brain structures in MS patients. Our data suggest that verbal and nonverbal memory as well as perceived retrospective and prospective memory deficits are related to alterations of discrete anatomical structures in the low-disability phase of MS. Copyright © 2013 Wiley Periodicals, Inc.

Association of UV radiation with multiple sclerosis prevalence and sex ratio in France.

PubMed

Orton, S-M; Wald, L; Confavreux, C; Vukusic, S; Krohn, J P; Ramagopalan, S V; Herrera, B M; Sadovnick, A D; Ebers, G C

2011-02-01

French farmers and their families constitute an informative population to study multiple sclerosis (MS) prevalence and related epidemiology. We carried out an ecological study to evaluate the association of MS prevalence and ultraviolet (UV) radiation, a candidate climatologic risk factor. Mean annual and winter (December-March) UVB irradiation values were systematically compared to MS prevalence rates in corresponding regions of France. UVB data were obtained from the solar radiation database (SoDa) service and prevalence rates from previously published data on 2,667 MS cases registered with the national farmer health insurance system, Mutualité Sociale Agricole (MSA). Pearson correlation was used to examine the relationship of annual and winter UVB values with MS prevalence. Male and female prevalence were also analyzed separately. Linear regression was used to test for interaction of annual and winter UVB with sex in predicting MS prevalence. There was a strong association between MS prevalence and annual mean UVB irradiation (r = -0.80, p < 0.001) and average winter UVB (r = -0.87, p < 0.001). Both female (r = -0.76, p < 0.001) and male (r = -0.46, p = 0.032) prevalence rates were correlated with annual UVB. Regression modeling showed that the effect of UVB on prevalence rates differed by sex; the interaction effect was significant for both annual UVB (p = 0.003) and winter UVB (p = 0.002). The findings suggest that regional UVB radiation is predictive of corresponding MS prevalence rates and supports the hypothesis that sunlight exposure influences MS risk. The evidence also supports a potential role for gender-specific effects of UVB exposure.

Extraction of temporal information in functional MRI

NASA Astrophysics Data System (ADS)

Singh, M.; Sungkarat, W.; Jeong, Jeong-Won; Zhou, Yongxia

2002-10-01

The temporal resolution of functional MRI (fMRI) is limited by the shape of the haemodynamic response function (hrf) and the vascular architecture underlying the activated regions. Typically, the temporal resolution of fMRI is on the order of 1 s. We have developed a new data processing approach to extract temporal information on a pixel-by-pixel basis at the level of 100 ms from fMRI data. Instead of correlating or fitting the time-course of each pixel to a single reference function, which is the common practice in fMRI, we correlate each pixel's time-course to a series of reference functions that are shifted with respect to each other by 100 ms. The reference function yielding the highest correlation coefficient for a pixel is then used as a time marker for that pixel. A Monte Carlo simulation and experimental study of this approach were performed to estimate the temporal resolution as a function of signal-to-noise ratio (SNR) in the time-course of a pixel. Assuming a known and stationary hrf, the simulation and experimental studies suggest a lower limit in the temporal resolution of approximately 100 ms at an SNR of 3. The multireference function approach was also applied to extract timing information from an event-related motor movement study where the subjects flexed a finger on cue. The event was repeated 19 times with the event's presentation staggered to yield an approximately 100-ms temporal sampling of the haemodynamic response over the entire presentation cycle. The timing differences among different regions of the brain activated by the motor task were clearly visualized and quantified by this method. The results suggest that it is possible to achieve a temporal resolution of /spl sim/200 ms in practice with this approach.

Brain-heart coupling at the P300 latency is linked to anterior cingulate cortex and insula--a cardio-electroencephalographic covariance tracing study.

PubMed

Panitz, Christian; Wacker, Jan; Stemmler, Gerhard; Mueller, Erik M

2013-09-01

Prior work on the coupling of cortical and cardiac responses to feedback demonstrated that feedback-evoked single-trial EEG magnitudes 300 ms post-stimulus predict the degree of subsequent cardiac acceleration. The main goal of the current study was to explore the neural sources of this phenomenon using (a) independent component analysis in conjunction with dipole fitting and (b) low resolution electromagnetic tomography (LORETA) in N=14 participants who performed a gambling task with feedback presented after each trial. It was shown that independent components localized near anterior cingulate cortex produced robust within-subjects correlations with feedback-evoked heart-period, suggesting that anterior cingulate cortex activity 300ms after feedback presentation predicts the strength of subsequent cardiac acceleration. Moreover, interindividual differences in evoked left insular cortex LORETA-estimated activity at around 300ms moderated within-subjects EEG-heart period correlations. These results suggest that key regions of central autonomic control are involved in cortico-cardiac coupling evoked by feedback stimuli. Copyright © 2013 Elsevier B.V. All rights reserved.

Epidemiologic evidence for multiple sclerosis as an infection.

PubMed Central

Kurtzke, J F

1993-01-01

The worldwide distribution of multiple sclerosis (MS) can be described within three zones of frequency: high, medium, and low. The disease has a predilection for white races and for women. Migration studies show that changing residence changes MS risk. Studies of persons moving from high- to low-risk areas indicate that in the high-risk areas, MS is acquired by about age 15. Moves from low- to high-risk areas suggest that susceptibility is limited to persons between about ages 11 and 45. MS on the Faroe Islands has occurred as four successive epidemics beginning in 1943. The disease appears to have been introduced by British troops who occupied the islands for 5 years from 1940, and it has remained geographically localized within the Faroes for half a century. What was introduced must have been an infection, called the primary MS affection (PMSA), that was spread to and from successive cohorts of Faroese. In this concept, PMSA is a single widespread systemic infectious disease (perhaps asymptomatic) that only seldom leads to clinical neurologic MS. PMSA is also characterized by a need for prolonged exposure, limited age of susceptibility, and prolonged incubation. I believe that clinical MS is the rare late outcome of a specific, but unknown, infectious disease of adolescence and young adulthood and that this infection could well be caused by a thus-far-unidentified (retro)virus. Images PMID:8269393

Interplay between Matrix Metalloproteinase-9, Matrix Metalloproteinase-2, and Interleukins in Multiple Sclerosis Patients

PubMed Central

Tamborino, Carmine; Baldi, Eleonora; Kostic, Vladimir; Drulovic, Jelena; Dujmovic, Irena

2016-01-01

Matrix Metalloproteases (MMPs) and cytokines have been involved in the pathogenesis of multiple sclerosis (MS). However, no studies have still explored the possible associations between the two families of molecules. The present study aimed to evaluate the contribution of active MMP-9, active MMP-2, interleukin- (IL-) 17, IL-18, IL-23, and monocyte chemotactic proteins-3 to the pathogenesis of MS and the possible interconnections between MMPs and cytokines. The proteins were determined in the serum and cerebrospinal fluid (CSF) of 89 MS patients and 92 other neurological disorders (OND) controls. Serum active MMP-9 was increased in MS patients and OND controls compared to healthy subjects (p < 0.001 and p < 0.01, resp.), whereas active MMP-2 and ILs did not change. CSF MMP-9, but not MMP-2 or ILs, was selectively elevated in MS compared to OND (p < 0.01). Regarding the MMPs and cytokines intercorrelations, we found a significant association between CSF active MMP-2 and IL-18 (r = 0.3, p < 0.05), while MMP-9 did not show any associations with the cytokines examined. Collectively, our results suggest that active MMP-9, but not ILs, might be a surrogate marker for MS. In addition, interleukins and MMPs might synergistically cooperate in MS, indicating them as potential partners in the disease process. PMID:27555667

Interplay between Matrix Metalloproteinase-9, Matrix Metalloproteinase-2, and Interleukins in Multiple Sclerosis Patients.

PubMed

Trentini, Alessandro; Castellazzi, Massimiliano; Cervellati, Carlo; Manfrinato, Maria Cristina; Tamborino, Carmine; Hanau, Stefania; Volta, Carlo Alberto; Baldi, Eleonora; Kostic, Vladimir; Drulovic, Jelena; Granieri, Enrico; Dallocchio, Franco; Bellini, Tiziana; Dujmovic, Irena; Fainardi, Enrico

2016-01-01

Matrix Metalloproteases (MMPs) and cytokines have been involved in the pathogenesis of multiple sclerosis (MS). However, no studies have still explored the possible associations between the two families of molecules. The present study aimed to evaluate the contribution of active MMP-9, active MMP-2, interleukin- (IL-) 17, IL-18, IL-23, and monocyte chemotactic proteins-3 to the pathogenesis of MS and the possible interconnections between MMPs and cytokines. The proteins were determined in the serum and cerebrospinal fluid (CSF) of 89 MS patients and 92 other neurological disorders (OND) controls. Serum active MMP-9 was increased in MS patients and OND controls compared to healthy subjects (p < 0.001 and p < 0.01, resp.), whereas active MMP-2 and ILs did not change. CSF MMP-9, but not MMP-2 or ILs, was selectively elevated in MS compared to OND (p < 0.01). Regarding the MMPs and cytokines intercorrelations, we found a significant association between CSF active MMP-2 and IL-18 (r = 0.3, p < 0.05), while MMP-9 did not show any associations with the cytokines examined. Collectively, our results suggest that active MMP-9, but not ILs, might be a surrogate marker for MS. In addition, interleukins and MMPs might synergistically cooperate in MS, indicating them as potential partners in the disease process.

Mainstream smoke and sidestream smoke affect the cardiac differentiation of mouse embryonic stem cells discriminately.

PubMed

Cheng, Wei; Zhou, Ren; Feng, Yan; Wang, Yan

2016-05-16

Epidemiology studies suggest that maternal smoking and passive smoking have strongly resulted in the occurrence of congenital heart defects (CHD) in offspring. Cigarette smoke (CS) can be divided into mainstream smoke (MS) and sidestream smoke (SS); CS chemistry study indicates that significant differences exist in the composition of MS and SS. Therefore, MS and SS were suspected to process toxicity dissimilarly. However, much less was known about the difference in the developmental effects induced by MS and SS. In the current study, heart development was mimicked by mouse embryonic stem cells (ESCs) differentiation. After MS and SS exposure, by tracing the bone morphogenetic protein (BMP)-Smad4 signalling pathway, interruption of downstream gene expression was observed, including Gata4, Mef2c and Nkx2.5, as well as myosin heavy chain and myosin light chain. Specifically, SS caused inhibition of Gata4 expression, even at non-cytotoxic concentration. Further, SS-induced hypoacetylation in promoter regions of Gata4 reflected the orchestration of CS-gene modulation-epigenetic regulation. Even though SS induced apoptosis in ESC-derived cardiomyocytes, the partial clearance in cells with down-regulated Gata4 caused these cells to survive and undergo further differentiation, which laid potential risk for abnormal heart development. These data uncovered the difference between MS and SS on heart development preliminarily. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effects of interstimulus intervals on behavioral, heart rate, and event-related potential indices of infant engagement and sustained attention

PubMed Central

Xie, Wanze; Richards, John E.

2016-01-01

Maximizing infant attention to stimulus presentation during an EEG or ERP experiment is important for making valid inferences about the neural correlates of infant cognition. The present study examined the effects of stimulus presentation interstimulus interval (ISI) on behavioral and physiological indices of infant attention including infants’ fixation to visual presentation, the amount of heart rate (HR) change during sustained attention, and ERP components. This study compared an ISI that is typically used in infant EEG/ERP studies (e.g., 1,500–2,000 ms) with two shorter durations (400–600 ms and 600–1,000 ms). Thirty-six infants were tested cross-sectionally at 3, 4.5, and 6 months. It was found that using the short (400–600 ms) and medium (600–1,000 ms) ISIs resulted in more visually fixated trials and reduced frequency of fixation disengagement per experimental block. We also found larger HR changes during sustained attention to both of the shorter ISIs compared with the long ISI, and larger ERP responses when using the medium ISI compared to using the short and long ISIs. These data suggest that utilizing an optimal ISI (e.g., 600– 1,000 ms), which increases the presentation complexity and provides sufficient time for information processing, can promote infant engagement and sustained attention during stimulus presentation. PMID:27159263

A randomized, controlled, single-blind, 6-month pilot study to evaluate the efficacy of MS-Line!: a cognitive rehabilitation programme for patients with multiple sclerosis.

PubMed

Gich, Jordi; Freixanet, Jordi; García, Rafael; Vilanova, Joan Carles; Genís, David; Silva, Yolanda; Montalban, Xavier; Ramió-Torrentà, Lluís

2015-09-01

MS-Line! was created to provide an effective treatment for cognitive impairment in multiple sclerosis (MS) patients. To assess the efficacy of MS-Line!. A randomized, controlled, single-blind, 6-month pilot study. Patients were randomly assigned to an experimental group (cognitive rehabilitation with the programme) or to a control group (no cognitive rehabilitation). Randomization was stratified by cognitive impairment level. Cognitive assessment included: selective reminding test, 10/36 spatial recall test (10/36 SPART), symbol digit modalities test, paced auditory serial addition test, word list generation (WLG), FAS test, subtests of WAIS-III, Boston naming test (BNT), and trail making test (TMT). Forty-three patients (22 in the experimental group, 21 in the control group) were analyzed. Covariance analysis showed significant differences in 10/36 SPART (P=0.0002), 10/36 SPART delayed recall (P=0.0021), WLG (P=0.0123), LNS (P=0.0413), BNT (P=0.0007) and TMT-A (P=0.010) scores between groups. The study showed a significant improvement related to learning and visual memory, executive functions, attention and information processing speed, and naming ability in those patients who received cognitive rehabilitation. The results suggest that MS-Line! is effective in improving cognitive impairment in MS patients. © The Author(s), 2015.

Rugged LC-MS/MS survey analysis for acrylamide in foods.

PubMed

Roach, John A G; Andrzejewski, Denis; Gay, Martha L; Nortrup, David; Musser, Steven M

2003-12-17

The described liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the detection of acrylamide in food entails aqueous room temperature extraction, SPE cleanup, and analysis by LC-MS/MS. The method is applicable to a wide variety of foods. [(13)C(3)]acrylamide is the internal standard. The limit of quantitation is 10 ppb (microg/kg). Data were obtained in duplicate from >450 products representing >35 different food types. The variability in analyte levels in certain food types suggests that it may be possible to reduce acrylamide levels in those foods.

Demonstrating Empathy for Foreign-Born Employees through Openness and Acceptance: A Quasi-Experimental Field Study.

ERIC Educational Resources Information Center

Stull, James B.

1986-01-01

Reports on a study measuring foreign-born employees' perceptions of supervisors' acceptance of and openness to "open" messages from the employee. Suggests ways to improve supervisory demonstrations of empathy. (MS)

Decision making under uncertainty, therapeutic inertia, and physicians' risk preferences in the management of multiple sclerosis (DIScUTIR MS).

PubMed

Saposnik, Gustavo; Sempere, Angel Perez; Raptis, Roula; Prefasi, Daniel; Selchen, Daniel; Maurino, Jorge

2016-05-04

The management of multiple sclerosis (MS) is rapidly changing by the introduction of new and more effective disease-modifying agents. The importance of risk stratification was confirmed by results on disease progression predicted by different risk score systems. Despite these advances, we know very little about medical decisions under uncertainty in the management of MS. The goal of this study is to i) identify whether overconfidence, tolerance to risk/uncertainty, herding influence medical decisions, and ii) to evaluate the frequency of therapeutic inertia (defined as lack of treatment initiation or intensification in patients not at goals of care) and its predisposing factors in the management of MS. This is a prospective study comprising a combination of case-vignettes and surveys and experiments from Neuroeconomics/behavioral economics to identify cognitive distortions associated with medical decisions and therapeutic inertia. Participants include MS fellows and MS experts from across Spain. Each participant will receive an individual link using Qualtrics platform(©) that includes 20 case-vignettes, 3 surveys, and 4 behavioral experiments. The total time for completing the study is approximately 30-35 min. Case vignettes were selected to be representative of common clinical encounters in MS practice. Surveys and experiments include standardized test to measure overconfidence, aversion to risk and ambiguity, herding (following colleague's suggestions even when not supported by the evidence), physicians' reactions to uncertainty, and questions from the Socio-Economic Panel Study (SOEP) related to risk preferences in different domains. By applying three different MS score criteria (modified Rio, EMA, Prosperini's scheme) we take into account physicians' differences in escalating therapy when evaluating medical decisions across case-vignettes. The present study applies an innovative approach by combining tools to assess medical decisions with experiments from Neuroeconomics that applies to common scenarios in MS care. Our results will help advance the field by providing a better understanding on the influence of cognitive factors (e.g., overconfidence, aversion to risk and uncertainty, herding) on medical decisions and therapeutic inertia in the management of MS which could lead to better outcomes.

Muscular, cardiac, ventilatory and metabolic dysfunction in patients with multiple sclerosis: Implications for screening, clinical care and endurance and resistance exercise therapy, a scoping review.

PubMed

Wens, Inez; Eijnde, Bert O; Hansen, Dominique

2016-08-15

In the treatment of multiple sclerosis (MS), exercise training is now considered a cornerstone. However, most clinicians tend to focus on neurologic deficits only, and thus prefer to prescribe rehabilitation programs specifically to counteract these deficits. However, the present comprehensive review shows that patients with MS (pwMS) also experience significant muscular, cardiac, ventilatory and metabolic dysfunction, which significantly contribute, next to neurologic deficits, to exercise intolerance. In addition, these anomalies also might increase the risk for frequent hospitalization and morbidity and can reduce life expectancy. Unfortunately, the impact of exercise intervention on these anomalies in pwMS are mostly unknown. Therefore, it is suggested that pwMS should be screened systematically for muscular, cardiac, ventilatory and metabolic function during exercise testing. The detection of such anomalies should lead to adaptations and optimisation of exercise training prescription and clinical care/medical treatment of pwMS. In addition, future studies should focus on the impact of exercise intervention on muscular, cardiac, ventilatory and metabolic (dys)function in pwMS, to contribute to improved treatment and care. Copyright © 2016. Published by Elsevier B.V.

Multiple sclerosis in Kashmir: Where we stand.

PubMed

Zahoor, Insha; Haq, Ehtishamul; Asimi, Ravouf

2017-02-15

Multiple sclerosis (MS) is a disabling neurological disorder commonly diagnosed in young adults. Its causes still remain inexplicable and presently it can only be managed by different drug treatments. There has been a remarkable shift in MS perspective across world. One of its peculiar attribute is unstable (changing) prevalence rate across different parts of the world. Earlier MS was believed to be less prevalent in India, however, there has been growing evidence suggesting its increasing prevalence which has changed its perspective from being less prevalent to more prevalent. There is a complete lack of data on the prevalence rate and epidemiological basis of MS in Kashmir Valley of India. By and large MS research in this region seems to be hampered due to lack of proper research infrastructure, absence of MS registry, inadequate funding and more importantly by absence of active local and foreign collaborations between scientists and clinicians. This review tries to raise some key issues encountered while conducting MS research in Kashmir and at the same time highlighting the measures to be adopted for carrying out a large scale molecular epidemiological study. Copyright © 2016 Elsevier B.V. All rights reserved.

Infectivity reduction efficacy of UV irradiation and peracetic acid-UV combined treatment on MS2 bacteriophage and murine norovirus in secondary wastewater effluent.

PubMed

Weng, ShihChi; Dunkin, Nathan; Schwab, Kellogg J; McQuarrie, James; Bell, Kati; Jacangelo, Joseph G

2018-09-01

Peracetic acid (PAA) is a strong oxidant/bactericide that has been applied in various industries (e.g., food processing, pharmaceuticals, medical device sterilization, etc.) as a disinfectant. There is increasing interest in using PAA for wastewater disinfection because it does not form halogenated byproducts, and no post-treatment quenching is required. Previous studies have demonstrated good efficiency in controlling bacteria in wastewater, but limited information is available for viruses, especially those hosted by mammals (e.g., norovirus). Therefore, a study on the infectivity reduction of murine norovirus (MNV) was undertaken to evaluate the disinfection efficacy of PAA or UV alone and in combination with UV irradiation in undisinfected secondary effluent from a municipal wastewater reclamation facility (MWW) and phosphate buffer solution (PBS) at pH 7. Experiments employing MS2 bacteriophage were also performed in parallel for comparison purposes. MS2 infectivity reduction was found to be lower than MNV infectivity reduction for each condition studied - PAA, PAA + UV, and UV disinfection. These data suggest that MS2 may not be an appropriate surrogate to accurately predict the reduction of MNV infectivity. UV irradiation, in a dose range of 5-250 mJ/cm 2 , provided linear log inactivation (-log (N/N 0 )) with a regression slope (cm 2 mJ -1 ) of 0.031-0.034 and 0.165-0.202 for MS2 and MNV, respectively. UV irradiation provided similar inactivation for MS2 and MNV in both suspensions (PBS or MWW). Low infectivity reduction of MS2 was observed when PAA was used alone at a practical dose of 1.5 mg/L and below. A greater reduction of both MNV and MS2 was observed in PAA disinfection experiments using PBS as the microbial suspension medium, than in secondary effluent. Similar results were observed in PAA + UV experiments, in which greater synergistic effects were found in PBS than in MWW. Results of OH radical formation experiments suggest the presence of radical scavengers in MWW, which resulted in less opportunity for MNV and MS2 to encounter OHradicals. This study also demonstrated that the type of water can have a substantial impact on wastewater disinfection when employing PAA or PAA + UV treatment due to the matrix effect and the presence of radical scavengers, respectively. The results from this study could be employed to aid in the conceptual design of PAA and UV disinfection facilities, especially when norovirus is the organism of concern. Copyright © 2018. Published by Elsevier Ltd.

Low DPP4 expression and activity in multiple sclerosis.

PubMed

Tejera-Alhambra, Marta; Casrouge, Armanda; de Andrés, Clara; Ramos-Medina, Rocío; Alonso, Bárbara; Vega, Janet; Albert, Matthew L; Sánchez-Ramón, Silvia

2014-02-01

Multiple sclerosis (MS) is a prototypic Th1/Th17 chronic autoimmune disease of the central nervous system. Dipeptidyl peptidase 4 (DPP4 or CD26) is a multifunctional molecule involved in autoimmune diseases' pathophysiology. We sought to integrate disparate pieces of data and analyze the plasma levels of sDPP4, DPP activity and DPP4 surface expression on T-cells in 129 MS patients with different clinical forms and 53 healthy controls, across two independent cohorts. Herein, we provide new evidence that sDPP4 concentration and DPP activity are significantly lower in MS patients than controls (p < 0.0001 and p < 0.01, respectively). In contrast, the frequency of circulating CD8(+)DPP4(hi) T-cells (p = 0.02) was increased in MS patients. This is the first study that simultaneously analyzes DPP4 expression and function in a large cohort of MS patients. Our data indicate a putative role for DPP4 in MS pathophysiology and suggest that a deeper understanding of surface versus shed DPP4 biology is warranted. Copyright © 2013 Elsevier Inc. All rights reserved.

Maternal separation as a risk factor for aggravation of neuropathic pain in later life in mice.

PubMed

Mizoguchi, Hiroyuki; Fukumoto, Kazuya; Sakamoto, Gaku; Jin, Shijie; Toyama, Asako; Wang, Tian; Suzumura, Akio; Sato, Jun

2018-06-20

Psychological stresses such as social loss and separation during childhood induce hardship, referred to as emotional pain. These experiences are well-documented risk factors for the development of physical pain in adulthood. However, the underlying neuronal mechanisms of this exacerbation of pain are largely unknown, and consequently there is no effective pharmacotherapy. In this study, we sought to determine whether infant maternal separation (MS) contributes to aggravation of neuropathic pain in adult mice. MS increased anxiety- and depression-like behavioral responses to adult stress. In MS animals, chronic constriction injury (CCI) heightened the sensory dimension of chronic pain relative to that of control mice. However, MS mice treated with fluoxetine for 4 weeks after MS did not exhibit augmentation of allodynia, and their emotional response was attenuated. Microglia were more abundant in the spinal cord in MS/CCI mice than in control/CCI mice. These results suggest that emotional impairment is related to augmentation of neuropathic pain, and that dysfunction of microglial activation contributes to heightened pain sensitivity. Copyright © 2018. Published by Elsevier B.V.

Exploring the Specific Needs of Persons with Multiple Sclerosis for mHealth Solutions for Physical Activity: Mixed-Methods Study

PubMed Central

Kool, Jan; Rivera Romero, Octavio; Dorronzoro Zubiete, Enrique

2018-01-01

Background Multiple sclerosis (MS) is one of the world’s most common neurologic disorders, with symptoms such as fatigue, cognitive problems, and issues with mobility. Evidence suggests that physical activity (PA) helps people with MS reduce fatigue and improve quality of life. The use of mobile technologies for health has grown in recent years with little involvement from relevant stakeholders. User-centered design (UCD) is a design philosophy with the goal of creating solutions specific to the needs and tasks of the intended users. UCD involves stakeholders early and often in the design process. In a preliminary study, we assessed the landscape of commercially available MS mobile health (mHealth) apps; to our knowledge, no study has explored what persons with MS and their formal care providers think of mHealth solutions for PA. Objective The aim of this study was to (1) explore MS-specific needs for MS mHealth solutions for PA, (2) detect perceived obstacles and facilitators for mHealth solutions from persons with MS and health care professionals, and (3) understand the motivational aspects behind adoption of mHealth solutions for MS. Methods A mixed-methods design study was conducted in Kliniken Valens, Switzerland, a clinic specializing in neurological rehabilitation. We explored persons with MS and health care professionals who work with them separately. The study had a qualitative part comprising focus groups and interviews, and a quantitative part with standardized tools such as satisfaction with life scale and electronic health (eHealth) literacy. Results A total of 12 persons with relapsing-remitting MS and 12 health care professionals from different backgrounds participated in the study. Participants were well-educated with an even distribution between genders. Themes identified during analysis were MS-related barriers and facilitators, mHealth design considerations, and general motivational aspects. The insights generated were used to create MS personas for design purposes. Desired mHealth features were as follows: (1) activity tracking, (2) incentives for completing tasks and objectives, (3) customizable goal setting, (4) optional sociability, and (5) game-like attitude among others. Potential barriers to mHealth apps adoption were as follows: (1) rough on-boarding experiences, (2) lack of clear use benefits, and (3) disruption of the health care provider-patient relationship. Potential facilitators were identified: (1) endorsements from experts, (2) playfulness, and (3) tailored to specific persons with MS needs. A total of 4 MS personas were developed to provide designers and computer scientists means to help in the creation of future mHealth solutions for MS. Conclusions mHealth solutions for increasing PA in persons with MS hold promise. Allowing for realistic goal setting and positive feedback, while minimizing usability burdens, seems to be critical for the adoption of such apps. Fatigue management is especially important in this population; more attention should be brought to this area. PMID:29426814

Isolation and analysis of a multifunctional triterpene synthase KcMS promoter region from mangrove plant kandelia candel

NASA Astrophysics Data System (ADS)

Basyuni, M.; Wati, R.; Sulistiyono, N.; Sumardi; Oku, H.; Baba, S.; Sagami, H.

2018-03-01

Molecular cloning of Kandelia candel KcMS gene has previously been cloned and encoded a multifunctional triterpene synthase. In this study, the KcMS gene promoter was cloned through Genome walking, sequenced, and analyzed. A 1,358 bp genomic DNA fragment of KcMS promoter was obtained. PLACE and PlantCARE analysis of the KcMS promoter revealed that there was some regulatory elements in response to environmental signals and involved in the regulation of gene expression. Results showed that four kinds of elements are regulated by hormone binding, namely 2 MeJA-responsiveness elements (CGTCA-motif and TGACG-motif), the ABRE (TACGTG) involved in abscisic acid responsiveness, gibberellin-related GARE-motif (AAACAGA), and the TGA-element (AACGAC) as an auxin-responsive element. Several elements in the KcMS have been shown in other plants to be responsive to abiotic stress. These motifs were MBS (CAACTG), TC-rich repeats, and eight light responsive elements. The KcMS promoter was also involved in the activation of defense genes in plants such as HSE (AAAAAATTC) and four circadian control elements (CAANNNNATC). The presence of multipotential regulatory motifs suggested that KcMS may be involved in regulation of plant tolerance to several types of stresses.

Application of MALDI-TOF MS Systems in the Rapid Identification of Campylobacter spp. of Public Health Importance.

PubMed

Hsieh, Ying-Hsin; Wang, Yun F; Moura, Hercules; Miranda, Nancy; Simpson, Steven; Gowrishankar, Ramnath; Barr, John; Kerdahi, Khalil; Sulaiman, Irshad M

2018-05-01

Campylobacteriosis is an infectious gastrointestinal disease caused by Campylobacter spp. In most cases, it is either underdiagnosed or underreported due to poor diagnostics and limited databases. Several DNA-based molecular diagnostic techniques, including 16S ribosomal RNA (rRNA) sequence typing, have been widely used in the species identification of Campylobacter. Nevertheless, these assays are time-consuming and require a high quality of bacterial DNA. Matrix-assisted laser desorption ionization (MALDI) time-of-flight (TOF) MS is an emerging diagnostic technology that can provide the rapid identification of microorganisms by using their intact cells without extraction or purification. In this study, we analyzed 24 American Type Culture Collection reference isolates of 16 Campylobacter spp. and five unknown clinical bacterial isolates for rapid identification utilizing two commercially available MADI-TOF MS platforms, namely the bioMérieux VITEK® MS and Bruker Biotyper systems. In addition, 16S rRNA sequencing was performed to confirm the species-level identification of the unknown clinical isolates. Both MALDI-TOF MS systems identified the isolates of C. jejuni, C. coli, C. lari, and C. fetus. The results of this study suggest that the MALDI-TOF MS technique can be used in the identification of Campylobacter spp. of public health importance.

Neural Plasticity in Multiple Sclerosis: The Functional and Molecular Background

PubMed Central

Glabinski, Andrzej

2015-01-01

Multiple sclerosis is an autoimmune neurodegenerative disorder resulting in motor dysfunction and cognitive decline. The inflammatory and neurodegenerative changes seen in the brains of MS patients lead to progressive disability and increasing brain atrophy. The most common type of MS is characterized by episodes of clinical exacerbations and remissions. This suggests the presence of compensating mechanisms for accumulating damage. Apart from the widely known repair mechanisms like remyelination, another important phenomenon is neuronal plasticity. Initially, neuroplasticity was connected with the developmental stages of life; however, there is now growing evidence confirming that structural and functional reorganization occurs throughout our lifetime. Several functional studies, utilizing such techniques as fMRI, TBS, or MRS, have provided valuable data about the presence of neuronal plasticity in MS patients. CNS ability to compensate for neuronal damage is most evident in RR-MS; however it has been shown that brain plasticity is also preserved in patients with substantial brain damage. Regardless of the numerous studies, the molecular background of neuronal plasticity in MS is still not well understood. Several factors, like IL-1β, BDNF, PDGF, or CB1Rs, have been implicated in functional recovery from the acute phase of MS and are thus considered as potential therapeutic targets. PMID:26229689

Metabolic Syndrome and Serum Liver Enzymes Level at Patients with Type 2 Diabetes Mellitus

PubMed Central

Music, Miralem; Dervisevic, Amela; Pepic, Esad; Lepara, Orhan; Fajkic, Almir; Ascic-Buturovic, Belma; Tuna, Enes

2015-01-01

Objectives: The aim of this study was to evaluate liver function in patients with type 2 diabetes mellitus (T2DM) with and without metabolic syndrome (MS) by determining serum levels of gamma glutamyltransferase (GGT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). We also investigated correlation between levels of liver enzymes and some components of MS in both groups of patients. Methods: This cross-sectional study included 96 patients (age 47–83 years) with T2DM. All patients were divided according to the criteria of the National Cholesterol Education Program (NCEP) in two groups: 50 patients with T2 DM and MS (T2DM-MS) and 46 patients with T2DM without MS (T2DM-Non MS). The analysis included blood pressure monitoring and laboratory tests: fasting blood glucose (FBG), total lipoprotein cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), fibrinogen and liver enzymes: GGT, ALT and AST. T2DM-MS group included patients which had FBG ≥ 6,1 mmol/L, TG ≥ 1,7 mmol/L and blood pressure ≥ 130/85 mm Hg. Results: T2DM-MS patients had significant higher values of systolic blood pressure, diastolic blood pressure and medium arterial pressure compared to T2DM-Non MS patients. Serum levels of TC, TG, LDL-C, VLDL-C and FBG were significantly higher in the T2DM-MS group compared to the T2DM-Non MS group. Serum fibrinogen level and GGT level were significantly higher in patients with T2DM-MS compared to the serum fibrinogen level and GGT level in T2DM-Non MS patients. Mean serum AST and ALT level were higher, but not significantly, in patients with T2DM and MS compared to the patients with T2DM without MS. Significant negative correlations were observed between TC and AST (r= -0,28, p<0,05), as well as between TC and ALT level (r= -0,29, p<0,05) in T2DM-MS group of patients. Conclusion: These results suggest that patients with T2DM and MS have markedly elevated liver enzymes. T2DM and MS probably play a role in increasing the risk of liver injury. PMID:26543313

Nonserotonergic projection neurons in the midbrain raphe nuclei contain the vesicular glutamate transporter VGLUT3.

PubMed

Jackson, Jesse; Bland, Brian H; Antle, Michael C

2009-01-01

The brainstem raphe nuclei are typically assigned a role in serotonergic brain function. However, numerous studies have reported that a large proportion of raphe projection cells are nonserotonergic. The identity of these projection cells is unknown. Recent studies have reported that the vesicular glutamate transporter VGLUT3 is found in both serotonergic and nonserotonergic neurons in both the median raphe (MR) and dorsal raphe (DR) nuclei. We injected the retrograde tracer cholera toxin subunit B into either the dorsal hippocampus or the medial septum (MS) and used triple labeled immunofluorescence to determine if nonserotonergic raphe cells projecting to these structures contained VGLUT3. Consistent with previous studies, only about half of retrogradely labeled MR neurons projecting to the hippocampus contained serotonin, whereas a majority of the retrogradely labeled nonserotonergic cells contained VGLUT3. Similar patterns were observed for MR cells projecting to the MS. About half of retrogradely labeled nonserotonergic neurons in the DR contained VGLUT3. Additionally, a large number of retrogradely labeled cells in the caudal linear and interpeduncular nuclei projecting to the MS were found to contain VGLUT3. These data suggest the enigmatic nonserotonergic projection from the MR to forebrain regions may be glutamatergic. In addition, these results demonstrate a dissociation between glutamatergic and serotonergic MR afferent inputs to the MS and hippocampus suggesting divergent and/or complementary roles of these pathways in modulating cellular activity within the septohippocampal network.

Ultratrace LC-MS/MS analysis of segmented calf hair for retrospective assessment of time of clenbuterol administration in Agriforensics.

PubMed

Duvivier, Wilco F; van Beek, Teris A; Meijer, Thijs; Peeters, Ruth J P; Groot, Maria J; Sterk, Saskia S; Nielen, Michel W F

2015-01-21

In agriforensics, time of administration is often debated when illegal drug residues, such as clenbuterol, are found in frequently traded cattle. In this proof-of-concept work, the feasibility of obtaining retrospective timeline information from segmented calf tail hair analyses has been studied. First, an ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) hair analysis method was adapted to accommodate smaller sample sizes and in-house validated. Then, longitudinal 1 cm segments of calf tail hair were analyzed to obtain clenbuterol concentration profiles. The profiles found were in good agreement with calculated, theoretical positions of the clenbuterol residues along the hair. Following assessment of the average growth rate of calf tail hair, time of clenbuterol administration could be retrospectively determined from segmented hair analysis data. The data from the initial animal treatment study (n = 2) suggest that time of treatment can be retrospectively estimated with an error of 3-17 days.

Numerical Investigation of Swimmer’s Gliding Stage with 6-DOF Movement

PubMed Central

Li, Tianzeng; Cai, Wenhao; Zhan, Jiemin

2017-01-01

The purpose of this study is to analyze the motion status of swimmers during their gliding stage using a numerical simulation method. This simulation strategy is conducted by solving the 3D incompressible Navier-Stokes equations using the Realizable k-ε turbulence closure equations in combination with the Six Degrees of Freedom (6-DOF) method. The uneven mass distribution of a swimmer and the roughness of the surface of the body are taken into consideration. The hydrodynamic characteristics and movement characteristics of the swimmers at different launch speeds were analyzed. The calculated results suggest that an optimal instant for starting propulsive movement is when the velocity of the swimmer decreases by 1.75 m/s to 2.0 m/s from an initial horizontal velocity of 3.1 m/s to 3.5 m/s. PMID:28125724

Multiple Sclerosis impact on employment and income in New Zealand.

PubMed

Pearson, J F; Alla, S; Clarke, G; Mason, D F; Anderson, T; Richardson, A; Miller, D H; Sabel, C E; Abernethy, D A; Willoughby, E W; Taylor, B V

2017-09-01

We investigated the demographic, social and clinical characteristics associated with employment status and income for people with multiple sclerosis (MS) in New Zealand (NZ). The NZ National MS Prevalence study included all persons resident in NZ on census day 2006 diagnosed with MS (96.7% coverage). Factors associated with employment and income status among the working age population (25-64 years) were identified by linear regression. Over 90% of working age people with MS (n=1727) had a work history, but 54% were not working. Work loss occurred early in the disease course, and at low disability (P<.001). Advancing age, progressive disease, longer disease duration, higher disability levels, partner loss and lower education were associated with work loss (P<.001). Working age people with MS had lower income than the NZ population (P<.0001). Higher qualifications yielded no additional income for MS females and about half the additional income for MS males (P<.0001). MS profoundly reduces employment and income early in the disease course, and at low levels of disability, however, unemployment is not entirely accounted for by clinical, social and demographic factors. These findings suggest social supports should be explored early in the disease course to reduce loss of income and unemployment for people with MS. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Factors associated with gait speed recovery after total knee arthroplasty: A longitudinal study.

PubMed

Pua, Yong-Hao; Seah, Felicia Jie-Ting; Clark, Ross Allan; Lian-Li Poon, Cheryl; Tan, John Wei-Ming; Chong, Hwei-Chi

2017-04-01

Gait speed limitations can remain significant issues after a total knee arthroplasty (TKA) but their associated factors are not well understood. This study aimed to identify the factors associated with acute gait speed recovery post-TKA. We performed a prospective longitudinal study of 1765 patients who underwent primary TKA between July 2013 and July 2015. At 4, 8, 12, and 16 weeks postsurgery, fast gait speed was measured. The factors associated with gait speed over time since TKA were identified using multivariable generalized least squares modeling. Lower postoperative quadriceps strength and knee flexion range of motion were closely associated with lower gait speed over time (0.084m/s, 0.064m/s, and 0.055m/s change in gait speed per interquartile range change in ipsilateral quadriceps strength, contralateral quadriceps strength, and knee flexion range of motion, respectively). Additional strong predictors of lower gait speed included older age (0.11m/s), lower levels of preoperative Short Form 36 physical function (0.066m/s), greater body mass (0.046m/s), and the preoperative use of a walking aid (overall P < 0.001). Patients who reported that they limited their daily activities due to a fear of falling also had poorer gait speed (0.033m/s and 0.054m/s slower gait speed for "Occasional" and "Often" categories, respectively, vs. "None"). Gait speed recovery post-TKA is driven by both physical and psychological factors, suggesting that identifying and treating the underlying physical and cognitive causes of gait speed limitations may be crucial to optimize functional recovery. Copyright © 2017 Elsevier Inc. All rights reserved.

Combined therapies to treat complex diseases: The role of the gut microbiota in multiple sclerosis.

PubMed

Calvo-Barreiro, Laura; Eixarch, Herena; Montalban, Xavier; Espejo, Carmen

2018-02-01

The commensal microbiota has emerged as an environmental risk factor for multiple sclerosis (MS). Studies in experimental autoimmune encephalomyelitis (EAE) models have shown that the commensal microbiota is an essential player in triggering autoimmune demyelination. Likewise, the commensal microbiota modulates the host immune system, alters the integrity and function of biological barriers and has a direct effect on several types of central nervous system (CNS)-resident cells. Moreover, a characteristic gut dysbiosis has been recognized as a consistent feature during the clinical course of MS, and the MS-related microbiota is gradually being elucidated. This review highlights animal studies in which commensal microbiota modulation was tested in EAE, as well as the mechanisms of action and influence of the commensal microbiota not only in the local milieu but also in the innate and adaptive immune system and the CNS. Regarding human research, this review focuses on studies that show how the commensal microbiota might act as a pathogenic environmental risk factor by directing immune responses towards characteristic pathogenic profiles of MS. We speculate how specific microbiome signatures could be obtained and used as potential pathogenic events and biomarkers for the clinical course of MS. Finally, we review recently published and ongoing clinical trials in MS patients regarding the immunomodulatory properties exerted by some microorganisms. Because MS is a complex disease with a large variety of associated environmental risk factors, we suggest that current treatments combined with strategies that modulate the commensal microbiota would constitute a broader immunotherapeutic approach and improve the clinical outcome for MS patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Health-Related Coping and Social Interaction in People with Multiple Sclerosis Supported by a Social Network: Pilot Study With a New Methodological Approach.

PubMed

Lavorgna, Luigi; Russo, Antonio; De Stefano, Manuela; Lanzillo, Roberta; Esposito, Sabrina; Moshtari, Fatemeh; Rullani, Francesco; Piscopo, Kyrie; Buonanno, Daniela; Brescia Morra, Vincenzo; Gallo, Antonio; Tedeschi, Gioacchino; Bonavita, Simona

2017-07-14

Social media are a vital link for people with health concerns who find in Web communities a valid and comforting source for information exchange, debate, and knowledge enrichment. This aspect is important for people affected by chronic diseases like multiple sclerosis (MS), who are very well informed about the disease but are vulnerable to hopes of being cured or saved by therapies whose efficacy is not always scientifically proven. To improve health-related coping and social interaction for people with MS, we created an MS social network (SMsocialnetwork.com) with a medical team constantly online to intervene promptly when false or inappropriate medical information are shared. The goal of this study was to assess the impact of SMsocialnetwork.com on the health-related coping and social interaction of people with MS by analyzing areas of interest through a Web-based survey. Referring to previous marketing studies analyzing the online platform's role in targeted health care, we conducted a 39-item Web-based survey. We then performed a construct validation procedure using a factorial analysis, gathering together like items of the survey related to different areas of interest such as utility, proximity, sharing, interaction, solving uncertainty, suggestion attitude, and exploration. We collected 130 Web-based surveys. The areas of interest analysis demonstrated that the users positively evaluated SMsocialnetwork.com to obtain information, approach and solve problems, and to make decisions (utility: median 4.2); improve feeling of closeness (proximity: median 5); catalyze relationships and text general personal opinions (sharing: median 5.6); get in touch with other users to receive innovative, effective, and practical solutions (interaction, solving uncertainty, and suggestion attitude medians were respectively: 4.1, 3, and 3); and share information about innovative therapeutic approaches and treatment options (suggestion attitude: median: 3.3). SMsocialnetwork.com was perceived by users to be a useful tool to support health-related coping and social interaction, and may suggest a new kind of therapeutic alliance between physicians and people with MS. ©Luigi Lavorgna, Antonio Russo, Manuela De Stefano, Roberta Lanzillo, Sabrina Esposito, Fatemeh Moshtari, Francesco Rullani, Kyrie Piscopo, Daniela Buonanno, Vincenzo Brescia Morra, Antonio Gallo, Gioacchino Tedeschi, Simona Bonavita. Originally published in the Interactive Journal of Medical Research (http://www.i-jmr.org/), 14.07.2017.

Multiple sclerosis in Canada 2011 to 2031: results of a microsimulation modelling study of epidemiological and economic impacts.

PubMed

Amankwah, Nana; Marrie, Ruth Ann; Bancej, Christina; Garner, Rochelle; Manuel, Douglas G; Wall, Ron; Finès, Philippe; Bernier, Julie; Tu, Karen; Reimer, Kim

2017-02-01

The objective of our study was to present model-based estimates and projections on current and future health and economic impacts of multiple sclerosis (MS) in Canada over a 20-year time horizon (2011-2031). Using Statistics Canada's Population Health Microsimulation Model (POHEM) framework, specifically the population-based longitudinal, microsimulation model named POHEM-Neurological, we identified people with MS from health administrative data sources and derived incidence and mortality rate parameters from a British Columbia population-based cohort for future MS incidence and mortality projections. We also included a utility-based measure (Health Utilities Index Mark 3) reflecting states of functional health to allow projections of health-related quality of life. Finally, we estimated caregiving parameters and health care costs from Canadian national surveys and health administrative data and included them as model parameters to assess the health and economic impact of the neurological conditions. The number of incident MS cases is expected to rise slightly from 4051 cases in 2011 to 4794 cases per 100 000 population in 2031, and the number of Canadians affected by MS will increase from 98 385 in 2011 to 133 635 in 2031. The total per capita health care cost (excluding out-of-pocket expenses) for adults aged 20 and older in 2011 was about $16 800 for individuals with MS, and approximately $2500 for individuals without a neurological condition. Thus, after accounting for additional expenditures due to MS (excluding out-of-pocket expenses), total annual health sector costs for MS are expected to reach $2.0 billion by 2031. As well, the average out-of-pocket expenditure for people with MS was around $1300 annually throughout the projection period. MS is associated with a significant economic burden on society, since it usually affects young adults during prime career- and family-building years. Canada has a particularly high prevalence of MS, so research such as the present study is essential to provide a better understanding of the current and future negative impacts of MS on the Canadian population, so that health care system policymakers can best plan how to meet the needs of patients who are affected by MS. These findings also suggest that identifying strategies to prevent MS and more effectively treat the disease are needed to mitigate these future impacts.

Multiple sclerosis in Canada 2011 to 2031: results of a microsimulation modelling study of epidemiological and economic impacts

PubMed Central

Nana, Amankwah; Ruth, Ann Marrie; Christina, Bancej; Rochelle, Garner; Douglas, G. Manuel; Ron, Wall; Philippe, Finès; Julie, Bernier; Karen, Tu; Kim, Reimer

2017-01-01

Introduction: The objective of our study was to present model-based estimates and projections on current and future health and economic impacts of multiple sclerosis (MS) in Canada over a 20-year time horizon (2011–2031). Methods: Using Statistics Canada’s Population Health Microsimulation Model (POHEM) framework, specifically the population-based longitudinal, microsimulation model named POHEM-Neurological, we identified people with MS from health administrative data sources and derived incidence and mortality rate parameters from a British Columbia population-based cohort for future MS incidence and mortality projections. We also included a utility-based measure (Health Utilities Index Mark 3) reflecting states of functional health to allow projections of health-related quality of life. Finally, we estimated caregiving parameters and health care costs from Canadian national surveys and health administrative data and included them as model parameters to assess the health and economic impact of the neurological conditions. Results: The number of incident MS cases is expected to rise slightly from 4051 cases in 2011 to 4794 cases per 100 000 population in 2031, and the number of Canadians affected by MS will increase from 98 385 in 2011 to 133 635 in 2031. The total per capita health care cost (excluding out-of-pocket expenses) for adults aged 20 and older in 2011 was about $16 800 for individuals with MS, and approximately $2500 for individuals without a neurological condition. Thus, after accounting for additional expenditures due to MS (excluding out-of-pocket expenses), total annual health sector costs for MS are expected to reach $2.0 billion by 2031. As well, the average out-of-pocket expenditure for people with MS was around $1300 annually throughout the projection period. Conclusion: MS is associated with a significant economic burden on society, since it usually affects young adults during prime career- and family-building years. Canada has a particularly high prevalence of MS, so research such as the present study is essential to provide a better understanding of the current and future negative impacts of MS on the Canadian population, so that health care system policymakers can best plan how to meet the needs of patients who are affected by MS. These findings also suggest that identifying strategies to prevent MS and more effectively treat the disease are needed to mitigate these future impacts. PMID:28273039

Native Mass Spectrometry Characterizes the Photosynthetic Reaction Center Complex from the Purple Bacterium Rhodobacter sphaeroides

NASA Astrophysics Data System (ADS)

Zhang, Hao; Harrington, Lucas B.; Lu, Yue; Prado, Mindy; Saer, Rafael; Rempel, Don; Blankenship, Robert E.; Gross, Michael L.

2017-01-01

Native mass spectrometry (MS) is an emerging approach to study protein complexes in their near-native states and to elucidate their stoichiometry and topology. Here, we report a native MS study of the membrane-embedded reaction center (RC) protein complex from the purple photosynthetic bacterium Rhodobacter sphaeroides. The membrane-embedded RC protein complex is stabilized by detergent micelles in aqueous solution, directly introduced into a mass spectrometer by nano-electrospray (nESI), and freed of detergents and dissociated in the gas phase by collisional activation. As the collision energy is increased, the chlorophyll pigments are gradually released from the RC complex, suggesting that native MS introduces a near-native structure that continues to bind pigments. Two bacteriochlorophyll a pigments remain tightly bound to the RC protein at the highest collision energy. The order of pigment release and their resistance to release by gas-phase activation indicates the strength of pigment interaction in the RC complex. This investigation sets the stage for future native MS studies of membrane-embedded photosynthetic pigment-protein and related complexes.

Matrix-Assisted Laser Desorption Ionization–Time of Flight (MALDI-TOF) Mass Spectrometry for Detection of Antibiotic Resistance Mechanisms: from Research to Routine Diagnosis

PubMed Central

Chudáčková, Eva; Walková, Radka

2013-01-01

Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) has been successfully applied as an identification procedure in clinical microbiology and has been widely used in routine laboratory practice because of its economical and diagnostic benefits. The range of applications of MALDI-TOF MS has been growing constantly, from rapid species identification to labor-intensive proteomic studies of bacterial physiology. The purpose of this review is to summarize the contribution of the studies already performed with MALDI-TOF MS concerning antibiotic resistance and to analyze future perspectives in this field. We believe that current research should continue in four main directions, including the detection of antibiotic modifications by degrading enzymes, the detection of resistance mechanism determinants through proteomic studies of multiresistant bacteria, and the analysis of modifications of target sites, such as ribosomal methylation. The quantification of antibiotics is suggested as a new approach to study influx and efflux in bacterial cells. The results of the presented studies demonstrate that MALDI-TOF MS is a relevant tool for the detection of antibiotic resistance and opens new avenues for both clinical and experimental microbiology. PMID:23297261

Cloning and characterization of a heme oxygenase-2 gene from alfalfa (Medicago sativa L.).

PubMed

Fu, Guang-Qing; Jin, Qi-Jiang; Lin, Yu-Ting; Feng, Jian-Fei; Nie, Li; Shen, Wen-Biao; Zheng, Tian-Qing

2011-11-01

Heme oxygenase (HO, EC 1.14.99.3) catalyzes the oxidation of heme and performs vital roles in plant development and stress responses. Two HO isozymes exist in plants. Between these, HO-1 is an oxidative stress-response protein, and HO-2 usually exhibited constitutive expression. Although alfalfa HO-1 gene (MsHO1) has been investigated previously, HO2 is still poorly understood. In this study, we report the cloning and characterization of HO2 gene, MsHO2, from alfalfa (Medica sativa L.). The full-length cDNA of MsHO2 contains an ORF of 870 bp and encodes for 290 amino acid residues with a predicted molecular mass of 33.3 kDa. Similar to MsHO1, MsHO2 also appears to have an N-terminal transit peptide sequence for chloroplast import. Many conserved residues in plant HO were also conserved in MsHO2. However, unlike HO-1, the conserved histidine (His) required for heme-iron binding and HO activity was replaced by tyrosine (Tyr) in MsHO2. Further biochemical activity analysis of purified mature MsHO2 showed no HO activity, suggesting that MsHO2 may not be a true HO in nature. Semi-quantitative RT-PCR confirmed its maximum expression in the germinating seeds. Importantly, the expression levels of MsHO2 were up-regulated under sodium nitroprusside (SNP) and H(2)O(2) (especially) treatment, respectively.

The efficacy of vitamin D in multiple sclerosis: A meta-analysis.

PubMed

Zheng, Chao; He, Liang; Liu, Lingling; Zhu, Jie; Jin, Tao

2018-05-12

Multiple sclerosis (MS) is a chronic inflammatory demyelination disorder in the central nervous system (CNS) leading to a high level of neurological disability. The pathogenesis of MS remains largely unknown, which explains the lack of significant efficacy of therapy in MS. Vitamin D deficiency is widely considered to be an environmental risk factor for MS. Many studies investigating the therapeutic effects of vitamin D on MS have been applied. The objective of this systematic review and meta-analysis was to evaluate the effectiveness of vitamin D in MS patients. To obtain a more comprehensive estimate of the efficacy of vitamin D on MS patients, we conducted a meta-analysis to determine the role of vitamin D in MS. The PubMed, EMBASE and Cochrane databases were searched in October 2017. Randomized, double-blind, placebo-controlled clinical trials recorded within the three main databases were considered. The analysis was conducted for two specific outcomes: Expanded Disability Status Scale (EDSS) score and annual relapse rate (ARR). Vitamin D 3 as add-on treatment had no significant therapeutic effect on MS according to EDSS score (mean difference -0.01 [95% CI -0.34 to 0.33]). The ARR was higher in the vitamin D group than in the placebo group (mean difference 0.05 [95% CI 0.01 to 0.1]). Our findings suggest that vitamin D appeared to have no therapeutic effect on EDSS score or ARR in the patients with MS. Copyright © 2018 Elsevier B.V. All rights reserved.

High doses of salicylate causes prepulse facilitation of onset-gap induced acoustic startle response.

PubMed

Sun, Wei; Doolittle, Lauren; Flowers, Elizabeth; Zhang, Chao; Wang, Qiuju

2014-01-01

Prepulse inhibition of acoustic startle reflex (PPI), a well-established method for evaluating sensorimotor gating function, has been used to detect tinnitus in animal models. Reduced gap induced PPI (gap-PPI) was considered as a sign of tinnitus. The silent gap used in the test contains both onset and offset signals. Tinnitus may affect these cues differently. In this experiment, we studied the effects of a high dose of salicylate (250 mg/kg, i.p.), an inducer of reversible tinnitus and sensorineural hearing loss, on gap-PPI induced by three different gaps: an onset-gap with 0.1 ms onset and 25 ms offset time, an offset-gap with 25 ms onset and 0.1 ms offset time, and an onset-offset-gap with 0.1 ms onset and offset time. We found that the onset-gaps induced smaller inhibitions than the offset-gaps before salicylate treatment. The offset-gap induced PPI was significantly reduced 1-3h after salicylate treatment. However, the onset-gap caused a facilitation of startle response. These results suggest that salicylate induced reduction of gap-PPI was not only caused by the decrease of offset-gap induced PPI, but also by the facilitation induced by the onset-gap. Since the onset-gap induced PPI is caused by neural offset response, our results suggest that salicylate may cause a facilitation of neural response to an offset acoustical signal. Treatment of vigabatrin (60 mg/kg/day, 14 days), which elevates the GABA level in the brain, blocked the offset-gap induced PPI and onset-gap induced facilitation caused by salicylate. These results suggest that enhancing GABAergic activities can alleviate salicylate induced tinnitus. Published by Elsevier B.V.

Depression in multiple sclerosis: The utility of common self-report instruments and development of a disease-specific measure.

PubMed

Strober, Lauren B; Arnett, Peter A

2015-01-01

The ultimate objective of the present investigation was to improve the detection of depression in multiple sclerosis (MS) by comparing common self-report depression measures to a new, modified measure, which takes into account the contribution that symptoms of MS may have on individuals' reports. There has been a longstanding concern regarding the accurate assessment of depression in MS, particularly with regard to the overlap of MS symptomatology and neurovegetative depression symptoms on self-report questionnaires, which may lead to an overdiagnosis of depression in MS. To address these difficulties, we previously proposed a "trunk and branch" of depression in MS. This model allows for the delineation of what symptoms are most reflective of depression in MS. By identifying these symptoms, it was possible to develop a modified Beck Depression Inventory (BDI) in which only the items found to be most related to depression in MS are included in the new measure, the MS Specific BDI (MS-BDI). We compared this measure to common self-report instruments (Beck Depression Inventory-Second Edition, BDI-II; Beck Depression Inventory-Fast Screen, BDI-FS; Chicago Multiscale Depression Inventory, CMDI). Results suggest that cutoffs of 4 on the BDI-FS and 23 on the CMDI Mood subscale are most useful when screening for depression in MS, with a sensitivity for both of 100%, while a cutoff of 19 on the BDI-II, a cutoff of 22 on the CMDI Evaluative scale, and a cutoff of 8 on the MS-BDI had high specificities, suggesting they can be used as to assist in diagnosing depression in MS.

Role of T1 mapping as a complementary tool to T2* for non-invasive cardiac iron overload assessment.

PubMed

Torlasco, Camilla; Cassinerio, Elena; Roghi, Alberto; Faini, Andrea; Capecchi, Marco; Abdel-Gadir, Amna; Giannattasio, Cristina; Parati, Gianfranco; Moon, James C; Cappellini, Maria D; Pedrotti, Patrizia

2018-01-01

Iron overload-related heart failure is the principal cause of death in transfusion dependent patients, including those with Thalassemia Major. Linking cardiac siderosis measured by T2* to therapy improves outcomes. T1 mapping can also measure iron; preliminary data suggests it may have higher sensitivity for iron, particularly for early overload (the conventional cut-point for no iron by T2* is 20ms, but this is believed insensitive). We compared T1 mapping to T2* in cardiac iron overload. In a prospectively large single centre study of 138 Thalassemia Major patients and 32 healthy controls, we compared T1 mapping to dark blood and bright blood T2* acquired at 1.5T. Linear regression analysis was used to assess the association of T2* and T1. A "moving window" approach was taken to understand the strength of the association at different levels of iron overload. The relationship between T2* (here dark blood) and T1 is described by a log-log linear regression, which can be split in three different slopes: 1) T2* low, <20ms, r2 = 0.92; 2) T2* = 20-30ms, r2 = 0.48; 3) T2*>30ms, weak relationship. All subjects with T2*<20ms had low T1; among those with T2*>20ms, 38% had low T1 with most of the subjects in the T2* range 20-30ms having a low T1. In established cardiac iron overload, T1 and T2* are concordant. However, in the 20-30ms T2* range, T1 mapping appears to detect iron. These data support previous suggestions that T1 detects missed iron in 1 out of 3 subjects with normal T2*, and that T1 mapping is complementary to T2*. The clinical significance of a low T1 with normal T2* should be further investigated.

Botulinum Toxin Treatment in Multiple Sclerosis-a Review.

PubMed

Safarpour, Yasaman; Mousavi, Tahereh; Jabbari, Bahman

2017-08-17

Purpose of review The purpose of this review is to provide updated information on the role of botulinum neurotoxin (BoNT) therapy in multiple sclerosis (MS). This review aims to answer which symptoms of multiple sclerosis may be amenable to BoNT therapy. Recent findings We searched the literature on the efficacy of BoNTs for treatment of MS symptoms up to April 1st 2017 via the Yale University Library's search engine including but not limited to Pub Med and Ovis SP. The level of efficacy was defined according to the assessment's criteria set forth by the Subcommittee on Guideline Development of the American Academy of Neurology. Significant efficacy was found for two indications based on the available blinded studies (class I and II) and has been suggested for several others through open-label clinical trials. Summary There is level A evidence (effective- two or more class I) that injection of BoNT-A into the bladder's detrusor muscle improves MS-related neurogenic detrusor overactivity (NDO) and MS-related overactive (OA) bladder. There is level B evidence (probably effective- two class II studies) for utility of intramuscular BoNT-A injections for spasticity of multiple sclerosis. Emerging data based on retrospective class IV studies demonstrates that intramuscular injection of BoNTs may help other symptoms of MS such as focal tonic spasms, focal myokymia, spastic dysphagia, and double vision in internuclear ophthalmoplegia. There is no data on MS-related trigeminal neuralgia and sialorrhea, two conditions which have been shown to respond to BoNT therapy in non-MS population.

Factors associated with recently transmitted Mycobacterium tuberculosis strain MS0006 in Hinds County, Mississippi.

PubMed

Temple, Brian; Kwara, Awewura; Sunesara, Imran; Mena, Leandro; Dobbs, Thomas; Henderson, Harold; Holcomb, Mike; Webb, Risa

2011-12-01

The objective of this study was to investigate risk factors associated with tuberculosis (TB) transmission that was caused by Mycobacterium tuberculosis strain MS0006 from 2004 to 2009 in Hinds County, Mississippi. DNA fingerprinting using spoligotyping, mycobacterial interspersed repetitive unit, and IS6110-based restriction fragment length polymorphism of culture-confirmed cases of TB was performed. Clinical and demographic factors associated with strain MS0006 were analyzed by univariate and multivariate analysis. Of the 144 cases of TB diagnosed during the study period, 117 were culture positive with fingerprints available. There were 48 different strains, of which 6 clustered strains were distributed among 74 patients. The MS0006 strain accounted for 46.2% of all culture-confirmed cases. Risk factors for having the MS0006 strain in a univariate analysis included homelessness, HIV co-infection, sputum smear negativity, tuberculin skin test negativity, and noninjectable drug use. Multivariate analysis identified homelessness (odds ratio 7.88, 95% confidence interval 2.90-21.35) and African American race (odds ratio 5.80, 95% confidence interval 1.37-24.55) as independent predictors of having TB caused by the MS0006 strain of M. tuberculosis. Our findings suggest that a majority of recently transmitted TB in the studied county was caused by the MS0006 strain. African American race and homelessness were significant risk factors for inclusion in the cluster. Molecular epidemiology techniques continue to provide in-depth analysis of disease transmission and play a vital role in effective contact tracing and interruption of ongoing transmission.

An electrophysiological study of the mental rotation of polygons.

PubMed

Pierret, A; Peronnet, F; Thevenet, M

1994-05-09

Reaction times and event-related potentials (ERPs) were recorded during a task requiring subjects to decide whether two sequentially presented polygons had the same shape regardless of differences in orientation. Reaction times increased approximately linearly with angular departure from upright orientation, which suggests that mental rotation was involved in the comparison process. The ERPs showed, between 665 and 1055 ms, a late posterior negativity also increasing with angular disparity from upright, which we assumed to reflect mental rotation. Two other activities were exhibited, from 265 to 665 ms, which may be related either to an evaluation of the stimulus or a predetermination of its orientation, and from 1055 to 1600 ms attributed to the decision process.

Factors associated with the development of atrial fibrillation in patients with rheumatic mitral stenosis.

PubMed

Ozaydin, Mehmet; Turker, Yasin; Varol, Ercan; Alaca, Sule; Erdogan, Dogan; Yilmaz, Nigar; Dogan, Abdullah

2010-06-01

The aim of this study was to evaluate the factors associated with the development of atrial fibrillation (AF) in patients with rheumatic mitral stenosis (MS). A total of 146 consecutive patients with rheumatic MS were screened. They were accepted to be in AF group and sinus rhythm group according to their rhythm in the baseline ECG. After screening, 38 patients were excluded due to hyperthyroidism (n = 13), chronic obstructive pulmonary disease (n = 22), malignancy (n = 2) and rheumatoid arthritis (n = 1). Therefore, remaining 108 patients, 74 of whom in sinus rhythm (MS-SR) and 34 of whom in AF (MS-AF) constituted study population. Fourty age- and gender-matched patients constituted control group. Factors associated with development of AF in multivariable analysis included High sensitivity C reactive protein (P = 0.005; odds ratio, 3.44; 95% confidence interval, 1.44-8.22), N-terminal of brain natriuretic peptide precursor (P < 0.0001; odds ratio, 1.03; 95% confidence interval, 1.02-1.06) and left atrial diameter (P < 0.0001; odds ratio, 1.68; 95% confidence interval, 1.32-2.14). Present study suggests that High sensitivity C reactive protein, N-terminal of brain natriuretic peptide precursor and left atrial diameter are associated with development AF in patients with MS.

Effects of transcranial random noise stimulation (tRNS) on affect, pain and attention in multiple sclerosis.

PubMed

Palm, Ulrich; Chalah, Moussa A; Padberg, Frank; Al-Ani, Tarik; Abdellaoui, Mohamed; Sorel, Marc; Dimitri, Dalia; Créange, Alain; Lefaucheur, Jean-Pascal; Ayache, Samar S

2016-01-01

Pain and cognitive impairment are frequent symptoms in patients with multiple sclerosis (MS). Neglecting experimental pain and paying attention to demanding tasks is reported to decrease the pain intensity. Little is known about the interaction between chronic neuropathic pain and attention disorders in MS. Recently, transcranial direct current stimulation (tDCS) was used to modulate various cognitive and motor symptoms in MS. We aimed to study the effects of transcranial random noise stimulation (tRNS), a form of transcranial electric stimulation, over the left dorsolateral prefrontal cortex (DLPFC) on attention and neuropathic pain in MS patients. 16 MS patients were included in a randomized, sham-controlled, cross-over study. Each patient randomly received two tRNS blocks, separated by three weeks of washout interval. Each block consisted of three consecutive daily sessions of either active or sham tRNS. The patients were evaluated for pain, attention and mood and further underwent an electrophysiological evaluation. Compared to sham, tRNS showed a trend to decrease the N2-P2 amplitudes of pain related evoked potentials and improve pain ratings. Attention performance and mood scales did not change after stimulations. This study suggests the role of tRNS in pain modulation, which could have been more evident with longer stimulation protocols.

The Representation of Inflammatory Signals in the Brain – A Model for Subjective Fatigue in Multiple Sclerosis

PubMed Central

Hanken, Katrin; Eling, Paul; Hildebrandt, Helmut

2014-01-01

In multiple sclerosis (MS) patients, fatigue is rated as one of the most common and disabling symptoms. However, the pathophysiology underlying this fatigue is not yet clear. Several lines of evidence suggest that immunological factors, such as elevated levels of pro-inflammatory cytokines, may contribute to subjective fatigue in MS patients. Pro-inflammatory cytokines represent primary mediators of immune-to-brain-communication, modulating changes in the neurophysiology of the central nervous system. Recently, we proposed a model arguing that fatigue in MS patients is a subjective feeling, which is related to inflammation. Moreover, it implies that fatigue can be measured behaviorally only by applying specific cognitive tasks related to alertness and vigilance. In the present review, we focus on the subjective feeling of MS-related fatigue. We examine the hypothesis that the subjective feeling of MS-related fatigue may be a variant of inflammation-induced sickness behavior, resulting from cytokine-mediated activity changes within brain areas involved in interoception and homeostasis including the insula, the anterior cingulate, and the hypothalamus. We first present studies demonstrating a relationship between pro-inflammatory cytokines and subjective fatigue in healthy individuals, in people with inflammatory disorders, and particularly in MS patients. Subsequently, we discuss studies analyzing the impact of anti-inflammatory treatment on fatigue. In the next part of this review, we present studies on the transmission and neural representation of inflammatory signals, with a special focus on possible neural concomitants of inflammation-induced fatigue. We also present two of our studies on the relationship between local gray and white matter atrophy and fatigue in MS patients. Finally, we discuss some implications of our findings and future perspectives. PMID:25566171

An 8-year study of people with multiple sclerosis in Isfahan, Iran: Association between environmental air pollutants and severity of disease.

PubMed

Ashtari, Fereshte; Esmaeil, Nafiseh; Mansourian, Marjan; Poursafa, Parinaz; Mirmosayyeb, Omid; Barzegar, Mahdi; Pourgheisari, Hajar

2018-06-15

The evidence for an impact of ambient air pollution on the incidence and severity of multiple sclerosis (MS) is still limited. In the present study, we assessed the association between daily air pollution levels and MS prevalence and severity in Isfahan city, Iran. Data related to MS patients has been collected from 2008 to 2016 in a referral university clinic. The air quality index (AQI) data, were collected from 6 monitoring stations of Isfahan department of environment. The distribution map presenting the sites of air pollution monitoring stations as well as the residential address of MS patients was plotted on geographical information system (GIS). An increase in AQI level in four areas of the city (north, west, east and south) was associated with higher expanded disability status scale (EDSS) of MS patients[logistic regression odds ratio = 1.01 (95% CI = 1.008,1.012)]. Moreover, significant inverse association between the complete remission after the first attack with AQI level in total areas [logistic regression odds ratio = 0.987 (95% CI = 0.977, 0.997)] was found in crude model. However, after adjustment for confounding variables through multivariate logistic regression, AQI level was associated with degree of complete remission after first attack 1.005 (95% CI = 1.004, 1.006). The results of our study suggest that air pollution could play a role in the severity and remission of MS disease. However, more detailed studies with considering the complex involvement of different environmental factors including sunlight exposure, diet, depression and vitamin D are needed to determine the outcome of MS. Copyright © 2018 Elsevier B.V. All rights reserved.

Comprehensive systematic review summary: Disease-modifying therapies for adults with multiple sclerosis: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

PubMed

Rae-Grant, Alexander; Day, Gregory S; Marrie, Ruth Ann; Rabinstein, Alejandro; Cree, Bruce A C; Gronseth, Gary S; Haboubi, Michael; Halper, June; Hosey, Jonathan P; Jones, David E; Lisak, Robert; Pelletier, Daniel; Potrebic, Sonja; Sitcov, Cynthia; Sommers, Rick; Stachowiak, Julie; Getchius, Thomas S D; Merillat, Shannon A; Pringsheim, Tamara

2018-04-24

To review evidence on starting, switching, and stopping disease-modifying therapies (DMTs) for multiple sclerosis (MS) in clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and progressive MS forms. Relevant, peer-reviewed research articles, systematic reviews, and abstracts were identified (MEDLINE, CENTRAL, EMBASE searched from inception to November 2016). Studies were rated using the therapeutic classification scheme. Prior published Cochrane reviews were also used. Twenty Cochrane reviews and an additional 73 full-text articles were selected for data extraction through an updated systematic review (completed November 2016). For people with RRMS, many DMTs are superior to placebo (annualized relapses rates [ARRs], new disease activity [new MRI T2 lesion burden], and in-study disease progression) (see summary and full text publications). For people with RRMS who experienced a relapse on interferon-β (IFN-β) or glatiramer acetate, alemtuzumab is more effective than IFN-β-1a 44 μg subcutaneous 3 times per week in reducing the ARR. For people with primary progressive MS, ocrelizumab is probably more effective than placebo (in-study disease progression). DMTs for MS have varying adverse effects. In people with CIS, glatiramer acetate and IFN-β-1a subcutaneous 3 times per week are more effective than placebo in decreasing risk of conversion to MS. Cladribine, immunoglobulins, IFN-β-1a 30 μg intramuscular weekly, IFN-β-1b subcutaneous alternate day, and teriflunomide are probably more effective than placebo in decreasing risk of conversion to MS. Suggestions for future research include studies considering comparative effectiveness, usefulness of high-efficacy treatment vs stepped-care protocols, and research into predictive biomarkers. © 2018 American Academy of Neurology.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shatsky, Maxim; Allen, Simon; Gold, Barbara

Numerous affinity purification – mass-spectrometry (AP-MS) and yeast two hybrid (Y2H) screens have each defined thousands of pairwise protein-protein interactions (PPIs), most between functionally unrelated proteins. The accuracy of these networks, however, is under debate. Here we present an AP-MS survey of the bacterium Desulfovibrio vulgaris together with a critical reanalysis of nine published bacterial Y2H and AP-MS screens. We have identified 459 high confidence PPIs from D. vulgaris and 391 from Escherichia coli. Compared to the nine published interactomes, our two networks are smaller; are much less highly connected; have significantly lower false discovery rates; and are much moremore » enriched in protein pairs that are encoded in the same operon, have similar functions, and are reproducibly detected in other physical interaction assays. Lastly, our work establishes more stringent benchmarks for the properties of protein interactomes and suggests that bona fide PPIs much more frequently involve protein partners that are annotated with similar functions or that can be validated in independent assays than earlier studies suggested.« less

Association of UV radiation with multiple sclerosis prevalence and sex ratio in France

PubMed Central

Orton, S.-M.; Wald, L.; Confavreux, C.; Vukusic, S.; Krohn, J.P.; Ramagopalan, S.V.; Herrera, B.M.; Sadovnick, A.D.

2011-01-01

Background: French farmers and their families constitute an informative population to study multiple sclerosis (MS) prevalence and related epidemiology. We carried out an ecological study to evaluate the association of MS prevalence and ultraviolet (UV) radiation, a candidate climatologic risk factor. Methods: Mean annual and winter (December–March) UVB irradiation values were systematically compared to MS prevalence rates in corresponding regions of France. UVB data were obtained from the solar radiation database (SoDa) service and prevalence rates from previously published data on 2,667 MS cases registered with the national farmer health insurance system, Mutualité Sociale Agricole (MSA). Pearson correlation was used to examine the relationship of annual and winter UVB values with MS prevalence. Male and female prevalence were also analyzed separately. Linear regression was used to test for interaction of annual and winter UVB with sex in predicting MS prevalence. Results: There was a strong association between MS prevalence and annual mean UVB irradiation (r = −0.80, p < 0.001) and average winter UVB (r = −0.87, p < 0.001). Both female (r = −0.76, p < 0.001) and male (r = −0.46, p = 0.032) prevalence rates were correlated with annual UVB. Regression modeling showed that the effect of UVB on prevalence rates differed by sex; the interaction effect was significant for both annual UVB (p = 0.003) and winter UVB (p = 0.002). Conclusions: The findings suggest that regional UVB radiation is predictive of corresponding MS prevalence rates and supports the hypothesis that sunlight exposure influences MS risk. The evidence also supports a potential role for gender-specific effects of UVB exposure. PMID:21282589

Lipopolysaccharide Binding Protein and Oxidative Stress in a Multiple Sclerosis Model.

PubMed

Escribano, Begoña M; Medina-Fernández, Francisco J; Aguilar-Luque, Macarena; Agüera, Eduardo; Feijoo, Montserrat; Garcia-Maceira, Fe I; Lillo, Rafael; Vieyra-Reyes, Patricia; Giraldo, Ana I; Luque, Evelio; Drucker-Colín, René; Túnez, Isaac

2017-01-01

Recent findings in experimental autoimmune encephalomyelitis (EAE) suggest that altering certain bacterial populations present in the gut may lead to a proinflammatory condition, that could result in the development of multiple sclerosis (MS). Also, Reactive Oxygen Species seem to be involved in the course of MS. In this study, it has been aimed to relate all these variables starting from an analysis of the lipopolysaccharide (LPS) and LPS-binding protein (LBP) with the determination of parameters related to oxidative stress in the blood, brain and spinal cord. For this purpose, samples obtained from EAE rats and relapsing-remitting (RRMS) MS patients were used. In addition, EAE rats were treated with Natalizumab, N-acetyl-cysteine and dimethyl fumarate. Natalizumab was also employed in RRMS. The results of this study revealed an improvement in the clinical symptoms of the EAE and MS with the treatments, as well as a reduction in the oxidative stress parameters and in LBP. Correlations between the clinical variables of the disease, i.e. oxidative damage and LBP, were established. Although the conclusions of this research are indeed relevant, further investigation would be necessary to establish the intrinsic mechanisms of the MS-oxidative stress-microbiota relationship.

Phylogenetic Analysis of the MS4A and TMEM176 Gene Families

PubMed Central

Zuccolo, Jonathan; Bau, Jeremy; Childs, Sarah J.; Goss, Greg G.; Sensen, Christoph W.; Deans, Julie P.

2010-01-01

Background The MS4A gene family in humans includes CD20 (MS4A1), FcRβ (MS4A2), Htm4 (MS4A3), and at least 13 other syntenic genes encoding membrane proteins, most having characteristic tetraspanning topology. Expression of MS4A genes is variable in tissues throughout the body; however, several are limited to cells in the hematopoietic system where they have known roles in immune cell functions. Genes in the small TMEM176 group share significant sequence similarity with MS4A genes and there is evidence of immune function of at least one of the encoded proteins. In this study, we examined the evolutionary history of the MS4A/TMEM176 families as well as tissue expression of the phylogenetically earliest members, in order to investigate their possible origins in immune cells. Principal Findings Orthologs of human MS4A genes were found only in mammals; however, MS4A gene homologs were found in most jawed vertebrates. TMEM176 genes were found only in mammals and bony fish. Several unusual MS4A genes having 2 or more tandem MS4A sequences were identified in the chicken (Gallus gallus) and early mammals (opossum, Monodelphis domestica and platypus, Ornithorhyncus anatinus). A large number of highly conserved MS4A and TMEM176 genes was found in zebrafish (Danio rerio). The most primitive organism identified to have MS4A genes was spiny dogfish (Squalus acanthus). Tissue expression of MS4A genes in S. acanthias and D. rerio showed no evidence of expression restricted to the hematopoietic system. Conclusions/Significance Our findings suggest that MS4A genes first appeared in cartilaginous fish with expression outside of the immune system, and have since diversified in many species into their modern forms with expression and function in both immune and nonimmune cells. PMID:20186339

Ecotoxicological assessment of flocculant modified soil for lake restoration using an integrated biotic toxicity index.

PubMed

Wang, Zhibin; Zhang, Honggang; Pan, Gang

2016-06-15

Flocculant modified soils/clays are being increasingly studied as geo-engineering materials for lake restoration and harmful algal bloom control. However, the potential impacts of adding these materials in aquatic ecological systems remain unclear. This study investigated the potential effects of chitosan, cationic starch, chitosan modified soils (MS-C) and cationic starch modified soils (MS-S) on the aquatic organisms by using a bioassay battery. The toxicity potential of these four flocculants was quantitatively assessed using an integrated biotic toxicity index (BTI). The test system includes four aquatic species, namely Chlorella vulgaris, Daphnia magna, Cyprinus carpio and Limnodrilus hoffmeisteri, which represent four trophic levels in the freshwater ecosystem. Results showed that median effect concentrations (EC50) of the MS-C and MS-S were 31-124 times higher than chitosan and cationic starch, respectively. D. magna was the most sensitive species to the four flocculants. Histological examination of C. carpio showed that significant pathological changes were found in gills. Different from chitosan and cationic starch, MS-C and MS-S significantly alleviated the acute toxicities of chitosan and cationic starch. The toxicity order of the four flocculants based on BTI were cationic starch > chitosan > MS-S > MS-C. The results suggested that BTI can be used as a quantitative and comparable indicator to assess biotic toxicity for aquatic geo-engineering materials. Chitosan or cationic starch modified soil/clay materials can be used at their optimal dosage without causing substantial adverse effects to the bioassay battery in aquatic ecosystem. Copyright © 2015 Elsevier Ltd. All rights reserved.

Parsing and Quantification of Raw Orbitrap Mass Spectrometer Data Using RawQuant.

PubMed

Kovalchik, Kevin A; Moggridge, Sophie; Chen, David D Y; Morin, Gregg B; Hughes, Christopher S

2018-06-01

Effective analysis of protein samples by mass spectrometry (MS) requires careful selection and optimization of a range of experimental parameters. As the output from the primary detection device, the "raw" MS data file can be used to gauge the success of a given sample analysis. However, the closed-source nature of the standard raw MS file can complicate effective parsing of the data contained within. To ease and increase the range of analyses possible, the RawQuant tool was developed to enable parsing of raw MS files derived from Thermo Orbitrap instruments to yield meta and scan data in an openly readable text format. RawQuant can be commanded to export user-friendly files containing MS 1 , MS 2 , and MS 3 metadata as well as matrices of quantification values based on isobaric tagging approaches. In this study, the utility of RawQuant is demonstrated in several scenarios: (1) reanalysis of shotgun proteomics data for the identification of the human proteome, (2) reanalysis of experiments utilizing isobaric tagging for whole-proteome quantification, and (3) analysis of a novel bacterial proteome and synthetic peptide mixture for assessing quantification accuracy when using isobaric tags. Together, these analyses successfully demonstrate RawQuant for the efficient parsing and quantification of data from raw Thermo Orbitrap MS files acquired in a range of common proteomics experiments. In addition, the individual analyses using RawQuant highlights parametric considerations in the different experimental sets and suggests targetable areas to improve depth of coverage in identification-focused studies and quantification accuracy when using isobaric tags.

Exercise Intensity and Incidence of Metabolic Syndrome: The SUN Project.

PubMed

Hidalgo-Santamaria, María; Fernandez-Montero, Alejandro; Martinez-Gonzalez, Miguel A; Moreno-Galarraga, Laura; Sanchez-Villegas, Almudena; Barrio-Lopez, María T; Bes-Rastrollo, Maira

2017-04-01

Emerging evidence suggests that vigorous physical activity may be associated with higher cardioprotective benefits than moderate physical activity. This study aimed to assess the long-term relationship between the intensity of leisure time physical activity (LTPA) and the risk of developing metabolic syndrome (MS) in a prospective cohort study. The Seguimiento Universidad de Navarra (SUN) Project comprises Spanish university graduates. Participants (n=10,145) initially free of MS were followed for a minimum of 6 years (2008-2014). Analysis was conducted in 2015. Physical activity was assessed though a validated questionnaire. The intensity of each physical activity was measured in METs. The intensity of LTPA was estimated by the ratio between total METs/week and total hours of LTPA/week, obtaining the mean METs/hour of LTPA. MS was defined according to the harmonizing definition. The association between the intensity of LTPA (METs/hour) and MS was assessed with logistic regression models adjusting for potential confounders. Among 10,145 participants initially free of any MS criteria, 412 new MS cases were observed. Vigorous LTPA was associated with a 37% relatively lower risk (AOR=0.63, 95% CI=0.44, 0.89) compared with light LTPA. For a given total energy expenditure, independent of the time spent on it, participants who performed vigorous LTPA exhibited a higher reduction in the risk of MS than those who performed light to moderate LTPA. Vigorous LTPA was significantly associated with lower risk of developing MS after a 6-year follow-up period. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Relationship between Spectral Characteristics of Spontaneous Postural Sway and Motion Sickness Susceptibility.

PubMed

Laboissière, Rafael; Letievant, Jean-Charles; Ionescu, Eugen; Barraud, Pierre-Alain; Mazzuca, Michel; Cian, Corinne

2015-01-01

Motion sickness (MS) usually occurs for a narrow band of frequencies of the imposed oscillation. It happens that this frequency band is close to that which are spontaneously produced by postural sway during natural stance. This study examined the relationship between reported susceptibility to motion sickness and postural control. The hypothesis is that the level of MS can be inferred from the shape of the Power Spectral Density (PSD) profile of spontaneous sway, as measured by the displacement of the center of mass during stationary, upright stance. In Experiment 1, postural fluctuations while standing quietly were related to MS history for inertial motion. In Experiment 2, postural stability measures registered before the onset of a visual roll movement were related to MS symptoms following the visual stimulation. Study of spectral characteristics in postural control showed differences in the distribution of energy along the power spectrum of the antero-posterior sway signal. Participants with MS history provoked by exposure to inertial motion showed a stronger contribution of the high frequency components of the sway signal. When MS was visually triggered, sick participants showed more postural sway in the low frequency range. The results suggest that subject-specific PSD details may be a predictor of the MS level. Furthermore, the analysis of the sway frequency spectrum provided insight into the intersubject differences in the use of postural control subsystems. The relationship observed between MS susceptibility and spontaneous posture is discussed in terms of postural sensory weighting and in relation to the nature of the provocative stimulus.

Mortality from multiple sclerosis in British military personnel.

PubMed

Harris, E Clare; Palmer, Keith T; Cox, Vanessa; Darnton, Andrew; Osman, John; Coggon, David

2017-08-01

While analysing trends in occupational mortality in England and Wales, we noticed an unexpectedly elevated proportion of deaths from multiple sclerosis (MS) among men in the armed forces. To document and explore possible explanations for the observed excess. We analysed data on underlying cause of death and last full-time occupation for 3,688,916 deaths among men aged 20-74 years in England and Wales during 1979-2010, calculating proportional mortality ratios (PMRs) standardised for age. We compared PMRs for MS in the armed forces with those for each main social class, and in selected other occupations. We also compared PMRs for MS with those for motor neurone disease (MND). The overall PMR for MS in the armed forces during 1979-2010 was 243 (95%CI 203-288). The excess was apparent in each of three separate decades of study (PMRs, ranging from 220 to 259), and across the entire age range. PMRs for MS were not elevated to the same extent in comparator occupations, nor in any of the main social classes. There was no parallel increase in PMRs for MND. These findings suggest that the high proportional mortality from MS in British military personnel is unlikely to have occurred by chance, or as an artefact of the method of investigation. However, the only military cohort study with published results on MS does not support an increased risk. It would be useful to analyse data on MS from other established military cohorts, to check for evidence of a hazard. © The Author 2017. Published by Oxford University Press on behalf of the Society of Occupational Medicine.

Prevalence of metabolic syndrome in 8–18-year-old school-going children of Srinagar city of Kashmir India

PubMed Central

Andrabi, Syed M.S.; Bhat, Mohd H.; Andrabi, Syed R.S.; Kamili, Mohd M.A.; Imran, Ali; Nisar, Iqra; Nisar, Umara

2013-01-01

Aim: Obesity is the most common cause of insulin resistance and metabolic syndrome (MS). These are the most important risk factors for coronary heart disease (CHD). No evidence exists regarding the prevalence of the MS in children in sSrinagar city of Kashmir India. We aimed to evaluate the prevalence of MS in 8–18-year-old school-going children of Kashmir, India. Materials and Methods: In this cross-sectional study, 758 respondents in 8–18 years of age were randomly selected using a simple random sampling method. The self-designed questionnaire was individually completed after receiving a written informed consent. The weight, height, waist circumference (WC), body mass index (BMI), and blood pressure were measured using standard tools. Ten milliliters of blood was taken for measuring lipid profile and fasting blood sugar (FBS) of the school children. We determined MS according to the modified Adult Treatment Panel III (ATP III) criteria. Results: The prevalence of the MS was 3.8% (boys: 3.9%, girls: 3.8%) and the prevalence of obesity was 9.9% (boys: 9.9%, girls: 10.6%) among the studied children. Obese subjects had the highest proportion of MS compared with those at risk for overweight and those with normal weight (30.7% vs. 2.5% and 0.5%, respectively; P = 0.000). Conclusion: The MS is prevalent even in young children, so we suggest screening programs for children aged 8–18 years to control obesity and MS in the developing world. PMID:23776859

Delayed P100-Like Latencies in Multiple Sclerosis: A Preliminary Investigation Using Visual Evoked Spread Spectrum Analysis

PubMed Central

Kiiski, Hanni S. M.; Ní Riada, Sinéad; Lalor, Edmund C.; Gonçalves, Nuno R.; Nolan, Hugh; Whelan, Robert; Lonergan, Róisín; Kelly, Siobhán; O'Brien, Marie Claire; Kinsella, Katie; Bramham, Jessica; Burke, Teresa; Ó Donnchadha, Seán; Hutchinson, Michael; Tubridy, Niall; Reilly, Richard B.

2016-01-01

Conduction along the optic nerve is often slowed in multiple sclerosis (MS). This is typically assessed by measuring the latency of the P100 component of the Visual Evoked Potential (VEP) using electroencephalography. The Visual Evoked Spread Spectrum Analysis (VESPA) method, which involves modulating the contrast of a continuous visual stimulus over time, can produce a visually evoked response analogous to the P100 but with a higher signal-to-noise ratio and potentially higher sensitivity to individual differences in comparison to the VEP. The main objective of the study was to conduct a preliminary investigation into the utility of the VESPA method for probing and monitoring visual dysfunction in multiple sclerosis. The latencies and amplitudes of the P100-like VESPA component were compared between healthy controls and multiple sclerosis patients, and multiple sclerosis subgroups. The P100-like VESPA component activations were examined at baseline and over a 3-year period. The study included 43 multiple sclerosis patients (23 relapsing-remitting MS, 20 secondary-progressive MS) and 42 healthy controls who completed the VESPA at baseline. The follow-up sessions were conducted 12 months after baseline with 24 MS patients (15 relapsing-remitting MS, 9 secondary-progressive MS) and 23 controls, and again at 24 months post-baseline with 19 MS patients (13 relapsing-remitting MS, 6 secondary-progressive MS) and 14 controls. The results showed P100-like VESPA latencies to be delayed in multiple sclerosis compared to healthy controls over the 24-month period. Secondary-progressive MS patients had most pronounced delay in P100-like VESPA latency relative to relapsing-remitting MS and controls. There were no longitudinal P100-like VESPA response differences. These findings suggest that the VESPA method is a reproducible electrophysiological method that may have potential utility in the assessment of visual dysfunction in multiple sclerosis. PMID:26726800

Partitioning the metabolic scope: the importance of anaerobic metabolism and implications for the oxygen- and capacity-limited thermal tolerance (OCLTT) hypothesis

PubMed Central

Ejbye-Ernst, Rasmus; Michaelsen, Thomas Y.; Tirsgaard, Bjørn; Wilson, Jonathan M.; Jensen, Lasse F.; Steffensen, John F.; Pertoldi, Cino; Aarestrup, Kim; Svendsen, Jon C.

2016-01-01

Ongoing climate change is predicted to affect the distribution and abundance of aquatic ectotherms owing to increasing constraints on organismal physiology, in particular involving the metabolic scope (MS) available for performance and fitness. The oxygen- and capacity-limited thermal tolerance (OCLTT) hypothesis prescribes MS as an overarching benchmark for fitness-related performance and assumes that any anaerobic contribution within the MS is insignificant. The MS is typically derived from respirometry by subtracting standard metabolic rate from the maximal metabolic rate; however, the methodology rarely accounts for anaerobic metabolism within the MS. Using gilthead sea bream (Sparus aurata) and Trinidadian guppy (Poecilia reticulata), this study tested for trade-offs (i) between aerobic and anaerobic components of locomotor performance; and (ii) between the corresponding components of the MS. Data collection involved measuring oxygen consumption rate at increasing swimming speeds, using the gait transition from steady to unsteady (burst-assisted) swimming to detect the onset of anaerobic metabolism. Results provided evidence of the locomotor performance trade-off, but only in S. aurata. In contrast, both species revealed significant negative correlations between aerobic and anaerobic components of the MS, indicating a trade-off where both components of the MS cannot be optimized simultaneously. Importantly, the fraction of the MS influenced by anaerobic metabolism was on average 24.3 and 26.1% in S. aurata and P. reticulata, respectively. These data highlight the importance of taking anaerobic metabolism into account when assessing effects of environmental variation on the MS, because the fraction where anaerobic metabolism occurs is a poor indicator of sustainable aerobic performance. Our results suggest that without accounting for anaerobic metabolism within the MS, studies involving the OCLTT hypothesis could overestimate the metabolic scope available for sustainable activities and the ability of individuals and species to cope with climate change. PMID:27293766

Enhanced approaches for identifying Amadori products: application to peanut allergens

USDA-ARS?s Scientific Manuscript database

The dry roasting of peanuts is suggested to influence allergenic sensitization due to formation of advanced glycation end products (AGE) on peanut proteins. Identifying AGEs is technically challenging. The AGE composition of peanut proteins was probed with nanoLC-ESI-MS and MS/MS analyses. Amadori ...

Synthesis and characterization of DNA nano-meso-microspheres as drug delivery carriers for intratumoral chemotherapy

NASA Astrophysics Data System (ADS)

Enriquez Schumacher, Iris Vanessa

Conventional cancer chemotherapy results in systemic toxicity which severely limits effectiveness and often adversely affects patient quality of life. There is a need to find new drugs and delivery methods for less toxic therapy. Previous studies concerning DNA complexing with chemotherapy drugs suggest unique opportunities for DNA as a mesosphere drug carrier. The overall objective of this research was devoted to the synthesis and evaluation of novel DNA-drug nano-mesospheres designed for localized chemotherapy via intratumoral injection. My research presents DNA nano-meso-microspheres (DNA-MS) that were prepared using a modified steric stabilization method originally developed in this lab for the preparation of albumin MS. DNA-MS were prepared with glutaraldehyde covalent crosslinking (genipin crosslinking was attempted) through the DNA base pairs. In addition, novel crosslinking of DNA-MS was demonstrated using chromium, gadolinium, or iron cations through the DNA phosphate groups. Covalent and ionic crosslinked DNA-MS syntheses yielded smooth and spherical particle morphologies with multimodal size distributions. Optimized DNA-MS syntheses produced particles with narrow and normal size distributions in the 50nm to 5mum diameter size range. In aqueous dispersions approximately 200% swelling was observed with dispersion stability for more than 48 hours. Typical process conditions included a 1550rpm initial mixing speed and particle filtration through 20mum filters to facilitate preparation. DNA-MS were in situ loaded during synthesis for the first time with mitoxantrone, 5-fluorouracil, and methotrexate. DNA-MS drug incorporation was 12%(w/w) for mitoxantrone, 9%(w/w) for methotrexate, and 5%(w/w) for 5-fluorouracil. In vitro drug release into phosphate buffered saline was observed for over 35 days by minimum sink release testing. The effect of gadolinium crosslink concentration on mitoxantrone release was evaluated at molar equivalences in the range of 20% to 120%. The most highly crosslinked DNA-MS exhibited the longest sustained release. The drug efficacy of mitoxantrone loaded DNA-MS was evaluated in vitro using a murine Lewis lung carcinoma cell line and a significant cytotoxic response was found at mitoxantrone doses as low as 1ppm. Drug release properties, DNA biodegradability, and observed cancer cell cytotoxicity of drug loaded DNA-MS suggest that they are appropriate for intratumoral chemotherapy evaluation aimed at improved and less toxic cancer therapy.

Association of gene polymorphism of the fat mass and obesity associated gene with metabolic syndrome: a retrospective cohort study in Japanese workers.

PubMed

Kawajiri, Tomoka; Osaki, Yoneatsu; Kishimoto, Takuji

2012-06-01

To investigate whether gene polymorphism of the fat mass and obesity associated gene (FTO) is associated with metabolic syndrome (MS), we used two MS criteria, the National Cholesterol Education Program-Adult Treatment panel III (NCEP-ATPIII) definition in 2003 and the Japanese definition in 2005. Subjects were respectively 859 and 865 Japanese workers at a company in Shimane Prefecture, Japan. They were non-MS individuals in 1998 and had regular health checkups between 1998 and 2006. The Cox proportional hazard regression was used to predict MS. Three SNPs in the FTO, rs9939609, rs1121980 and rs1558902, were genotyped by the TaqMan PCR assay and a retrospective study was performed. The three SNPs in the FTO were significantly associated with body mass index, and rs1121980 and rs1558902 were associated with fasting plasma glucose. MS defined by the NCEP-ATPIII definition was significantly associated with additive and dominant models of rs9939609 and rs1121980, and the dominant model of rs1558902, even after adjusting for confounding factors such as age, sex and lifestyle. MS defined by the Japanese definition was significantly associated with the additive model of rs1121980 and additive and dominant models of rs1558902 in multivariate analysis. These results suggested that FTO gene polymorphisms, rs9939609, rs1121980 and rs1558902, were associated with an increased risk of MS among Japanese workers.

Isolation and identification of calcium-chelating peptides from Pacific cod skin gelatin and their binding properties with calcium.

PubMed

Wu, Wenfei; Li, Bafang; Hou, Hu; Zhang, Hongwei; Zhao, Xue

2017-12-13

A calcium-chelating peptide is considered to have the ability to improve calcium absorption. In this study, Pacific cod skin gelatin hydrolysates treated with trypsin for 120 min exhibited higher calcium-chelating activity. Sequential chromatography, involving hydroxyapatite affinity chromatography and reversed phase high performance liquid chromatography, was used for the purification of calcium-chelating peptides. Two novel peptides with the typical characteristics of collagen were sequenced as GDKGESGEAGER and GEKGEGGHR based on LC-HRMS/MS, which showed a high affinity to calcium. Calcium-peptide complexation was further characterized by ESI-MS (MS and MS/MS) and FTIR spectroscopy. The results showed that the complexation of the two peptides with calcium was conducted mainly at the ratio of 1 : 1. The amino terminal group and the peptide bond of the peptide backbone as well as the amino group of the lysine side chain and the carboxylate of the glutamate side chain were the possible calcium binding sites for the two peptides. Meanwhile, several amino acid side chain groups, including the hydroxyl (Ser) and carboxylate (Asp) of GDKGESGEAGER and the imine (His) of GEKGEGGHR, were crucial in the complexation. The arginine residue in GEKGEGGHR also participated in the calcium coordination. Additionally, several active fragments with calcium-chelating activity were obtained using MS/MS spectra, including GDKGESGEAGE, GEAGER, GEK, EKG and KGE. This study suggests that gelatin-derived peptides have the potential to be used as a calcium-chelating ingredient to combat calcium deficiency.

Osteopontin (OPN) as a CSF and blood biomarker for multiple sclerosis: A systematic review and meta-analysis.

PubMed

Agah, Elmira; Zardoui, Arshia; Saghazadeh, Amene; Ahmadi, Mona; Tafakhori, Abbas; Rezaei, Nima

2018-01-01

Identifying a reliable biomarker may accelerate diagnosis of multiple sclerosis (MS) and lead to early management of the disease. Accumulating evidence suggest that cerebrospinal fluid (CSF) and peripheral blood concentration of osteopontin (OPN) may have diagnostic and prognostic value in MS. We conducted a systematic review and meta-analysis of studies that measured peripheral blood and CSF levels of OPN in MS patients and controls to evaluate the diagnostic potential of this biomarker better. We searched PubMed, Web of Science and Scopus databases to find articles that measured OPN concentration in peripheral blood and CSF samples from MS patients up to October 19, 2016. Q statistic tests and the I2 index were applied for heterogeneity assessment. If the I2 index was less than 40%, the fixed-effects model was used for meta-analysis. Random-effects meta-analysis was chosen if the I2 value was greater than 40%. After removal of duplicates, 918 articles were identified, and 27 of them fulfilled the inclusion criteria. We included 22 eligible studies in the final meta-analysis. MS patients, in general, had considerably higher levels of OPN in their CSF and blood when compared to all types of controls (p<0.05). When the comparisons were made between different subtypes of MS patients and controls, the results pointed to significantly higher levels of OPN in CSF of MS subgroups (p<0.05). All subtypes of MS patients, except CIS patients, had increased blood levels of OPN compared to controls (p<0.05). In the second set of meta-analyses, we compared the peripheral blood and CSF concentrations of OPN between MS patient subtypes. CIS patients had significantly lower levels of OPN both in their peripheral blood and CSF compared to patients with progressive subtypes of MS (p<0.05). CSF concentration of OPN was significantly higher among RRMS patients compared to the CIS patients and SPMS patients (P<0.05). Finally, patients with active MS had significantly higher OPN levels in their CSF compared to patients with stable disease (P = 0.007). The result of this study confirms that increased levels of OPN exist in CSF and peripheral blood of MS patients and strengthens the evidence regarding the clinical utility of OPN as a promising and validated biomarker for MS.

Mental toughness, sleep disturbances, and physical activity in patients with multiple sclerosis compared to healthy adolescents and young adults

PubMed Central

Sadeghi Bahmani, Dena; Gerber, Markus; Kalak, Nadeem; Lemola, Sakari; Clough, Peter J; Calabrese, Pasquale; Shaygannejad, Vahid; Pühse, Uwe; Holsboer-Trachsler, Edith; Brand, Serge

2016-01-01

Background Multiple sclerosis (MS) is the most common chronic autoimmune demyelinating and inflammatory disease of the central nervous system, afflicting both the body and mind. The risk of suffering from MS is 2.5–3.5 times greater in females than in males. While there is extant research on fatigue, depression, and cognitive impairment in patients with MS during its clinical course, there is a lack of research focusing on sleep, psychological functioning, and physical activity (PA) at the point of disease onset. The aims of the present study were therefore, to assess the markers of mental toughness (MT) as a dimension of psychological functioning, sleep disturbances (SD), and PA among patients at the moment of disease onset and to compare these with the corresponding values for healthy adolescents and young adults. Methods A total of 23 patients with MS at disease onset (mean age =32.31 years; 91% females), 23 healthy adolescents (mean age =17.43 years; 82% females), and 25 healthy young adults (mean age =20.72 years; 80% females) took part in the study. They completed questionnaires covering sociodemographic data, MT, SD, and PA. Results Patients with MS had similar scores for MT traits as those in healthy adolescents and healthy young adults, and equivalent levels of moderate-intensity PA and SD as young adults. MS patients reported lower levels of vigorous PA compared to both healthy adolescents and young adults. Conclusion The pattern of the results of the present study suggests that the onset of MS is not associated with poor MT, poor sleep, or reduced moderate-intensity PA. Lower levels of vigorous PA were observed in MS patients. Low levels of vigorous PA may lead to decreased cardiorespiratory fitness in patients with MS and, in the long run, to reduced cardiovascular health and degraded psychological functioning. PMID:27390520

Mental toughness, sleep disturbances, and physical activity in patients with multiple sclerosis compared to healthy adolescents and young adults.

PubMed

Sadeghi Bahmani, Dena; Gerber, Markus; Kalak, Nadeem; Lemola, Sakari; Clough, Peter J; Calabrese, Pasquale; Shaygannejad, Vahid; Pühse, Uwe; Holsboer-Trachsler, Edith; Brand, Serge

2016-01-01

Multiple sclerosis (MS) is the most common chronic autoimmune demyelinating and inflammatory disease of the central nervous system, afflicting both the body and mind. The risk of suffering from MS is 2.5-3.5 times greater in females than in males. While there is extant research on fatigue, depression, and cognitive impairment in patients with MS during its clinical course, there is a lack of research focusing on sleep, psychological functioning, and physical activity (PA) at the point of disease onset. The aims of the present study were therefore, to assess the markers of mental toughness (MT) as a dimension of psychological functioning, sleep disturbances (SD), and PA among patients at the moment of disease onset and to compare these with the corresponding values for healthy adolescents and young adults. A total of 23 patients with MS at disease onset (mean age =32.31 years; 91% females), 23 healthy adolescents (mean age =17.43 years; 82% females), and 25 healthy young adults (mean age =20.72 years; 80% females) took part in the study. They completed questionnaires covering sociodemographic data, MT, SD, and PA. Patients with MS had similar scores for MT traits as those in healthy adolescents and healthy young adults, and equivalent levels of moderate-intensity PA and SD as young adults. MS patients reported lower levels of vigorous PA compared to both healthy adolescents and young adults. The pattern of the results of the present study suggests that the onset of MS is not associated with poor MT, poor sleep, or reduced moderate-intensity PA. Lower levels of vigorous PA were observed in MS patients. Low levels of vigorous PA may lead to decreased cardiorespiratory fitness in patients with MS and, in the long run, to reduced cardiovascular health and degraded psychological functioning.

Estimation of the marginal effect of regular drug use on multiple sclerosis in the Iranian population.

PubMed

Abdollahpour, Ibrahim; Nedjat, Saharnaz; Mansournia, Mohammad Ali; Schuster, Tibor

2018-01-01

There are only few reports regarding the role of lifetime drug or substance use in multiple sclerosis (MS) etiology. In this study, we investigated the potential effect of drug or substance exposure on the onset of MS diagnosis. We conducted a population-based incident case control study in Tehran. Cases (n = 547) were 15-50 years old persons with MS identified from the Iranian Multiple Sclerosis Society (IMSS) register during August 7, 2013, and November 17, 2015. Population-based controls (n = 1057) were 15-50 years old and were recruited by random digit telephone dialing. Inverse-probability-of-treatment weighing (IPTW) using two sets of propensity scores (PSs) was used to estimate marginal incidence odds ratios (ORs) for MS contrasting pre-specified substance use. The estimated marginal OR was 6.03 (95% confidence interval: 3.54;10.3, using trimmed weights at the 95th percentile of the stabilized weight distribution) in both IPTW analyses comparing lifetime substance use (opioids, cannabis, inhalants, hallucinogens and stimulants) for at least one time monthly during a six-months or longer period vs. no such history of drug use. Subject to limitation of causal claims based on case-control studies, this study suggests that monthly drug or substance use for a period of at least six consecutive months, may increase the risk of MS by factor 3.5 or higher.

Preliminary study on application of urine amino acids profiling for monitoring of renal tubular injury using GLC-MS.

PubMed

Kazubek-Zemke, Maja; Rybka, Jacek; Marchewka, Zofia; Rybka, Wojciech; Pawlik, Krzysztof; Długosz, Anna

2014-11-14

The early diagnosis of the nephrotoxic effect of xenobiotics and drugs is still an unsolved problem. Recent studies suggest a correlation between the nephrotoxic activity of xenobiotics and increased concentration of amino acids in urine. The presented study was focused on the application of GLC-MS method for amino acids profiling in human urine as a noninvasive method for monitoring of kidney condition and tubular injury level. The analytic method is based on the conversion of the amino acids present in the sample to tert-butyldimethylsilyl (TBDMS) derivatives and their analysis by gas-liquid chromatography-mass spectrometry (GLC-MS). The procedure of urine sample preparation for chromatographic analysis was optimized. The presence of 12 amino acids in most of the tested healthy human urine samples was detected. The significant differences in the levels of particular amino acids between patients with tubular injury and healthy controls were found, especially for lysine, valine, serine, alanine and leucine (on average 30.0, 7.5, 3.6, 2.9 and 0.5 fold respectively). We found that this approach based on GLC-MS detection can be used in nephrotoxicity studies for urine amino acids monitoring in exposure to xenobiotics and drugs.

Degradation of the herbicide 2, 4-dichlorophenoxyacetic acid (2,4-D) dimethylamine salt by gamma radiation from cobalt-60 in aqueous solution containing humic acid

NASA Astrophysics Data System (ADS)

Campos, Sandro X.; Vieira, Eny M.; Cordeiro, Paulo J. M.; Rodrigues-Fo, Edson; Murgu, Michael

2003-12-01

In this study, gamma radiation from cobalt-60 was used to degrade the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) dimethylamine salt in water in the presence of humic acid. The 2,4-D dimethylamine salt 1.13×10 -4 mol dm -3 solution was irradiated with different doses. HPLC was used as an analytical technique to determine the degradation rate of herbicide studied. The results showed that the herbicide was completely degraded at an absorbed dose of 3 kGy. Degradation decreased when humic acid was added to all the doses. ESI/MS and MS/MS were used to identify the radiolytic degradation products. A fragmentation path for production of 4.6-dichlororesorcinol, is suggested. The radiolytic yields ( G) were calculated.

Antiarthritic activity of Majoon Suranjan (a polyherbal Unani formulation) in rat

PubMed Central

Singh, Surender; Nair, Vinod; Gupta, Y.K.

2011-01-01

Background & objectives: Majoon Suranjan (MS) is a polyherbal formulation used in Unani system of medicine for the treatment of rheumatoid arthritis (RA). The present study evaluates the antiarthritic efficacy of this formulation in three different experimental models. Methods: The anti-inflammatory activity of MS (in doses of 450, 900 and 1800 mg/kg body wt) was evaluated using the turpentine oil induced paw oedema model and the antiarthritic efficacy was evaluated using the formaldehyde and complete Freund's adjuvant (CFA) induced arthritis models. Aspirin (100 mg/kg body wt) was used as the standard drug in all the models. In order to assess the safety of the test drug, oral acute and 28 day toxicity studies were also carried out. Results: MS produced a dose dependent protective effect in all the experimental models. Its antiarthritic efficacy was comparable to aspirin in formaldehyde induced arthritis and was superior to aspirin in turpentine oil induced paw oedema and CFA induced arthritis. MS also inhibited the delayed increase in joint diameter as seen in control and aspirin treated animals in CFA induced arthritis. Oral LD50 of MS was found to be >5000 mg/kg in rats. Chronic administration did not produce any significant physiological changes in the tested animals. Interpretation & conclusions: Results of the present study suggest that the antiarthritic activity of MS was due to the interplay between its anti-inflammatory and disease modifying activities, thus supporting its use in traditional medicine for the treatment of RA. PMID:21985823

Primary hyperparathyroidism is associated with subclinical peripheral neural alterations.

PubMed

Diniz, Erik Trovão; Bandeira, Francisco; Lins, Otávio Gomes; Cavalcanti, Érica Nogueira Bezerra; de Arruda, Tiago Matos; Januário, Alexandre Medeiros Sampaio; Diniz, Kaisa Trovão; Marques, Thyciara Fontenele; Azevedo, Hildo

2013-01-01

Some case reports have suggested primary hyperparathyroidism (PHPT) and peripheral polyneuropathy (PPN) are associated; however, there are no reports of studies examining this possible relationship. The aim of this study was to evaluate peripheral nerve conduction in subjects with PHPT. The study involved 17 patients with PHPT. Mean patient age was 60.5 ± 12.9 years, serum calcium concentration was 11.5 ± 1.0 mg/dL, and the serum parathyroid hormone (PTH) level was 315 ± 569 pg/dL. The control group comprised 17 individuals without PHPT. The mean age of controls was 60.8 ± 12.5 years and the serum calcium concentration was 9.8 ± 0.3 mg/dL. Motor and sensory nerve conduction was assessed by electroneurography (ENG). The following ENG parameters differed significantly between the PHPT and control groups: right (R) sural sensory nerve action potential conduction velocity (52.7 ± 6.3 m/s versus 58.0 ± 8.0 m/s; P = .041); R median compound muscle action potential (CMAP) amplitude (7.4 ± 1.6 mV versus 8.9 ± 1.7 mV; P = .002); R median CMAP latency (4.3 ± 1.2 ms versus 3.6 ± 0.6 ms; P = .032); R tibial CMAP latency (4.2 ± 1.1 ms versus 3.3 ± 0.4 ms; P = .001). The neurological examination was normal in all patients. Our data demonstrate an association between PHPT and peripheral neurological alterations, consistent with subclinical sensory-motor PPN.

Concerns about Quadrupole ICP-MS Lead Isotopic Data and Interpretations in the Environment and Health Fields.

PubMed

Gulson, Brian; Kamenov, George D; Manton, William; Rabinowitz, Michael

2018-04-11

There has been a massive increase in recent years of the use of lead (Pb) isotopes in attempts to better understand sources and pathways of Pb in the environment and in man or experimental animals. Unfortunately, there have been many cases where the quality of the isotopic data, especially that obtained by quadrupole inductively coupled plasma mass spectrometry (Q-ICP-MS), are questionable, resulting in questionable identification of potential sources, which, in turn, impacts study interpretation and conclusions. We present several cases where the isotopic data have compromised interpretation because of the use of only the major isotopes 208 Pb/ 206 Pb and 207 Pb/ 206 Pb, or their graphing in other combinations. We also present some examples comparing high precision data from thermal ionization (TIMS) or multi-collector plasma mass spectrometry (MC-ICP-MS) to illustrate the deficiency in the Q-ICP-MS data. In addition, we present cases where Pb isotopic ratios measured on Q-ICP-MS are virtually impossible for terrestrial samples. We also evaluate the Pb isotopic data for rat studies, which had concluded that Pb isotopic fractionation occurs between different organs and suggest that this notion of biological fractionation of Pb as an explanation for isotopic differences is not valid. Overall, the brief review of these case studies shows that Q-ICP-MS as commonly practiced is not a suitable technique for precise and accurate Pb isotopic analysis in the environment and health fields.

Genotyping of Coxiella burnetii from domestic ruminants and human in Hungary: indication of various genotypes.

PubMed

Sulyok, Kinga M; Kreizinger, Zsuzsa; Hornstra, Heidie M; Pearson, Talima; Szigeti, Alexandra; Dán, Ádám; Balla, Eszter; Keim, Paul S; Gyuranecz, Miklós

2014-05-07

Information about the genotypic characteristic of Coxiella burnetii from Hungary is lacking. The aim of this study is to describe the genetic diversity of C. burnetii in Hungary and compare genotypes with those found elsewhere. A total of 12 samples: (cattle, n = 6, sheep, n = 5 and human, n = 1) collected from across Hungary were studied by a 10-loci multispacer sequence typing (MST) and 6-loci multiple-locus variable-number of tandem repeat analysis (MLVA). Phylogenetic relationships among MST genotypes show how these Hungarian samples are related to others collected around the world. Three MST genotypes were identified: sequence type (ST) 20 has also been identified in ruminants from other European countries and the USA, ST28 was previously identified in Kazakhstan, and the proposed ST37 is novel. All MST genotypes yielded different MLVA genotypes and three different MLVA genotypes were identified within ST20 samples alone. Two novel MLVA types 0-9-5-5-6-2 (AG) and 0-8-4-5-6-2 (AF) (Ms23-Ms24-Ms27-Ms28-Ms33-Ms34) were defined in the ovine materials correlated with ST28 and ST37. Samples from different parts of the phylogenetic tree were associated with different hosts, suggesting host-specific adaptations. Even with the limited number of samples analysed, this study revealed high genetic diversity among C. burnetii in Hungary. Understanding the background genetic diversity will be essential in identifying and controlling outbreaks.

Concerns about Quadrupole ICP-MS Lead Isotopic Data and Interpretations in the Environment and Health Fields

PubMed Central

Gulson, Brian; Manton, William; Rabinowitz, Michael

2018-01-01

There has been a massive increase in recent years of the use of lead (Pb) isotopes in attempts to better understand sources and pathways of Pb in the environment and in man or experimental animals. Unfortunately, there have been many cases where the quality of the isotopic data, especially that obtained by quadrupole inductively coupled plasma mass spectrometry (Q-ICP-MS), are questionable, resulting in questionable identification of potential sources, which, in turn, impacts study interpretation and conclusions. We present several cases where the isotopic data have compromised interpretation because of the use of only the major isotopes 208Pb/206Pb and 207Pb/206Pb, or their graphing in other combinations. We also present some examples comparing high precision data from thermal ionization (TIMS) or multi-collector plasma mass spectrometry (MC-ICP-MS) to illustrate the deficiency in the Q-ICP-MS data. In addition, we present cases where Pb isotopic ratios measured on Q-ICP-MS are virtually impossible for terrestrial samples. We also evaluate the Pb isotopic data for rat studies, which had concluded that Pb isotopic fractionation occurs between different organs and suggest that this notion of biological fractionation of Pb as an explanation for isotopic differences is not valid. Overall, the brief review of these case studies shows that Q-ICP-MS as commonly practiced is not a suitable technique for precise and accurate Pb isotopic analysis in the environment and health fields. PMID:29641487

The Moderating Role of Executive Functioning in Older Adults' Responses to a Reminder of Mortality

PubMed Central

Maxfield, Molly; Pyszczynski, Tom; Greenberg, Jeff; Pepin, Renee; Davis, Hasker P.

2011-01-01

In previous research, older adults responded to mortality salience (MS) with increased tolerance, whereas younger persons responded with increased punitiveness. One possible explanation for this is that many older adults adapt to challenges of later life, such as the prospect of mortality, by becoming more flexible. Recent studies suggest that positively-oriented adaptation is more likely for older adults with high levels of executive functioning. We thus hypothesized that the better an older adult's executive functioning, the more likely MS would result in increased tolerance. Older and younger adults were randomly assigned to MS or control conditions, and then evaluated moral transgressors. As in previous research, younger adults were more punitive following reminders of mortality; executive functioning did not affect their responses. Among older adults, high functioning individuals responded to MS with increased tolerance rather than intolerance, whereas those low in functioning became more punitive. PMID:21728445

A tandem mass spectrometric method for singlet oxygen measurement.

PubMed

Karonen, Maarit; Mattila, Heta; Huang, Ping; Mamedov, Fikret; Styring, Stenbjörn; Tyystjärvi, Esa

2014-01-01

Singlet oxygen, a harmful reactive oxygen species, can be quantified with the substance 2,2,6,6-tetramethylpiperidine (TEMP) that reacts with singlet oxygen, forming a stable nitroxyl radical (TEMPO). TEMPO has earlier been quantified with electron paramagnetic resonance (EPR) spectroscopy. In this study, we designed an ultra-high-performance liquid chromatographic-tandem mass spectrometric (UHPLC-ESI-MS/MS) quantification method for TEMPO and showed that the method based on multiple reaction monitoring (MRM) can be used for the measurements of singlet oxygen from both nonbiological and biological samples. Results obtained with both UHPLC-ESI-MS/MS and EPR methods suggest that plant thylakoid membranes produce 3.7 × 10(-7) molecules of singlet oxygen per chlorophyll molecule in a second when illuminated with the photosynthetic photon flux density of 2000 μmol m(-2 ) s(-1). © 2014 The American Society of Photobiology.

Terror mismanagement: evidence that mortality salience exacerbates attentional bias in social anxiety.

PubMed

Finch, Emma C; Iverach, Lisa; Menzies, Ross G; Jones, Mark

2016-11-01

Death anxiety is a basic fear underlying a range of psychological conditions, and has been found to increase avoidance in social anxiety. Given that attentional bias is a core feature of social anxiety, the aim of the present study was to examine the impact of mortality salience (MS) on attentional bias in social anxiety. Participants were 36 socially anxious and 37 non-socially anxious individuals, randomly allocated to a MS or control condition. An eye-tracking procedure assessed initial bias towards, and late-stage avoidance of, socially threatening facial expressions. As predicted, socially anxious participants in the MS condition demonstrated significantly more initial bias to social threat than non-socially anxious participants in the MS condition and socially anxious participants in the control condition. However, this effect was not found for late-stage avoidance of social threat. These findings suggest that reminders of death may heighten initial vigilance towards social threat.

Terror mismanagement: evidence that mortality salience exacerbates attentional bias in social anxiety

PubMed Central

Finch, Emma C.; Iverach, Lisa; Menzies, Ross G.; Jones, Mark

2016-01-01

ABSTRACT Death anxiety is a basic fear underlying a range of psychological conditions, and has been found to increase avoidance in social anxiety. Given that attentional bias is a core feature of social anxiety, the aim of the present study was to examine the impact of mortality salience (MS) on attentional bias in social anxiety. Participants were 36 socially anxious and 37 non-socially anxious individuals, randomly allocated to a MS or control condition. An eye-tracking procedure assessed initial bias towards, and late-stage avoidance of, socially threatening facial expressions. As predicted, socially anxious participants in the MS condition demonstrated significantly more initial bias to social threat than non-socially anxious participants in the MS condition and socially anxious participants in the control condition. However, this effect was not found for late-stage avoidance of social threat. These findings suggest that reminders of death may heighten initial vigilance towards social threat. PMID:26211552

Tolerating dissimilar other when primed with death: neural evidence of self-control engaged by interdependent people in Japan.

PubMed

Yanagisawa, Kuniaki; Kashima, Emiko S; Moriya, Hiroki; Masui, Keita; Furutani, Kaichiro; Yoshida, Hiroshi; Ura, Mitsuhiro; Nomura, Michio

2017-06-01

Mortality salience (MS) has been shown to lead to derogation of others with dissimilar worldviews, yet recent research has shown that Asian-Americans who presumably adopt an interdependent self-construal (SC) tend to reveal greater tolerance after MS induction. In the present study, we demonstrated that Japanese individuals who are high on interdependent SC indeed show greater tolerance toward worldview-threatening other in the MS (vs control) condition, thus replicating the prior research. Extending this research, we also found that interdependent people's tolerance toward worldview-threatening other was mediated by increased activity in the right ventrolateral prefrontal cortex in the MS condition. These data suggested that when exposed to death-related stimuli, highly interdependent individuals may spontaneously activate their neural self-control system which may serve to increase tolerance toward others. © The Author (2017). Published by Oxford University Press.

Chronic cerebro-spinal venous insufficiency (CCSVI) and multiple sclerosis.

PubMed

Ghezzi, A; Comi, G; Federico, A

2011-02-01

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS caused by the interplay of genetic and environmental factors. In the last years, it has been suggested that an abnormal venous drainage due to stenosis or malformation of the internal jugular and/or azygous veins may play a major pathogenetic role in MS. This abnormality called chronic cerebro-spinal venous insufficiency (CCSVI) could result in increased permeability of blood brain barrier, local iron deposition and secondary multifocal inflammation. In the present paper, literature data in favour and against this hypothesis are reported. A great variability of CCSVI has been found in both MS patients (ranging from 0 to 100%) and in control subjects (from 0 to 23%). This large variability is explained by methodological aspects, problems in assessing CCSVI, and differences among clinical series. It is urgent to perform appropriate epidemiological studies to define the possible relationship between CCSVI and MS.

Occurrence of Multiple Sclerosis After Drug Exposure: Insights From Evidence Mapping.

PubMed

Antonazzo, Ippazio Cosimo; Raschi, Emanuel; Vignatelli, Luca; Baldin, Elisa; Riise, Trond; D'Alessandro, Roberto; De Ponti, Fabrizio; Poluzzi, Elisabetta

2017-09-01

The role of drugs in the occurrence of multiple sclerosis (MS) is perceived to be insufficiently investigated. The aim of this study was to map and assess the evidence on MS occurrence after drug exposure, in order to identify possible signals of causal association. A search strategy was performed in MEDLINE and Embase as of July 2016; references consistent with the aim of the study were analysed to extract relevant measures of causal association between drugs and MS. The Newcastle-Ottawa Scale and appropriate guidelines from the International Society for Pharmacoepidemiology (ISPE) and the International Society of Pharmacovigilance (ISoP) were used to assess the quality of included studies. After screening 832 articles, 58 were selected (of which 14 were found by checking the reference lists of reviews): 30 case reports and case series, 24 longitudinal studies and four randomized controlled trials. Seven longitudinal studies had good (at least 7 out of 9) quality scores, whereas case reports/case series presented several limitations. Half of included articles focused on immunomodulatory drugs (etanercept, infliximab and adalimumab), especially in case reports/series, suggesting an association with MS occurrence. Contraceptives and antibacterials were investigated in some population-based studies, without definite results. A heterogeneous pharmacological profile of identified classes emerged. Low strength of evidence and conflicting results highlighted the difficulties in addressing the possible contribution of drugs in MS occurrence. Methodological advances are needed, especially to control the confounding role of underlying disease for specific drug classes.

Anticipation of direction and time of perturbation modulates the onset latency of trunk muscle responses during sitting perturbations.

PubMed

Milosevic, Matija; Shinya, Masahiro; Masani, Kei; Patel, Kramay; McConville, Kristiina M V; Nakazawa, Kimitaka; Popovic, Milos R

2016-02-01

Trunk muscles are responsible for maintaining trunk stability during sitting. However, the effects of anticipation of perturbation on trunk muscle responses are not well understood. The objectives of this study were to identify the responses of trunk muscles to sudden support surface translations and quantify the effects of anticipation of direction and time of perturbation on the trunk neuromuscular responses. Twelve able-bodied individuals participated in the study. Participants were seated on a kneeling chair and support surface translations were applied in the forward and backward directions with and without direction and time of perturbation cues. The trunk started moving on average approximately 40ms after the perturbation. During unanticipated perturbations, average latencies of the trunk muscle contractions were in the range between 103.4 and 117.4ms. When participants anticipated the perturbations, trunk muscle latencies were reduced by 16.8±10.0ms and the time it took the trunk to reach maximum velocity was also reduced, suggesting a biomechanical advantage caused by faster muscle responses. These results suggested that trunk muscles have medium latency responses and use reflexive mechanisms. Moreover, anticipation of perturbation decreased trunk muscles latencies, suggesting that the central nervous system modulated readiness of the trunk based on anticipatory information. Copyright © 2015 Elsevier Ltd. All rights reserved.

Classification of metabolic syndrome according to lipid alterations: analysis from the Mexican National Health and Nutrition Survey 2006.

PubMed

Pedroza-Tobias, Andrea; Trejo-Valdivia, Belem; Sanchez-Romero, Luz M; Barquera, Simon

2014-10-09

There are 16 possible Metabolic Syndrome (MS) combinations out of 5 conditions (glucose intolerance, low levels of high-density lipoprotein Cholesterol (HDL-C), high triglycerides, high blood pressure and abdominal obesity), when selecting those with at least three. Studies suggest that some combinations have different cardiovascular risk. However evaluation of all 16 combinations is complex and difficult to interpret. The purpose of this study is to describe and explore a classification of MS groups according to their lipid alterations. This is a cross-sectional study with data from the Mexican National Health and Nutrition Survey 2006. Subjects (n = 5,306) were evaluated for the presence of MS; four mutually-exclusive MS groups were considered: mixed dyslipidemia (altered triglycerides and HDL-C), hypoalphalipoproteinemia: (normal triglycerides but low HDL-C), hypertriglyceridemia (elevated triglycerides and normal HDL-C) and without dyslipidemia (normal triglycerides and HDL-C). A multinomial logistic regression model was fitted in order to identify characteristics that were associated with the groups. The most frequent MS group was hypoalphalipoproteinemia in females (51.3%) and mixed dyslipidemia in males (43.5%). The most prevalent combination of MS for both genders was low HDL-C + hypertension + abdominal obesity (20.4% females, 19.4% males). The hypoalphalipoproteinemia group was characteristic of women and less developed areas of the country. The group without dyslipidemia was more frequent in the highest socioeconomic level and less prevalent in the south of the country. The mixed dyslipidemia group was characteristic of men, and the Mexico City region. A simple system to classify MS based on lipid alterations was useful to evaluate prevalences by diverse biologic and sociodemographic characteristics. This system may allow prevention and early detection strategies with emphasis on population-specific components and may serve as a guide for future studies on MS and cardiovascular risk.

A tale of two anomalies: Depletion, dispersion, and the connection between the stellar lithium spread and inflated radii on the pre-main sequence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Somers, Garrett; Pinsonneault, Marc H., E-mail: somers@astronomy.ohio-state.edu, E-mail: pinsono@astronomy.ohio-state.edu

2014-07-20

We investigate lithium depletion in standard stellar models (SSMs) and main sequence (MS) open clusters, and explore the origin of the Li dispersion in young, cool stars of equal mass, age, and composition. We first demonstrate that SSMs accurately predict the Li abundances of solar analogs at the zero-age main sequence (ZAMS) within theoretical uncertainties. We then measure the rate of MS Li depletion by removing the [Fe/H]-dependent ZAMS Li pattern from three well-studied clusters, and comparing the detrended data. MS depletion is found to be mass-dependent, in the sense of more depletion at low mass. A dispersion in Limore » abundance at fixed T{sub eff} is nearly universal, and sets in by ∼200 Myr. We discuss mass and age dispersion trends, and the pattern is mixed. We argue that metallicity impacts the ZAMS Li pattern, in agreement with theoretical expectations but contrary to the findings of some previous studies, and suggest Li as a test of cluster metallicity. Finally, we argue that a radius dispersion in stars of fixed mass and age, during the epoch of pre-MS Li destruction, is responsible for the spread in Li abundances and the correlation between rotation and Li in young cool stars, most well known in the Pleiades. We calculate stellar models, inflated to match observed radius anomalies in magnetically active systems, and the resulting range of Li abundances reproduces the observed patterns of young clusters. We discuss ramifications for pre-MS evolutionary tracks and age measurements of young clusters, and suggest an observational test.« less

Dissociable Electroencephalograph Correlates of Visual Awareness and Feature-Based Attention

PubMed Central

Chen, Yifan; Wang, Xiaochun; Yu, Yanglan; Liu, Ying

2017-01-01

Background: The relationship between awareness and attention is complex and controversial. A growing body of literature has shown that the neural bases of consciousness and endogenous attention (voluntary attention) are independent. The important role of exogenous attention (reflexive attention) on conscious experience has been noted in several studies. However, exogenous attention can also modulate subliminal processing, suggesting independence between the two processes. The question of whether visual awareness and exogenous attention rely on independent mechanisms under certain circumstances remains unanswered. Methods: In the current study, electroencephalograph recordings were conducted using 64 channels from 16 subjects while subjects attempted to detect faint speed changes of colored rotating dots. Awareness and attention were manipulated throughout trials in order to test whether exogenous attention and visual awareness rely on independent mechanisms. Results: Neural activity related to consciousness was recorded in the following cue-locked time-windows (event related potential, cluster- based permutation test): 0–50, 150–200, and 750–800 ms. With a more liberal threshold, the inferior occipital lobe was found to be the source of awareness-related activity in the 0–50 ms range. In the later 150–200 ms range, activity in the fusiform and post-central gyrus was related to awareness. Awareness-related activation in the later 750–800 ms range was more widely distributed. This awareness-related activation pattern was quite different from that of attention. Attention-related neural activity was emphasized in the 750–800 ms time window and the main source of attention-related activity was localized to the right angular gyrus. These results suggest that exogenous attention and visual consciousness correspond to different and relatively independent neural mechanisms and are distinct processes under certain conditions. PMID:29180950

Development of a patient reported outcome scale for fatigue in multiple sclerosis: The Neurological Fatigue Index (NFI-MS)

PubMed Central

2010-01-01

Background Fatigue is a common and debilitating symptom in multiple sclerosis (MS). Best-practice guidelines suggest that health services should repeatedly assess fatigue in persons with MS. Several fatigue scales are available but concern has been expressed about their validity. The objective of this study was to examine the reliability and validity of a new scale for MS fatigue, the Neurological Fatigue Index (NFI-MS). Methods Qualitative analysis of 40 MS patient interviews had previously contributed to a coherent definition of fatigue, and a potential 52 item set representing the salient themes. A draft questionnaire was mailed out to 1223 people with MS, and the resulting data subjected to both factor and Rasch analysis. Results Data from 635 (51.9% response) respondents were split randomly into an 'evaluation' and 'validation' sample. Exploratory factor analysis identified four potential subscales: 'physical', 'cognitive', 'relief by diurnal sleep or rest' and 'abnormal nocturnal sleep and sleepiness'. Rasch analysis led to further item reduction and the generation of a Summary scale comprising items from the Physical and Cognitive subscales. The scales were shown to fit Rasch model expectations, across both the evaluation and validation samples. Conclusion A simple 10-item Summary scale, together with scales measuring the physical and cognitive components of fatigue, were validated for MS fatigue. PMID:20152031

Molecular cloning and functional analysis of the drought tolerance gene MsHSP70 from alfalfa (Medicago sativa L.).

PubMed

Li, Zhenyi; Long, Ruicai; Zhang, Tiejun; Wang, Zhen; Zhang, Fan; Yang, Qingchuan; Kang, Junmei; Sun, Yan

2017-03-01

Heat shock proteins (HSPs) are a ubiquitously expressed class of protective proteins that play a key role in plant response to stressful conditions. This study aimed to characterize and investigate the function of an HSP gene in alfalfa (Medicago sativa). MsHSP70, which contains a 2028-bp open reading frame, was identified through homology cloning. MsHSP70 shares high sequence identity (94.47%) with HSP70 from Medicago truncatula. Expression analysis of MsHSP70 in alfalfa organs revealed a relatively higher expression level in aerial organs such as flowers, stems and leaves than in roots. MsHSP70 was induced by heat shock, abscisic acid (ABA) and hydrogen peroxide. Transgenic Arabidopsis seedlings overexpressing MsHSP70 were hyposensitive to polyethylene glycol (PEG) and ABA treatments, suggesting that exogenous expression of MsHSP70 enhanced Arabidopsis tolerance to these stresses. Examination of physiological indexes related to drought and ABA stress demonstrated that in comparison with non-transgenic plants, T3 transgenic Arabidopsis plants had an increased proline content, higher superoxide dismutase (SOD) activity, and decreased malondialdehyde (MDA) content. Furthermore, higher relative water content (RWC) was detected in transgenic plants compared with non-transgenic plants under drought stress. These findings clearly indicate that molecular manipulation of MsHSP70 in plants can have substantial effects on stress tolerance.

High efficiency induction of callus and regeneration of sporophytes of Laminaria japonica (Phaeophyta)

NASA Astrophysics Data System (ADS)

Wang, Xi-Hua; Qin, Song; Li, Xin-Ping; Jiang, Peng; Zeng, Cheng-Kui; Qin, Mei

1998-03-01

Four media (PESI solid, MS liquid, MS solid and ASP-C-I solid medium) were used to induce callus from excised tissues of the kelp Laminaria japonica. Only PESI solid medium and MS solid medium produced calli. Modified MS solid medium supplemented with mannitol (3%,W/V), yeast extract (0.1%, W/V), VB2 (0.5 mg/ml), VB12 (0.5 mg/ml), kinetin (0.108 μg/ml) and NAA (1.860μg/ml) showed much better effect on callus induction than non-modified MS solid medium. After 24 days of induction 75.5% of tissues in PESI solid medium showed callus formation. For modified MS solid medium, after three months of induction 67.3% of tissues dedifferentiated into calli. No callus could be found after five months of induction in either MS liquid or ASP-C-I solid medium. When calli were squashed and cultured in N-P enriched autoclaved seawater, MS liquid medium and ASP12-NTA liquid medium (both modified with kelp extract), differentiation of cells and regeneration of sporophytes were only observed in ASP12-NTA medium supplemented with kelp extract. Gametophyte-like filaments formed first, then eggs were released. It was suggested that sporophyte formation could be a process of parthenogenesis. Sterilization techniques in tissue culture of L. japonica were also tested in this study.

Information processing characteristics in subtypes of multiple sclerosis.

PubMed

De Sonneville, L M J; Boringa, J B; Reuling, I E W; Lazeron, R H C; Adèr, H J; Polman, C H

2002-01-01

The purpose of this study was to evaluate information processing characteristics in patients with multiple sclerosis (MS). We selected 53 patients with MS and 58 matched healthy controls. Using computerized tests, we investigated focused, divided, sustained attention, and executive function, and attempted to pinpoint deficits in attentional control to peripheral or central processing stages. The results substantiate the hypothesis that the slowing of attention-demanding (controlled) information processing underlying more complex cognitive skills is general, i.e. irrespective of type of controlled processing, with MS patients being 40% slower than controls. MS patients may suffer from focused, and divided and sustained attention deficits, as well as from compromised central processing stages, with secondary progressive (SP) patients showing the most extensive range of deficits, closely followed by primary progressive (PP) patients, while relapsing-remitting (RR) patients appear to be much less affected. General slowing appears to be highest in PP and SP type MS patients (50% slower) versus relapsing-remitting MS (24% slower). In contrast to most previous results, (complex) processing speed appeared to be robustly correlated with severity of MS as measured by the expanded disability status scale and with disease duration. Patients did much less differ in accuracy of processing from controls, suggesting the importance of using time strategies in planning everyday life and job activities to compensate for or alleviate MS-related speed handicaps. Copyright 2002 Elsevier Science Ltd.

Comparative analysis of soybean plasma membrane proteins under osmotic stress using gel-based and LC MS/MS-based proteomics approaches.

PubMed

Nouri, Mohammad-Zaman; Komatsu, Setsuko

2010-05-01

To study the soybean plasma membrane proteome under osmotic stress, two methods were used: a gel-based and a LC MS/MS-based proteomics method. Two-day-old seedlings were subjected to 10% PEG for 2 days. Plasma membranes were purified from seedlings using a two-phase partitioning method and their purity was verified by measuring ATPase activity. Using the gel-based proteomics, four and eight protein spots were identified as up- and downregulated, respectively, whereas in the nanoLC MS/MS approach, 11 and 75 proteins were identified as up- and downregulated, respectively, under PEG treatment. Out of osmotic stress responsive proteins, most of the transporter proteins and all proteins with high number of transmembrane helices as well as low-abundance proteins could be identified by the LC MS/MS-based method. Three homologues of plasma membrane H(+)-ATPase, which are transporter proteins involved in ion efflux, were upregulated under osmotic stress. Gene expression of this protein was increased after 12 h of stress exposure. Among the identified proteins, seven proteins were mutual in two proteomics techniques, in which calnexin was the highly upregulated protein. Accumulation of calnexin in plasma membrane was confirmed by immunoblot analysis. These results suggest that under hyperosmotic conditions, calnexin accumulates in the plasma membrane and ion efflux accelerates by upregulation of plasma membrane H(+)-ATPase protein.

Brain volume in early MS patients with and without IgG oligoclonal bands in CSF.

PubMed

Fenu, G; Lorefice, L; Sechi, V; Loi, L; Contu, F; Cabras, F; Coghe, G; Frau, J; Secci, M A; Melis, C; Schirru, L; Costa, G; Melas, V; Arru, M; Barracciu, M A; Marrosu, M G; Cocco, E

2018-01-01

Oligoclonal bands of IgG (OB) are proposed as an early prognostic factor of the disease. Growing attention is directed towards brain volume evaluation as a possible marker of the severity of MS. Previous studies found that MS patients lacking OB have less brain atrophy. to evaluate a possible relationship between OB and cerebral volume in a cohort of early MS patients. Inclusion criteria were: diagnosis of relapsing-remitting MS; CSF analysis and MRI acquired simultaneously and within 12 months from clinical onset. A total of 15 healthy controls underwent MRI. In 20 MS patients, CSF analysis did not show OB synthesis (OB negative group). A control group of 25 MS patients in whom OB was detected was also randomly recruited (OB positive group). T test showed a significant difference in NWV between the OB positive and OB negative groups (P value = 0.01), and between the OB positive group and the healthy controls (P value = 0.001). No differences were detected between OB negative group and healthy controls. Multivariable linear regression showed a relationship between NWV and OB synthesis (P value = 0.02) controlling for age, gender, and EDSS. Our preliminary results suggest that OB positive patients show more atrophy of white matter since early phases of the disease, supporting the role of CSF analysis as a prognostic factor in MS. Copyright © 2017 Elsevier B.V. All rights reserved.

Altered locomotor and stereotyped responses to acute methamphetamine in adolescent, maternally separated rats

PubMed Central

Pritchard, Laurel M.; Hensleigh, Emily; Lynch, Sarah

2012-01-01

Rationale Neonatal maternal separation (MS) has been used to model the effects of early life stress in rodents. MS alters behavioral responses to a variety of abused drugs, but few studies have examined its effects on methamphetamine sensitivity. Objectives We sought to determine the effects of MS on locomotor and stereotyped responses to low-to-moderate doses of methamphetamine in male and female adolescent rats. Methods Male and female rat pups were subjected to three hours per day of MS on postnatal days (PN) 2–14, or a brief handling control procedure during the same period. During adolescence (approximately PN 40), all rats were tested for locomotor activity and stereotyped behavior in response to acute methamphetamine administration (0, 1.0 or 3.0 mg/kg, s.c.). Results MS rats of both sexes exhibited increased locomotor activity in a novel environment, relative to handled controls. MS increased the locomotor response to METH, and this effect occurred at different doses for male (3.0 mg/kg) and female (1.0 mg/kg) rats. MS also increased stereotyped behavior in response to METH (1.0 mg/kg) in both sexes. Conclusions MS enhances the locomotor response to METH in a dose- and sex-dependent manner. These results suggest that individuals with a history of early life stress may be particularly vulnerable to the psychostimulant effects of METH, even at relatively low doses. PMID:22414962

Investigation of enrofloxacin residues in broiler tissues using ELISA and LC-MS/MS.

PubMed

Panzenhagen, Pedro Henrique N; Aguiar, Waldemir S; Gouvêa, Raquel; de Oliveira, Andréa M G; Barreto, Fabiano; Pereira, Virgínia L A; Aquino, Maria Helena C

2016-01-01

This study investigated the efficiency of an enrofloxacin ELISA test kit to detect the presence of enrofloxacin residues in broiler tissues compared with LC-MS/MS. Broiler tissues from 72 samples consisting of 60 breast muscle, six pools of livers (500 g each) and six pools of kidneys (500 g each) were obtained from six different slaughterhouses. Breast muscle from 10 carcasses and pools of livers and kidneys from approximately 200 carcasses of the same flock were collected from each slaughterhouse. ELISA and HPLC were used to identify and quantify the contamination of the samples with enrofloxacin. A total of 72% of the analysed samples contained enrofloxacin residues detected by the ELISA and 22.2% were detected by LC-MS/MS. The mean values of enrofloxacin contamination found in chicken breast by ELISA and HPLC were 8.63 and 12.25 μg kg(-1), respectively. None of the samples exceeded the maximum limit of 100 μg kg(-1) by both methods set by the European Union as well as the Brazilian Agriculture Ministry. All positive samples for enrofloxacin residues detected by LC-MS/MS were also positive by ELISA. These data confirm the efficiency of the ELISA test, and suggest its use as a screening method for enrofloxacin residues in poultry tissues due to its quick results, low price and ease of applicability.

Multiple Sclerosis/Chronic Fatigue Syndrome overlap: When two common disorders collide.

PubMed

Gaber, Tarek A-Z K; Oo, Wah Wah; Ringrose, Hollie

2014-01-01

Fatigue is a major cause of disability and handicap in Multiple Sclerosis (MS) patients. The management of this common problem is often difficult. Chronic Fatigue Syndrome (CFS/ME) is another common cause of fatigue which is prevalent in the same population of middle aged females commonly affected by MS. This report aims at examining the potential coexistence of MS and CFS/ME in the same patients. This is a retrospective study examining a cohort of MS patients referred for rehabilitation. The subjects were screened for CFS/ME symptoms. Sixty-four MS patients (43 females) were screened for CFS/ME. Nine patients (14%) with a mean age 52 (SD 9.7) who were all females fulfilled the Fukuda criteria for diagnosis of CFS/ME. Their symptoms, including muscular and joint pain, malaise and recurrent headaches, were not explained by the pattern of their MS. MS and CFS/ME are two common conditions with increased prevalence in middle aged females. As the diagnosis of CFS/ME is clinical with no positive clinical signs or investigations; it can be made with difficulty in the presence of another clear explanation for the disabling fatigue. Our results suggest that the two conditions may co-exist. Considering CFS/ME as a potential co-morbidity may lead to more focused and appropriate management.

[Prevalence and factors associated with metabolic syndrome in users of primary healthcare units in São Paulo--SP, Brazil].

PubMed

Leitão, Maria Paula Carvalho; Martins, Ignez Salas

2012-01-01

To determine the relationship between metabolic syndrome (MS) and socioeconomic level, life style, health status, family history of morbidity, and residence areas. This is a cross-sectional cohort study. The random sample consisted of users of two primary health care units (Unidades Básicas de Saúde--UBSs) in the city of São Paulo--Jardim Comercial (UBS1), and Jardim Germânia (UBS2), a total of 452 subjects. The NCEP ATP IIIcriterion was used to diagnose MS. Weight, height, abdominal and hip circumferences were measured for the anthropometric evaluation. A general questionnaire was used to obtain sociodemographic and socioeconomic data; family history; medical history; behavioral habits such as smoking, drinking, and physical activity. Multivariate logistic regression was used to establish the association between explanatory variables of interest and MS. At UBS1, MS percentage was 56.1%; at UBS2, 34.0%. There was a direct and significant association between MS and age, female gender, race, smoking, drinking, physical activity level, stress, and family history of heart disease and diabetes mellitus. Education level showed an inverse association. Subjects living in a lower socioeconomic level neighborhood had a higher MS risk. The results suggest that the morbidities that compose MS are a serious publichealth problem in that population.

Influence of temperature changes on multiple sclerosis: critical review of mechanisms and research potential.

PubMed

Guthrie, T C; Nelson, D A

1995-03-01

In 1890, Uhthoff studied multiple sclerosis (MS) patients who developed amblyopia following exercise, a phenomenon later discovered to be secondary to elevated body temperature from muscular activity. Six decades later, the hot bath test and various other heating reactions (HR) began to be used diagnostically. They were essentially discontinued after 1983, being replaced by more specific and safer tests and procedures. Over 80% of MS patients develop a panoply of neurological signs during hyperthermia, 60% of which are "new" to that patient. The literature contains a number of unexplained paradoxical responses of MS patients during induced hyperthermia. These challenge the current hypothesis that, in MS, hyperthermia induces a heat-linked neuro-blockade of partially demyelinated axons. Some MS patients developed signs before temperature elevations occurred; others showed clearing of signs while temperatures were elevated or were ascending. Several MS patients improved for about 3 hours after being tested, a rebound phenomenon known as "overshoot." Conversely, other MS patients developed persistent neurological deficits after hyperthermia. The etiology of HR may be multifactorial. This includes heat itself, effects of serum calcium, blockade of ion channels, circulatory changes, heat shock proteins, and unidentified humoral substances. Research techniques are suggested to continue investigations into the enigma of HR, hopefully to widen knowledge of demyelination.

Expanding the use of administrative claims databases in conducting clinical real-world evidence studies in multiple sclerosis.

PubMed

Capkun, Gorana; Lahoz, Raquel; Verdun, Elisabetta; Song, Xue; Chen, Weston; Korn, Jonathan R; Dahlke, Frank; Freitas, Rita; Fraeman, Kathy; Simeone, Jason; Johnson, Barbara H; Nordstrom, Beth

2015-05-01

Administrative claims databases provide a wealth of data for assessing the effect of treatments in clinical practice. Our aim was to propose methodology for real-world studies in multiple sclerosis (MS) using these databases. In three large US administrative claims databases: MarketScan, PharMetrics Plus and Department of Defense (DoD), patients with MS were selected using an algorithm identified in the published literature and refined for accuracy. Algorithms for detecting newly diagnosed ('incident') MS cases were also refined and tested. Methodology based on resource and treatment use was developed to differentiate between relapses with and without hospitalization. When various patient selection criteria were applied to the MarketScan database, an algorithm requiring two MS diagnoses at least 30 days apart was identified as the preferred method of selecting patient cohorts. Attempts to detect incident MS cases were confounded by the limited continuous enrollment of patients in these databases. Relapse detection algorithms identified similar proportions of patients in the MarketScan and PharMetrics Plus databases experiencing relapses with (2% in both databases) and without (15-20%) hospitalization in the 1 year follow-up period, providing findings in the range of those in the published literature. Additional validation of the algorithms proposed here would increase their credibility. The methods suggested in this study offer a good foundation for performing real-world research in MS using administrative claims databases, potentially allowing evidence from different studies to be compared and combined more systematically than in current research practice.

Significant but weak spousal concordance of metabolic syndrome components in Japanese couples.

PubMed

Okuda, Tomoko; Miyazaki, Tadayoshi; Sakuragi, Sonoko; Moriguchi, Jiro; Tachibana, Hiroshi; Ohashi, Fumiko; Ikeda, Masayuki

2014-03-01

This study was initiated to investigate if spousal concordance in metabolic syndrome (MS) components exist in Japan. In all, 756 couples (mean age: 48.9 and 47.3 years for husbands and wives, respectively) were identified. Each subject was classified as an MS, MS reserves (MSRES) or no risk of MS (NonMS) case after Japanese Ministry of Health, Labour and Welfare (JMHLW) criteria. Criteria of the National Cholesterol Education Program and of the Joint Interim Statement were also applied. With Japanese Ministry of Health, Labor and Welfare (JMHLW) criteria, MS, MSRES and NonMS cases accounted for 11.9, 14.7 and 73.4 % in husbands and 1.6, 3.7 and 94.7 % in wives. Waist circumference (WC), body mass index (BMI), systolic blood pressure (SBP) and hemoglobin A1c (HbA1c) showed significant correlation (p < 0.01). Correlation was also significant (p < 0.05) for mean blood pressure (MBP) and fasting plasma glucose (FPG). When adjusted for age, correlations were significant only for WC, BMI and HbA1c. Furthermore, none of the correlation coefficients were greater than 0.2. Logistic regression analyses did not suggest significant mutual influence in MS status between the couples. Spousal concordance in MS components was detected for WC, BMI, SBP, MBP, FPG and HbA1c, but the correlation was generally weak and modest in Japanese couples.

Evaluation of multiple reaction monitoring cubed for the analysis of tachykinin related peptides in rat spinal cord using a hybrid triple quadrupole-linear ion trap mass spectrometer.

PubMed

Pailleux, Floriane; Beaudry, Francis

2014-02-01

Targeted peptide methods generally use HPLC-MS/MRM approaches. Although dependent on the instrumental resolution, interferences may occur while performing analysis of complex biological matrices. HPLC-MS/MRM(3) is a technique, which provides a significantly better selectivity, compared with HPLC-MS/MRM assay. HPLC-MS/MRM(3) allows the detection and quantitation by enriching standard MRM with secondary product ions that are generated within the linear ion trap. Substance P (SP) and neurokinin A (NKA) are tachykinin peptides playing a central role in pain transmission. The objective of this study was to verify whether HPLC-MS/MRM(3) could provide significant advantages over a more traditional HPLC-MS/MRM assay for the quantification of SP and NKA in rat spinal cord. The results suggest that reconstructed MRM(3) chromatograms display significant improvements with the nearly complete elimination of interfering peaks but the sensitivity (i.e. signal-to-noise ratio) was severely reduced. The precision (%CV) observed was between 3.5% and 24.1% using HPLC-MS/MRM and in the range of 4.3-13.1% with HPLC-MS/MRM(3), for SP and NKA. The observed accuracy was within 10% of the theoretical concentrations tested. HPLC-MS/MRM(3) may improve the assay sensitivity to detect difference between samples by reducing significantly the potential of interferences and therefore reduce instrumental errors. Copyright © 2014 Elsevier B.V. All rights reserved.

Natural killer cell subsets in cerebrospinal fluid of patients with multiple sclerosis

PubMed Central

Rodríguez-Martín, E; Picón, C; Costa-Frossard, L; Alenda, R; Sainz de la Maza, S; Roldán, E; Espiño, M; Villar, L M; Álvarez-Cermeño, J C

2015-01-01

Changes in blood natural killer (NK) cells, important players of the immune innate system, have been described in multiple sclerosis (MS). We studied percentages and total cell counts of different effector and regulatory NK cells in cerebrospinal fluid (CSF) of MS patients and other neurological diseases to gain clearer knowledge of the role of these cells in neuroinflammation. NK cell subsets were assessed by flow cytometry in CSF of 85 consecutive MS patients (33 with active disease and 52 with stable MS), 16 with other inflammatory diseases of the central nervous system (IND) and 17 with non-inflammatory neurological diseases (NIND). MS patients showed a decrease in percentages of different CSF NK subpopulations compared to the NIND group. However, absolute cell counts showed a significant increase of all NK subsets in MS and IND patients, revealing that the decrease in percentages does not reflect a real reduction of these immune cells. Remarkably, MS patients showed a significant increase of regulatory/effector (CD56bright/CD56dim) NK ratio compared to IND and NIND groups. In addition, MS activity associated with an expansion of NK T cells. These data show that NK cell subsets do not increase uniformly in all inflammatory neurological disease and suggest strongly that regulatory CD56bright and NK T cells may arise in CSF of MS patients as an attempt to counteract the CNS immune activation characteristic of the disease. PMID:25565222

Meeting the mental health needs of people with multiple sclerosis: a qualitative study of patients and professionals.

PubMed

Methley, Abigail; Campbell, Stephen; Cheraghi-Sohi, Sudeh; Chew-Graham, Carolyn

2017-06-01

To explore perspectives and experiences of people with multiple sclerosis (MS) and health care professionals of mental health support for MS in the UK. 24 people with MS, 13 practice nurses, 12 general practitioners (GPs) and 9 MS specialist nurses were recruited through community groups and primary care practices across North West England. Semi-structured interviews were conducted, and data analyzed thematically using constant comparative analysis within and across the data sets. The theoretical framework of candidacy was used to interrogate data. Four themes were identified: candidates for care, management choices, defining roles, and permeability and responsiveness. Candidacy for care, and symptom management, depended on the framing of symptoms through a social or medical model of depression. Normalizing symptoms could prevent help-seeking by patients. Reported referral behavior varied by professional group, based on perceived remit, competency and training needs. GPs were perceived by patients and other professionals as central for management of mental health needs in MS, but may not perceive this role themselves, suggesting a need for increased knowledge, training, and improved access to specialist care. Implications for Rehabilitation Anxiety and depression are common in people with MS. Management of mental health needs in people with MS relies on complex decisions made by both people with MS and health care professionals. General practitioners may play a key role in the ongoing management of mental health needs of people with MS.

Functional assessment of the visual pathway with multifocal visual evoked potentials, and their relationship with disability in patients with multiple sclerosis.

PubMed

Blanco, Román; Pérez-Rico, Consuelo; Puertas-Muñoz, Inmaculada; Ayuso-Peralta, Lucía; Boquete, Luciano; Arévalo-Serrano, Juan

2014-02-01

To objectively evaluate the visual function, and the relationship between disability and optic nerve dysfunction, in patients with multiple sclerosis (MS) and optic neuritis (ON), using multifocal visual evoked potentials (mfVEP). This observational, cross-sectional study assessed 28 consecutive patients with clinically definite MS, according to the McDonald criteria, and 19 age-matched healthy subjects. Disability was recorded using the Expanded Disability Status Scale (EDSS) score. The patients' mfVEP were compared to their clinical, psychophysical (Humphrey perimetry) and structural (optic coherence tomography (OCT)) diagnostic test data. We observed a significant agreement between mfVEP amplitude and Humphrey perimetry/OCT in MS-ON eyes, and between mfVEP amplitude and OCT in MS but non-ON eyes. We found significant differences in EDSS score between patients with abnormal and normal mfVEP amplitudes. Abnormal mfVEP amplitude defects (from interocular and monocular probability analysis) were found in 67.9% and 73.7% of the MS-ON and MS-non-ON group eyes, respectively. Delayed mfVEP latencies (interocular and monocular probability analysis) were seen in 70.3% and 73.7% of the MS-ON and MS-non-ON groups, respectively. We found a significant relationship between mfVEP amplitude and disease severity, as measured by EDSS score, that suggested there is a role for mfVEP amplitude as a functional biomarker of axonal loss in MS.

Bacterial Interactomes: Interacting Protein Partners Share Similar Function and Are Validated in Independent Assays More Frequently Than Previously Reported*

PubMed Central

Shatsky, Maxim; Allen, Simon; Gold, Barbara L.; Liu, Nancy L.; Juba, Thomas R.; Reveco, Sonia A.; Elias, Dwayne A.; Prathapam, Ramadevi; He, Jennifer; Yang, Wenhong; Szakal, Evelin D.; Liu, Haichuan; Singer, Mary E.; Geller, Jil T.; Lam, Bonita R.; Saini, Avneesh; Trotter, Valentine V.; Hall, Steven C.; Fisher, Susan J.; Brenner, Steven E.; Chhabra, Swapnil R.; Hazen, Terry C.; Wall, Judy D.; Witkowska, H. Ewa; Biggin, Mark D.; Chandonia, John-Marc; Butland, Gareth

2016-01-01

Numerous affinity purification-mass spectrometry (AP-MS) and yeast two-hybrid screens have each defined thousands of pairwise protein-protein interactions (PPIs), most of which are between functionally unrelated proteins. The accuracy of these networks, however, is under debate. Here, we present an AP-MS survey of the bacterium Desulfovibrio vulgaris together with a critical reanalysis of nine published bacterial yeast two-hybrid and AP-MS screens. We have identified 459 high confidence PPIs from D. vulgaris and 391 from Escherichia coli. Compared with the nine published interactomes, our two networks are smaller, are much less highly connected, and have significantly lower false discovery rates. In addition, our interactomes are much more enriched in protein pairs that are encoded in the same operon, have similar functions, and are reproducibly detected in other physical interaction assays than the pairs reported in prior studies. Our work establishes more stringent benchmarks for the properties of protein interactomes and suggests that bona fide PPIs much more frequently involve protein partners that are annotated with similar functions or that can be validated in independent assays than earlier studies suggested. PMID:26873250

Emotion processing in the visual brain: a MEG analysis.

PubMed

Peyk, Peter; Schupp, Harald T; Elbert, Thomas; Junghöfer, Markus

2008-06-01

Recent functional magnetic resonance imaging (fMRI) and event-related brain potential (ERP) studies provide empirical support for the notion that emotional cues guide selective attention. Extending this line of research, whole head magneto-encephalogram (MEG) was measured while participants viewed in separate experimental blocks a continuous stream of either pleasant and neutral or unpleasant and neutral pictures, presented for 330 ms each. Event-related magnetic fields (ERF) were analyzed after intersubject sensor coregistration, complemented by minimum norm estimates (MNE) to explore neural generator sources. Both streams of analysis converge by demonstrating the selective emotion processing in an early (120-170 ms) and a late time interval (220-310 ms). ERF analysis revealed that the polarity of the emotion difference fields was reversed across early and late intervals suggesting distinct patterns of activation in the visual processing stream. Source analysis revealed the amplified processing of emotional pictures in visual processing areas with more pronounced occipito-parieto-temporal activation in the early time interval, and a stronger engagement of more anterior, temporal, regions in the later interval. Confirming previous ERP studies showing facilitated emotion processing, the present data suggest that MEG provides a complementary look at the spread of activation in the visual processing stream.

Stephen L. Gans overseas lecture. Mass screening for neuroblastoma in Japan: lessons learned and future directions.

PubMed

Suita, Sachiyo

2002-07-01

Since 1985, a nationwide mass screening program (MS) for neuroblastoma has been conducted for 6-month-old infants throughout Japan, resulting in the detection of more than 1,900 cases of neuroblastoma. The outcome of these patients has been excellent: more than 97% of them are alive. Yet, several reports suggest that the number of advanced-stage neuroblastoma patients over 1 year of age has not changed substantially. The current report focuses on the 15-year experience with MS of the Kyushu Pediatric Oncology Study Group. The clinical and biological features of neuroblastoms detected (n = 320) and not detected by MS (n = 245) were compared. Regional and national statistics for neuroblastoma before and after 1985 were analyzed using standard epidemiologic measures for the occurrence of disease. The majority of the MS-positive cases were biologically favorable and had an excellent outcome. In contrast, the majority of non-MS patients in whom neuroblastoma later developed had advanced-stage, unfavorable-prognosis tumors. The overall mortality rate of neuroblastoma in the Kyushu area was not improved by MS. The optimal time for screening is the point at which neuroblastomas regressing spontaneously can no longer be detected, but more aggressive disease can be found. A birth cohort study could determine the optimal timing for a second screening. Identification of other new prognostic factors may be required. Copyright 2002, Elsevier Science (USA). All rights reserved.

Multiple Sclerosis and EIF2B5: A Paradox or a Missing Link.

PubMed

Zahoor, Insha; Haq, Ehtishamul; Asimi, Ravouf

2017-01-01

Multiple sclerosis (MS) is an encumbering inflammatory condition of the central nervous system (CNS) caused by axonal demyelination. There is sufficient evidence suggesting role of eukaryotic translation initiation factor 2B (EIF2B) gene family encoding the five subunits of eIF2B complex-α, β, γ, δ and ε respectively, in causing vanishing white matter (VWM) disease of the brain. Incidentally researchers have proposed overlapping between MS and VWM in terms of clinical, biochemical and genetic aspects, which incited us to write this chapter to explore the association between EIF2B5 and MS. eIF2B plays an essential role in translation initiation and its regulation in eukaryotes. Among EIF2B gene family, EIF2B5 gene encodes the catalytic and a crucial epsilon subunit of the eIF2B protein as most of the alterations have been found in this gene. The recent findings on the association between EIF2B5 and MS susceptibility point towards unfathomable and contentious role of EIF2B5 in MS development. This chapter briefly reviews the insights gleaned from recent studies conducted in understanding the association between EIF2B5 and MS risk. The need of hour is to conduct large scale conclusive studies aimed at expounding the mechanisms behind this relationship.

Persistent visual impairment in multiple sclerosis: prevalence, mechanisms and resulting disability.

PubMed

Jasse, Laurence; Vukusic, Sandra; Durand-Dubief, Françoise; Vartin, Cristina; Piras, Carolina; Bernard, Martine; Pélisson, Denis; Confavreux, Christian; Vighetto, Alain; Tilikete, Caroline

2013-10-01

The objective of this article is to evaluate in multiple sclerosis (MS) patients the prevalence of persistent complaints of visual disturbances and the mechanisms and resulting functional disability of persistent visual complaints (PVCs). Firstly, the prevalence of PVCs was calculated in 303 MS patients. MS-related data of patients with or without PVCs were compared. Secondly, 70 patients with PVCs performed an extensive neuro-ophthalmologic assessment and a vision-related quality of life questionnaire, the National Eye Institute Visual Functionary Questionnaire (NEI-VFQ-25). PVCs were reported in 105 MS patients (34.6%). Patients with PVCs had more frequently primary progressive MS (30.5% vs 13.6%) and more neuro-ophthalmologic relapses (1.97 vs 1.36) than patients without PVCs. In the mechanisms/disability study, an afferent visual and an ocular-motor pathways dysfunction were respectively diagnosed in 41 and 59 patients, mostly related to bilateral optic neuropathy and bilateral internuclear ophthalmoplegia. The NEI-VFQ 25 score was poor and significantly correlated with the number of impaired neuro-ophthalmologic tests. Our study emphasizes the high prevalence of PVC in MS patients. Regarding the nature of neuro-ophthalmologic deficit, our results suggest that persistent optic neuropathy, as part of the progressive evolution of the disease, is not rare. We also demonstrate that isolated ocular motor dysfunctions induce visual disability in daily life.

Global map of physical interactions among differentially expressed genes in multiple sclerosis relapses and remissions.

PubMed

Tuller, Tamir; Atar, Shimshi; Ruppin, Eytan; Gurevich, Michael; Achiron, Anat

2011-09-15

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.

A high calorie diet causes memory loss, metabolic syndrome and oxidative stress into hippocampus and temporal cortex of rats.

PubMed

Treviño, Samuel; Aguilar-Alonso, Patrícia; Flores Hernandez, Jose Angel; Brambila, Eduardo; Guevara, Jorge; Flores, Gonzalo; Lopez-Lopez, Gustavo; Muñoz-Arenas, Guadalupe; Morales-Medina, Julio Cesar; Toxqui, Veronica; Venegas, Berenice; Diaz, Alfonso

2015-09-01

A high calorie intake can induce the appearance of the metabolic syndrome (MS), which is a serious public health problem because it affects glucose levels and triglycerides in the blood. Recently, it has been suggested that MS can cause complications in the brain, since chronic hyperglycemia and insulin resistance are risk factors for triggering neuronal death by inducing a state of oxidative stress and inflammatory response that affect cognitive processes. This process, however, is not clear. In this study, we evaluated the effect of the consumption of a high-calorie diet (HCD) on both neurodegeneration and spatial memory impairment in rats. Our results demonstrated that HCD (90 day consumption) induces an alteration of the main energy metabolism markers, indicating the development of MS in rats. Moreover, an impairment of spatial memory was observed. Subsequently, the brains of these animals showed activation of an inflammatory response (increase in reactive astrocytes and interleukin1-β as well as tumor necrosis factor-α) and oxidative stress (reactive oxygen species and lipid peroxidation), causing a reduction in the number of neurons in the temporal cortex and hippocampus. Altogether, these results suggest that a HCD promotes the development of MS and contributes to the development of a neurodegenerative process and cognitive failure. In this regard, it is important to understand the relationship between MS and neuronal damage in order to prevent the onset of neurodegenerative disorders. © 2015 Wiley Periodicals, Inc.

Reduced transcript stabilization restricts TNF-alpha expression in RAW264.7 macrophages infected with pathogenic mycobacteria: evidence for an involvement of lipomannan.

PubMed

Basler, Tina; Holtmann, Helmut; Abel, Jens; Eckstein, Torsten; Baumer, Wolfgang; Valentin-Weigand, Peter; Goethe, Ralph

2010-01-01

Despite the critical role that TNF-alpha plays in the containment of mycobacterial infection, the mechanisms involved in regulation of its expression by mycobacteria are poorly defined. We addressed this question by studying MAP, which causes a chronic enteritis in ruminants and is linked to human Crohn's disease. We found that in MAP infected macrophages, TNF-alpha gene expression was substantially lower than in macrophages infected with nonpathogenic MS or stimulated with LPS. TNF-alpha transcriptional one could not fully explain the differential TNF-alpha mRNA expression, suggesting that there must be a substantial contribution by post-transcriptional mechanisms.Accordingly, we found reduced TNF-alpha mRNA stability in MAP-infected macrophages. Further comparison of MAP- and MS-infected macrophages revealed that lower TNF-alpha mRNA stability combined with lower mRNA and protein expression in MAP-infected macrophages correlated with lower p38 MAPK phosphorylation. These findings were independent of viability of MAP and MS. We demonstrate that the major mycobacterial cell-wall lipoglycan LM of MAP and MS induced TNF-alpha mRNA transcription,but only the MS-LM induced p38 MAPK-dependent transcript stabilization. Overall, our data suggest that pathogenic mycobacteria cause weak p38 and TNF-alpha mRNA stabilization as a result of their structural cell-wall components such as LM and thereby, restrict TNF-alpha expression in macrophages.

Neural time course of visually enhanced echo suppression.

PubMed

Bishop, Christopher W; London, Sam; Miller, Lee M

2012-10-01

Auditory spatial perception plays a critical role in day-to-day communication. For instance, listeners utilize acoustic spatial information to segregate individual talkers into distinct auditory "streams" to improve speech intelligibility. However, spatial localization is an exceedingly difficult task in everyday listening environments with numerous distracting echoes from nearby surfaces, such as walls. Listeners' brains overcome this unique challenge by relying on acoustic timing and, quite surprisingly, visual spatial information to suppress short-latency (1-10 ms) echoes through a process known as "the precedence effect" or "echo suppression." In the present study, we employed electroencephalography (EEG) to investigate the neural time course of echo suppression both with and without the aid of coincident visual stimulation in human listeners. We find that echo suppression is a multistage process initialized during the auditory N1 (70-100 ms) and followed by space-specific suppression mechanisms from 150 to 250 ms. Additionally, we find a robust correlate of listeners' spatial perception (i.e., suppressing or not suppressing the echo) over central electrode sites from 300 to 500 ms. Contrary to our hypothesis, vision's powerful contribution to echo suppression occurs late in processing (250-400 ms), suggesting that vision contributes primarily during late sensory or decision making processes. Together, our findings support growing evidence that echo suppression is a slow, progressive mechanism modifiable by visual influences during late sensory and decision making stages. Furthermore, our findings suggest that audiovisual interactions are not limited to early, sensory-level modulations but extend well into late stages of cortical processing.

Detection of Amyloid Beta (Aβ) Oligomeric Composition Using Matrix-Assisted Laser Desorption Ionization Mass Spectrometry (MALDI MS)

NASA Astrophysics Data System (ADS)

Wang, Jasmine S.-H.; Whitehead, Shawn N.; Yeung, Ken K.-C.

2018-02-01

The use of MALDI MS as a fast and direct method to detect the Aβ oligomers of different masses is examined in this paper. Experimental results suggest that Aβ oligomers are ionized and detected as singly charged ions, and thus, the resulting mass spectrum directly reports the oligomer size distribution. Validation experiments were performed to verify the MS data against artifacts. Mass spectra collected from modified Aβ peptides with different propensities for aggregation were compared. Generally, the relative intensities of multimers were higher from samples where oligomerization was expected to be more favorable, and vice versa. MALDI MS was also able to detect the differences in oligomeric composition before and after the incubation/oligomerization step. Such differences in sample composition were also independently confirmed with an in vitro Aβ toxicity study on primary rat cortical neurons. An additional validation was accomplished through removal of oligomers from the sample using molecular weight cutoff filters; the resulting MS data correctly reflected the removal at the expected cutoff points. The results collectively validated the ability of MALDI MS to assess the monomeric/multimeric composition of Aβ samples. [Figure not available: see fulltext.

The possible effects of the solar and geomagnetic activity on multiple sclerosis.

PubMed

Papathanasopoulos, Panagiotis; Preka-Papadema, Panagiota; Gkotsinas, Anastasios; Dimisianos, Nikolaos; Hillaris, Alexandros; Katsavrias, Christos; Antonakopoulos, Gregorios; Moussas, Xenophon; Andreadou, Elisabeth; Georgiou, Vasileios; Papachristou, Pinelopi; Kargiotis, Odysseas

2016-07-01

Increasing observational evidence on the biological effects of Space Weather suggests that geomagnetic disturbances may be an environmental risk factor for multiple sclerosis (MS) relapses. In the present study, we aim to investigate the possible effect of geomagnetic disturbances on MS activity. MS patient admittance rates were correlated with the solar and geophysical data covering an eleven-year period (1996-2006, 23rd solar cycle). We also examined the relationship of patterns of the solar flares, the coronal mass ejections (CMEs) and the solar wind with the recorded MS admission numbers. The rate of MS patient admittance due to acute relapses was found to be associated with the solar and geomagnetic events. There was a "primary" peak in MS admittance rates shortly after intense geomagnetic storms followed by a "secondary" peak 7-8 months later. We conclude that the geomagnetic and solar activity may represent an environmental health risk factor for multiple sclerosis and we discuss the possible mechanisms underlying this association. More data from larger case series are needed to confirm these preliminary results and to explore the possible influence of Space Weather on the biological and radiological markers of the disease. Copyright © 2016 Elsevier B.V. All rights reserved.

Transepithelial D-glucose and D-fructose transport across the American lobster, Homarus americanus, intestine.

PubMed

Obi, Ijeoma E; Sterling, Kenneth M; Ahearn, Gregory A

2011-07-15

Transepithelial transport of dietary D-glucose and d-fructose was examined in the lobster Homarus americanus intestine using D-[(3)H]glucose and D-[(3)H]fructose. Lobster intestines were mounted in a perfusion chamber to determine transepithelial mucosal to serosal (MS) and serosal to mucosal (SM) transport mechanisms of glucose and fructose. Both MS glucose and fructose transport, as functions of luminal sugar concentration, increased in a hyperbolic manner, suggesting the presence of mucosal transport proteins. Phloridizin inhibited the MS flux of glucose, but not that of fructose, suggesting the presence of a sodium-dependent (SGLT1)-like glucose co-transporter. Immunohistochemical analysis, using a goat anti-rabbit GLUT5 polyclonal antibody, revealed the localization of a brush border GLUT5-like fructose transport protein. MS fructose transport was decreased in the presence of mucosal phloretin in warm spring/summer animals, but the same effect was not observed in cold autumn/winter animals, suggesting a seasonal regulation of sugar transporters. Mucosal phloretin had no effect on MS glucose transport. Both SM glucose and SM fructose transport were decreased in the presence of increasing concentrations of serosal phloretin, providing evidence for the presence of a shared serosal GLUT2 transport protein for the two sugars. The transport of d-glucose and d-fructose across lobster intestine is similar to sugar uptake in mammalian intestine, suggesting evolutionarily conserved absorption processes for these solutes.

Earnings and Financial Compensation from Social Security Systems Correlate Strongly with Disability for Multiple Sclerosis Patients.

PubMed

Kavaliunas, Andrius; Wiberg, Michael; Tinghög, Petter; Glaser, Anna; Gyllensten, Hanna; Alexanderson, Kristina; Hillert, Jan

2015-01-01

Multiple sclerosis (MS) patients earn lower incomes and receive higher benefits. However, there is limited knowledge of how this is correlated with their disability. To elucidate sources and levels of income among MS patients with different disability, assessed with the Expanded Disability Status Scale. A total of 7929 MS patients aged 21-64 years and living in Sweden in 2010 were identified for this cross-sectional study. Descriptive statistics, logistic and truncated linear regression models were used to estimate differences between MS patients regarding earnings, disability pension, sickness absence, disability allowance, unemployment compensation, and social assistance. The average level of earnings was ten times lower and the average level of health- related benefits was four times higher when comparing MS patients with severe and mild disability. MS patients with severe disability had on average SEK 166,931 less annual income from earnings and SEK 54,534 more income from benefits compared to those with mild disability. The combined average income for MS patients was 35% lower when comparing patients in the same groups. The adjusted risk ratio for having earnings among MS patients with severe disability compared to the patients with mild disability was 0.33 (95% CI 0.29-0.39), while the risk ratio for having benefits was 1.93 (95% CI 1.90-1.94). Disease progression affects the financial situation of MS patients considerably. Correlations between higher disability and patient income were observed, suggesting that earnings and benefits could be used as measures of MS progression and proxies of disability.

Investigation of epigallocatechin-3-O-caffeoate and epigallocatechin-3-O-p-coumaroate in tea leaves by LC/MS-MS analysis.

PubMed

Umehara, Masahiro; Yanae, Koji; Maruki-Uchida, Hiroko; Sai, Masahiko

2017-12-01

(-)-Epigallocatechin-3-O-gallate (EGCG), the major catechin present in green tea, exhibits potent antioxidant activity. We thereby investigated the presence of unknown components bearing the (-)-epigallocatechin (EGC) moiety in fresh tea leaf samples. Initially, liquid chromatography tandem mass spectrometry (LC-MS/MS) was employed to examine fresh tea leaves of the Yabukita, the most popular tea cultivar in Japan, which suggested the presence of the EGC phenylpropanoid derivatives, (-)-epigallocatechin-3-O-p-coumaroate (EGCpCA) and (-)-epigallocatechin-3-O-caffeoate (EGCCA). The structures of the detected EGCpCA and EGCCA were then confirmed by LC-MS/MS using synthesized EGCpCA and EGCCA as standards. In addition, EGCpCA and EGCCA were evaluated for their antioxidant activity in the ORAC (oxygen radical antioxidant capacity) and DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assays, where EGCCA (8.60μmolTE/μmol, TE=Trolox equivalents) exhibited a stronger antioxidant activity than EGCG (5.52μmolTE/μmol) in the ORAC assay. Finally, EGCpCA and EGCCA were quantitated in several tea leaf samples using LC-MS/MS, and it was found that these compounds were present in lower quantities (EGCpCA, 16.8-345.8μg/g, EGCCA, 4.3-75.1μg/g in the dry tea leaves) than the major catechins. In this study, we found the potent antioxidant EGCCA using LC-MS/MS and revealed its wide existence in various tea leaves. Copyright © 2017 Elsevier Ltd. All rights reserved.

Drug exposure and the risk of multiple sclerosis: A systematic review.

PubMed

Yong, Heather Y; McKay, Kyla A; Daley, Cole G J; Tremlett, Helen

2018-02-01

Several environmental and lifestyle factors have been associated with multiple sclerosis (MS) risk, including some pharmacological treatments. We systematically reviewed the literature on prescription drug exposure and MS risk. Six databases were searched for original observational studies reporting drug exposure and MS risk published before 2017. Thirteen articles fulfilled inclusion criteria. Exposure to neither amiloride nor valproic acid was associated with MS (adjusted hazard ratio (adj.HR = 1.34;95% CI:0.81-2.20; adj.HR = 1.30;95%CI:0.44-3.80, respectively). Four studies explored oral contraceptive exposure and reported no association with MS; while a single study found an increased risk (odds ratio [adj.OR] = 1.52;95%CI:1.21-1.91). While penicillin exposure was associated with reduced risk of developing MS (adj.OR = 0.5;95%CI:0.3-0.9), a later study observed an elevated risk for penicillin (adj.OR = 1.21;95%CI:1.10-1.27) and all antibiotics (adj.OR = 1.41;95%CI:1.29-1.53), which was potentially attributed to underlying infection. Anti-tumor necrosis factor-alpha (TNFα) was not associated with MS risk in persons with inflammatory bowel disease (standard morbidity ratio = 4.2;95%CI:0.1-23.0) and arthritis (standardized incidence ratio = 1.38;95%CI:0.69-2.77); however, men exposed to anti-TNFα who also had arthritis and individuals with ankylosing spondylitis were at an increased risk (standardized incidence ratios = 3.91;95%CI:1.47-10.42 and 3.48;95%CI:1.45-8.37, respectively). A reduced risk of MS was observed with exposure to the beta2-adrenergic agonist fenoterol (adj.OR = 0.58;95%CI:0.45-0.76), and the sedating histamine 1-receptor antagonists (adj.OR = 0.2;95%CI:0.1-0.8), but not the non-sedating equivalent (adj.OR = 0.8;95%CI:0.4-1.6). The suggestion that some drugs may prevent MS is intriguing and warrants further study. In addition, further pharmacovigilance is needed to assess the safety of anti-TNFα drugs in specific populations in the context of MS risk. Copyright © 2017 John Wiley & Sons, Ltd.

Syllabic encoding during overt speech production in Cantonese: Evidence from temporal brain responses.

PubMed

Wong, Andus Wing-Kuen; Wang, Jie; Ng, Tin-Yan; Chen, Hsuan-Chih

2016-10-01

The time course of phonological encoding in overt Cantonese disyllabic word production was investigated using a picture-word interference task with concurrent recording of the event-related brain potentials (ERPs). Participants were asked to name aloud individually presented pictures and ignore a distracting Chinese character. Participants' naming responses were faster, relative to an unrelated control, when the distractor overlapped with the target's word-initial or word-final syllables. Furthermore, ERP waves in the syllable-related conditions were more positive-going than those in the unrelated control conditions from 500ms to 650ms post target onset (i.e., a late positivity). The mean and peak amplitudes of this late positivity correlated with the size of phonological facilitation. More importantly, the onset of the late positivity associated with word-initial syllable priming was 44ms earlier than that associated with word-final syllable priming, suggesting that phonological encoding in overt speech runs incrementally and the encoding duration for one syllable unit is approximately 44ms. Although the size of effective phonological units might vary across languages, as suggested by previous speech production studies, the present data indicate that the incremental nature of phonological encoding is a universal mechanism. Copyright © 2016 Elsevier B.V. All rights reserved.

Human endogenous retrovirus type W envelope expression in blood and brain cells provides new insights into multiple sclerosis disease

PubMed Central

Germi, Raphaëlle; Bernard, Corinne; Garcia-Montojo, Marta; Deluen, Cécile; Farinelli, Laurent; Faucard, Raphaël; Veas, Francisco; Stefas, Ilias; Fabriek, Babs O; Van-Horssen, Jack; Van-der-Valk, Paul; Gerdil, Claire; Mancuso, Roberta; Saresella, Marina; Clerici, Mario; Marcel, Sébastien; Creange, Alain; Cavaretta, Rosella; Caputo, Domenico; Arru, Giannina; Morand, Patrice; Lang, Alois B; Sotgiu, Stefano; Ruprecht, Klemens; Rieckmann, Peter; Villoslada, Pablo; Chofflon, Michel; Boucraut, Jose; Pelletier, Jean; Hartung, Hans-Peter

2012-01-01

Background: The envelope protein from multiple sclerosis (MS) associated retroviral element (MSRV), a member of the Human Endogenous Retroviral family ‘W’ (HERV-W), induces dysimmunity and inflammation. Objective: The objective of this study was to confirm and specify the association between HERV-W/MSRV envelope (Env) expression and MS. Methods: 103 MS, 199 healthy controls (HC) and controls with other neurological diseases (28), chronic infections (30) or autoimmunity (30) were analysed with an immunoassay detecting Env in serum. Env RNA or DNA copy numbers in peripheral blood mononuclear cells (PBMC) were determined by a quantitative polymerase chain reaction (PCR). Env was detected by immunohistology in the brains of patients with MS with three specific monoclonals. Results: Env antigen was detected in a serum of 73% of patients with MS with similar prevalence in all clinical forms, and not in chronic infection, systemic lupus, most other neurological diseases and healthy donors (p<0.01). Cases with chronic inflammatory demyelinating polyneuropathy (5/8) and rare HC (4/103) were positive. RNA expression in PBMC and DNA copy numbers were significantly elevated in patients with MS versus HC (p<0.001). In patients with MS, DNA copy numbers were significantly increased in chronic progressive MS (secondary progressive MS vs relapsing–remitting MS (RRMS) p<0.001; primary progressive MS vs RRMS –<0.02). Env protein was evidenced in macrophages within MS brain lesions with particular concentrations around vascular elements. Conclusion: The association between MS disease and the MSRV-type HERV-W element now appears quite strong, as evidenced ex-vivo from serum and PBMC with post-mortem confirmation in brain lesions. Chronic progressive MS, RRMS and clinically isolated syndrome show different ELISA (Enzyme-Linked Immunosorbent Assay) and/or PCR profiles suggestive of an increase with disease evolution, and amplicon sequencing confirms the association with particular HERV-W elements. PMID:22457345

Sun Exposure across the Life Course Significantly Modulates Early Multiple Sclerosis Clinical Course.

PubMed

Simpson, Steve; van der Mei, Ingrid; Lucas, Robyn M; Ponsonby, Anne-Louise; Broadley, Simon; Blizzard, Leigh; Taylor, Bruce

2018-01-01

Low vitamin D and/or sun exposure have been associated with increased risk of multiple sclerosis (MS) onset. However, comparatively, few studies have prospectively examined associations between these factors and clinical course. To evaluate the association of sun exposure parameters and vitamin D levels with conversion to MS and relapse risk in a prospectively monitored cohort of 145 participants followed after a first demyelinating event up to 5-year review (AusLong Study). Sun exposure prior to and after onset measured by annual questionnaire; ultraviolet radiation (UVR) "load" estimated by location of residence over the life course and ambient UVR levels. Serum 25-hydroxyvitamin D [25(OH)D] concentrations measured at baseline, 2/3-year, and 5-year review. MS conversion and relapse assessed by neurologist assessment and medical record review. Over two-thirds (69%) of those followed to 5-year review (100/145) converted to MS, with a total of 252 relapses. Higher pre-MS onset sun exposure was associated with reduced risk of MS conversion, with internal consistency between measures and dose-response relationships. Analogous associations were also seen with risk of relapse, albeit less strong. No consistent associations were observed between postonset sun exposure and clinical course, however. Notably, those who increased their sun exposure during follow-up had significantly reduced hazards of MS conversion and relapse. Serum 25(OH)D levels and vitamin D supplementation were not associated with conversion to MS or relapse hazard. We found that preonset sun exposure was protective against subsequent conversion to MS and relapses. While consistent associations between postonset sun exposure or serum 25(OH)D level and clinical course were not evident, possibly masked by behavior change, those participants who markedly increased their sun exposure demonstrated a reduced MS conversion and relapse hazard, suggesting beneficial effects of sun exposure on clinical course.

Multiple sclerosis and pregnancy: a single-centre prospective comparative study.

PubMed

Cuello, J P; Martínez Ginés, M L; Martin Barriga, M L; de Andrés, C

2017-03-01

Multiple sclerosis (MS) is a autoimmune disorder which preferentially affects young women of childbearing age. During pregnancy, the annualized relapse rate (AAR) is modified, but pregnancy has no harm effect on the long-term course of the disease. We aimed to study the clinical course of our MS patients during pregnancy, and compare their obstetrics outcomes with a control group of non-MS patients. A single centre prospective observational study was conducted. We assessed the reproductive history, MS history, pregnancy course and new-born outcome of a cohort of MS patients who had had a pregnancy between january 2007 and july 2012. We compared the global outcomes with a control cohort of 58 age-matched healthy pregnancies. Complete data from 35 consecutive women were analyzed, 40 deliveries. Control groups: 58 patients, 60 deliveries. EDSS at pregnancy 0,7. ARR before pregnancy 0,5. During pregnancy 0,3, after pregnancy 0,4. Twelve patients were on disease-modifying drugs (DMD) before pregnancy, 4 prenatal exposure occurs. The comparison between relapse rate and EDSS before, during and after delivery showed no statistically significant difference. In addition, compared to control group, there were also no differences in the obstetric outcomes. In MS cohort, we found a higher incidence of assisted reproductive treatments and lower breastfeeding rate, both statistically significant. Our series confirms that pregnancy has no negative long term impact on the progression of MS and also suggest that there is no additional morbidity in the pregnancy, comparing to the rest of the population. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Association of prolidase activity, oxidative parameters, and presence of atrial fibrillation in patients with mitral stenosis.

PubMed

Rabus, Murat; Demirbag, Recep; Yildiz, Ali; Tezcan, Orhan; Yilmaz, Remzi; Ocak, A Riza; Alp, Mete; Erel, Ozcan; Aksoy, Nurten; Yakut, Cevat

2008-07-01

Mitral stenosis (MS) is a common cause of atrial fibrillation (AF). Oxidative stress and inflammation factors were shown to be involved in atrial remodeling. The study aim was to compare the oxidative parameters and prolidase activity in severe MS patients with and without AF. The study population was comprised of 33 patients with MS and sinus rhythm (group I), 27 patients with MS and AF (group II), and 25 healthy controls (group III). Plasma prolidase activity, total antioxidant capacity (TAC), total oxidative status (TOS), and oxidative stress index (OSI) were determined. Additionally, we measured tissue TOS and TAC in patients with mitral valve replacement. TAC and OSI were higher, but TOS and prolidase were lower in patients with MS than control (all p <0.001). These parameters were similar in group I and group II (ANOVA p >0.05). Tissue TAC was significantly lower in group II than group I (0.015 +/- 0.01 vs. 0.026 +/- 0.01 mmol Trolox equiv/L, p = 0.014), tissue TOS was similar between groups I and II (0.24 +/- 0.06 vs. 0.22 +/- 0.05 mmol Trolox equiv/L, p = 0.161). Presence of AF was correlated with systolic blood pressure, left atrial diameter, plasma TAC, tissue TAC, plasma TOS, plasma OSI, and plasma prolidase activity. Tissue TAC level (beta = -0.435, p = 0.006) and left atrial diameter (beta = 0.460, p = 0.003) were independently related with presence of AF in patients with MS. This study suggested that the presence of AF in patients with severe MS may be associated with the plasma prolidase activity, tissue and plasma oxidative parameters.

Feasibility of matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) networking in university hospitals in Brussels.

PubMed

Martiny, D; Cremagnani, P; Gaillard, A; Miendje Deyi, V Y; Mascart, G; Ebraert, A; Attalibi, S; Dediste, A; Vandenberg, O

2014-05-01

The mutualisation of analytical platforms might be used to address rising healthcare costs. Our study aimed to evaluate the feasibility of networking a unique matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) system for common use in several university hospitals in Brussels, Belgium. During a one-month period, 1,055 successive bacterial isolates from the Brugmann University Hospital were identified on-site using conventional techniques; these same isolates were also identified using a MALDI-TOF MS system at the Porte de Hal Laboratory by sending target plates and identification projects via transportation and the INFECTIO_MALDI software (Infopartner, Nancy, France), respectively. The occurrence of transmission problems (<2 %) and human errors (<1 %) suggested that the system was sufficiently robust to be implemented in a network. With a median time-to-identification of 5 h and 11 min (78 min, min-max: 154-547), MALDI-TOF MS networking always provided a faster identification result than conventional techniques, except when chromogenic culture media and oxidase tests were used (p < 0.0001). However, the limited clinical benefits of the chromogenic culture media do not support their extra cost. Our financial analysis also suggested that MALDI-TOF MS networking could lead to substantial annual cost savings. MALDI-TOF MS networking presents many advantages, and few conventional techniques (optochin and oxidase tests) are required to ensure the same quality in patient care from the distant laboratory. Nevertheless, such networking should not be considered unless there is a reorganisation of workflow, efficient communication between teams, qualified technologists and a reliable IT department and helpdesk to manage potential connectivity problems.

Feasibility of a 6-Month Yoga Program to Improve the Physical and Psychosocial Status of Persons with Multiple Sclerosis and their Family Members.

PubMed

Kahraman, Turhan; Ozdogar, Asiye Tuba; Yigit, Pinar; Hosgel, Ilknur; Mehdiyev, Zaur; Ertekin, Ozge; Ozakbas, Serkan

To the best of our knowledge, there has been no study on yoga that includes both persons with multiple sclerosis (MS) and their family members. Because yoga has therapeutic effects in both persons with MS and healthy persons, we hypothesized that it would be an effective method to improve not only the physical and psychosocial status but also the time persons with MS and their family members spend together. To examine the feasibility of a 6-month (long-term) yoga program to improve the physical and psychosocial status of persons with MS and their family members. Uncontrolled clinical trial. The protocol was developed at the Department of Neurology, Faculty of Medicine, and School of Physical Therapy and Rehabilitation, Dokuz Eylül University, Izmir, Turkey. Persons with MS and healthy family members. Walking, balance, fatigue, health-related quality of life, depression, pain, and kinesiophobia. Yoga training was given once a week (at least 1h) for 6 months. The same assessors who assessed at baseline also performed the same assessments immediately after the end of the training (i.e., after 6 months). In total, 44 participants (27 persons with MS and 17 healthy family members) participated in the study. Twelve persons with MS and three healthy family members completed the 6-month yoga intervention. The completion rate for persons with MS and healthy subjects was 44.4% and 17.6%, respectively. In persons with MS, the mental dimension of health-related quality of life, walking speed, fatigue, and depression levels significantly improved after the yoga program (p < .05). However, there was no significant change in the self-reported walking impact, balance, pain, physical dimension of health-related quality of life, and kinesiophobia levels in the persons with MS (p > .05). This study suggests that a 6-month yoga program can improve the mental dimension of health-related quality of life, walking speed, fatigue, and depression in the persons with MS. However, the 6-month yoga program does not appear to be a feasible method to increase the time that persons with MS spend together with their family members. Copyright © 2018 Elsevier Inc. All rights reserved.

Iron accumulation in multiple sclerosis: an early pathogenic event.

PubMed

LeVine, Steven M; Bilgen, Mehmet; Lynch, Sharon G

2013-03-01

Iron has been shown to accumulate in deep gray matter structures in many forms of multiple sclerosis (MS), but detecting its presence early in the disease course (e.g., clinically isolated syndrome [CIS]) has been less clear. Here, we review a recent study where MRI scanning at 7 T together with susceptibility mapping was performed to assess iron deposition in CIS and control subjects. Susceptibility indicative of iron deposition was found to be increased in the globus pallidus, caudate, putamen and pulvinar of CIS patients compared with controls. The findings suggest that iron deposition is a pathological change that occurs early in the development of MS. Identifying the mechanisms of iron accumulation and determining whether iron promotes pathogenesis in MS are important areas of future research.

Determination of a steroid profile in heel prick blood using LC-MS/MS.

PubMed

Boelen, Anita; Ruiter, An F C; Claahsen-van der Grinten, Hedi L; Endert, Erik; Ackermans, Mariette T

2016-01-01

The aim of this study was to improve the sensitivity of the congenital adrenal hyperplasia (CAH) neonatal screening by including second-tier steroid profiling on a DBS using LC-MS. We developed a method to measure the steroid profile in DBS and established gestational age-specific reference ranges of cortisol, cortisone, 11-deoxycortisol, 21-deoxycortisol, 17-hydroxyprogesterone, testosterone, Δ4-androstenedione, corticosterone and 11-deoxycorticosterone using 450 heel prick samples of neonates, participating in the Dutch Screening Program. Analyzing 92 cards with a positive CAH screening showed that only 21-deoxycortisol was 100% specific for diagnosed CAH patients. Steroid precursors can be measured in DBS and we suggest to implement the method as a second tier testing for CAH in The Netherlands.

Predictors of life satisfaction among caregivers of individuals with multiple sclerosis.

PubMed

Waldron-Perrine, Brigid; Rapport, Lisa J; Ryan, Kelly A; Harper, Kaja Telmet

2009-04-01

Research on life satisfaction among caregivers of persons with multiple sclerosis (MS) is sparse. This study examined the extent to which MS-specific disease and psychosocial characteristics predict caregiver life satisfaction. Participants were 64 caregivers of patients with MS and the patients for whom they care. Multiple regression analysis indicated that caregiver perception of illness uncertainty and patients' unawareness of deficits have unique value in predicting caregiver life satisfaction, even after accounting for general financial status. Gender and level of social support were also important contributing factors to caregiver life satisfaction. The findings suggest that duration and severity of the patients' illness take a greater toll on life satisfaction of caregivers with low versus high social support, particularly among women caregivers.

Combination of Weight-Bearing Training and Anti-MSTN Polyclonal Antibody Improve Bone Quality In Rats.

PubMed

Tang, Liang; Gao, Xiaohang; Yang, Xiaoying; Zhang, Didi; Zhang, Xiaojun; Du, Haiping; Han, Yanqi; Sun, Lijun

2016-12-01

Weight-bearing exercise is beneficial to bone health. Myostatin (MSTN) deficiency has a positive effect on bone formation. We wondered if a combination of weight-bearing training and polyclonal antibody for MSTN (MsAb) would augment bone formation to a greater degree than single treatment. In this study, rats were randomly assigned to four groups: Control, weight-bearing training (WT), MsAb, and WT+MsAb. The trained rats ran at 15 m/min bearing with 35% of their body weight, 40 min/day (2 min of running followed by 2 min of rest), 6 days/week, for 8 weeks. The rats with MsAb were injected once a week with MsAb for 8 weeks. MicroCT analysis showed that compared with the MsAb group, WT+MsAb significantly enhanced cortical bone mineral density (BMD) (p < .01), bone volume over total volume (BV/TV) (p < .01), trabecular thickness (p < .05), and reduced trabecular separation (Tb.Sp) (p < .01). Compared with the WT group, WT+MsAb significantly increased trabecular BMD (p < .05), BV/TV (p < .05), and decreased Tb.Sp (p < .05). Three-point bending test demonstrated that MsAb failed to improve bone biomechanical properties (p > .05), weight-bearing training significantly increased energy absorption (p < .05) and elastic modulus (p < .05). However, when they combined, biomechanical properties including maximum load (p < .05), stiffness (p < .05), elastic modulus (p < .01) and energy absorption (p < .01) were all significantly enhanced. In conclusion, the combination of weight-bearing training and MsAb have a greater positive effect on bone than treatment with either MsAb or weight-bearing training alone, suggesting that resistance training in combination with MSTN antagonists could be an effective approach for improving bone health and reducing osteoporosis risk.

Malva Sylvestris Attenuates Cognitive Deficits in a Repetitive Mild Traumatic Brain Injury Rat Model by Reducing Neuronal Degeneration and Astrocytosis in the Hippocampus

PubMed Central

Qin, Hailin; Qin, Jie; Hu, Junmin; Huang, He; Ma, Lianting

2017-01-01

Background The aim of our study was to evaluate the effect of Malva sylvestris (MS) on cognitive dysfunction in a repetitive mild traumatic brain injury (MTBI). Material/Methods MTBI was induced in all the study animals by hitting a metallic pendulum near the parietal-occipital area of the skull three times a day for ten days. Animals were treated with MS (250 mg/kg and 500 mg/kg) intragastrically per day for seven consecutive days. Cognitive function was estimated by the Morris water maze (MWM) method. Histopathology studies were performed on the hippocampal region by Nissl staining and anti GFAP staining. Concentrations of reactive oxygen species (ROS), and oxidative parameters including superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation (LPO), and inflammatory cytokines in the brain tissues were measured. Result Treatment with MS significantly improved cognitive function compared to the negative control. Histopathology studies suggested that treatment with MS significantly decreased (p<0.01) the count of neurodegenerative cells and induction of astrocytosis in the MTBI treated group compared to the negative control group. However, the concentrations of ROS and LPO, and the activities of SOD and CAT were significantly decreased in the MS treated groups of MTBI rats compared to the negative control group. Inflammatory cytokines, such as IL-1β, IL6, and TNF-α were significantly decreased (p<0.01) in the brain tissues of the MTBI treated group compared to the control group of rats. Conclusions This study concluded that treatment with MS significantly improved cognitive dysfunction by reducing neurodegeneration and astrocytosis in brain tissues via decreasing oxidative stress and inflammation in neuronal cells. PMID:29276216

The use of in vitro technologies coupled with high resolution accurate mass LC-MS for studying drug metabolism in equine drug surveillance.

PubMed

Scarth, James P; Spencer, Holly A; Timbers, Sarah E; Hudson, Simon C; Hillyer, Lynn L

2010-01-01

The detection of drug abuse in horseracing often requires knowledge of drug metabolism, especially if urine is the matrix of choice. In this study, equine liver/lung microsomes/S9 tissue fractions were used to study the phase I metabolism of eight drugs of relevance to equine drug surveillance (acepromazine, azaperone, celecoxib, fentanyl, fluphenazine, mepivacaine, methylphenidate and tripelennamine). In vitro samples were analyzed qualitatively alongside samples originating from in vivo administrations using LC-MS on a high resolution accurate mass Thermo Orbitrap Discovery instrument and by LC-MS/MS on an Applied Biosystems Sciex 5500 Q Trap.Using high resolution accurate mass full-scan analysis on the Orbitrap, the in vitro systems were found to generate at least the two most abundant phase I metabolites observed in vitro for all eight drugs studied. In the majority of cases, in vitro experiments were also able to generate the minor in vivo metabolites and sometimes metabolites that were only observed in vitro. More detailed analyses of fentanyl incubates using LC-MS/MS showed that it was possible to generate good quality spectra from the metabolites generated in vitro. These data support the suggestion of using in vitro incubates as metabolite reference material in place of in vivo post-administration samples in accordance with new qualitative identification guidelines in the 2009 International Laboratory Accreditation Cooperation-G7 (ILAC-G7) document.In summary, the in vitro and in vivo phase I metabolism results reported herein compare well and demonstrate the potential of in vitro studies to compliment, refine and reduce the existing equine in vivo paradigm. © 2010 John Wiley & Sons, Ltd.

Incidence of Metabolic Syndrome in Patients Admitted to Medical Wards with ST Elevation Myocardial Infarction

PubMed Central

Karanayil, Lekshmi Sankar

2017-01-01

Introduction Metabolic Syndrome (MS) consists of a cluster of metabolic abnormalities that confer exaggerated risk of cardiovascular disease. MS is a novel risk factor for Coronary Artery Disease (CAD) and is a rising disease entity in Asia. Incidence of ST Elevation Myocardial Infarction (STEMI) is high in patients with MS. There is limited data on prevalence of MS in patients with Acute Myocardial Infarction (AMI). Aim To determine frequency of MS in patients admitted with STEMI. Materials and Methods Hundred Consecutive patients between 25 to 75 years who were admitted with STEMI at Govt medical college Thrissur were included in this prospective study. Subjects were assessed for five-component conditions of metabolic syndrome. Criteria to identify MS were based on a “Consensus statement for diagnosis of metabolic syndrome for Asian Indians”. Presence of three or more of following suggest MS, Waist Circumference (WC)>90 cm in men and 80 cm in women, Blood pressure >130/85 mm Hg, Fasting Plasma Glucose (FPG) >100 mg%, serum triglycerides >150 mg/dl, High Density Lipoprotein (HDL)<40 mg/dl in male and<50 mg/dl in female. Statistical analysis was performed using Epi-Info software. Data expressed as numbers and percents were compared by Chi-square test. Results Study enrolled 100 patients (males 80, females 20) with a mean age of 58. Frequency of MS in patients with STEMI was 40% (36% of males and 55% of females). Prevalence of components in the MS group was WC >80/90 -31(71%), BP>130/85- 23(58%), FPG >100 - 37(93%), HDL <40 (male)/ 50 (female) - 18(45%), TG >150 -15(37.5%). Conclusion The present study concluded that there is a remarkably high occurrence of metabolic syndrome and central obesity in patients with ST elevation Myocardial Infarction (MI) in our local population especially in females. Considering this fact the role of specific and targeted intervention for clinical detection and management of MS including lifestyle modifications needs to be addressed. PMID:28511428

Heterogeneity of ventricular repolarization in newborns with intrauterine growth restriction.

PubMed

Fouzas, Sotirios; Karatza, Ageliki A; Davlouros, Periklis A; Chrysis, Dionisios; Alexopoulos, Dimitrios; Mantagos, Stefanos; Dimitriou, Gabriel

2014-12-01

Intrauterine growth restriction (IUGR) is associated with structural and functional cardiac alterations but the electrophysiological consequences of these disturbances remain unknown. To explore the distribution of ventricular repolarization and its relation to myocardial mechanics in newborns with IUGR. STUDY DESIGN, SUBJECTS AND OUTCOME MEASUREMENTS: Conventional and tissue Doppler echocardiographic data, and electrocardiographic parameters used to describe the distribution of ventricular repolarization (dispersion of QT [QTd] and JT [JTd]), were obtained on the second (D2) and fifth (D5) postnatal day and compared between 25 IUGR newborns and 25 matched-for-gestational age controls. IUGR was associated with relative interventricular septum hypertrophy, increased left ventricular (LV) E/E' ratio and higher LV myocardial performance index (MPI). On both study days, the IUGR infants presented higher QTd and JTd compared to controls (QTd-D2: 66±20 ms vs. 36±12 ms, P<0.001; JTd-D2: 54±13 ms vs. 34±9 ms, P<0.001; QTd-D5: 61±14 ms vs. 27±12 ms, P<0.001; JTd-D5: 54±13 ms vs. 27±9 ms, P<0.001). The association between QTd and LV E/E' (D2: regression coefficient beta 0.747, R(2) 0.585; D5: beta 0.843, R(2) 0.646) and QTd and MPI (D2: beta 0.680, R(2) 0.576; D5: beta 0.698, R(2) 0.650) was also significant (P<0.001 for all analyses). Our findings suggest that IUGR is associated with electrophysiological remodeling of the neonatal heart, a process which is closely related to the underlying alterations in ventricular mechanics and might predispose to adverse electrophysiological events. Copyright © 2014 Elsevier Ltd. All rights reserved.

Iconic Meaning in Music: An Event-Related Potential Study.

PubMed

Cai, Liman; Huang, Ping; Luo, Qiuling; Huang, Hong; Mo, Lei

2015-01-01

Although there has been extensive research on the processing of the emotional meaning of music, little is known about other aspects of listeners' experience of music. The present study investigated the neural correlates of the iconic meaning of music. Event-related potentials (ERP) were recorded while a group of 20 music majors and a group of 20 non-music majors performed a lexical decision task in the context of implicit musical iconic meaning priming. ERP analysis revealed a significant N400 effect of congruency in time window 260-510 ms following the onset of the target word only in the group of music majors. Time-course analysis using 50 ms windows indicated significant N400 effects both within the time window 410-460 ms and 460-510 ms for music majors, whereas only a partial N400 effect during time window 410-460 ms was observed for non-music majors. There was also a trend for the N400 effects in the music major group to be stronger than those in the non-major group in the sub-windows of 310-360 ms and 410-460 ms. Especially in the sub-window of 410-460 ms, the topographical map of the difference waveforms between congruent and incongruent conditions revealed different N400 distribution between groups; the effect was concentrated in bilateral frontal areas for music majors, but in central-parietal areas for non-music majors. These results imply probable neural mechanism differences underlying automatic iconic meaning priming of music. Our findings suggest that processing of the iconic meaning of music can be accomplished automatically and that musical training may facilitate the understanding of the iconic meaning of music.

Iconic Meaning in Music: An Event-Related Potential Study

PubMed Central

Luo, Qiuling; Huang, Hong; Mo, Lei

2015-01-01

Although there has been extensive research on the processing of the emotional meaning of music, little is known about other aspects of listeners’ experience of music. The present study investigated the neural correlates of the iconic meaning of music. Event-related potentials (ERP) were recorded while a group of 20 music majors and a group of 20 non-music majors performed a lexical decision task in the context of implicit musical iconic meaning priming. ERP analysis revealed a significant N400 effect of congruency in time window 260-510 ms following the onset of the target word only in the group of music majors. Time-course analysis using 50 ms windows indicated significant N400 effects both within the time window 410-460 ms and 460-510 ms for music majors, whereas only a partial N400 effect during time window 410-460 ms was observed for non-music majors. There was also a trend for the N400 effects in the music major group to be stronger than those in the non-major group in the sub-windows of 310-360ms and 410-460ms. Especially in the sub-window of 410-460 ms, the topographical map of the difference waveforms between congruent and incongruent conditions revealed different N400 distribution between groups; the effect was concentrated in bilateral frontal areas for music majors, but in central-parietal areas for non-music majors. These results imply probable neural mechanism differences underlying automatic iconic meaning priming of music. Our findings suggest that processing of the iconic meaning of music can be accomplished automatically and that musical training may facilitate the understanding of the iconic meaning of music. PMID:26161561

Importance of cerebrospinal fluid analysis in the era of McDonald 2010 criteria: a German-Austrian retrospective multicenter study in patients with a clinically isolated syndrome.

PubMed

Huss, André M; Halbgebauer, Steffen; Öckl, Patrick; Trebst, Corinna; Spreer, Annette; Borisow, Nadja; Harrer, Andrea; Brecht, Isabel; Balint, Bettina; Stich, Oliver; Schlegel, Sabine; Retzlaff, Nele; Winkelmann, Alexander; Roesler, Romy; Lauda, Florian; Yildiz, Özlem; Voß, Elke; Muche, Rainer; Rauer, Sebastian; Bergh, Florian Then; Otto, Markus; Paul, Friedemann; Wildemann, Brigitte; Kraus, Jörg; Ruprecht, Klemens; Stangel, Martin; Buttmann, Mathias; Zettl, Uwe K; Tumani, Hayrettin

2016-12-01

The majority of patients presenting with a first clinical symptom suggestive of multiple sclerosis (MS) do not fulfill the MRI criteria for dissemination in space and time according to the 2010 revision of the McDonald diagnostic criteria for MS and are thus classified as clinically isolated syndrome (CIS). To re-evaluate the utility of cerebrospinal fluid (CSF) analysis in the context of the revised McDonald criteria from 2010, we conducted a retrospective multicenter study aimed at determining the prevalence and predictive value of oligoclonal IgG bands (OCBs) in patients with CIS. Patients were recruited from ten specialized MS centers in Germany and Austria. We collected data from 406 patients; at disease onset, 44/406 (11 %) fulfilled the McDonald 2010 criteria for MS. Intrathecal IgG OCBs were detected in 310/362 (86 %) of CIS patients. Those patients were twice as likely to convert to MS according to McDonald 2010 criteria as OCB-negative individuals (hazard ratio = 2.1, p = 0.0014) and in a shorter time period of 25 months (95 % CI 21-34) compared to 47 months in OCB-negative individuals (95 % CI 36-85). In patients without brain lesions at first attack and presence of intrathecal OCBs (30/44), conversion rate to MS was 60 % (18/30), whereas it was only 21 % (3/14) in those without OCBs. Our data confirm that in patients with CIS the risk of conversion to MS substantially increases if OCBs are present at onset. CSF analysis definitely helps to evaluate the prognosis in patients who do not have MS according to the revised McDonald criteria.

Comparison of aerobic versus resistance exercise training effects on metabolic syndrome (from the Studies of a Targeted Risk Reduction Intervention Through Defined Exercise - STRRIDE-AT/RT).

PubMed

Bateman, Lori A; Slentz, Cris A; Willis, Leslie H; Shields, A Tamlyn; Piner, Lucy W; Bales, Connie W; Houmard, Joseph A; Kraus, William E

2011-09-15

Aerobic training (AT) improves the metabolic syndrome (MS) and its component risk factors; however, to our knowledge, no randomized clinical studies have addressed whether resistance training (RT) improves the MS when performed alone or combined with AT. Sedentary, overweight dyslipidemic men and women, aged 18 to 70 years completed a 4-month inactive run-in period and were randomized to 1 of 3 eight-month exercise programs (n = 196). The exercise programs were (1) RT (3 days/week, 3 sets/day of 8 to 12 repetitions of 8 different exercises targeting all major muscle groups); (2) AT (∼120 minutes/week at 75% of the maximum oxygen uptake), and (3) AT and RT combined (AT/RT) (exact combination of AT and RT). Of the 196 randomized patients, 144 completed 1 of the 3 exercise programs. The 86 participants with complete data for all 5 MS criteria were used in the present analysis, and a continuous MS z score was calculated. Eight months of RT did not change the MS score. AT improved the MS score (p <0.07) and showed a trend toward significance compared to RT (p <0.10). AT/RT significantly decreased the MS score and was significantly different from RT alone. In conclusion, RT was not effective at improving the MS score; however, AT was effective. Combined AT and RT was similarly effective but not different from AT alone. When weighing the time commitment versus health benefit, the data suggest that AT alone was the most efficient mode of exercise for improving cardiometabolic health. Published by Elsevier Inc.

Aged Garlic Extract Improves Adiponectin Levels in Subjects with Metabolic Syndrome: A Double-Blind, Placebo-Controlled, Randomized, Crossover Study

PubMed Central

Gómez-Arbeláez, Diego; Lahera, Vicente; Oubiña, Pilar; Valero-Muñoz, Maria; de las Heras, Natalia; Rodríguez, Yudy; García, Ronald Gerardo; Camacho, Paul Anthony; López-Jaramillo, Patricio

2013-01-01

Background. Garlic (Allium sativum) has been shown to have important benefits in individuals at high cardiovascular risk. The aim of the present study was to evaluate the effects of the administration of aged garlic extract (AGE) on the risk factors that constitute the cluster of metabolic syndrome (MS). Methods and Design. Double-blind, crossover, randomized, placebo-controlled clinical trial to assess the effect of 1.2 g/day of AGE (Kyolic), for 24 weeks of treatment (12 weeks of AGE and 12 weeks of placebo), on subjects with MS. Results. The administration of AGE increased the plasma levels of adiponectin (P = 0.027). No serious side effects associated with the intervention were reported. Conclusion. The present results have shown for the first time that the administration of AGE for 12 weeks increased plasma adiponectin levels in patients with MS. This suggests that AGE might be a useful, novel, nonpharmacological therapeutic intervention to increase adiponectin and to prevent cardiovascular (CV) complications in individuals with MS. PMID:23533302

Subliminal perception of complex visual stimuli.

PubMed

Ionescu, Mihai Radu

2016-01-01

Rationale: Unconscious perception of various sensory modalities is an active subject of research though its function and effect on behavior is uncertain. Objective: The present study tried to assess if unconscious visual perception could occur with more complex visual stimuli than previously utilized. Methods and Results: Videos containing slideshows of indifferent complex images with interspersed frames of interest of various durations were presented to 24 healthy volunteers. The perception of the stimulus was evaluated with a forced-choice questionnaire while awareness was quantified by self-assessment with a modified awareness scale annexed to each question with 4 categories of awareness. At values of 16.66 ms of stimulus duration, conscious awareness was not possible and answers regarding the stimulus were random. At 50 ms, nonrandom answers were coupled with no self-reported awareness suggesting unconscious perception of the stimulus. At larger durations of stimulus presentation, significantly correct answers were coupled with a certain conscious awareness. Discussion: At values of 50 ms, unconscious perception is possible even with complex visual stimuli. Further studies are recommended with a focus on a range of interest of stimulus duration between 50 to 16.66 ms.

Structural elucidation of new urinary tamoxifen metabolites by liquid chromatography quadrupole time-of-flight mass spectrometry.

PubMed

Lu, Jianghai; He, Chunji; He, Genye; Wang, Xiaobing; Xu, Youxuan; Wu, Yun; Dong, Ying; Ouyang, Gangfeng

2014-07-01

In this study, tamoxifen metabolic profiles were investigated carefully. Tamoxifen was administered to two healthy male volunteers and one female patient suffering from breast cancer. Urinary extracts were analyzed by liquid chromatography quadruple time-of-flight mass spectrometry using full scan and targeted MS/MS techniques with accurate mass measurement. Chromatographic peaks for potential metabolites were selected by using the theoretical [M + H](+) as precursor ion in full-scan experiment and m/z 72, 58 or 44 as characteristic product ions for N,N-dimethyl, N-desmethyl and N,N-didesmethyl metabolites in targeted MS/MS experiment, respectively. Tamoxifen and 37 metabolites were detected in extraction study samples. Chemical structures of seven unreported metabolites were elucidated particularly on the basis of fragmentation patterns observed for these metabolites. Several metabolic pathways containing mono- and di-hydroxylation, methoxylation, N-desmethylation, N,N-didesmethylation, oxidation and combinations were suggested. All the metabolites were detected in the urine samples up to 1 week. Copyright © 2014 John Wiley & Sons, Ltd.

Effects of Clove Oil as a Euthanasia Agent on Blood Collection Efficiency and Serum Cortisol Levels in Danio rerio

PubMed Central

Davis, Daniel J; Klug, Jenna; Hankins, Miriam; Doerr, Holly M; Monticelli, Stephanie R; Song, Ava; Gillespie, Catherine H; Bryda, Elizabeth C

2015-01-01

Zebrafish are an important laboratory animal model for biomedical research and are increasingly being used for behavioral neuroscience. Tricaine methanesulfonate (MS222) is the standard agent used for euthanasia of zebrafish. However, recent studies of zebrafish behavior suggest that MS222 may be aversive, and clove oil might be a possible alternative. In this study, we compared the effects of MS222 or clove oil as a euthanasia agent in zebrafish on the volume of blood collected and on serum levels of cortisol. Greater amounts of serum could be collected and lower serum levels of cortisol were present in fish euthanized with clove oil compared with equipotent dose of MS222. Euthanasia with clove oil did not blunt the expected elevation of serum cortisol levels elicited by an acute premortem stress. According to our findings, clove oil is a fast-acting agent that minimizes the cortisol response to euthanasia in zebrafish and allows the collection of large volumes of blood postmortem. These results represent a significant refinement in euthanasia methods for zebrafish. PMID:26424256

Effects of Clove Oil as a Euthanasia Agent on Blood Collection Efficiency and Serum Cortisol Levels in Danio rerio.

PubMed

Davis, Daniel J; Klug, Jenna; Hankins, Miriam; Doerr, Holly M; Monticelli, Stephanie R; Song, Ava; Gillespie, Catherine H; Bryda, Elizabeth C

2015-09-01

Zebrafish are an important laboratory animal model for biomedical research and are increasingly being used for behavioral neuroscience. Tricaine methanesulfonate (MS222) is the standard agent used for euthanasia of zebrafish. However, recent studies of zebrafish behavior suggest that MS222 may be aversive, and clove oil might be a possible alternative. In this study, we compared the effects of MS222 or clove oil as a euthanasia agent in zebrafish on the volume of blood collected and on serum levels of cortisol. Greater amounts of serum could be collected and lower serum levels of cortisol were present in fish euthanized with clove oil compared with equipotent dose of MS222. Euthanasia with clove oil did not blunt the expected elevation of serum cortisol levels elicited by an acute premortem stress. According to our findings, clove oil is a fast-acting agent that minimizes the cortisol response to euthanasia in zebrafish and allows the collection of large volumes of blood postmortem. These results represent a significant refinement in euthanasia methods for zebrafish.

The impact of self-transcendence on physical health status promotion in multiple sclerosis patients attending peer support groups.

PubMed

JadidMilani, Maryam; Ashktorab, Tahereh; AbedSaeedi, Zhila; AlaviMajd, Hamid

2015-12-01

This study aimed to investigate the effect of self-transcendence on the physical health of multiple sclerosis (MS) patients attending peer support groups. This study was a quasi-experimental before-and-after design including 33 MS patients in three groups: 10 men in the men-only group, 11 women in the women-only group, and 12 men and women in the mixed group. Participants were required to attend eight weekly sessions of 2 h each. Instruments included the physical health section of the Multiple Sclerosis Quality of Life Inventory and Reed's Self-Transcendence Scale. Peer support group attendance was found to have a significant positive effect on the physical health and self-transcendence of MS patients when comparing average scores before and after attendance. Regression analysis showed that improvement in self-transcendence predicted improvement in physical health. Results show the positive effects of peer support groups on self-transcendence and physical health in MS patients, and suggest that improvement in well-being can be gained by promoting self-transcendence and physical health. © 2015 Wiley Publishing Asia Pty Ltd.

Comparison of corrected QT interval as measured on electroencephalography versus 12-lead electrocardiography in children with a history of syncope.

PubMed

Massey, Shavonne L; Wise, Marshall S; Madan, Nandini; Carvalho, Karen; Khurana, Divya; Legido, Agustin; Valencia, Ignacio

2011-11-01

Long QT syndrome can present with neurological manifestations, including syncope and seizure-like activity. These patients often receive an initial neurologic evaluation, including electroencephalography (EEG). Our previous retrospective study suggested an increased prevalence of prolonged corrected QT interval (QTc) measured during the EEG of patients with syncope. The aim of the current study is to assess the accuracy of the EEG QTc reading compared with the nonsimultaneous 12-lead electrocardiography (ECG) in children with syncope. Abnormal QTc was defined as ≥450 ms in boys, ≥460 ms in girls. Forty-two children were included. There was no significant correlation between QTc readings in the EEG and ECG. EEG failed to identify 2 children with prolonged QTc in the ECG and overestimated the QTc in 3 children with normal QTc in the ECG. This study suggests that interpretation of the QTc segment during an EEG is limited. Further studies with simultaneous EEG and 12-lead ECG are warranted.

Quantitative assessments of arousal by analyzing microsaccade rates and pupil fluctuations prior to slow eye movements.

PubMed

Honda, Shogo; Kohama, Takeshi; Tanaka, Tatsuro; Yoshida, Hisashi

2014-01-01

It is well known that a decline of arousal level causes of poor performance of movements or judgments. Our previous study indicates that microsaccade (MS) rates and pupil fluctuations change before slow eye movements (SEMs) (Honda et al. 2013). However, SEM detection of this study was obscure and insufficient. In this study, we propose a new SEM detection method and analyze MS rates and pupil fluctuations while subjects maintain their gaze on a target. We modified Shin et al.'s method, which is optimized for EOG (electrooculography) signals, to extract the period of sustaining SEMs using a general eye tracker. After SEM detection, we analyzed MS rates and pupil fluctuations prior to the initiation of SEMs. As a result, we were able to detect SEMs more precisely than in our previous study. Moreover, the results of eye movements and pupil fluctuations analyses show that gradual rise of MS rate and longitudinal miosis are observed prior to the initiation of SEMs, which is consistent with our previous study. These findings suggest that monitoring eye movements and pupil fluctuations may evaluate the arousal level more precisely. Further, we found that these tendencies become more significant when they are restricted to the initial SEMs.

Lipid and protein composition as driving force for multiple sclerosis

NASA Astrophysics Data System (ADS)

Beck, Roy; Shaharabani, Rona

Physical models and experiments often reduce the number of components aiming to address the fundamental mechanisms. Nevertheless, the inherent heterogeneity is an essential ingredient in the biological context. We present our recent efforts to model and understand the development of multiple sclerosis (MS) from a biophysical perspective. Myelin sheath is a multilamellar complex of various lipids and proteins that surround axons and acts as an insulating layer for proper nerve conduction. In MS the myelin structure is disrupted impairing its function. Previous studies showed that MS is correlated with small lipid composition variation and reduction in the adhesive myelin basic protein. We found that such alterations result in pathological phase transition from a lamellar to inverted hexagonal that involve enhanced local curvature. Similar curvatures are also found in vivo in diseased myelin sheaths. Since the etiology and recovery pathways of MS are currently unclear, these findings delineate novel functional roles to dominant constituents in cytoplasmic myelin sheaths, shed new light on mechanisms disrupting lipid-protein complexes, and suggest new courses for diagnosis and treatment for MS.

A comparison of the y-Radiolysis of TODGA and T(EH)DGA using UHPLC-ESI-MS analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zarzana, Christopher A.; Groenewold, Gary S.; Mincher, Bruce J.

2015-04-27

Solutions of the diglycolamide extractants TODGA and T(EH)DGA in n-dodecane were subjected to γ- irradiation in the presence and absence of an acidic aqueous phase. These solutions were then analyzed using UHPLC-ESI-MS to determine the rates of radiolytic decay of the two extractants neat and in contact with respect to the acidity of the contacted aqueous phase, as well as to identify radiolysis products. The presence or absence of an acidic aqueous phase was shown to have no influence on the measured decay rates, nor did the side-chain have an influence. A number of radiolysis products were identified, consistent with thosemore » previously identified for these two compounds using GC-MS. The identity of these radiolysis products suggests that the bonds most vulnerable to radiolytic attack are those in the dyglycolamide center of these molecules, and not on the side-chains.  The agreement of these results with previous work using GC-MS indicates supports the further use of UHPLC-ESI-MS as a tool for studying diglycolamide extractant systems.« less

Analysis of Renal Cell Carcinoma as a First Step for Developing Mass Spectrometry-Based Diagnostics

NASA Astrophysics Data System (ADS)

Yoshimura, Kentaro; Chen, Lee Chuin; Mandal, Mridul Kanti; Nakazawa, Tadao; Yu, Zhan; Uchiyama, Takahito; Hori, Hirokazu; Tanabe, Kunio; Kubota, Takeo; Fujii, Hideki; Katoh, Ryohei; Hiraoka, Kenzo; Takeda, Sen

2012-10-01

Immediate diagnosis of human specimen is an essential prerequisites in medical routines. This study aimed to establish a novel cancer diagnostics system based on probe electrospray ionization-mass spectrometry (PESI-MS) combined with statistical data processing. PESI-MS uses a very fine acupuncture needle as a probe for sampling as well as for ionization. To demonstrate the applicability of PESI-MS for cancer diagnosis, we analyzed nine cases of clear cell renal cell carcinoma (ccRCC) by PESI-MS and processed the data by principal components analysis (PCA). Our system successfully delineated the differences in lipid composition between non-cancerous and cancerous regions. In this case, triacylglycerol (TAG) was reproducibly detected in the cancerous tissue of nine different individuals, the result being consistent with well-known profiles of ccRCC. Moreover, this system enabled us to detect the boundaries of cancerous regions based on the expression of TAG. These results strongly suggest that PESI-MS will be applicable to cancer diagnosis, especially when the number of data is augmented.

Mass spectrometry-based metabolite profiling in the mouse liver following exposure to ultraviolet B radiation.

PubMed

Park, Hye Min; Shon, Jong Cheol; Lee, Mee Youn; Liu, Kwang-Hyeon; Kim, Jeong Kee; Lee, Sang Jun; Lee, Choong Hwan

2014-01-01

Although many studies have been performed on the effects of ultraviolet (UV) radiation on the skin, only a limited number of reports have investigated these effects on non-skin tissue. This study aimed to describe the metabolite changes in the liver of hairless mice following chronic exposure to UVB radiation. We did not observe significant macroscopic changes or alterations in hepatic cholesterol and triglyceride levels in the liver of UVB-irradiated mice, compared with those for normal mice. In this study, we detected hepatic metabolite changes by UVB exposure and identified several amino acids, fatty acids, nucleosides, carbohydrates, phospholipids, lysophospholipids, and taurine-conjugated cholic acids as candidate biomarkers in response to UVB radiation in the mouse liver by using various mass spectrometry (MS)-based metabolite profiling including ultra-performance liquid chromatography-quadrupole time-of-flight (TOF)-MS, gas chromatography-TOF-MS and nanomate LTQ-MS. Glutamine exhibited the most dramatic change with a 5-fold increase in quantity. The results from altering several types of metabolites suggest that chronic UVB irradiation may impact significantly on major hepatic metabolism processes, despite the fact that the liver is not directly exposed to UVB radiation. MS-based metabolomic approach for determining regulatory hepatic metabolites following UV irradiation will provide a better understanding of the relationship between internal organs and UV light.

Autoantigen cross-reactive environmental antigen can trigger multiple sclerosis-like disease.

PubMed

Reynolds, Catherine J; Sim, Malcolm J W; Quigley, Kathryn J; Altmann, Daniel M; Boyton, Rosemary J

2015-05-13

Multiple sclerosis is generally considered an autoimmune disease resulting from interaction between predisposing genes and environmental factors, together allowing immunological self-tolerance to be compromised. The precise nature of the environmental inputs has been elusive, infectious agents having received considerable attention. A recent study generated an algorithm predicting naturally occurring T cell receptor (TCR) ligands from the proteome database. Taking the example of a multiple sclerosis patient-derived anti-myelin TCR, the study identified a number of stimulatory, cross-reactive peptide sequences from environmental and human antigens. Having previously generated a spontaneous multiple sclerosis (MS) model through expression of this TCR, we asked whether any of these could indeed function in vivo to trigger CNS disease by cross-reactive activation. A number of myelin epitope cross-reactive epitopes could stimulate T cell immunity in this MS anti-myelin TCR transgenic model. Two of the most stimulatory of these 'environmental' epitopes, from Dictyostyelium slime mold and from Emiliania huxleyi, were tested for the ability to induce MS-like disease in the transgenics. We found that immunization with cross-reactive peptide from Dictyostyelium slime mold (but not from E. huxleyi) induces severe disease. These specific environmental epitopes are unlikely to be common triggers of MS, but this study suggests that our search for the cross-reactivity triggers of autoimmune activation leading to MS should encompass epitopes not just from the 'infectome' but also from the full environmental 'exposome.'

Enhanced GABAergic transmission in the central nucleus of the amygdala of genetically selected Marchigian Sardinian rats: alcohol and CRF effects

PubMed Central

Herman, Melissa; Kallupi, Marsida; Luu, George; Oleata, Christopher; Heilig, Markus; Koob, George F.; Ciccocioppo, Roberto; Roberto, Marisa

2012-01-01

The GABAergic system in the central amygdala (CeA) plays a major role in ethanol dependence and the anxiogenic-like response to ethanol withdrawal. Alcohol dependence is associated with increased corticotropin releasing factor (CRF) influence on CeA GABA release and CRF type 1 receptor (CRF1) antagonists prevent the excessive alcohol consumption associated with dependence. Genetically-selected Marchigian Sardinian (msP) rats have an overactive extrahypothalamic CRF1 system, are highly sensitive to stress, and display an innate preference for alcohol. The present study examined differences in CeA GABAergic transmission and the effects of ethanol, CRF and a CRF1 antagonist in msP, Sprague-Dawley, and Wistar rats using an electrophysiological approach. We found no significant differences in membrane properties or mean amplitude of evoked GABAA-inhibitory postsynaptic potentials (IPSPs). However, paired-pulse facilitation (PPF) ratios of evoked IPSPs were significantly lower and spontaneous miniature inhibitory postsynaptic current (mIPSC) frequencies were higher in msP rats, suggesting increased CeA GABA release in msP as compared to Sprague-Dawley and Wistar rats. The sensitivity of spontaneous GABAergic transmission to ethanol (44 mM), CRF (200 nM) and CRF1 antagonist (R121919, 1 μM) was comparable in msP, Sprague Dawley, and Wistar rats. However, a history of ethanol drinking significantly increased the baseline mIPSC frequency and decreased the effects of a CRF1 antagonist in msP rats, suggesting increased GABA release and decreased CRF1 sensitivity. These results provide electrophysiological evidence that msP rats display distinct CeA GABAergic activity as compared to Sprague Dawley and Wistar rats. The elevated GABAergic transmission observed in naïve mSP rats is consistent with the neuroadaptations reported in Sprague Dawley rats after the development of ethanol dependence. PMID:23220399

The time course of face processing: startle eyeblink response modulation by face gender and expression.

PubMed

Duval, Elizabeth R; Lovelace, Christopher T; Aarant, Justin; Filion, Diane L

2013-12-01

The purpose of this study was to investigate the effects of both facial expression and face gender on startle eyeblink response patterns at varying lead intervals (300, 800, and 3500ms) indicative of attentional and emotional processes. We aimed to determine whether responses to affective faces map onto the Defense Cascade Model (Lang et al., 1997) to better understand the stages of processing during affective face viewing. At 300ms, there was an interaction between face expression and face gender with female happy and neutral faces and male angry faces producing inhibited startle. At 3500ms, there was a trend for facilitated startle during angry compared to neutral faces. These findings suggest that affective expressions are perceived differently in male and female faces, especially at short lead intervals. Future studies investigating face processing should take both face gender and expression into account. © 2013.

Auditory sensory memory and language abilities in former late talkers: a mismatch negativity study.

PubMed

Grossheinrich, Nicola; Kademann, Stefanie; Bruder, Jennifer; Bartling, Juergen; Von Suchodoletz, Waldemar

2010-09-01

The present study investigated whether (a) a reduced duration of auditory sensory memory is found in late talking children and (b) whether deficits of sensory memory are linked to persistent difficulties in language acquisition. Former late talkers and children without delayed language development were examined at the age of 4 years and 7 months using mismatch negativity (MMN) with interstimulus intervals (ISIs) of 500 ms and 2000 ms. Additionally, short-term memory, language skills, and nonverbal intelligence were assessed. MMN mean amplitude was reduced for the ISI of 2000 ms in former late talking children both with and without persistent language deficits. In summary, our findings suggest that late talkers are characterized by a reduced duration of auditory sensory memory. However, deficits in auditory sensory memory are not sufficient for persistent language difficulties and may be compensated for by some children.

Enhancing the Ability of Experimental Autoimmune Encephalomyelitis to Serve as a More Rigorous Model of Multiple Sclerosis through Refinement of the Experimental Design

PubMed Central

Emerson, Mitchell R; Gallagher, Ryan J; Marquis, Janet G; LeVine, Steven M

2009-01-01

Advancing the understanding of the mechanisms involved in the pathogenesis of multiple sclerosis (MS) likely will lead to new and better therapeutics. Although important information about the disease process has been obtained from research on pathologic specimens, peripheral blood lymphocytes and MRI studies, the elucidation of detailed mechanisms has progressed largely through investigations using animal models of MS. In addition, animal models serve as an important tool for the testing of putative interventions. The most commonly studied model of MS is experimental autoimmune encephalomyelitis (EAE). This model can be induced in a variety of species and by various means, but there has been concern that the model may not accurately reflect the disease process, and more importantly, it may give rise to erroneous findings when it is used to test possible therapeutics. Several reasons have been given to explain the shortcomings of this model as a useful testing platform, but one idea provides a framework for improving the value of this model, and thus, it deserves careful consideration. In particular, the idea asserts that EAE studies are inadequately designed to enable appropriate evaluation of putative therapeutics. Here we discuss problem areas within EAE study designs and provide suggestions for their improvement. This paper is principally directed at investigators new to the field of EAE, although experienced investigators may find useful suggestions herein. PMID:19389303

ASCA Observation of MS 1603.6+2600 (=UW Coronae Borealis): A Dipping Low-Mass X-ray Binary in the Outer Halo?

NASA Technical Reports Server (NTRS)

Mukai, Koji; Smale, Alan; Stahle, Caroline K.; Schlegel, Eric M.; Wijnands, Rudy; White, Nicholas E. (Technical Monitor)

2001-01-01

MS 1603.6+2600 is a high-latitude X-ray binary with a 111 min orbital period, thought to be either an unusual cataclysmic variable or an unusual low-mass X-ray binary. In an ASCA observation in 1997 August, we find a burst whose light curve suggests a Type 1 (thermonuclear flash) origin. We also find an orbital X-ray modulation in MS 1603.6+2600, which is likely to be periodic dips, presumably due to azimuthal structure in the accretion disk. Both are consistent with this system being a normal low-mass X-ray binary harboring a neutron star, but at a great distance. We tentatively suggest that MS 1603.6+2600 is located in the outer halo of the Milky Way, perhaps associated with the globular cluster Palomar 14, 11 deg away from MS 1603.6+2600 on the sky at an estimated distance of 73.8 kpc.

Multiple Sclerosis Walking Scale-12, translation, adaptation and validation for the Persian language population.

PubMed

Nakhostin Ansari, Noureddin; Naghdi, Soofia; Mohammadi, Roghaye; Hasson, Scott

2015-02-01

The Multiple Sclerosis Walking Scale-12 (MSWS-12) is a multi-item rating scale used to assess the perspectives of patients about the impact of MS on their walking ability. The aim of this study was to examine the reliability and validity of the MSWS-12 in Persian speaking patients with MS. The MSWS-12 questionnaire was translated into Persian language according to internationally adopted standards involving forward-backward translation, reviewed by an expert committee and tested on the pre-final version. In this cross-sectional study, 100 participants (50 patients with MS and 50 healthy subjects) were included. The MSWS-12 was administered twice 7 days apart to 30 patients with MS for test and retest reliability. Internal consistency reliability was Cronbach's α 0.96 for test and 0.97 for retest. There were no significant floor or ceiling effects. Test-retest reliability was excellent (intraclass correlation coefficient [ICC] agreement of 0.98, 95% CI, 0.95-0.99) confirming the reproducibility of the Persian MSWS-12. Construct validity using known group methods was demonstrated through a significant difference in the Persian MSWS-12 total score between the patients with MS and healthy subjects. Factor analysis extracted 2 latent factors (79.24% of the total variance). A second factor analysis suggested the 9-item Persian MSWS as a unidimensional scale for patients with MS. The Persian MSWS-12 was found to be valid and reliable for assessing walking ability in Persian speaking patients with MS. Copyright © 2014 Elsevier B.V. All rights reserved.

Gut microbiota in early pediatric multiple sclerosis: a case-control study.

PubMed

Tremlett, Helen; Fadrosh, Douglas W; Faruqi, Ali A; Zhu, Feng; Hart, Janace; Roalstad, Shelly; Graves, Jennifer; Lynch, Susan; Waubant, Emmanuelle

2016-08-01

Alterations in the gut microbial community composition may be influential in neurological disease. Microbial community profiles were compared between early onset pediatric multiple sclerosis (MS) and control children similar for age and sex. Children ≤18 years old within 2 years of MS onset or controls without autoimmune disorders attending a University of California, San Francisco, USA, pediatric clinic were examined for fecal bacterial community composition and predicted function by 16S ribosomal RNA sequencing and phylogenetic reconstruction of unobserved states (PICRUSt) analysis. Associations between subject characteristics and the microbiota, including beta diversity and taxa abundance, were identified using non-parametric tests, permutational multivariate analysis of variance and negative binomial regression. Eighteen relapsing-remitting MS cases and 17 controls (mean age 13 years; range 4-18) were studied. Cases had a short disease duration (mean 11 months; range 2-24) and half were immunomodulatory drug (IMD) naïve. Whilst overall gut bacterial beta diversity was not significantly related to MS status, IMD exposure was (Canberra, P < 0.02). However, relative to controls, MS cases had a significant enrichment in relative abundance for members of the Desulfovibrionaceae (Bilophila, Desulfovibrio and Christensenellaceae) and depletion in Lachnospiraceae and Ruminococcaceae (all P and q < 0.000005). Microbial genes predicted as enriched in MS versus controls included those involved in glutathione metabolism (Mann-Whitney, P = 0.017), findings that were consistent regardless of IMD exposure. In recent onset pediatric MS, perturbations in the gut microbiome composition were observed, in parallel with predicted enrichment of metabolic pathways associated with neurodegeneration. Findings were suggestive of a pro-inflammatory milieu. © 2016 EAN.

The Effect of Mystery Shopper Reports on Age Verification for Tobacco Purchases

PubMed Central

KREVOR, BRAD S.; PONICKI, WILLIAM R.; GRUBE, JOEL W.; DeJONG, WILLIAM

2011-01-01

Mystery shops (MS) involving attempted tobacco purchases by young buyers have been employed to monitor retail stores’ performance in refusing underage sales. Anecdotal evidence suggests that MS visits with immediate feedback to store personnel can improve age verification. This study investigated the impact of monthly and twice-monthly MS reports on age verification. Forty-five Walgreens stores were each visited 20 times by mystery shoppers. The stores were randomly assigned to one of three conditions. Control group stores received no feedback, whereas two treatment groups received feedback communications every visit (twice monthly) or every second visit (monthly) after baseline. Logit regression models tested whether each treatment group improved verification rates relative to the control group. Post-baseline verification rates were higher in both treatment groups than in the control group, but only the stores receiving monthly communications had a significantly greater improvement than control group stores. Verification rates increased significantly during the study period for all three groups, with delayed improvement among control group stores. Communication between managers regarding the MS program may account for the delayed age-verification improvements observed in the control group stores. Encouraging inter-store communication might extend the benefits of MS programs beyond those stores that receive this intervention. PMID:21541874

Disturbed Glucose Metabolism in Rat Neurons Exposed to Cerebrospinal Fluid Obtained from Multiple Sclerosis Subjects

PubMed Central

Mathur, Deepali; María-Lafuente, Eva; Ureña-Peralta, Juan R.; Sorribes, Lucas; Hernández, Alberto; Casanova, Bonaventura; López-Rodas, Gerardo; Coret-Ferrer, Francisco; Burgal-Marti, Maria

2017-01-01

Axonal damage is widely accepted as a major cause of permanent functional disability in Multiple Sclerosis (MS). In relapsing-remitting MS, there is a possibility of remyelination by myelin producing cells and restoration of neurological function. The purpose of this study was to delineate the pathophysiological mechanisms underpinning axonal injury through hitherto unknown factors present in cerebrospinal fluid (CSF) that may regulate axonal damage, remyelinate the axon and make functional recovery possible. We employed primary cultures of rat unmyelinated cerebellar granule neurons and treated them with CSF obtained from MS and Neuromyelitis optica (NMO) patients. We performed microarray gene expression profiling to study changes in gene expression in treated neurons as compared to controls. Additionally, we determined the influence of gene-gene interaction upon the whole metabolic network in our experimental conditions using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) program. Our findings revealed the downregulated expression of genes involved in glucose metabolism in MS-derived CSF-treated neurons and upregulated expression of genes in NMO-derived CSF-treated neurons. We conclude that factors in the CSF of these patients caused a perturbation in metabolic gene(s) expression and suggest that MS appears to be linked with metabolic deformity. PMID:29267205

Alkaloids Profiling of Fumaria capreolata by Analytical Platforms Based on the Hyphenation of Gas Chromatography and Liquid Chromatography with Quadrupole-Time-of-Flight Mass Spectrometry.

PubMed

Contreras, María Del Mar; Bribi, Noureddine; Gómez-Caravaca, Ana María; Gálvez, Julio; Segura-Carretero, Antonio

2017-01-01

Two analytical platforms, gas chromatography (GC) coupled to quadrupole-time-of-flight (QTOF) mass spectrometry (MS) and reversed-phase ultrahigh performance liquid chromatography (UHPLC) coupled to diode array (DAD) and QTOF detection, were applied in order to study the alkaloid profile of Fumaria capreolata . The use of these mass analyzers enabled tentatively identifying the alkaloids by matching their accurate mass signals and suggested molecular formulae with those previously reported in libraries and databases. Moreover, the proposed structures were corroborated by studying their fragmentation pattern obtained by both platforms. In this way, 8 and 26 isoquinoline alkaloids were characterized using GC-QTOF-MS and RP-UHPLC-DAD-QTOF-MS, respectively, and they belonged to the following subclasses: protoberberine, protopine, aporphine, benzophenanthridine, spirobenzylisoquinoline, morphinandienone, and benzylisoquinoline. Moreover, the latter analytical method was selected to determine at 280 nm the concentration of protopine (9.6 ± 0.7 mg/g), a potential active compound of the extract. In conclusion, although GC-MS has been commonly used for the analysis of this type of phytochemicals, RP-UHPLC-DAD-QTOF-MS provided essential complementary information. This analytical method can be applied for the quality control of phytopharmaceuticals containing Fumaria extracts currently found in the market.

Alkaloids Profiling of Fumaria capreolata by Analytical Platforms Based on the Hyphenation of Gas Chromatography and Liquid Chromatography with Quadrupole-Time-of-Flight Mass Spectrometry

PubMed Central

Bribi, Noureddine; Gómez-Caravaca, Ana María

2017-01-01

Two analytical platforms, gas chromatography (GC) coupled to quadrupole-time-of-flight (QTOF) mass spectrometry (MS) and reversed-phase ultrahigh performance liquid chromatography (UHPLC) coupled to diode array (DAD) and QTOF detection, were applied in order to study the alkaloid profile of Fumaria capreolata. The use of these mass analyzers enabled tentatively identifying the alkaloids by matching their accurate mass signals and suggested molecular formulae with those previously reported in libraries and databases. Moreover, the proposed structures were corroborated by studying their fragmentation pattern obtained by both platforms. In this way, 8 and 26 isoquinoline alkaloids were characterized using GC-QTOF-MS and RP-UHPLC-DAD-QTOF-MS, respectively, and they belonged to the following subclasses: protoberberine, protopine, aporphine, benzophenanthridine, spirobenzylisoquinoline, morphinandienone, and benzylisoquinoline. Moreover, the latter analytical method was selected to determine at 280 nm the concentration of protopine (9.6 ± 0.7 mg/g), a potential active compound of the extract. In conclusion, although GC-MS has been commonly used for the analysis of this type of phytochemicals, RP-UHPLC-DAD-QTOF-MS provided essential complementary information. This analytical method can be applied for the quality control of phytopharmaceuticals containing Fumaria extracts currently found in the market. PMID:29348751

Liver biopsy in type 2 diabetes mellitus: Steatohepatitis represents the sole feature of liver damage.

PubMed

Masarone, Mario; Rosato, Valerio; Aglitti, Andrea; Bucci, Tommaso; Caruso, Rosa; Salvatore, Teresa; Sasso, Ferdinando Carlo; Tripodi, Marie Francoise; Persico, Marcello

2017-01-01

Recent studies report a prevalence of non-alcoholic fatty liver disease (NAFLD) of between 70% and 80% in patients with metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM). Nevertheless, it is not possible to differentiate between simple steatosis and non-alcoholic steatohepatitis (NASH) with non-invasive tests. The aim of this study was to differentiate between simple steatosis and NASH by liver biopsy in patients with hypertransaminasemia and MS or T2DM. Two hundred and fifteen patients with increased ALT levels and MS, and 136 patients at their first diagnosis of T2DM regardless of ALT values were consecutively admitted to a tertiary hepatology center between January 2004 and November 2014. Exclusion criteria were other causes of liver disease/ALT increase. Each patient underwent a clinical, laboratory and ultrasound evaluation, and a liver biopsy. Gender distribution, age, and body mass index were similar in the two groups of patients, whereas cholesterol levels, glycemia and blood pressure were significantly different between the two groups. The prevalence of NAFLD was 94.82% in MS patients and 100% in T2DM patients. NASH was present in 58.52% of MS patients and 96.82% of T2DM. Consequently, this study reveals that, by using liver biopsy, almost all patients with T2DM or MS have NAFLD, which in patients with T2DM means NASH. Importantly, it suggests that NASH may be one of the early complications of T2DM due to its pathophysiological correlation with insulin resistance.

Female-dependent impaired fear memory of adult rats induced by maternal separation, and screening of possible related genes in the hippocampal CA1.

PubMed

Sun, Xiu-Min; Tu, Wen-Qiang; Shi, Yan-Wei; Xue, Li; Zhao, Hu

2014-07-01

Early life stress is one of the major susceptible factors for stress-related pathologies like posttraumatic stress disorder (PTSD). Recent studies in rats suggest that rather than being overall unfavorable, early life stress may prepare the organism to perform optimally to stressful environments later in life. In this study, severely adverse early life stress was conducted by six consecutive hours of maternal separation (MS), from PND1 to PND21, and contextual fear conditioning model was used on PND90 to mimic the second stress in adulthood and the re-experiencing symptom of PTSD. It was observed that in this investigation pups experienced MS showed decreased sensibility to contextual fear conditioning in adulthood, and there sex plays an important role. For example, female rats suffered MS had much lower freezing than males and controls. Meanwhile, Morris water maze test indicated that MS did not impair rat's performance of spatial learning and memory. Furthermore, suppression subtractive hybridization (SSH) was used to screen the related genes of fear memory, by examining the changes of mRNA expression in CA1 area between female MS and control rats after contextual fear conditioning. Finally, nine up-regulated and one down-regulated genes, including β2-MG, MAF, Nd1-L, TorsinA and MACF1 gene were found in this study. It is assumed that the TorsinA, MACF1 and Nd1-L gene may contribute to the decreased sensitivity of PTSD induced by MS. Copyright © 2014 Elsevier B.V. All rights reserved.

Regulatory T, natural killer T and γδ T cells in multiple sclerosis and chronic fatigue syndrome/myalgic encephalomyelitis: a comparison.

PubMed

Ramos, Sandra; Brenu, Ekua; Broadley, Simon; Kwiatek, Richard; Ng, Jennifer; Nguyen, Thao; Freeman, Susan; Staines, Donald; Marshall-Gradisnik, Sonya

2016-12-01

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), and Multiple Sclerosis (MS) may share some similarities in relation to reduced NK cell activity. It is likely that other cells such as regulatory T (Tregs), invariant Natural Killer T (iNKT) and gamma delta T (γδ T) cells may also be dysregulated in CFS/ME and MS. To evaluate and compare specific immune regulatory cells of patients with CFS/ME, patients with MS and healthy controls. Sixty three volunteers were included in this study: 24 were CFS/ME patients, 11 were MS patients and 27 were healthy controls. Blood samples were obtained from all participants for flow cytometry analysis of iNKT cells, Tregs and γδ T cell phenotypes. We observed a significant increase in Tregs in the CFS/ME group (p≤0.05) compared to the healthy control group. Total γδ and γδ2 T cells were significantly reduced in MS patients in comparison with the healthy control group. Conversely, CD4+iNKT percentage of iNKT, was significantly increased in the CFS/ME group compared with healthy controls and the double-negative iNKT percentage of iNKT significantly decreased compared with the healthy control group. This study has not identified any immunological disturbances that are common in both MS and CFS/ME patients. However, the differential expression of cell types between the conditions investigated suggests different pathways of disease. These differences need to be explored in further studies.

Lactobacillus acidophilus contributes to a healthy environment for vaginal epithelial cells.

PubMed

Pi, Woojin; Ryu, Jae-Sook; Roh, Jaesook

2011-09-01

Lactobacillus species in the female genital tract are thought to act as a barrier to infection. Several studies have demonstrated that lactobacilli can adhere to vaginal epithelial cells. However, little is known about how the adherence of lactobacilli to vaginal epithelial cells affects the acidity, cell viability, or proliferation of the lactobacilli themselves or those of vaginal epithelial cells. Lactobacillus acidophilus was co-cultured with immortalized human vaginal epithelial cells (MS74 cell line), and the growth of L. acidophilus and the acidity of the culture medium were measured. MS74 cell density and viability were also assessed by counting cell numbers and observing the cell attachment state. L. acidophilus showed exponential growth for the first 6 hr until 9 hr, and the pH was maintained close to 4.0-5.0 at 24 hr after culture, consistent with previous studies. The growth curve of L. acidophilus or the pH values were relatively unaffected by co-culture with MS74 cells, confirming that L. acidophilus maintains a low pH in the presence of MS74 cells. This co-culture model could therefore potentially be used to mimic vaginal conditions for future in vitro studies. On the other hand, MS74 cells co-cultured with L. acidophilus more firmly attached to the culture plate, and a higher number of cells were present compared to cells cultured in the absence of L. acidophilus. These results indicate that L. acidophilus increases MS74 cell proliferation and viability, suggesting that lactobacilli may contribute to the healthy environment for vaginal epithelial cells.

Identification and formation mechanism of individual degradation products in lithium-ion batteries studied by liquid chromatography/electrospray ionization mass spectrometry and atmospheric solid analysis probe mass spectrometry.

PubMed

Takeda, Sahori; Morimura, Wataru; Liu, Yi-Hung; Sakai, Tetsuo; Saito, Yuria

2016-08-15

Improvement of lithium ion batteries (LIBs) in terms of performance and robustness requires good understanding of the reaction processes. The analysis of the individual degradation products in LIB electrolytes and on the surface of the electrodes provides vital information in this regard. In this study, mass spectrometric analytical methods were utilized for the identification of the individual degradation products. The degradation products in the electrolytes recovered from cycle-tested cells were separated by liquid chromatography (LC) and their mass spectrometric analysis was conducted by electrospray ionization mass spectrometry (ESI-MS). For identification of degradation products on the surface of electrodes, atmospheric solid analysis probe (ASAP)-MS analysis was conducted by time-of-flight mass spectrometry with an ASAP probe and an atmospheric pressure chemical ionization source. The degradation products in the electrolytes, namely carbonate oligomers and organophosphates, were identified simultaneously by LC/ESI-MS. Their formation mechanisms were estimated, which explain their different compositions at different temperatures. One degradation product was found on the anode surface by ASAP-MS, and its formation mechanism was explained similarly to those in the electrolyte. The results suggest that the electrolyte degradation is correlated with the formation of a solid electrolyte interphase, which is an important factor in the performance of LIBs. We expect that further investigation of the degradation products by LC/ESI-MS and ASAP-MS will be helpful for studying their degradation processes in LIBs. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

[Relationship between vitamin D deficiency and metabolic syndrome in adult population of the Community of Madrid].

PubMed

Gradillas-García, Antonio; Álvarez, Julia; Rubio, José Antonio; de Abajo, Francisco J

2015-04-01

Previous studies have suggested an association between MS and vitamin D deficiency, but data are not conclusive. This study was intended to find out if metabolic syndrome, according to the 2009 IDF/AHA/NHLBI, is associated to the presence of vitamin D deficiency. A cross-sectional study was conducted on a sample of 326 subjects aged 18 years or older, recruited from a health center in Alcalá de Henares. Participants underwent an interview and a standardized clinical examination. In a second visit, blood tests were performed in 255 subjects to quantify serum levels of 25-hydroxyvitamin D (25 OH-VitD) and different laboratory parameters associated to MS. The association between vitamin D deficiency and metabolic syndrome (and each of its components) was examined. In the study population, MS prevalence was 36.1% and prevalence of vitamin D deficiency (25 OH-Vit D<20 ng/mL) was 56.3%. MS was more common in the group of patients with vitamin D deficiency (43.4%) than in the group with no deficiency (26.8%, P=.006), with an estimated prevalence ratio of 1.62 (95% CI: 1.13-2.31). Adjustment for age, sex, and body mass index did not change such association. There is a significant association between vitamin D deficiency and MS. Both conditions are highly prevalent in our population. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

Effect of Mindfulness-Based Stress Reduction on Anxiety, Depression and Stress in Women With Multiple Sclerosis

PubMed Central

Kolahkaj, Bentolhoda; Zargar, Fatemeh

2015-01-01

Background: Studies suggest that mindfulness-based interventions can improve anxiety, depression and stress in patients with multiple sclerosis (MS). However, no study investigated the effectiveness of this method in patients with a combination of problems such as depression, anxiety and stress simultaneously. However, comorbidities of depression and anxiety in MS are prevalent. Objectives: This study aimed to assess the effects of mindfulness-based stress reduction (MBRS) on anxiety, depression and stress in women with multiple sclerosis. Patients and Methods: This randomized controlled clinical trial was performed in 2013 in Ahvaz MS Society. Forty eight patients were selected by convenient sampling and randomly assigned in experimental and control groups. The patients in the two groups filled out depression, anxiety and stress scale (DASS-21) at initiation of study, 8 weeks later and 1 month after the end of intervention. The experimental group received 8 sessions of MBRS, while the control group treated as usual. Finally, data of 40 patients analyzed using t-test, chi square and repeated measures analysis of variance. Results: In the MBSR group, the mean depression, anxiety and stress were reduced significantly (P < 0.001). The mean depression score was 8.35 ± 1.78 before the intervention and reduced to 4.80 ± 0.83 and 4.45 ± 0.60 after the intervention and follow-up (P < 0.001). Also the mean anxiety score was 8.90 ± 1.97 before the intervention, which was significantly reduced to 4.70 ± 1.38 and 4.55 ± 0.99 after the intervention and follow-up (P < 0.001). The mean stress score was also 8.80 ± 2.35 before treatment and 4.80 ± 1.67 and 4.70 ± 1.34 after the intervention and follow-up (P < 0.001). Conclusions: This study showed that MBSR training can reduce mean depression, anxiety and stress scores in patients with MS. These findings suggest that MBSR is useful for psychological problems such as depression, anxiety and stress in patients with MS. PMID:26835467

Systematic review of serum steroid reference intervals developed using mass spectrometry.

PubMed

Tavita, Nevada; Greaves, Ronda F

2017-12-01

The aim of this study was to perform a systematic review of the published literature to determine the available serum/plasma steroid reference intervals generated by mass spectrometry (MS) methods across all age groups in healthy subjects and to suggest recommendations to achieve common MS based reference intervals for serum steroids. MEDLINE, EMBASE and PubMed databases were used to conduct a comprehensive search for English language, MS-based reference interval studies for serum/plasma steroids. Selection of steroids to include was based on those listed in the Royal College of Pathologists of Australasia Quality Assurance Programs, Chemical Pathology, Endocrine Program. This methodology has been registered onto the PROSPERO International prospective register of systematic reviews (ID number: CRD42015029637). After accounting for duplicates, a total of 60 manuscripts were identified through the search strategy. Following critical evaluation, a total of 16 studies were selected. Of the 16 studies, 12 reported reference intervals for testosterone, 11 for 17 hydroxy-progesterone, nine for androstenedione, six for cortisol, three for progesterone, two for dihydrotestosterone and only one for aldosterone and dehydroepiandrosterone sulphate. No studies established MS-based reference intervals for oestradiol. As far as we are aware, this report provides the first comparison of the peer reviewed literature for serum/plasma steroid reference intervals generated by MS-based methods. The reference intervals based on these published studies can be used to inform the process to develop common reference intervals, and agreed reporting units for mass spectrometry based steroid methods. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Lexical access and evoked traveling alpha waves

PubMed Central

Zauner, Andrea; Gruber, Walter; Himmelstoß, Nicole Alexandra; Lechinger, Julia; Klimesch, Wolfgang

2014-01-01

Retrieval from semantic memory is usually considered within a time window around 300–600 ms. Here we suggest that lexical access already occurs at around 100 ms. This interpretation is based on the finding that semantically rich and frequent words exhibit a significantly shorter topographical latency difference between the site with the shortest P1 latency (leading site) and that with the longest P1 latency (trailing site). This latency difference can be described in terms of an evoked traveling alpha wave as was already shown in earlier studies. PMID:24486978

Immunomodulatory effects of orally administered cannabinoids in multiple sclerosis.

PubMed

Killestein, J; Hoogervorst, E L J; Reif, M; Blauw, B; Smits, M; Uitdehaag, B M J; Nagelkerken, L; Polman, C H

2003-04-01

Cannabinoids can modulate the function of immune cells. We here present the first human in vivo study measuring immune function in 16 MS patients treated with oral cannabinoids. A modest increase of TNF-alpha in LPS-stimulated whole blood was found during cannabis plant-extract treatment (p=0.037), with no change in other cytokines. In the subgroup of patients with high adverse event scores, we found an increase in plasma IL-12p40 (p=0.002). The results suggest pro-inflammatory disease-modifying potential of cannabinoids in MS.

Music mnemonics aid Verbal Memory and Induce Learning – Related Brain Plasticity in Multiple Sclerosis

PubMed Central

Thaut, Michael H.; Peterson, David A.; McIntosh, Gerald C.; Hoemberg, Volker

2014-01-01

Recent research on music and brain function has suggested that the temporal pattern structure in music and rhythm can enhance cognitive functions. To further elucidate this question specifically for memory, we investigated if a musical template can enhance verbal learning in patients with multiple sclerosis (MS) and if music-assisted learning will also influence short-term, system-level brain plasticity. We measured systems-level brain activity with oscillatory network synchronization during music-assisted learning. Specifically, we measured the spectral power of 128-channel electroencephalogram (EEG) in alpha and beta frequency bands in 54 patients with MS. The study sample was randomly divided into two groups, either hearing a spoken or a musical (sung) presentation of Rey’s auditory verbal learning test. We defined the “learning-related synchronization” (LRS) as the percent change in EEG spectral power from the first time the word was presented to the average of the subsequent word encoding trials. LRS differed significantly between the music and the spoken conditions in low alpha and upper beta bands. Patients in the music condition showed overall better word memory and better word order memory and stronger bilateral frontal alpha LRS than patients in the spoken condition. The evidence suggests that a musical mnemonic recruits stronger oscillatory network synchronization in prefrontal areas in MS patients during word learning. It is suggested that the temporal structure implicit in musical stimuli enhances “deep encoding” during verbal learning and sharpens the timing of neural dynamics in brain networks degraded by demyelination in MS. PMID:24982626

A comparison between the pathophysiology of multiple sclerosis and normal pressure hydrocephalus: is pulse wave encephalopathy a component of MS?

PubMed

Bateman, Grant A; Lechner-Scott, Jeannette; Lea, Rodney A

2016-09-22

It has been suggested there is a chronic neurodegenerative disorder, underlying the pathophysiology of multiple sclerosis (MS), which is distinct from the more obvious immune-mediated attack on the white matter. Limited data exists indicating there is an alteration in pulse wave propagation within the craniospinal cavity in MS, similar to the findings in normal pressure hydrocephalus (NPH). It is hypothesized MS may harbor pulse wave encephalopathy. The purpose of this study is to compare blood flow and pulse wave measurements in MS patients with a cohort of NPH patients and control subjects, to test this hypothesis. Twenty patients with MS underwent magnetic resonance (MR) flow quantification techniques. Mean blood flow and stroke volume were measured in the arterial inflow and venous out flow from the sagittal (SSS) and straight sinus (ST). The arteriovenous delay (AVD) was defined. The results were compared with both age-matched controls and NPH patients. In MS there was a 35 % reduction in arteriovenous delay and a 5 % reduction in the percentage of the arterial inflow returning via the sagittal sinus compared to age matched controls. There was an alteration in pulse wave propagation, with a 26 % increase in arterial stroke volume but 30 % reduction in SSS and ST stroke volume. The AVD and blood flow changes were in the same direction to those of NPH patients. There are blood flow and pulsation propagation changes in MS patients which are similar to those of NPH patients. The findings would be consistent with an underlying pulse wave encephalopathy component in MS.

Evaluation of Tamoxifen and metabolites by LC-MS/MS and HPLC Methods

PubMed Central

Heath, D.D.; Flatt, S.W.; Wu, A.H.B.; Pruitt, M.A.; Rock, C.L.

2015-01-01

Epidemiological and laboratory evidence suggests that quantification of serum or plasma levels of tamoxifen and the metabolites of tamoxifen, 4-hydroxy-N-desmethyl-tamoxifen (endoxifen), Z-4-hydroxy-tamoxifen (4HT), N-desmethyl-tamoxifen (ND-tam) is a clinically useful tool in the assessment and monitoring of breast cancer status in patients taking adjuvant tamoxifen. A liquid chromatographic mass spectrometric method (LC-MS/MS) was used to measure the blood levels of tamoxifen and the metabolites of tamoxifen. This fully automated analytical method is specific, accurate and sensitive. The LC-MS/MS automated technique has now become a widely accepted reference method. We analyzed a randomly selected batch of blood samples from participants enrolled in a breast cancer study to compare results from this reference method in 40 samples with those obtained from a recently developed high performance liquid chromatography (HPLC) method with fluorescence detection. The mean (SD) concentration for the LC-MS/MS (endoxifen 12.6 [7.5] ng/mL, tamoxifen 105 [44] ng/mL, 4-HT 1.9 [1.0] ng/mL, ND-tam 181 [69] ng/mL) and the HPLC (endoxifen 13.1 [7.8] ng/mL, tamoxifen 108[55]ng/mL, 4-HT 1.8 [0.8] ng/mL, ND-tam 184 [81] ng/mL), the methods did not show any significant differences. Our results confirm that the HPLC method offers an accurate and comparable alternative for the quantification of tamoxifen and tamoxifen metabolites. PMID:24693573

Prospective memory in multiple sclerosis: The impact of cue distinctiveness and executive functioning.

PubMed

Dagenais, Emmanuelle; Rouleau, Isabelle; Tremblay, Alexandra; Demers, Mélanie; Roger, Élaine; Jobin, Céline; Duquette, Pierre

2016-11-01

Prospective memory (PM), the ability to remember to do something at the appropriate time in the future, is crucial in everyday life. One way to improve PM performance is to increase the salience of a cue announcing that it is time to act. Multiple sclerosis (MS) patients often report PM failures and there is growing evidence of PM deficits among this population. However, such deficits are poorly characterized and their relation to cognitive status remains unclear. To better understand PM deficits in MS patients, this study investigated the impact of cue salience on PM, and its relation to retrospective memory (RM) and executive deficits. Thirty-nine (39) MS patients were compared to 18 healthy controls on a PM task modulating cue salience during an ongoing general knowledge test. MS patients performed worse than controls on the PM task, regardless of cue salience. MS patients' executive functions contributed significantly to the variance in PM performance, whereas age, education and RM did not. Interestingly, low- and high-executive patients' performance differed when the cue was not salient, but not when it was, suggesting that low-executive MS patients benefited more from cue salience. These findings add to the growing evidence of PM deficits in MS and highlight the contribution of executive functions to certain aspects of PM. In low-executive MS patients, high cue salience improves PM performance by reducing the detection threshold and need for environmental monitoring. Copyright © 2016 Elsevier Inc. All rights reserved.

Androgen Concentrations in Umbilical Cord Blood and Their Association with Maternal, Fetal and Obstetric Factors

PubMed Central

Keelan, Jeffrey A.; Mattes, Eugen; Tan, HaiWei; Dinan, Andrew; Newnham, John P.; Whitehouse, Andrew J. O.; Jacoby, Peter; Hickey, Martha

2012-01-01

The aim of this study was to measure umbilical blood androgen concentrations in a birth cohort using a highly specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay and assesses the effects of sex, labor, and gestational age on fetal androgen levels at birth. We performed a prospective cohort study of androgen concentrations in mixed arterial and venous umbilical cord serum from 803 unselected singleton pregnancies from a general obstetric population in Western Australia. Total testosterone (TT), Δ4-androstenedione, and dehydroepiandrosterone were extracted from archived cord serum samples and measured using LC-MS/MS. SHBG was measured by ELISA; free testosterone (FT) and bioavailable testosterone (BioT) values were also calculated. Median values for all three androgens were generally lower than previously published values. Levels of TT, FT, BioT, and SHBG were significantly higher in male verses female neonates (P<0.0001), while dehydroepiandrosterone levels were higher in females (P<0.0001). Labor was associated with a significant (∼15–26%) decrease in median cord blood TT and FT levels (both sexes combined), but a modest (∼16–31%) increase in SHBG, Δ4-androstenedione, and dehydroepiandrosterone concentrations. TT and FT were significantly negatively correlated with gestational age at delivery, while SHBG, Δ4-androstenedione, and dehydroepiandrosterone were positively correlated. Antenatal glucocorticoid administration also had a significant effect in the multiple regression models. This is the first study to report umbilical cord androgen levels in a large unselected population of neonates using LC-MS/MS. Our findings suggest that previous studies have over-estimated cord androgen levels, and that fetal, maternal, and obstetric factors influence cord androgen levels differentially. Caution should be exercised when interpreting previously-published data that have not taken all of these factors into account. PMID:22916165

Prevalence of metabolic syndrome and its association with educational inequalities among Brazilian adults: a population-based study.

PubMed

Gronner, M F; Bosi, P L; Carvalho, A M; Casale, G; Contrera, D; Pereira, M A; Diogo, T M; Torquato, M T C G; Souza, G M D; Oishi, J; Leal, A M O

2011-07-01

The present study estimated the prevalence of metabolic syndrome (MS) according to the criteria established by the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) and the International Diabetes Federation (IDF) and analyzed the contribution of social factors in an adult urban population in the Southeastern region of Brazil. The sample plan was based on multistage probability sampling according to family head income and educational level. A random sample of 1116 subjects aged 30 to 79 years was studied. Participants answered a questionnaire about socio-demographic variables and medical history. Fasting capillary glucose (FCG), total cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglycerides were determined and all non-diabetic subjects were submitted to the 75-g oral glucose tolerance test. Body mass index (BMI, kg/m(2)), waist circumference and blood pressure (BP) were determined. Age- and gender-adjusted prevalence of MS was 35.9 and 43.2% according to NCEP-ATPIII and IDF criteria, respectively. Substantial agreement was found between NCEP-ATPIII and IDF definitions. Low HDL-C levels and high BP were the most prevalent MS components according to NCEP-ATPIII criteria (76.3 and 59.2%, respectively). Considering the diagnostic criteria adopted, 13.5% of the subjects had diabetes and 9.7% had FCG ≥100 mg/dL. MS prevalence was significantly associated with age, skin color, BMI, and educational level. This cross-sectional population-based study in the Southeastern region of Brazil indicates that MS is highly prevalent and associated with an important social indicator, i.e., educational level. This result suggests that in developing countries health policy planning to reduce the risk of MS, in particular, should consider improvement in education.

No association between dietary sodium intake and the risk of multiple sclerosis.

PubMed

Cortese, Marianna; Yuan, Changzheng; Chitnis, Tanuja; Ascherio, Alberto; Munger, Kassandra L

2017-09-26

To prospectively investigate the association between dietary sodium intake and multiple sclerosis (MS) risk. In this cohort study, we assessed dietary sodium intake by a validated food frequency questionnaire administered every 4 years to 80,920 nurses in the Nurses' Health Study (NHS) (1984-2002) and to 94,511 in the Nurses' Health Study II (NHSII) (1991-2007), and calibrated it using data from a validation study. There were 479 new MS cases during follow-up. We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the effect of energy-adjusted dietary sodium on MS risk, adjusting also for age, latitude of residence at age 15, ancestry, body mass index at age 18, supplemental vitamin D intake, cigarette smoking, and total energy intake in each cohort. The results in both cohorts were pooled using fixed effects models. Total dietary intake of sodium at baseline was not associated with MS risk (highest [medians: 3.2 g/d NHS; 3.5 g/d NHSII] vs lowest [medians: 2.5 g/d NHS; 2.8 g/d NHSII] quintile: HR pooled 0.98, 95% CI 0.74-1.30, p for trend = 0.75). Cumulative average sodium intake during follow-up was also not associated with MS risk (highest [medians: 3.3 g/d NHS; 3.4 g/d NHSII] vs lowest [medians: 2.7 g/d NHS; 2.8 g/d NHSII] quintile: HR pooled 1.02, 95% CI 0.76-1.37, p for trend = 0.76). Comparing more extreme sodium intake in deciles yielded similar results ( p for trend = 0.95). Our findings suggest that higher dietary sodium intake does not increase the risk of developing MS. © 2017 American Academy of Neurology.

Bacterial interactomes: Interacting protein partners share similar function and are validated in independent assays more frequently than previously reported.

DOE PAGES

Shatsky, Maxim; Allen, Simon; Gold, Barbara; ...

2016-05-01

Numerous affinity purification – mass-spectrometry (AP-MS) and yeast two hybrid (Y2H) screens have each defined thousands of pairwise protein-protein interactions (PPIs), most between functionally unrelated proteins. The accuracy of these networks, however, is under debate. Here we present an AP-MS survey of the bacterium Desulfovibrio vulgaris together with a critical reanalysis of nine published bacterial Y2H and AP-MS screens. We have identified 459 high confidence PPIs from D. vulgaris and 391 from Escherichia coli. Compared to the nine published interactomes, our two networks are smaller; are much less highly connected; have significantly lower false discovery rates; and are much moremore » enriched in protein pairs that are encoded in the same operon, have similar functions, and are reproducibly detected in other physical interaction assays. Lastly, our work establishes more stringent benchmarks for the properties of protein interactomes and suggests that bona fide PPIs much more frequently involve protein partners that are annotated with similar functions or that can be validated in independent assays than earlier studies suggested.« less

Sequence Analysis and Domain Motifs in the Porcine Skin Decorin Glycosaminoglycan Chain*

PubMed Central

Zhao, Xue; Yang, Bo; Solakylidirim, Kemal; Joo, Eun Ji; Toida, Toshihiko; Higashi, Kyohei; Linhardt, Robert J.; Li, Lingyun

2013-01-01

Decorin proteoglycan is comprised of a core protein containing a single O-linked dermatan sulfate/chondroitin sulfate glycosaminoglycan (GAG) chain. Although the sequence of the decorin core protein is determined by the gene encoding its structure, the structure of its GAG chain is determined in the Golgi. The recent application of modern MS to bikunin, a far simpler chondroitin sulfate proteoglycans, suggests that it has a single or small number of defined sequences. On this basis, a similar approach to sequence the decorin of porcine skin much larger and more structurally complex dermatan sulfate/chondroitin sulfate GAG chain was undertaken. This approach resulted in information on the consistency/variability of its linkage region at the reducing end of the GAG chain, its iduronic acid-rich domain, glucuronic acid-rich domain, and non-reducing end. A general motif for the porcine skin decorin GAG chain was established. A single small decorin GAG chain was sequenced using MS/MS analysis. The data obtained in the study suggest that the decorin GAG chain has a small or a limited number of sequences. PMID:23423381

Ethics of placebo-controlled clinical trials in multiple sclerosis: a reassessment.

PubMed

Polman, C H; Reingold, S C; Barkhof, F; Calabresi, P A; Clanet, M; Cohen, J A; Cutter, G R; Freedman, M S; Kappos, L; Lublin, F D; McFarland, H F; Metz, L M; Miller, A E; Montalban, X; O'Connor, P W; Panitch, H; Richert, J R; Petkau, J; Schwid, S R; Sormani, M P; Thompson, A J; Weinshenker, B G; Wolinsky, J S

2008-03-25

The increasing number of established effective therapies for relapsing multiple sclerosis (MS) and emerging consensus for early treatment raise practical concerns and ethical dilemmas for placebo-controlled clinical trials in this disease. An international group of clinicians, ethicists, statisticians, regulators, and representatives from the pharmaceutical industry convened to reconsider prior recommendations regarding the ethics of placebo-controlled trials in MS. The group concluded that placebo-controlled trials can still be done ethically, with restrictions. For patients with relapsing MS for which established effective therapies exist, placebo-controlled trials should only be offered with rigorous informed consent if the subjects refuse to use these treatments, have not responded to them, or if these treatments are not available to them for other reasons (e.g., economics). Suggestions are provided to protect subject autonomy and improve informed consent procedures. Recommendations are tighter than previously suggested for placebo-controlled trials in "resource-restricted" environments where established therapies may not be available. Guidance is also provided on the ethics of alternative trial designs and the balance between study subject burden and risk, scientific rationale and interpretability of trial outcomes.

MS205 Minisatellite Diversity in Basques: Evidence for a Pre-Neolithic Component

PubMed Central

Alonso, Santos; Armour, John A.L.

1998-01-01

A number of studies have suggested that Basques might be a relic of Mesolithic Europeans who escaped much of the homogenization brought about by the Neolithic expansion. In an attempt to add new insights into this hypothesis, MS205 minisatellite diversity has been investigated by Minisatellite Variant Repeat (MVR) analysis in a sample of >100 autochthonous individuals from the Basque Country, along with 24 Castilian (N. Spain) and 23 individuals from the United Kingdom. These populations were examined in the context of the available world database for MS205 alleles. To deduce the similarities among populations, we have applied a phylogenetic approach that takes into account similarity between alleles. The variability of these populations seems to be a subset of the greater and presumably older African diversity, as has been suggested previously for non-Africans. Within non-Africans, Basques seem to cluster with other Northern European populations; however, some apparently Basque-specific alleles can be dated back to post-Aurignacian times, supporting the continuity of some lineages of this population since the Upper Paleolithic period. PMID:9872983

Simultaneous quantification of adalimumab and infliximab in human plasma by liquid chromatography-tandem mass spectrometry.

PubMed

Jourdil, Jean-François; Némoz, Benjamin; Gautier-Veyret, Elodie; Romero, Charlotte; Stanke-Labesque, Françoise

2018-03-30

Adalimumab (ADA) and infliximab (IFX) are therapeutic monoclonal antibodies (TMabs) targeting tumor necrosis factor-alpha (TNFα). They are used to treat inflammatory diseases. Clinical trials have suggested that therapeutic drug monitoring for ADA or IFX could improve treatment response and cost-effectiveness. However, ADA and IFX were quantified by ELISA in all these studies, and the discrepancies between the results obtained raise questions about their reliability.We describe here the validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of ADA and IFX in human samples. Full-length antibodies labeled with stable isotopes were added to plasma samples as an internal standard. Samples were then prepared using Mass Spectrometry Immuno Assay (MSIA) followed by trypsin digestion prior ADA and IFX quantification by LC-MS/MS.ADA and IFX were quantified in serum from patients treated with ADA (n=21) or IFX (n=22), and the concentrations obtained were compared with those obtained with a commercial ELISA kit. The chromatography run lasted 8.6 minutes and the quantification range was 1 to 26 mg/L. The method was reproducible, repeatable and accurate. For both levels of internal quality control, for ADA and IFX inter and intra-day coefficients of variation and accuracies were all within 15%, in accordance with FDA recommendations. No significant cross-contamination effect was noted.Good agreement was found between LC-MS/MS and ELISA results, for both ADA and IFX. This LC-MS/MS method can be used for the quantification of ADA and IFX in a single analytical run and for the optimization of LC-MS/MS resource use in clinical pharmacology laboratories.

Theta-rhythmic drive between medial septum and hippocampus in slow-wave sleep and microarousal: a Granger causality analysis.

PubMed

Kang, D; Ding, M; Topchiy, I; Shifflett, L; Kocsis, B

2015-11-01

Medial septum (MS) plays a critical role in controlling the electrical activity of the hippocampus (HIPP). In particular, theta-rhythmic burst firing of MS neurons is thought to drive lasting HIPP theta oscillations in rats during waking motor activity and REM sleep. Less is known about MS-HIPP interactions in nontheta states such as non-REM sleep, in which HIPP theta oscillations are absent but theta-rhythmic burst firing in subsets of MS neurons is preserved. The present study used Granger causality (GC) to examine the interaction patterns between MS and HIPP in slow-wave sleep (SWS, a nontheta state) and during its short interruptions called microarousals (a transient theta state). We found that during SWS, while GC revealed a unidirectional MS→HIPP influence over a wide frequency band (2-12 Hz, maximum: ∼8 Hz), there was no theta peak in the hippocampal power spectra, indicating a lack of theta activity in HIPP. In contrast, during microarousals, theta peaks were seen in both MS and HIPP power spectra and were accompanied by bidirectional GC with MS→HIPP and HIPP→MS theta drives being of equal magnitude. Thus GC in a nontheta state (SWS) vs. a theta state (microarousal) primarily differed in the level of HIPP→MS. The present findings suggest a modification of our understanding of the role of MS as the theta generator in two regards. First, a MS→HIPP theta drive does not necessarily induce theta field oscillations in the hippocampus, as found in SWS. Second, HIPP theta oscillations entail bidirectional theta-rhythmic interactions between MS and HIPP. Copyright © 2015 the American Physiological Society.

Characterization of the Organic Component of Low-Molecular-Weight Chromium-Binding Substance and Its Binding of Chromium123

PubMed Central

Chen, Yuan; Watson, Heather M.; Gao, Junjie; Sinha, Sarmistha Halder; Cassady, Carolyn J.; Vincent, John B.

2011-01-01

Chromium was proposed to be an essential element over 50 y ago and was shown to have therapeutic potential in treating the symptoms of type 2 diabetes; however, its mechanism of action at a molecular level is unknown. One chromium-binding biomolecule, low-molecular weight chromium-binding substance (LMWCr or chromodulin), has been found to be biologically active in in vitro assays and proposed as a potential candidate for the in vivo biologically active form of chromium. Characterization of the organic component of LMWCr has proven difficult. Treating bovine LMWCr with trifluoroacetic acid followed by purification on a graphite powder micro-column generates a heptapeptide fragment of LMWCr. The peptide sequence of the fragment was analyzed by MS and tandem MS (MS/MS and MS/MS/MS) using collision-induced dissociation and post-source decay. Two candidate sequences, pEEEEGDD and pEEEGEDD (where pE is pyroglutamate), were identified from the MS/MS experiments; additional tandem MS suggests the sequence is pEEEEGDD. The N-terminal glutamate residues explain the inability to sequence LMWCr by the Edman method. Langmuir isotherms and Hill plots were used to analyze the binding constants of chromic ions to synthetic peptides similar in composition to apoLMWCr. The sequence pEEEEGDD was found to bind 4 chromic ions per peptide with nearly identical cooperativity and binding constants to those of apoLMWCr. This work should lead to further studies elucidating or eliminating a potential role for LMWCr in treating the symptoms of type 2 diabetes and other conditions resulting from improper carbohydrate and lipid metabolism. PMID:21593351

Epidemiology of multiple sclerosis in US veterans: VII. Risk factors for MS.

PubMed

Kurtzke, J F; Page, W F

1997-01-01

In previous papers of this series, we explored the epidemiology of MS, examining the effects of race, sex, geography, latitude and climate, migration, age at onset, population ancestry, and individual ethnicity on the risk of MS, using an unusually large cohort of MS cases and pre-illness matched controls comprising US veterans of World War II (WWII) and the Korean Conflict (KC). In this paper, we examine primarily the effect of other factors on the risk of MS in this cohort and their relation to those previously studied. We found here that latitude tier of residence at entry into active duty (EAD), years of education, and socioeconomic class (coded from occupation) were similarly associated with MS risk among white men, black men, and white women. Higher levels of each factor showed increased MS risk. Multivariate analyses indicated that for white male WWII subjects an urban address, 9 or more years of education, uncorrected visual acuity less than 20/20 at EAD, a more northern latitude, and a higher proportion of the subject's EAD state population reporting Swedish ancestry each significantly increased the risk of MS. White male KC subjects showed roughly the same patterns, except that uncorrected visual acuity less than 20/20 was associated with lower MS risk (ancestry/ethnicity was not studied). For black male WWII and KC subjects combined, a similar analysis (omitting ancestry/ethnicity) showed that only latitude at EAD and 9 or more years of education were independently associated with a significantly higher MS risk, and for WWII plus KC white women (also without ancestry/ethnicity), only latitude was a significant risk factor in these multivariate analyses. The smaller number of subjects, especially in these last two groups, limited the power to detect statistically significant risks in these last analyses. Similarities to white men of WWII in univariate analyses for all other groups suggest that findings for the former would otherwise apply to the latter. Although the interpretations of these associations may be obscure, in addition to geography, age, sex, and race, per se, higher socioeconomic status is significantly associated with higher MS risk in black and white men and in white women in the United States.

Cost-effectiveness analysis of interferon beta-1b for the treatment of patients with a first clinical event suggestive of multiple sclerosis.

PubMed

Caloyeras, John P; Zhang, Bin; Wang, Cheng; Eriksson, Marianne; Fredrikson, Sten; Beckmann, Karola; Knappertz, Volker; Pohl, Christoph; Hartung, Hans-Peter; Shah, Dhvani; Miller, Jeffrey D; Sandbrink, Rupert; Lanius, Vivian; Gondek, Kathleen; Russell, Mason W

2012-05-01

To assess, from a Swedish societal perspective, the cost effectiveness of interferon β-1b (IFNB-1b) after an initial clinical event suggestive of multiple sclerosis (MS) (ie, early treatment) compared with treatment after onset of clinically definite MS (CDMS) (ie, delayed treatment). A Markov model was developed, using patient level data from the BENEFIT trial and published literature, to estimate health outcomes and costs associated with IFNB-1b for hypothetical cohorts of patients after an initial clinical event suggestive of MS. Health states were defined by Kurtzke Expanded Disability Status Scale (EDSS) scores. Model outcomes included quality-adjusted life years (QALYs), total costs (including both direct and indirect costs), and incremental cost-effectiveness ratios. Sensitivity analyses were performed on key model parameters to assess the robustness of model results. In the base case scenario, early IFNB-1b treatment was economically dominant (ie, less costly and more effective) versus delayed IFNB-1b treatment when QALYs were used as the effectiveness metric. Sensitivity analyses showed that the cost-effectiveness results were sensitive to model time horizon. Compared with the delayed treatment strategy, early treatment of MS was also associated with delayed EDSS progressions, prolonged time to CDMS diagnosis, and a reduction in frequency of relapse. Early treatment with IFNB-1b for a first clinical event suggestive of MS was found to improve patient outcomes while controlling costs. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Chronic cerebrospinal venous insufficiency in multiple sclerosis: clinical correlates from a multicentre study

PubMed Central

2011-01-01

Background Chronic cerebrospinal venous insufficiency (CCSVI) has recently been reported to be associated with multiple sclerosis (MS). However, its actual prevalence, possible association with specific MS phenotypes, and potential pathophysiological role are debated. Method We analysed the clinical data of 710 MS patients attending six centres (five Italian and one Canadian). All were submitted to venous Doppler sonography and diagnosed as having or not having CCSVI according to the criteria of Zamboni et al. Results Overall, CCSVI was diagnosed in 86% of the patients, but the frequency varied greatly between the centres. Even greater differences were found when considering singly the five diagnostic criteria proposed by Zamboni et al. Despite these differences, significant associations with clinical data were found, the most striking being age at disease onset (about five years greater in CCSVI-positive patients) and clinical severity (mean EDSS score about one point higher in CCSVI-positive patients). Patients with progressive MS were more likely to have CCSVI than those with relapsing-remitting MS. Conclusion The methods for diagnosing CCSVI need to be refined, as the between-centre differences, particularly in single criteria, were excessively high. Despite these discrepancies, the strong associations between CCSVI and MS phenotype suggest that the presence of CCSVI may favour a later development of MS in patients with a lower susceptibility to autoimmune diseases and may increase its severity. PMID:22029656

Recolonization of mutans Streptococci after application of chlorhexidine gel.

PubMed

Vale, Glauber Campos; Cury, Altair Antoninha Del Bel; Arthur, Rodrigo Alex; Cury, Jaime Aparecido; Tabchoury, Cínthia Pereira Machado

2014-01-01

Streptococcus mutans is specifically suppressed by intensive treatment with chlorhexidine gel, but the time for recolonization and the effect on other oral bacteria are not totally clear. In this study, recolonization of mutans streptococci was evaluated in nine healthy adult volunteers, who were highly colonized with this microorganism. Stimulated saliva was collected before (baseline) and at 1, 7, 14, 21 and 28 days after application of 1% chlorhexidine gel on volunteers' teeth for two consecutive days. On each day, the gel was applied using disposable trays for 3 x 5 min with intervals of 5 min between each application. Saliva was plated on blood agar to determine total microorganisms (TM); on mitis salivarius agar to determine total streptococci (TS) and on mitis salivarius agar plus bacitracin to determine mutans streptococci (MS). Chlorhexidine was capable of reducing the counts of MS and the proportion of MS with regard to total microorganisms (%MS/TM) (p<0.05), but these values did not differ statistically from baseline (p>0.05) after 14 days for MS and 21 days for %MS/TM. The counts of TM and TS and the proportion of MS to total streptococci did not differ statistically from baseline (p>0.05) after chlorhexidine treatment. The results suggest that the effect of chlorhexidine gel treatment on suppression of mutans streptococci is limited to less than a month in highly colonized individuals.

Walking and talking: an investigation of cognitive-motor dual tasking in multiple sclerosis.

PubMed

Hamilton, F; Rochester, L; Paul, L; Rafferty, D; O'Leary, C P; Evans, J J

2009-10-01

Deficits in motor functioning, including walking, and in cognitive functions, including attention, are known to be prevalent in multiple sclerosis (MS), though little attention has been paid to how impairments in these areas of functioning interact. This study investigated the effects of performing a concurrent cognitive task when walking in people with MS. Level of task demand was manipulated to investigate whether this affected level of dual-task decrement. Eighteen participants with MS and 18 healthy controls took part. Participants completed walking and cognitive tasks under single- and dual-task conditions. Compared to healthy controls, MS participants showed greater decrements in performance under dual-task conditions in cognitive task performance, walking speed and swing time variability. In the MS group, the degree of decrement under dual-task conditions was related to levels of fatigue, a measure of general cognitive functioning and self-reported everyday cognitive errors, but not to measures of disease severity or duration. Difficulty with walking and talking in MS may be a result of a divided attention deficit or of overloading of the working memory system, and further investigation is needed. We suggest that difficulty with walking and talking in MS may lead to practical problems in everyday life, including potentially increasing the risk of falls. Clinical tools to assess cognitive-motor dual-tasking ability are needed.

In Vitro Wound Healing Potential and Identification of Bioactive Compounds from Moringa oleifera Lam

PubMed Central

Muhammad, Abubakar Amali; Pauzi, Nur Aimi Syarina; Arulselvan, Palanisamy; Abas, Faridah; Fakurazi, Sharida

2013-01-01

Moringa oleifera Lam. (M. oleifera) from the monogeneric family Moringaceae is found in tropical and subtropical countries. The present study was aimed at exploring the in vitro wound healing potential of M. oleifera and identification of active compounds that may be responsible for its wound healing action. The study included cell viability, proliferation, and wound scratch test assays. Different solvent crude extracts were screened, and the most active crude extract was further subjected to differential bioguided fractionation. Fractions were also screened and most active aqueous fraction was finally obtained for further investigation. HPLC and LC-MS/MS analysis were used for identification and confirmation of bioactive compounds. The results of our study demonstrated that aqueous fraction of M. oleifera significantly enhanced proliferation and viability as well as migration of human dermal fibroblast (HDF) cells compared to the untreated control and other fractions. The HPLC and LC-MS/MS studies revealed kaempferol and quercetin compounds in the crude methanolic extract and a major bioactive compound Vicenin-2 was identified in the bioactive aqueous fraction which was confirmed with standard Vicenin-2 using HPLC and UV spectroscopic methods. These findings suggest that bioactive fraction of M. oleifera containing Vicenin-2 compound may enhance faster wound healing in vitro. PMID:24490175

Structural dynamics of ribosome subunit association studied by mixing-spraying time-resolved cryo-EM

PubMed Central

Chen, Bo; Kaledhonkar, Sandip; Sun, Ming; Shen, Bingxin; Lu, Zonghuan; Barnard, David; Lu, Toh-Ming; Gonzalez, Ruben L.; Frank, Joachim

2015-01-01

Ribosomal subunit association is a key checkpoint in translation initiation, but its structural dynamics are poorly understood. Here, we used a recently developed mixing-spraying, time-resolved, cryogenic electron microscopy (cryo-EM) method to study ribosomal subunit association in the sub-second time range. We have improved this method and increased the cryo-EM data yield by tenfold. Pre-equilibrium states of the association reaction were captured by reacting the mixture of ribosomal subunits for 60 ms and 140 ms. We also identified three distinct ribosome conformations in the associated ribosomes. The observed proportions of these conformations are the same in these two time points, suggesting that ribosomes equilibrate among the three conformations within less than 60 ms upon formation. Our results demonstrate that the mixing-spraying method can capture multiple states of macromolecules during a sub-second reaction. Other fast processes, such as translation initiation, decoding and ribosome recycling, are amenable to study with this method. PMID:26004440

Metabonomic study of biochemical changes in the urine of Morning Glory Seed treated rat.

PubMed

Ma, Chao; Bi, Kaishun; Zhang, Ming; Su, Dan; Fan, Xinxin; Ji, Wei; Wang, Chao; Chen, Xiaohui

2010-11-02

This paper was designed to study metabonomic characters of the nephrotoxicity induced by Morning Glory Seed (MGS), a well-known traditional Chinese medicine which was used for the treatment of edema, simple obesity and lung fever. Urinary samples from control and MGS treated rats were analyzed by ultra-performance liquid chromatography/mass spectrometry (UPLC-MS) in positive ionization mode. Blood biochemistry and histopathology were examined to identify specific changes of renal damage. The results affirmatively suggested that ethanol extract of Morning Glory Seed (EMGS), instead of water extract of Morning Glory Seed (WMGS), should be responsible for the nephrotoxicity caused by this herbal medicine. The UPLC-MS analysis revealed that the levels of 8 endogenous metabolites as biomarkers were significantly changed in urine from EMGS treated rats. The underlying regulations of EMGS-perturbed metabolic pathways were discussed according to the identified metabolites. The present study proves the potential of UPLC-MS based metabonomics in mapping metabolic response for toxicology. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Evaluation of peptide adsorption-controlled liquid chromatography-tandem mass spectrometric (PAC-LC-MS/MS) method for simple and simultaneous quantitation of amyloid β 1-38, 1-40, 1-42 and 1-43 peptides in dog cerebrospinal fluid.

PubMed

Goda, Ryoya; Kobayashi, Nobuhiro

2012-05-01

To evaluate the usefulness of the peptide adsorption-controlled liquid chromatography-tandem mass spectrometry (PAC-LC-MS/MS) for reproducible measurement of peptides in biological fluids, simultaneous quantitation of amyloid β 1-38, 1-40, 1-42 and 1-43 peptides (Aβ38, Aβ40, Aβ42 and Aβ43) in dog cerebrospinal fluid (CSF) was tried. Each stable isotope labeled Aβ was used as the internal standard to minimize the influence of CSF matrix on the reproducible Aβ quantitation. To reduce a loss of Aβ during the pretreatment procedures, the dog CSF diluted by water-acetic acid-methanol (2:6:1, v/v/v) was loaded on PAC-LC-MS/MS directly. Quantification of the Aβ in the diluted dog CSF was carried out using multiple reaction monitoring (MRM) mode. The [M+5H(5+)] and b(5+) ion fragment of each peptide were chosen as the precursor and product ions for MRM transitions of each peptide. The calibration curves were drawn from Aβ standard calibration solutions using PAC-LC-MS/MS. Analysis of dog CSF samples suggests that the basal concentration of Aβ38, Aβ40, Aβ42 and Aβ43 in dog CSF is approximately 300, 900, 200 and 30 pM, respectively. This is the first time Aβ concentrations in dog CSF have been reported. Additionally, the evaluation of intra- and inter-day reproducibility of analysis of Aβ standard solution, the freeze-thaw stability and the room temperature stability of Aβ standard solution suggest that the PAC-LC-MS/MS method enables reproducible Aβ quantitation. Copyright © 2012 Elsevier B.V. All rights reserved.

Central Obesity is the Key Component in the Association of Metabolic Syndrome With Left Ventricular Global Longitudinal Strain Impairment.

PubMed

Cañon-Montañez, Wilson; Santos, Angela B S; Nunes, Lisandra A; Pires, Julio C G; Freire, Claudia M V; Ribeiro, Antonio L P; Mill, José G; Bessel, Marina; Duncan, Bruce B; Schmidt, Maria Inês; Foppa, Murilo

2017-11-13

Subclinical systolic dysfunction is one of the proposed mechanisms for increased cardiovascular risk associated with metabolic syndrome (MS). This study investigated the association between MS and impaired left ventricular global longitudinal strain (GLS) and the role of each MS criteria in this association. We analyzed a random sample of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) after excluding participants with prevalent heart disease. Among the 1055 participants fulfilling the inclusion criteria (53% women; 52±9 years), 444 (42%) had MS. Those with MS had worse GLS (-18.0%±2.5%) than those without (-19.0%±2.4%; P<.0001). In multiple linear regression models, MS was associated with worse GLS after adjustment for various risk factors (GLS difference=0.86%; P <.0001), even after inclusion of body mass index. Adjusted PR for impaired GLS as assessed by 3 cutoffs (1, 1.5, and 2 standard deviations) were higher among participants with than without MS: GLS -16.1% (PR, 1.76; 95%CI, 1.30-2.39); GLS -14.8% (PR, 2.35; 95%CI, 1.45-3.81); and GLS -13.5% (PR, 2.07; 95%CI, 0.97-4.41). After inclusion of body mass index in the models, these associations were attenuated, suggesting that they may, at least in part, be mediated by obesity. In quantile regression analyses, elevated waist circumference was the only MS component found to be independently associated with GLS across the whole range of values. Metabolic syndrome is independently associated with impaired GLS. Among the MS criteria, central obesity best depicted the link between metabolic derangement and cardiac function. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Physiological measures in participants with chronic fatigue syndrome, multiple sclerosis and healthy controls following repeated exercise: a pilot study.

PubMed

Hodges, L D; Nielsen, T; Baken, D

2017-08-07

To compare physiological responses of chronic fatigue syndrome (CFS/ME), multiple sclerosis (MS) and healthy controls (HC) following a 24-h repeated exercise test. Ten CFS, seven MS and 17 age- and gender-matched healthy controls (10, CFS HC; and seven, MS HC) were recruited. Each participant completed a maximal incremental cycle exercise test on day 1 and again 24 h later. Heart rate (HR), blood pressure (BP), rating of perceived exertion (RPE), oxygen consumption (V˙O2), carbon dioxide production and workload (WL) were recorded. Data analysis investigated these responses at anaerobic threshold (AT) and peak work rate (PWR). On day 2, both CFS and MS had significantly reduced max workload compared to HC. On day 2, significant differences were apparent in WL between CFS and CFS HC (93 ± 37 W, 132 ± 42 W, P<0·042). CFS workload decreased on day 2, alongside a decrease in HR but with an increase in V˙O2 (ml   kg   min -1 ). This was in comparison with an increase in WL, HR and V˙O2 for CFS HC. MS demonstrated a decreased WL compared to MS HC on both days of the study (D1 81 ± 30 W, 116 ±30 W; D2 84 ± 29 W, 118 ± 36 W); however, patients with MS were able to achieve a higher WL on day 2 alongside MS HC. These results suggest that exercise exhibits a different physiological response in MS and CFS/ME, demonstrating repeated cardiovascular exercise testing as a valid measure for differentiating between fatigue conditions. © 2017 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Top-down and bottom-up lipidomic analysis of rabbit lipoproteins under different metabolic conditions using flow field-flow fractionation, nanoflow liquid chromatography and mass spectrometry.

PubMed

Byeon, Seul Kee; Kim, Jin Yong; Lee, Ju Yong; Chung, Bong Chul; Seo, Hong Seog; Moon, Myeong Hee

2015-07-31

This study demonstrated the performances of top-down and bottom-up approaches in lipidomic analysis of lipoproteins from rabbits raised under different metabolic conditions: healthy controls, carrageenan-induced inflammation, dehydration, high cholesterol (HC) diet, and highest cholesterol diet with inflammation (HCI). In the bottom-up approach, the high density lipoproteins (HDL) and the low density lipoproteins (LDL) were size-sorted and collected on a semi-preparative scale using a multiplexed hollow fiber flow field-flow fractionation (MxHF5), followed by nanoflow liquid chromatography-ESI-MS/MS (nLC-ESI-MS/MS) analysis of the lipids extracted from each lipoprotein fraction. In the top-down method, size-fractionated lipoproteins were directly infused to MS for quantitative analysis of targeted lipids using chip-type asymmetrical flow field-flow fractionation-electrospray ionization-tandem mass spectrometry (cAF4-ESI-MS/MS) in selected reaction monitoring (SRM) mode. The comprehensive bottom-up analysis yielded 122 and 104 lipids from HDL and LDL, respectively. Rabbits within the HC and HCI groups had lipid patterns that contrasted most substantially from those of controls, suggesting that HC diet significantly alters the lipid composition of lipoproteins. Among the identified lipids, 20 lipid species that exhibited large differences (>10-fold) were selected as targets for the top-down quantitative analysis in order to compare the results with those from the bottom-up method. Statistical comparison of the results from the two methods revealed that the results were not significantly different for most of the selected species, except for those species with only small differences in concentration between groups. The current study demonstrated that top-down lipid analysis using cAF4-ESI-MS/MS is a powerful high-speed analytical platform for targeted lipidomic analysis that does not require the extraction of lipids from blood samples. Copyright © 2015 Elsevier B.V. All rights reserved.

Lidocaine Hydrochloride Compared with MS222 for the Euthanasia of Zebrafish (Danio rerio).

PubMed

Collymore, Chereen; Banks, E Kate; Turner, Patricia V

2016-11-01

Despite several shortcomings, MS222 is the most commonly used chemical agent for euthanasia of zebrafish. Although lidocaine hydrochloride has some advantages over MS222, its effectiveness as a euthanasia agent for zebrafish is unknown. Larvae at 9 to 16 d postfertilization were exposed to 250 mg/L MS222 or 400, 500, 600, 700, 800, 900, or 1000 mg/L lidocaine and observed for cessation of heartbeat. Adult zebrafish were exposed to 250 mg/L MS222 or 400, 500, or 600 mg/L lidocaine; times to loss of righting reflex, cessation of opercular movement, and complete recovery; body length; aversive behavior; and gross and microscopic evidence of acute toxicity were evaluated. The heartbeat was not lost from any larvae in any group, regardless of drug or dosage. For adults, time to loss of righting reflex was greatest in the 500-mg/L lidocaine group. Opercular movement ceased earlier in all lidocaine groups compared with the MS222 group. Fish in the 500-mg/L lidocaine group were smaller than those in other groups. Fewer fish in the lidocaine groups displayed aversive behavior (erratic swimming and piping) compared with the MS222 group. No fish in the lidocaine hydrochloride groups (n = 30) recovered from euthanasia, whereas one fish in the MS222 group did (n = 10). Neither the MS222 nor lidocaine groups showed any gross or histologic changes suggestive of acute toxicity. Our results suggest that lidocaine hydrochloride may be an effective alternative chemical euthanasia agent for adult zebrafish but should not be used in larval fish.

Lidocaine Hydrochloride Compared with MS222 for the Euthanasia of Zebrafish (Danio rerio)

PubMed Central

Collymore, Chereen; Banks, E Kate; Turner, Patricia V

2016-01-01

Despite several shortcomings, MS222 is the most commonly used chemical agent for euthanasia of zebrafish. Although lidocaine hydrochloride has some advantages over MS222, its effectiveness as a euthanasia agent for zebrafish is unknown. Larvae at 9 to 16 d postfertilization were exposed to 250 mg/L MS222 or 400, 500, 600, 700, 800, 900, or 1000 mg/L lidocaine and observed for cessation of heartbeat. Adult zebrafish were exposed to 250 mg/L MS222 or 400, 500, or 600 mg/L lidocaine; times to loss of righting reflex, cessation of opercular movement, and complete recovery; body length; aversive behavior; and gross and microscopic evidence of acute toxicity were evaluated. The heartbeat was not lost from any larvae in any group, regardless of drug or dosage. For adults, time to loss of righting reflex was greatest in the 500-mg/L lidocaine group. Opercular movement ceased earlier in all lidocaine groups compared with the MS222 group. Fish in the 500-mg/L lidocaine group were smaller than those in other groups. Fewer fish in the lidocaine groups displayed aversive behavior (erratic swimming and piping) compared with the MS222 group. No fish in the lidocaine hydrochloride groups (n = 30) recovered from euthanasia, whereas one fish in the MS222 group did (n = 10). Neither the MS222 nor lidocaine groups showed any gross or histologic changes suggestive of acute toxicity. Our results suggest that lidocaine hydrochloride may be an effective alternative chemical euthanasia agent for adult zebrafish but should not be used in larval fish. PMID:27931323

Multi- and unisensory visual flash illusions.

PubMed

Courtney, Jon R; Motes, Michael A; Hubbard, Timothy L

2007-01-01

The role of stimulus structure in multisensory and unisensory interactions was examined. When a flash (17 ms) was accompanied by multiple tones (each 7 ms, SOA < or =100 ms) multiple flashes were reported, and this effect has been suggested to reflect the role of stimulus continuity in multisensory interactions. In experiments 1 and 2 we examined if stimulus continuity would affect concurrently presented stimuli. When a relatively longer flash (317 ms) was accompanied by multiple tones (each 7 ms), observers reported perceiving multiple flashes. In experiment 3 we tested whether a flash presented near fixation would induce an illusory flash further in the periphery. One flash (17 ms) presented 5 degrees below fixation was reported as multiple flashes if presented with two flashes (each 17 ms, SOA =100 ms) 2 degrees above fixation. The extent to which these data support a phenomenological continuity principle and whether this principle applies to unisensory perception is discussed.

Stability of Mental Toughness, Sleep Disturbances, and Physical Activity in Patients With Multiple Sclerosis (MS)—A Longitudinal and Pilot Study

PubMed Central

Sadeghi Bahmani, Dena; Esmaeili, Leila; Shaygannejad, Vahid; Gerber, Markus; Kesselring, Juerg; Lang, Undine E.; Holsboer-Trachsler, Edith; Brand, Serge

2018-01-01

Background: Previous research of patients with multiple sclerosis (MS) focused prevalently on fatigue, depression, and cognitive dysfunction during the clinical course. By contrast, research on the longer-term characteristics of physical activity (PA), psychological functioning, and sleep problems is scarce. The aims of the present study were therefore to examine changes in PA, mental toughness (MT) as a proxy of psychological functioning, and sleep disturbances over a 2-year period of time after disease onset. Methods: A total of 18 patients with diagnosed MS (mean age: M = 34.29 years) took part in this longitudinal study. First, 1–4 weeks after the first symptoms, a neurologist diagnosed the MS. Second, they completed a series of questionnaires covering socio-demographic data, PA, MT, and sleep disturbances. Third, the same questionnaires were completed again 2 years later (follow-up). Last, a neurologist assessed the degree of disability with the Expanded Disability Status Scale (EDSS). Results: Two years after MS onset, patients had lower levels of vigorous PA, but no statistically significant changes in moderate PA were observed. Further, walking time increased and sedentary time decreased. Patients with sleep disturbances at disease onset also reported poor sleep 2 years later. MT scores remained stable over time. EDSS scores worsened, though, change in EDSS was not associated with PA, MT, or sleep. Conclusions: Two years after disease onset, patients with MS reported similar MT levels and sleep disturbances. PA shifted from vigorous PA toward walking and a less sedentary lifestyle, while moderate PA remained unchanged. The pattern of results of the present pilot study suggests that at the early stage of the MS course, there is no obstacle for being physically active, nor did sleep and MT as a proxy of psychological functioning decrease in a substantial way. PMID:29867606

Complementary and alternative medicine for the treatment of multiple sclerosis

PubMed Central

Yadav, Vijayshree; Shinto, Lynne; Bourdette, Dennis

2010-01-01

Multiple sclerosis (MS) is a chronic disabling disease of the CNS that affects people during early adulthood. Despite several US FDA-approved medications, the treatment options in MS are limited. Many people with MS explore complementary and alternative medicine (CAM) treatments to help control their MS and treat their symptoms. Surveys suggest that up to 70% of people with MS have tried one or more CAM treatment for their MS. People with MS using CAM generally report deriving some benefit from the therapies. The CAM therapies most frequently used include diet, omega-3 fatty acids and antioxidants. There is very limited research evaluating the safety and effectiveness of CAM in MS. The most promising among CAM therapies that warrant further investigation are a low-fat diet, omega-3 fatty acids, lipoic acid and vitamin D supplementation as potential anti-inflammatory and neuroprotective agents in both relapsing and progressive forms of MS. There is very limited research evaluating the safety and effectiveness of CAM in MS. However, in recent years, the NIH and the National MS Society have been actively supporting the research in this very important area. PMID:20441425

Prognostic value of free light chains lambda and kappa in early multiple sclerosis.

PubMed

Voortman, Margarete M; Stojakovic, Tatjana; Pirpamer, Lukas; Jehna, Margit; Langkammer, Christian; Scharnagl, Hubert; Reindl, Markus; Ropele, Stefan; Seifert-Held, Thomas; Archelos, Juan-Jose; Fuchs, Siegrid; Enzinger, Christian; Fazekas, Franz; Khalil, Michael

2017-10-01

Cerebrospinal fluid (CSF) immunoglobulin free light chains (FLC) have been suggested as quantitative alternative to oligoclonal bands (OCB) in the diagnosis of multiple sclerosis (MS). However, little is known on their role in predicting clinical and paraclinical disease progression, particularly in early stages. To assess the prognostic value of FLC in OCB-positive patients with clinically isolated syndrome (CIS) suggestive of MS and early MS. We determined FLC kappa (KFLC) and lambda (LFLC) in CSF and serum by nephelometry in 61 patients (CIS ( n = 48), relapsing-remitting multiple sclerosis ( n = 13)) and 60 non-inflammatory neurological controls. Median clinical follow-up time in CIS was 4.8 years (interquartile range (IQR), 1.5-6.5 years). Patients underwent 3T magnetic resonance imaging (MRI) at baseline and follow-up (median time interval, 2.2 years; IQR, 1.0-3.7 years) to determine T2 lesion load (T2LL) and percent brain volume change (PBVC). CSF FLC were significantly increased in CIS/MS compared to controls (all p < 0.001). A lower KFLC/LFLC CSF ratio was associated with CIS-clinically definite multiple sclerosis (CDMS) conversion (hazard ratio (HR) = 2.89; 95% confidence interval (CI) = 1.17-7.14; p < 0.05). No correlations were found for FLC variables with T2LL or PBVC. Our study confirms increased intrathecal synthesis of FLC in CIS/MS which supports their diagnostic contribution. The KFLC/LFLC CSF ratio appears to have a prognostic value in CIS beyond OCB.

The analysis of oral air using selected ion flow tube mass spectrometry in persons with and without a history of oral malodour.

PubMed

Ross, B M; Dadgostar, N; Bloom, M; McKeown, L

2009-05-01

Oral malodour is a common disorder predominantly caused by bacterial metabolism of food stuffs in the mouth. It is routinely diagnosed and monitored by either the subjective rating or the measurement of oral volatile sulphur compound (VSC) levels. Non-sulphur compounds are also believed to contribute significantly to the condition although there is currently no direct means to assess their levels. In this study, we utilized selective flow tube mass spectrometry (SIFT-MS) to measure, in real time, a range of sulphur and non-sulphur containing compounds in oral air to determine whether the technique can be used to objectively monitor oral malodour. Oral malodour was assessed using organoleptic scores in subjects with and without a history of oral malodour (n = 18) by a trained rater, while the chemical composition of oral air was analysed by both VSC sensor and SIFT-MS. Total VSC levels were significantly correlated with levels of hydrogen sulphide and methylmercaptan measured by SIFT-MS, but not with organoleptic scores. In subjects with elevated organoleptic score, only levels of methylmercaptan were significantly elevated. In three subjects with elevated tongue organoleptic scores but normal total VSC levels, SIFT-MS suggested that one subject possessed high levels of oral acetone while another had high oral levels of acetic acid. Our data suggest that SIFT-MS can be used to assess a wide range of compounds in oral air in addition to VSC to provide a clearer picture of the chemical nature of malodour. This may assist in the diagnosis and monitoring of the condition.

NHANES Monitoring of Serum 25-Hydroxyvitamin D: A Roundtable Summary123

PubMed Central

Yetley, Elizabeth A.; Pfeiffer, Christine M.; Schleicher, Rosemary L.; Phinney, Karen W.; Lacher, David A.; Christakos, Sylvia; Eckfeldt, John H.; Fleet, James C.; Howard, George; Hoofnagle, Andrew N.; Hui, Siu L.; Lensmeyer, Gary L.; Massaro, Joseph; Peacock, Munro; Rosner, Bernard; Wiebe, Donald; Bailey, Regan L.; Coates, Paul M.; Looker, Anne C.; Sempos, Christopher; Johnson, Clifford L.; Picciano, Mary Frances

2010-01-01

A roundtable to discuss monitoring of serum 25-hydroxyvitamin D [25(OH)D] in the NHANES was held in late July 2009. Topics included the following: 1) options for dealing with assay fluctuations in serum 25(OH)D in the NHANES conducted between 1988 and 2006; 2) approaches for transitioning between the RIA used in the NHANES between 1988 and 2006 to the liquid chromatography tandem MS (LC-MS/MS) measurement procedure to be used in NHANES 2007 and later; 3) approaches for integrating the recently available standard reference material for vitamin D in human serum (SRM 972) from the National Institute of Standards and Technology (NIST) into the NHANES; 4) questions regarding whether the C-3 epimer of 25-hydroxyvitamin D3 [3-epi-25(OH)D3] should be measured in NHANES 2007 and later; and 5) identification of research and educational needs. The roundtable experts agreed that the NHANES data needed to be adjusted to control for assay fluctuations and offered several options for addressing this issue. The experts suggested that the LC-MS/MS measurement procedure developed by NIST could serve as a higher order reference measurement procedure. They noted the need for a commutability study for the recently released NIST SRM 972 across a range of measurement procedures. They suggested that federal agencies and professional organizations work with manufacturers to improve the quality and comparability of measurement procedures across all laboratories. The experts noted the preliminary nature of the evidence of the 3-epi-25(OH)D3 but felt that it should be measured in 2007 NHANES and later. PMID:20881084

Isolation and determination of ivermectin in post-mortem and in vivo tissues of dung beetles using a continuous solid phase extraction method followed by LC-ESI+-MS/MS

PubMed Central

Ortiz, Antonio J.; Cortez, Vieyle; Azzouz, Abdelmonaim

2017-01-01

A new analytical method based on solvent extraction, followed by continuous solid-phase extraction (SPE) clean-up using a polymeric sorbent, was demonstrated to be applicable for the detection of ivermectin in complex biological matrices of dung beetles (hemolymph, excreta or dry tissues) using liquid chromatography combined with positive electrospray ionization tandem mass spectrometry (LC/ESI+–MS/MS). Using a signal-to-noise ratio of 3:1, the limit of detection (LOD) in the insect matrices at trace levels was 0.01 ng g–1 and the limit of quantification (LOQ) was 0.1 ng g–1. The proposed method was successfully used to quantitatively determine the levels of ivermectin in the analysis of small samples in in vivo and post mortem samples, demonstrating the usefulness for quantitative analyses that are focused on future pharmacokinetic and bioavailability studies in insects and the establishment of a new protocol to study the impact of ivermectin on non-target arthropods such as dung beetles and other insects that are related with the “dung community”. Because satisfactory precision and accuracy values were obtained in both in vivo matrices, we suggest that the method can be consistently used for quantitative determinations that are focused on future pharmacokinetic and bioavailability studies in insects. Furthermore, this new analytical method was successfully applied to biological samples of dead dung beetles from the field suggesting that the method can be used to establish a new routine analysis of ivermectin residues in insect carcasses that is applied to complement typical mortality tests. PMID:28207908

Factors affecting bone mineral density in multiple sclerosis patients

PubMed Central

Ayatollahi, Azin; Mohajeri-Tehrani, Mohammad Reza

2013-01-01

Background Multiple sclerosis (MS) is a demyelinating disease which can cause many disabilities for the patient. Recent data suggests that MS patients have higher risk for osteoporosis. This study was performed to investigate if the osteoporosis prevalence is higher in MS patients and to determine the possible factors affecting bone mineral density (BMD). Methods 51 definite relapsing-remitting MS patients according to McDonald's criteria (45 females, 6 males aged between 20 and 50 years) participated in this study. The control group included 407 females aged from 20 to 49 years; they were healthy and had no history of the diseases affecting bone metabolism. Femoral and lumbar BMD were measured by Dual Energy X-ray Absorptiometry (DXA). The disability of MS patients was evaluated by Expanded Disability Status Scale (EDSS). The patient's quality of life was evaluated by the validated Persian version of multiple sclerosis impact scale (MSIS-29). Results Patients’ mean age was 36 ± 3.3 years and their mean disease duration was 8.7 ± 1.7 years. The mean EDSS score and the mean body mass index (BMI) of the patients were 3 ± 0.9 and 23.5 ± 2.3 kg/m2, respectively. 29% of the patients had never been treated by ß-interferon and 6% of them had not received glucocorticoids (GCs) pulses since their MS had been diagnosed. 26% of the patients had a history of fracture.18% of our patients were osteoporotic and 43% of them were osteopenic. Femoral BMD was significantly lower among MS patients than age matched controls (P < 0.001), but lumbar BMD showed no difference. There was no correlation between administration of GCs pulses, interferon and BMD; however, we found a significant correlation between EDSS score, quality of life (QoL), disease duration and BMD of both site. Conclusion As a result of this study, bone loss inevitably occurs in MS patients. The major factor of BMD loss is immobility. Osteoporosis should be managed as part of MS patients’ treatment protocols. PMID:24250892

Integrative topological analysis of mass spectrometry data reveals molecular features with clinical relevance in esophageal squamous cell carcinoma

PubMed Central

Gao, She-Gan; Liu, Rui-Min; Zhao, Yun-Gang; Wang, Pei; Ward, Douglas G.; Wang, Guang-Chao; Guo, Xiang-Qian; Gu, Juan; Niu, Wan-Bin; Zhang, Tian; Martin, Ashley; Guo, Zhi-Peng; Feng, Xiao-Shan; Qi, Yi-Jun; Ma, Yuan-Fang

2016-01-01

Combining MS-based proteomic data with network and topological features of such network would identify more clinically relevant molecules and meaningfully expand the repertoire of proteins derived from MS analysis. The integrative topological indexes representing 95.96% information of seven individual topological measures of node proteins were calculated within a protein-protein interaction (PPI) network, built using 244 differentially expressed proteins (DEPs) identified by iTRAQ 2D-LC-MS/MS. Compared with DEPs, differentially expressed genes (DEGs) and comprehensive features (CFs), structurally dominant nodes (SDNs) based on integrative topological index distribution produced comparable classification performance in three different clinical settings using five independent gene expression data sets. The signature molecules of SDN-based classifier for distinction of early from late clinical TNM stages were enriched in biological traits of protein synthesis, intracellular localization and ribosome biogenesis, which suggests that ribosome biogenesis represents a promising therapeutic target for treating ESCC. In addition, ITGB1 expression selected exclusively by integrative topological measures correlated with clinical stages and prognosis, which was further validated with two independent cohorts of ESCC samples. Thus the integrative topological analysis of PPI networks proposed in this study provides an alternative approach to identify potential biomarkers and therapeutic targets from MS/MS data with functional insights in ESCC. PMID:26898710

Cerebral white matter blood flow and energy metabolism in multiple sclerosis.

PubMed

Steen, Christel; D'haeseleer, Miguel; Hoogduin, Johannes M; Fierens, Yves; Cambron, Melissa; Mostert, Jop P; Heersema, Dorothea J; Koch, Marcus W; De Keyser, Jacques

2013-09-01

Cerebral blood flow (CBF) is reduced in normal-appearing white matter (NAWM) of subjects with multiple sclerosis (MS), but the underlying mechanism is unknown. The objective of this article is to assess the relationship between reduced NAWM CBF and both axonal mitochondrial metabolism and astrocytic phosphocreatine (PCr) metabolism. Ten healthy controls and 25 MS subjects were studied with 3 Tesla magnetic resonance imaging. CBF was measured using pseudo-continuous arterial spin labeling. N-acetylaspartate/creatine (NAA/Cr) ratios (axonal mitochondrial metabolism) were obtained using (1)H-MR spectroscopy and PCr/β-ATP ratios using (31)P-MR spectroscopy. In centrum semiovale NAWM, we assessed correlations between CBF and both NAA/Cr and PCr/β-ATP ratios. Subjects with MS had a widespread reduction in CBF of NAWM (centrum semiovale, periventricular, frontal and occipital), and gray matter (frontoparietal cortex and thalamus). Compared to controls, NAA/Cr in NAWM of the centrum semiovale of MS subjects was decreased, whereas PCr/β-ATP was increased. We found no correlations between CBF and PCr/β-ATP. CBF and NAA/Cr correlated in controls (p = 0.02), but not in MS subjects (p = 0.68). Our results suggest that in MS patients there is no relationship between reduced CBF in NAWM and impaired axonal mitochondrial metabolism or astrocytic PCr metabolism.

Adolescent girls' experiences and gender-related beliefs in relation to their motivation in math/science and english.

PubMed

Leaper, Campbell; Farkas, Timea; Brown, Christia Spears

2012-03-01

Although the gender gap has dramatically narrowed in recent decades, women remain underrepresented in many science, technology, engineering, and mathematics (STEM) fields. This study examined social and personal factors in relation to adolescent girls' motivation in STEM (math/science) versus non-STEM (English) subjects. An ethnically diverse sample of 579 girls ages 13-18 years (M = 15) in the U.S. completed questionnaires measuring their academic achievement, ability beliefs, values, and experiences. Social and personal factors were hypothesized to predict motivation (expectancy-value) differently in math/science (M/S) and English. Social factors included perceived M/S and English support from parents and peers. Personal factors included facets of gender identity (felt conformity pressure, gender typicality, gender-role contentedness), gender-related attitudes, and exposure to feminism. In addition, grades, age, parents' education, and ethnicity were controlled. Girls' M/S motivation was positively associated with mother M/S support, peer M/S support, gender-egalitarian beliefs, and exposure to feminism; it was negatively related to peer English support. Girls' English motivation was positively associated with peer English support as well as felt pressure from parents; it was negatively related to peer M/S support and felt peer pressure. The findings suggest that social and personal factors may influence girls' motivation in domain-specific ways.

Physical activity behaviors in individuals with multiple sclerosis: roles of overall and specific symptoms, and self-efficacy.

PubMed

Snook, Erin M; Motl, Robert W

2008-07-01

Multiple sclerosis (MS) is associated with a large reduction in physical activity behavior, and emerging evidence indicates that this reduction might be correlated with symptoms and self-efficacy. The present study examined the nature of the associations among MS-related symptoms, exercise self-efficacy, and physical activity behavior in 80 individuals with a definite diagnosis of MS. Participants completed a measure of MS-related symptoms and self-efficacy and then wore an accelerometer for seven days. Both the frequency of overall symptoms and the frequency of motor symptoms had significant moderate inverse relationships with physical activity behavior (r=-0.47, P<0.0001 and r=-0.49, P<0.0001, respectively). Additionally, exercise self-efficacy was significantly and moderately correlated with physical activity (r=0.39, P<0.0001) and had significant and moderate inverse relationships with overall symptom frequency (r=-0.40, P<0.0001) and motor symptom frequency (r=-0.30, P=0.008). Path analysis demonstrated that both overall symptoms and motor symptoms had direct effects on physical activity as well as indirect effects on physical activity by way of self-efficacy. Such results suggest that the management and monitoring of MS-related symptoms may play an important role in encouraging physical activity adoption and maintenance in individuals with MS.

Increased determinism in brain electrical activity occurs in association with multiple sclerosis.

PubMed

Carrubba, Simona; Minagar, Alireza; Chesson, Andrew L; Frilot, Clifton; Marino, Andrew A

2012-04-01

Increased determinism (decreased complexity) of brain electrical activity has been associated with some brain diseases. Our objective was to determine whether a similar association occurred for multiple sclerosis (MS). Ten subjects with a relapsing-remitting course of MS who were in remission were studied; the controls were age- and gender-matched clinically normal subjects. Recurrence plots were calculated using representative electroencephalogram (EEG) epochs (1-7 seconds) from six derivations; the plots were quantified using the nonlinear variables percent recurrence (%R) and percent determinism (%D). The results were averaged over all derivations for each participant, and the means were compared between the groups. As a linear control procedure the groups were also compared using spectral analysis. The mean±SD of %R for the MS subjects was 6·6±1·3%, compared with 5·1±1·3% in the normal group (P = 0·017), indicating that brain activity in the subjects with MS was less complex, as hypothesized. The groups were not distinguishable using %D or spectral analysis. Taken together with our earlier report that %R could be used to discriminate between MS and normal subjects based on the ability to exhibit evoked potentials, the evidence suggests that complexity analysis of the EEG has potential for development as a diagnostic test for MS.

Mobility, balance and falls in persons with multiple sclerosis.

PubMed

Sosnoff, Jacob J; Socie, Michael J; Boes, Morgan K; Sandroff, Brian M; Pula, John H; Suh, Yoojin; Weikert, Madeline; Balantrapu, Swathi; Morrison, Steven; Motl, Robert W

2011-01-01

There is a lack of information concerning the relation between objective measures of gait and balance and fall history in persons with MS (PwMS). This investigation assessed the relation between demographic, clinical, mobility and balance metrics and falls history in persons with multiple sclerosis (MS). 52 ambulatory persons with MS (PwMS) participated in the investigation. All persons provided demographic information including fall history over the last 12 months. Disease status was assessed with Expanded Disability Status Scale (EDSS). Walking speed, coordination, endurance and postural control were quantified with a multidimensional mobility battery. Over 51% of the participants fell in the previous year with 79% of these people being suffering recurrent falls. Overall, fallers were older, had a greater prevalence of assistive devices use, worse disability, decreased walking endurance, and greater postural sway velocity with eyes closed compared to non-fallers. Additionally, fallers had greater impairment in cerebellar, sensory, pyramidal, and bladder/bowel subscales of the EDSS. The current observations suggest that PwMS who are older, more disabled, utilize an assistive device, have decreased walking coordination and endurance and have diminished balance have fallen in the previous year. This suggests that individuals who meet these criteria need to be carefully monitored for future falls. Future research is needed to determine a prospective model of falls specific to PwMS. Additionally, the utility of interventions aimed at reducing falls and fall risk in PwMS needs to be established.

Mobility, Balance and Falls in Persons with Multiple Sclerosis

PubMed Central

Sosnoff, Jacob J.; Socie, Michael J.; Boes, Morgan K.; Sandroff, Brian M.; Pula, John H.; Suh, Yoojin; Weikert, Madeline; Balantrapu, Swathi; Morrison, Steven; Motl, Robert W.

2011-01-01

Background There is a lack of information concerning the relation between objective measures of gait and balance and fall history in persons with MS (PwMS). This investigation assessed the relation between demographic, clinical, mobility and balance metrics and falls history in persons with multiple sclerosis (MS). Methods 52 ambulatory persons with MS (PwMS) participated in the investigation. All persons provided demographic information including fall history over the last 12 months. Disease status was assessed with Expanded Disability Status Scale (EDSS). Walking speed, coordination, endurance and postural control were quantified with a multidimensional mobility battery. Results Over 51% of the participants fell in the previous year with 79% of these people being suffering recurrent falls. Overall, fallers were older, had a greater prevalence of assistive devices use, worse disability, decreased walking endurance, and greater postural sway velocity with eyes closed compared to non-fallers. Additionally, fallers had greater impairment in cerebellar, sensory, pyramidal, and bladder/bowel subscales of the EDSS. Conclusions The current observations suggest that PwMS who are older, more disabled, utilize an assistive device, have decreased walking coordination and endurance and have diminished balance have fallen in the previous year. This suggests that individuals who meet these criteria need to be carefully monitored for future falls. Future research is needed to determine a prospective model of falls specific to PwMS. Additionally, the utility of interventions aimed at reducing falls and fall risk in PwMS needs to be established. PMID:22132196

Comparative epidemiology of multiple sclerosis and dental caries.

PubMed Central

Craelius, W

1978-01-01

The geographical distribution and other epidemiological characteristics of multiple sclerosis (MS) are compared with those of dental caries. The rates of death due to MS in Australian states are linearly related to the numbers of decayed, missing, and filled (DMF) teeth found in individuals from those states (r=0.97, P less than 0.002). In the United States of America, a strong positive correlation (r=0.55, P less than 0.001) also exists between MS death rates and dental caries indices. The prevalence of MS in 45 countries or areas correlates well with the frequencies of DMF teeth among children of school age in those locations (r=0.78, P less than 0.001). The prevalence of MS also correlates well with the percentage of edentulous individuals in certain countries (r=0.99, P less than 0.001). A review of the literature shows that the risk for dental caries is lower among the following groups: the lower socioeconomic classes in the United States of America; Chinese immigrants to England compared with natives; blacks compared with whites; and males compared with females. The dental caries risk is higher during pregnancy and lactation. All these trends have been described for MS as well. It is suggested that dental caries may be a more accurate epidemiological model for MS than poliomyelitis. It is also suggested that MS and dental caries may share certain aetiological factors, two of which may be dietary excess of certain fats, and vitamin D deficiency. PMID:711974

Reflexes in the shoulder muscles elicited from the human coracoacromial ligament.

PubMed

Diederichsen, Louise Pyndt; Nørregaard, Jesper; Krogsgaard, Michael; Fischer-Rasmussen, Torsten; Dyhre-Poulsen, Poul

2004-09-01

Morphological studies have demonstrated mechanoreceptors in the capsuloligamentous structures of the shoulder joint, however knowledge of the role these joint receptors play in the control of shoulder stability is limited. We therefore investigated the effect of electrically induced afferent activity from mechanoreceptors in the coracoacromial ligament (CAL) on the activity of voluntary activated shoulder muscles in healthy humans. In study I, wire electrodes, for electrical stimulation, were inserted into the CAL in eight normal shoulders. In study II, a needle electrode was inserted into the CAL in seven normal shoulders. Electric activity was recorded from eight shoulder muscles by surface and intramuscular electrodes. During isometric contractions, electrical stimulation was applied to the CAL at two different stimulus intensities, a weak stimulus (stim-1) and a stronger stimulus (stim-2). In both experiments, electrical stimulation of the CAL elicited a general inhibition in the voluntary activated shoulder muscles. In study I the average latencies (mean+/-SE) of the muscular inhibition were 66+/-4 ms (stim-1) and 62+/-4 ms (stim-2) during isometric flexion and 73+/-3 ms (stim-1) and 73+/-5 ms (stim-2) during isometric extension. In study II the average latency (mean+/-SE) of the response was 66+/-4 ms (stim-1) during isometric flexion. Our results demonstrated a response, probably of reflex origin, from mechanoreceptors in the CAL to the shoulder muscles. The existence of this synaptic connection between mechanoreceptors in CAL and the shoulder muscles suggest a role of these receptors in muscle coordination and in the functional joint stability.

Lung Inflammatory Effects, Tumorigenesis, and Emphysema Development in a Long-Term Inhalation Study with Cigarette Mainstream Smoke in Mice

PubMed Central

Stabbert, Regina

2013-01-01

Cigarette smoking is the leading cause of lung cancer and chronic obstructive pulmonary disease, yet there is little mechanistic information available in the literature. To improve this, laboratory models for cigarette mainstream smoke (MS) inhalation–induced chronic disease development are needed. The current study investigated the effects of exposing male A/J mice to MS (6h/day, 5 days/week at 150 and 300mg total particulate matter per cubic meter) for 2.5, 5, 10, and 18 months in selected combinations with postinhalation periods of 0, 4, 8, and 13 months. Histopathological examination of step-serial sections of the lungs revealed nodular hyperplasia of the alveolar epithelium and bronchioloalveolar adenoma and adenocarcinoma. At 18 months, lung tumors were found to be enhanced concentration dependently (up to threefold beyond sham exposure), irrespective of whether MS inhalation had been performed for the complete study duration or was interrupted after 5 or 10 months and followed by postinhalation periods. Morphometric analysis revealed an increase in the extent of emphysematous changes after 5 months of MS inhalation, which did not significantly change over the following 13 months of study duration, irrespective of whether MS exposure was continued or not. These changes were found to be accompanied by a complex pattern of transient and sustained pulmonary inflammatory changes that may contribute to the observed pathogeneses. Data from this study suggest that the A/J mouse model holds considerable promise as a relevant model for investigating smoking-related emphysema and adenocarcinoma development. PMID:23104432

Estimating the Marginal Causal Effect of Fish Consumption during Adolescence on Multiple Sclerosis: A Population-Based Incident Case-Control Study.

PubMed

Abdollahpour, Ibrahim; Nedjat, Saharnaz; Mansournia, Mohammad Ali; Sahraian, Mohammad Ali; Kaufman, Jay S

2018-01-01

Adolescence is considered as a critical time period in multiple sclerosis (MS) etiology. Nonetheless, there are insufficient reports regarding the potential role of fresh and canned fish consumptions during adolescence in MS etiology. The authors investigated the association between fresh and canned fish consumptions and MS. This was a population-based incident case-control study conducted in Tehran. Cases (n = 547) identified from Iranian Multiple Sclerosis Society between August 7, 2013, and November 17, 2015 were included in the study. Population-based controls (n = 1,057) were recruited by random digit telephone dialing without any matching. Inverse-probability-of-treatment weighing (IPTW) using 2 sets of propensity scores and model-based standardization were used to separately estimate the marginal odds ratio between fresh and canned fish consumptions in adolescence and MS. The marginal OR for fresh fish was 0.72 (95% CI 0.58-0.90; p = 0.005) in both IPTW analyses. Similarly, the marginal OR for canned fish consumption was 0.75 (95% CI 0.60-0.95; p = 0.014).The model-based standardized OR was 0.72 (95% CI 0.58-0.91; p = 0.008) for fresh and 0.73 (95% CI 0.59-0.94; p = 0.006) for canned fish consumption in adolescence. Subject to limitation of case-control studies in interpreting associations causally, this study suggests that both fresh and canned fish consumptions in adolescence can decrease the risk of MS. © 2018 S. Karger AG, Basel.

Electrochemical behavior of meso-substituted iron porphyrins in alkaline aqueous media

NASA Astrophysics Data System (ADS)

Berezina, N. M.; Bazanov, M. I.; Maksimova, A. A.; Semeikin, A. S.

2017-12-01

The effect meso-substitution in iron porphyrin complexes has on their redox behavior in alkaline aqueous solutions is studied via cyclic voltammetry. The voltammetric features of the reduction of iron pyridylporphyrins suggest that the sites of electron transfer lie at the ligand, the metal ion, and the pyridyl moieties. The electron transfer reactions between the different forms of these compounds, including the oxygen reduction reaction they mediate, are outlined to show the sequence and potential ranges in which they occur in alkaline aqueous media. Under our experimental conditions, the iron porphyrins exist as μ-oxo dimmers whose activity for the electrocatalytic reduction of oxygen displays a considerable dependence on the nature of the substitutents and nitrogen isomerization (for pyridylporphyrins) and grows in the order (Fe( ms-Ph)4P)2O, (Fe[ ms-(Py-3)Ph3]P)2O, (Fe[ ms-(Py-4)4]P)2O, and (Fe[ ms-(Py-3)4]P)2O.

Evaluation of the matrix effect on gas chromatography--mass spectrometry with carrier gas containing ethylene glycol as an analyte protectant.

PubMed

Fujiyoshi, Tomoharu; Ikami, Takahito; Sato, Takashi; Kikukawa, Koji; Kobayashi, Masato; Ito, Hiroshi; Yamamoto, Atsushi

2016-02-19

The consequences of matrix effects in GC are a major issue of concern in pesticide residue analysis. The aim of this study was to evaluate the applicability of an analyte protectant generator in pesticide residue analysis using a GC-MS system. The technique is based on continuous introduction of ethylene glycol into the carrier gas. Ethylene glycol as an analyte protectant effectively compensated the matrix effects in agricultural product extracts. All peak intensities were increased by this technique without affecting the GC-MS performance. Calibration curves for ethylene glycol in the GC-MS system with various degrees of pollution were compared and similar response enhancements were observed. This result suggests a convenient multi-residue GC-MS method using an analyte protectant generator instead of the conventional compensation method for matrix-induced response enhancement adding the mixture of analyte protectants into both neat and sample solutions. Copyright © 2016 Elsevier B.V. All rights reserved.

Non-target screening of Allura Red AC photodegradation products in a beverage through ultra high performance liquid chromatography coupled with hybrid triple quadrupole/linear ion trap mass spectrometry.

PubMed

Gosetti, Fabio; Chiuminatto, Ugo; Mazzucco, Eleonora; Calabrese, Giorgio; Gennaro, Maria Carla; Marengo, Emilio

2013-01-15

The study deals with the identification of the degradation products formed by simulated sunlight photoirradiation in a commercial beverage that contains Allura Red AC dye. An UHPLC-MS/MS method, that makes use of hybrid triple quadrupole/linear ion trap, was developed. In the identification step the software tool information dependent acquisition (IDA) was used to automatically obtain information about the species present and to build a multiple reaction monitoring (MRM) method with the MS/MS fragmentation pattern of the species considered. The results indicate that the identified degradation products are formed from side-reactions and/or interactions among the dye and other ingredients present in the beverage (ascorbic acid, citric acid, sucrose, aromas, strawberry juice, and extract of chamomile flowers). The presence of aromatic amine or amide functionalities in the chemical structures proposed for the degradation products might suggest potential hazards to consumer health. Copyright © 2012 Elsevier Ltd. All rights reserved.

Overexpression of an alfalfa GDP-mannose 3, 5-epimerase gene enhances acid, drought and salt tolerance in transgenic Arabidopsis by increasing ascorbate accumulation.

PubMed

Ma, Lichao; Wang, Yanrong; Liu, Wenxian; Liu, Zhipeng

2014-11-01

GDP-mannose 3', 5'-epimerase (GME) catalyses the conversion of GDP-D-mannose to GDP-L-galactose, an important step in the ascorbic acid (ascorbic acid) biosynthetic pathway in higher plants. In this study, a novel cDNA fragment (MsGME) encoding a GME protein was isolated and characterised from alfalfa (Medicago sativa). An expression analysis confirmed that MsGME expression was induced by salinity, PEG and acidity stresses. MsGME overexpression in Arabidopsis enhanced tolerance of the transgenic plants to salt, drought and acid. Real-time PCR analysis revealed that the transcript levels of GDP-D-mannose pyrophosphorylase (GMP), L-galactose-phosphate 1-P phosphatase (GP) and GDP-L-galactose phosphorylase (GGP) were increased in transgenic Arabidopsis (T3 generation). Moreover, the ascorbate content was increased in transgenic Arabidopsis. Our results suggest that MsGME can effectively enhance tolerance of transgenic Arabidopsis to acid, drought and salt by increasing ascorbate accumulation.

Rapid and highly resolving associative affective learning: convergent electro- and magnetoencephalographic evidence from vision and audition.

PubMed

Steinberg, Christian; Bröckelmann, Ann-Kathrin; Rehbein, Maimu; Dobel, Christian; Junghöfer, Markus

2013-03-01

Various pathway models for emotional processing suggest early prefrontal contributions to affective stimulus evaluation. Yet, electrophysiological evidence for such rapid modulations is still sparse. In a series of four MEG/EEG studies which investigated associative learning in vision and audition using a novel MultiCS Conditioning paradigm, many different neutral stimuli (faces, tones) were paired with aversive and appetitive events in only two to three learning instances. Electrophysiological correlates of neural activity revealed highly significant amplified processing for conditioned stimuli within distributed prefrontal and sensory cortical networks. In both, vision and audition, affect-specific responses occurred in two successive waves of rapid (vision: 50-80 ms, audition: 25-65 ms) and mid-latency (vision: >130 ms, audition: >100 ms) processing. Interestingly, behavioral measures indicated that MultiCS Conditioning successfully prevented contingency awareness. We conclude that affective processing rapidly recruits highly elaborate and widely distributed networks with substantial capacity for fast learning and excellent resolving power. Copyright © 2012 Elsevier B.V. All rights reserved.

Evidence of gushing induction by Penicillium oxalicum proteins.

PubMed

Vogt, E I; Kupfer, V M; Vogel, R F; Niessen, L

2017-03-01

The aim of this study was to elucidate whether grape-associated fungi exert an influence on gushing by their production of surface-active compounds. In preliminary experiments, 58 grape-associated isolates of species within Penicillium and Aspergillus genera were tested for their ability to modify the surface activity of culture supernatants. As the genus Penicillium had a higher potential to change surface activity, further research focused on that genus. Subsequently, supernatants of 36 Penicillium isolates were assessed for their potential to induce gushing in a model system. Isolates of Penicillium oxalicum had the highest potential. Different external factors were investigated for their influence on the intensity of gushing. By using reversed-phase high performance liquid chromatography and subsequent MALDI-TOF MS, SDS-PAGE and nano-ESI-LC-MS/MS analysis, two proteins in the exoproteome of P. oxalicum were identified, which could be linked to the induction of gushing. Our results suggest that infection of grapes by P. oxalicum may contribute to gushing in sparkling wine. In contrast to gushing of beer, the reason for its development in sparkling wine is widely unexplored. Nonetheless, sparkling wine producers have also been affected by this economically damaging phenomenon. This study has first suggested about the occurrence of primary gushing in sparkling wine. © 2016 The Society for Applied Microbiology.

Pure spinal multiple sclerosis: A possible novel entity within the multiple sclerosis disease spectrum.

PubMed

Schee, Jie Ping; Viswanathan, Shanthi

2018-05-01

We identified five female patients retrospectively with relapsing short-segment partial myelitis whose clinical and paraclinical features were suggestive of cord involvement of multiple sclerosis (MS)-type albeit not rigidly fulfilling the 2017 McDonald criteria. Notably, these patients had not developed any typical MS-like brain lesions despite repeated neuroimaging assessments over years. Comprehensive work-up for differential diagnoses of MS and other causes of transverse myelitis particularly neuromyelitis optica spectrum disorders had been consistently negative on longitudinal follow-up. Thus, we postulate a possible entity of pure spinal MS which may represent a novel forme fruste within the MS disease spectrum.

A report on mood and cognitive outcomes with right unilateral ultrabrief pulsewidth (0.3 ms) ECT and retrospective comparison with standard pulsewidth right unilateral ECT.

PubMed

Loo, Colleen; Sheehan, Patrick; Pigot, Melissa; Lyndon, William

2007-11-01

Electroconvulsive therapy (ECT) is a highly effective treatment for depression but its use is limited by the risk of cognitive side effects. This study explored the potential of a novel approach, ultrabrief pulsewidth (0.3 ms) right unilateral (RUL-UB) ECT, to minimise cognitive effects while preserving efficacy. Mood and neuropsychological functioning were objectively rated in 30 patients over a course of RUL-UB ECT at 6 times seizure threshold. Results (mood outcomes, ECT treatment parameters) were compared with a retrospectively assessed group of 30 age and gender matched patients who received RUL ECT (1.0 ms pulsewidth, 3.5 times seizure threshold) at the same hospital. Six treatments of RUL-UB ECT resulted in relatively few cognitive side effects, compared to reports of previous studies. The number of responders did not differ between groups but significantly more treatments were required in the RUL-UB group, suggesting a slower speed of response. Patients were not randomised to the two forms of ECT and data was obtained retrospectively in the RUL ECT comparison group. This study suggests that RUL-UB ECT can be effective in treating depression while incurring lesser cognitive side effects than a commonly used form of RUL ECT, but a greater number of treatments may be required for response.

Dynamic neural processing of linguistic cues related to death.

PubMed

Liu, Xi; Shi, Zhenhao; Ma, Yina; Qin, Jungang; Han, Shihui

2013-01-01

Behavioral studies suggest that humans evolve the capacity to cope with anxiety induced by the awareness of death's inevitability. However, the neurocognitive processes that underlie online death-related thoughts remain unclear. Our recent functional MRI study found that the processing of linguistic cues related to death was characterized by decreased neural activity in human insular cortex. The current study further investigated the time course of neural processing of death-related linguistic cues. We recorded event-related potentials (ERP) to death-related, life-related, negative-valence, and neutral-valence words in a modified Stroop task that required color naming of words. We found that the amplitude of an early frontal/central negativity at 84-120 ms (N1) decreased to death-related words but increased to life-related words relative to neutral-valence words. The N1 effect associated with death-related and life-related words was correlated respectively with individuals' pessimistic and optimistic attitudes toward life. Death-related words also increased the amplitude of a frontal/central positivity at 124-300 ms (P2) and of a frontal/central positivity at 300-500 ms (P3). However, the P2 and P3 modulations were observed for both death-related and negative-valence words but not for life-related words. The ERP results suggest an early inverse coding of linguistic cues related to life and death, which is followed by negative emotional responses to death-related information.

Maternal Separation Enhances Neuronal Activation and Cardiovascular Responses to Acute Stress in Borderline Hypertensive Rats

PubMed Central

Sanders, Brian J.; Anticevic, Alan

2007-01-01

There is much evidence suggesting early life events, such has handling or repeated separations from the nest, can have a long term effect on the biological and behavioral development of rats. The current study examined the effect of repeated maternal separation (MS) on the behavioral, cardiovascular, and neurobiological responses to stress in subjects vulnerable to environmental stressors as adults. Borderline hypertensive rats (BHR), which are the first generation offspring of spontaneously hyperternsive and Wistar-Kyoto rats, were separated from the dams for 3 hours per day from post-natal day 1 through 14. Non-separated controls remained in the home cage. When allowed to explore the open field chamber for 60 minutes as adults, MS subjects had significantly greater locomotor activity compared to controls. All subjects were exposed to 30 minutes of restraint stress during which time mean arterial pressure (MAP) and heart rate (HR) were measured. Although both groups had comparable increases in MAP, MS animals displayed significantly higher HR throughout the stress period. Finally, MS subjects had significantly more stress-induced Fos positive cells, an estimate of neuronal activation, in the central nucleus of the amygdala (CeA), paraventricular nucleus of the hypothalamus (PVN), and the bed nucleus of the stria terminalis (BNST), each of which plays an important role in organizing the biobehavioral response to stress. These results suggest that maternal separation can further enhance stress reactivity in this model and may represent a useful approach for studying the relationship between early life events and future vulnerability to stressful situations. PMID:17604851

The influence of aluminium, steel and polyurethane shoeing systems and of the unshod hoof on the injury risk of a horse kick. An ex vivo experimental study.

PubMed

Sprick, Miriam; Fürst, Anton; Baschnagel, Fabio; Michel, Silvain; Piskoty, Gabor; Hartnack, Sonja; Jackson, Michelle A

2017-09-12

To evaluate the damage inflicted by an unshod hoof and by the various horseshoe materials (steel, aluminium and polyurethane) on the long bones of horses after a simulated kick. Sixty-four equine radii and tibiae were evaluated using a drop impact test setup. An impactor with a steel, aluminium, polyurethane, or hoof horn head was dropped onto prepared bones. An impactor velocity of 8 m/s was initially used with all four materials and then testing was repeated with a velocity of 12 m/s with the polyurethane and hoof horn heads. The impact process was analysed using a high-speed camera, and physical parameters, including peak contact force and impact duration, were calculated. At 8 m/s, the probability of a fracture was 75% for steel and 81% for aluminium, whereas polyurethane and hoof horn did not damage the bones. At 12 m/s, the probability of a fracture was 25% for polyurethane and 12.5% for hoof horn. The peak contact force and impact duration differed significantly between 'hard materials' (aluminium and steel) and 'soft materials' (polyurethane and hoof horn). The observed bone injuries were similar to those seen in analogous experimental studies carried out previously and comparable to clinical fracture cases suggesting that the simulated kick was realistic. The probability of fracture was significantly higher for steel and aluminium than for polyurethane and hoof horn, which suggests that the horseshoe material has a significant influence on the risk of injury for humans or horses kicked by a horse.

Changes to anti-JCV antibody levels in a Swedish national MS cohort

PubMed Central

Warnke, Clemens; Ramanujam, Ryan; Plavina, Tatiana; Bergström, Tomas; Goelz, Susan; Subramanyam, Meena; Kockum, Ingrid; Rahbar, Afsar; Kieseier, Bernd C; Holmén, Carolina; Olsson, Tomas; Hillert, Jan; Fogdell-Hahn, Anna

2013-01-01

Background The anti-JC virus (JCV) antibody status has been introduced to stratify patients with multiple sclerosis (MS) for higher or lower risk of progressive multifocal leukoencephalopathy (PML). Objective To assess the potential utility of anti-JCV antibody levels for earlier diagnosis or prediction of PML. Methods An analytically validated antibody assay was used to determine serological status, normalised optical density values, and dilution titres for anti-JCV antibodies. The method was applied to stored sera of 1157 patients with MS including five cases of PML, all enrolled in the Swedish pharmacovigilance study for natalizumab (NAT). Anticytomegalovirus (CMV) and antivaricella-zoster (VZV) antibody levels served as controls. Results Prior to treatment with NAT, anti-JCV antibody levels were stable in the anti-JCV positive patients. During therapy, a slight decrease in anti-JCV and anti-VZV antibody levels, but not anti-CMV antibody levels, was observed. All five patients who developed PML showed a mild to moderate increase in anti-JCV antibody levels at time of PML diagnosis; pre-PML samples suggested that this increase might start already prior to diagnosis of PML. Conclusions Treatment initiation with NAT may lead to a slight decrease in anti-JCV and anti-VZV antibody levels, suggestive of a mild suppressive effect of NAT on antibody levels. Our findings in five cases of PML demonstrate that the onset of PML can be accompanied by increasing anti-JCV antibodies in serum. Monitoring of anti-JCV antibody levels could potentially be used as a tool for prediction or earlier diagnosis of PML during NAT treatment for MS. Further studies are warranted. PMID:23463870

Changes to anti-JCV antibody levels in a Swedish national MS cohort.

PubMed

Warnke, Clemens; Ramanujam, Ryan; Plavina, Tatiana; Bergström, Tomas; Goelz, Susan; Subramanyam, Meena; Kockum, Ingrid; Rahbar, Afsar; Kieseier, Bernd C; Holmén, Carolina; Olsson, Tomas; Hillert, Jan; Fogdell-Hahn, Anna

2013-11-01

The anti-JC virus (JCV) antibody status has been introduced to stratify patients with multiple sclerosis (MS) for higher or lower risk of progressive multifocal leukoencephalopathy (PML). To assess the potential utility of anti-JCV antibody levels for earlier diagnosis or prediction of PML. An analytically validated antibody assay was used to determine serological status, normalised optical density values, and dilution titres for anti-JCV antibodies. The method was applied to stored sera of 1157 patients with MS including five cases of PML, all enrolled in the Swedish pharmacovigilance study for natalizumab (NAT). Anticytomegalovirus (CMV) and antivaricella-zoster (VZV) antibody levels served as controls. Prior to treatment with NAT, anti-JCV antibody levels were stable in the anti-JCV positive patients. During therapy, a slight decrease in anti-JCV and anti-VZV antibody levels, but not anti-CMV antibody levels, was observed. All five patients who developed PML showed a mild to moderate increase in anti-JCV antibody levels at time of PML diagnosis; pre-PML samples suggested that this increase might start already prior to diagnosis of PML. Treatment initiation with NAT may lead to a slight decrease in anti-JCV and anti-VZV antibody levels, suggestive of a mild suppressive effect of NAT on antibody levels. Our findings in five cases of PML demonstrate that the onset of PML can be accompanied by increasing anti-JCV antibodies in serum. Monitoring of anti-JCV antibody levels could potentially be used as a tool for prediction or earlier diagnosis of PML during NAT treatment for MS. Further studies are warranted.

Rate-dependent electrical, contractile and restitution properties of isolated left ventricular myocytes in guinea-pig hypertrophy.

PubMed

Davey, P; Bryant, S; Hart, G

2001-01-01

Left ventricular hypertrophy predisposes to sudden cardiac death (SCD) and studies of human SCD suggest that the antecedent heart rate (HR) is usually < 100 beats min(-1). This is surprising in view of the known association between adrenergic receptor stimulation and SCD which by itself would suggest that it is more likely to occur from high rather than low HR. We therefore hypothesized that there may be electrical or mechanical abnormalities present in myocytes isolated from animals with left ventricular hypertrophy that predispose to SCD at low stimulation frequencies but which may not be present at high HR. Mild left ventricular hypertrophy was induced in guinea-pigs by infra-renal aortic banding. Electrical and mechanical properties of isolated myocytes were studied at different stimulation frequencies between 0.1 and 3 Hz. Action potential duration (APD) is prolonged in hypertrophy at stimulation frequencies < 1 Hz but not at faster rates. Contraction size, time-to-peak contraction (TTPC) and half-relaxation time are greatly enhanced in hypertrophy at all frequencies between 0.1 and 3 Hz. Electrical (50.3 +/- 5.2 ms in hypertrophy and 78.4 +/- 12.1 ms in control, P < 0.03) and mechanical (205 +/- 16 ms for hypertrophy and 266 +/- 24 ms for control cells, P < 0.03) restitution time constants are quicker in hypertrophy. The finding of APD prolongation at low but not at high frequencies is consistent with the finding that SCD arises from low and not high HR. This data supports the role of abnormal repolarization in SCD.

Kidney tissue targeted metabolic profiling of glucocorticoid-induced osteoporosis and the proposed therapeutic effects of Rhizoma Drynariae studied using UHPLC/MS/MS.

PubMed

Huang, Yue; Liu, Xinyu; Zhao, Longshan; Li, Famei; Xiong, Zhili

2014-06-01

Traditional Chinese medicine and modern science have indicated that there is a close relationship between bone and kidney. In light of this, this project was designed to study the metabolic profiling by UHPLC/MS/MS of glucocorticoid-induced osteoporosis in kidney tissue and the possible therapeutic effects of Rhizoma Drynariae (RD), a classic traditional Chinese medicine, in improving the kidney function and strengthening bone. Twenty-one Wistar rats were divided into three groups: control group (rats before prednisolone inducing), a model group (prednisolone-induced group) and a treatment group (prednisolone-induced rats that were then administered RD ethanol extracts). By using pattern recognition analysis, a significant change in the metabolic profile of kidney tissue samples was observed in the model group and restoration of the profile was observed after the administration of RD ethanol extracts. Some significantly changed biomarkers related to osteoporosis such as sphingolipids (C16 dihydrosphingosine, C18 dihydrosphingosine, C18 phytosphingosine, C20 phytosphingosine), lysophosphatidycholines (C16:0 LPC, C18:0 LPC) and phenylalanine were identified. As a complement to the metabolic profiling of RD in plasma, these biomarkers suggest that kidney damage, cell cytotoxicity and apoptosis exist in osteoporosis rats, which is helpful in further understanding the underlying process of glucocorticoid-induced osetoporosis and the suggested therapeutic effects of RD. The method shows that tissue target metabonomics might provide a powerful tool to further understand the process of disease and the mechanism of therapeutic effect of Chinese medicines. Copyright © 2014 John Wiley & Sons, Ltd.

Effects of an alkaloid-rich extract from Mitragyna speciosa leaves and fluoxetine on sleep profiles, EEG spectral frequency and ethanol withdrawal symptoms in rats.

PubMed

Cheaha, Dania; Keawpradub, Niwat; Sawangjaroen, Kitja; Phukpattaranont, Pimpimol; Kumarnsit, Ekkasit

2015-10-15

Many antidepressants are effective in alleviating ethanol withdrawal symptoms. However, most of them suppress rapid eye movement (REM) sleep. Thus, development of antidepressants without undesirable side effects would be preferable. Previously, crude alkaloid extract from Mitragyna speciosa (MS) Korth was found to produce antidepressant activities. It was hypothesized that the alkaloid extract from MS may attenuate ethanol withdrawal without REM sleep disturbance. Adult male Wistar rats implanted with electrodes over the frontal and parietal cortices were used for two separated studies. For an acute study, 10 mg/kg fluoxetine or 60 mg/kg alkaloid extract from MS were administered intragastrically. Electroencephalographic (EEG) signals were recorded for 3 h to examine sleep profiles and EEG fingerprints. Another set of animal was used for an ethanol withdrawal study. They were rendered dependent on ethanol via a modified liquid diet (MLD) containing ethanol ad libitum for 28 days. On day 29, fluoxetine (10 mg/kg) or alkaloid extract from MS (60 mg/kg) were administered 15 min before the ethanol-containing MLD was replaced with an isocaloric ethanol-free MLD to induced ethanol withdrawal symptoms. The sleep analysis revealed that alkaloid extract from MS did not change any REM parameters which included average duration of each REM episode, total REM time, number of REM episode and REM latency whereas fluoxetine significantly suppressed all REM parameters and delayed REM latency. However, power spectral analysis revealed similar fingerprints for fluoxetine and alkaloid extract from MS characterized by decreasing powers in the slow frequency range in frontal and parietal cortical EEG. Neither treatment affected spontaneous motor activity. Finally, both alkaloid extract from MS and fluoxetine were found to significantly attenuate ethanol withdrawal-induced hyperexcitability (increases gamma activity) in both cortices and to reduce locomotor activity. The present study demonstrated that the alkaloid extract from MS alleviates ethanol withdrawal severity with no side effect on REM sleep. In addition, these data suggest that suppressive effects on slow frequency powers but not REM sleep may be hallmarks of effective antidepressants for ethanol withdrawal treatment. Copyright © 2015 Elsevier GmbH. All rights reserved.

Dipole source localization of event-related brain activity indicative of an early visual selective attention deficit in ADHD children.

PubMed

Jonkman, L M; Kenemans, J L; Kemner, C; Verbaten, M N; van Engeland, H

2004-07-01

This study was aimed at investigating whether attention-deficit hyperactivity disorder (ADHD) children suffer from specific early selective attention deficits in the visual modality with the aid of event-related brain potentials (ERPs). Furthermore, brain source localization was applied to identify brain areas underlying possible deficits in selective visual processing in ADHD children. A two-channel visual color selection task was administered to 18 ADHD and 18 control subjects in the age range of 7-13 years and ERP activity was derived from 30 electrodes. ADHD children exhibited lower perceptual sensitivity scores resulting in poorer target selection. The ERP data suggested an early selective-attention deficit as manifested in smaller frontal positive activity (frontal selection positivity; FSP) in ADHD children around 200 ms whereas later occipital and fronto-central negative activity (OSN and N2b; 200-400 ms latency) appeared to be unaffected. Source localization explained the FSP by posterior-medial equivalent dipoles in control subjects, which may reflect the contribution of numerous surrounding areas. ADHD children have problems with selective visual processing that might be caused by a specific early filtering deficit (absent FSP) occurring around 200 ms. The neural sources underlying these problems have to be further identified. Source localization also suggested abnormalities in the 200-400 ms time range, pertaining to the distribution of attention-modulated activity in lateral frontal areas.

Comparison of clonazepam compliance by measurement of urinary concentration by immunoassay and LC-MS/MS in pain management population.

PubMed

West, Robert; Pesce, Amadeo; West, Cameron; Crews, Bridgit; Mikel, Charles; Almazan, Perla; Rosenthal, Murray; Latyshev, Sergey

2010-01-01

Physicians determine patient compliance with their medications by use of urine drug testing. It is known that measurement of benzodiazepines is limited by immunoassay specificity and cutoff limits and therefore does not offer physicians an accurate picture of their patients' compliance with these medications. A few studies have used lower cutoffs to demonstrate patient compliance. To define more appropriate cutoffs for compliance monitoring of patients prescribed clonazepam as determined using immunoassay and liquid chromatography-tandem mass spectrometry (LC-MS/MS). A diagnostic accuracy study of the urinary excretion of clonazepam. Millennium Laboratories performed measurements on the urinary excretion of pain patients prescribed clonazepam as the indicator test. This benzodiazepine was chosen because it forms one major metabolite, 7-aminoclonazepam which is specific for that drug. Patients whose only benzodiazepine medication was clonazepam were selected as the test population. The Millennium Laboratories test database was filtered first to select patients on clonazepam, then a second filter was used to eliminate patients with any other listed benzodiazepine medications. Samples were tested using the Microgenics DRI benzodiazepine assay with a 200 ng/mL cutoff. The same samples were quantitatively assessed for 7-aminoclonazepam by LC-MS/MS with a cutoff of 40 ng/mL. The results from the immunoassay were scored as positive or negative while the quantitative results from the LC-MS/MS were also scored as positive or negative depending upon their concentration. Samples from 180 patients met these medication criteria. The positivity rates were 21% (38 samples) by immunoassay. The positivity rate was 70% (126 samples) if the LC-MS/MS cutoff was set at 200 ng/mL. However, the positivity rate was 87% (157 samples) if the LC-MS/MS was set at 40 ng/mL. Concentration distributions revealed a significant fraction (7%) in the 40 - 100 ng/mL range. A limitation of the study was the inability to measure lower than 40 ng/mL. There may be another fraction of the population that was positive below the cutoff value. The difference in positivity rate between the immunoassay and the LC-MS/MS result showed that the nominal 200 ng/mL cutoff of the immunoassay did not apply to 7-aminoclonazepam. This low immunoassay positivity rate is inconsistent with the manufacturer's published cross reactivity data for clonazepam and 7-aminoclonazepam. These data illustrate the limitations of using a 200 ng/mL cutoff to monitor clonazepam compliance and suggest that a cutoff of 40 ng/mL or less is needed to reliably monitor use of this drug.

Race Differences: Use of Walking Speed to Identify Community-Dwelling Women at Risk for Poor Health Outcomes--Osteoarthritis Initiative Study.

PubMed

Kirkness, Carmen S; Ren, Jinma

2015-07-01

Onset of disability, risk for future falls, frailty, functional decline, and mortality are strongly associated with a walking speed of less than 1.0 m/s. The study objective was to determine whether there were differences in slow walking speed (<1.0 m/s) between community-dwelling African American and white American adult women with osteoarthritis symptoms. An additional aim was to examine whether racial differences in walking speed can be attributed to age, obesity, socioeconomic factors, disease severity, or comorbidities. A cross-sectional design was used. Community-dwelling adults were recruited from Baltimore, Maryland; Columbus, Ohio; Pittsburgh, Pennsylvania; and Pawtucket, Rhode Island. Participants were 2,648 women (23% African American) who were 45 to 79 years of age and had a self-selected baseline walking speed of 20 m/s in the Osteoarthritis Initiative Study. Mixed-effects logistic regression models were used to examine racial differences in walking speed (<1.0 m/s versus ≥1.0 m/s), with adjustments for demographic factors, socioeconomic factors, disease severity, and comorbidities. Walking speed was significantly slower for African American women than for white American women (mean walking speed=1.19 and 1.33 m/s, respectively). The prevalence of a walking speed of less than 1.0 m/s in this cohort of middle-aged women was 9%; about 50% of the women with a walking speed of less than 1.0 m/s were younger than 65 years. Women with a walking speed of less than 1.0 m/s had lower values for socioeconomic factors, higher values for disease severity, and higher prevalences of obesity and comorbidities than those with a walking speed of ≥1.0 m/s. After controlling for these covariates, it was found that African American women were 3 times (odds ratio=2.9; 95% confidence interval=2.0, 4.1) more likely to have a walking speed of less than 1.0 m/s than white American women. The study design made it impossible to know whether a walking speed of less than 1.0 m/s in women who were 45 years of age or older was a predictor of future poor health outcomes. In this study, race was independently associated with a walking speed of less than 1.0 m/s in community-dwelling women who had or were at risk for osteoarthritis, with African American women having 3 times the risk for slow walking as white American women. This finding suggests that middle-aged African American women have an increased risk for poor health outcomes. Further longitudinal evaluations are needed to confirm the long-term health outcomes in a middle-aged population and to establish walking speed as a useful tool for identifying middle-aged women at high risk for poor health outcomes. © 2015 American Physical Therapy Association.

Counteracting Fatigue in Multiple Sclerosis with Right Parietal Anodal Transcranial Direct Current Stimulation.

PubMed

Hanken, Katrin; Bosse, Mona; Möhrke, Kim; Eling, Paul; Kastrup, Andreas; Antal, Andrea; Hildebrandt, Helmut

2016-01-01

Fatigue in multiple sclerosis (MS) patients appears to correlate with vigilance decrement as reflected in an increase in reaction time (RT) and errors with prolonged time-on-task. The aim of this study was to investigate whether anodal transcranial direct current stimulation (tDCS) over the right parietal or frontal cortex counteracts fatigue-associated vigilance decrement and subjective fatigue. In study I, a randomized double-blind placebo-controlled study, anodal tDCS (1.5 mA) was delivered to the right parietal cortex or the right frontal cortex of 52 healthy participants during the first 20 min of a 40-min lasting visual vigilance task. Study II, also a randomized double-blind placebo-controlled study, investigated the effect of anodal tDCS (1.5 mA) over the right parietal cortex in 46 MS patients experiencing cognitive fatigue. tDCS was delivered for 20 min before patients performed a 20-min lasting visual vigilance task. Study I showed that right parietal stimulation, but not right frontal stimulation, counteracts the increase in RT associated with vigilance decrement. Hence, only right parietal stimulation was applied to the MS patients in study II. Stimulation had a significant effect on vigilance decrement in mildly to moderately cognitively fatigued MS patients. Vigilance testing significantly increased the feeling of fatigue independent of stimulation. Anodal tDCS over the right parietal cortex can counteract the increase in RTs during vigilance performance, but not the increase in subjective fatigue. This finding is compatible with our model of fatigue in MS, suggesting a dissociation between the feeling and the behavioral characteristics of fatigue.

Arabidopsis MALE STERILITY1 Encodes a PHD-Type Transcription Factor and Regulates Pollen and Tapetum Development[W

PubMed Central

Ito, Takuya; Nagata, Noriko; Yoshiba, Yoshu; Ohme-Takagi, Masaru; Ma, Hong; Shinozaki, Kazuo

2007-01-01

The Arabidopsis thaliana MALE STERILITY1 (MS1) gene encodes a nuclear protein with Leu zipper–like and PHD-finger motifs and is important for postmeiotic pollen development. Here, we examined MS1 function using both cell biological and molecular biological approaches. We introduced a fusion construct of MS1 and a transcriptional repression domain (MS1-SRDX) into wild-type Arabidopsis, and the transgenic plants showed a semisterile phenotype similar to that of ms1. Since the repression domain can convert various kinds of transcriptional activators to dominant repressors, this suggested that MS1 functioned as a transcriptional activator. The Leu zipper–like region and the PHD motif were required for the MS1 function. Phenotypic analysis of the ms1 mutant and the MS1-SRDX transgenic Arabidopsis indicated that MS1 was involved in formation of pollen exine and pollen cytosolic components as well as tapetum development. Next, we searched for MS1 downstream genes by analyzing publicly available microarray data and identified 95 genes affected by MS1. Using a transgenic ms1 plant showing dexamethasone-inducible recovery of fertility, we further examined whether these genes were immediately downstream of MS1. From these results, we discuss a role of MS1 in pollen and tapetum development and the conservation of MS1 function in flowering plants. PMID:18032630

Severe brachial plexopathy after an ultrasound-guided single-injection nerve block for total shoulder arthroplasty in a patient with multiple sclerosis.

PubMed

Koff, Matthew D; Cohen, Jeffrey A; McIntyre, John J; Carr, Charles F; Sites, Brian D

2008-02-01

DESPITE the known benefits of regional anesthesia for patients undergoing joint arthroplasty, the performance of peripheral nerve blocks in patients with multiple sclerosis (MS) remains controversial. MS has traditionally been described as an isolated disease of the central nervous system, without involvement of the peripheral nerves, and peripheral nerve blockade has been suggested to be safe. However, careful review of the literature suggests that MS may also be associated with involvement of the peripheral nervous system, challenging traditional teachings. There is a paucity of evidence with regard to safety in using peripheral nerve regional anesthesia in these patients. This makes it difficult to provide adequate "informed consent" to these patients. This case report describes a patient with MS who sustained a severe brachial plexopathy after a total shoulder arthroplasty during combined general anesthesia and interscalene nerve block.

Systematic, Evidence-Based Review of Exercise, Physical Activity, and Physical Fitness Effects on Cognition in Persons with Multiple Sclerosis.

PubMed

Sandroff, Brian M; Motl, Robert W; Scudder, Mark R; DeLuca, John

2016-09-01

Cognitive dysfunction is highly prevalent, disabling, and poorly-managed in persons with multiple sclerosis (MS). Recent evidence suggests that exercise might have beneficial effects on cognition in this population. The current systematic, evidence-based review examined the existing literature on exercise, physical activity, and physical fitness effects on cognition in MS to accurately describe the current status of the field, offer recommendations for clinicians, and identify study-specific and participant-specific characteristics for providing future direction for ongoing MS research. We performed an open-dated search of Medline, PsychInfo, and CINAHL in December 2015. The search strategy involved using the terms 'exercise' OR 'physical activity' OR 'physical fitness' OR 'aerobic' OR 'resistance' OR 'balance' OR 'walking' OR 'yoga' OR 'training' OR 'rehabilitation' AND 'multiple sclerosis'. Articles were eliminated from the systematic review if it was a review article, theoretical paper, or textbook chapter; did not involve persons with MS; involved only persons with pediatric-onset MS; did not involve neuropsychological outcomes; did not include empirical data to evaluate outcomes; involved pharmacological interventions; or was not available in English. The selected articles were first classified as examining exercise, physical activity, or physical fitness, and were then randomly assigned to 2 independent reviewers who rated each article for level of evidence based on American Academy of Neurology criteria. Reviewers further completed a table to characterize important elements of each study (i.e., intervention characteristics), the cognitive domain(s) that were targeted, participant-specific characteristics, outcome measures, and study results. The present review resulted in 26 studies on the effects of exercise, physical activity, and physical fitness on cognition in persons with MS. This included 1 Class I study, 3 Class II studies, 8 Class III studies, and 14 Class IV studies. Of the 26 total studies, 6 were randomized controlled trials. Overall, there is conflicting evidence for the effects of exercise on cognition in MS, and overall positive, but not definitive evidence for the effects of physical activity and physical fitness, respectively, on cognition in this population. Collectively, there is insufficient well-designed research to definitively conclude that exercise, physical activity, and physical fitness are effective for improving cognition in MS. This is based, in part, on methodological issues of Class I and II studies, such as inclusion of cognition as a secondary outcome (35 % of reviewed studies), poorly-developed exercise interventions, and paucity of research that included cognitively-impaired MS samples. However, promising evidence from Class III and Class IV studies may be useful for informing the development of better intervention research.

Plantarflexor weakness negatively impacts walking in persons with multiple sclerosis more than plantarflexor spasticity

PubMed Central

Wagner, Joanne M.; Kremer, Theodore R.; Van Dillen, Linda R.; Naismith, Robert T.

2014-01-01

Objective To determine if plantarflexor (PF) spasticity or ankle strength best predicts variance in walking capacity or self-perceived limitations in walking in persons with multiple sclerosis (pwMS), and if pwMS with PF spasticity are weaker and have greater walking dysfunction than pwMS without PF spasticity. Design Cross-sectional study. Setting University research laboratory. Participants Forty-two pwMS (age: 42.9 ± 10.1 years; Expanded Disability Status Scale (EDSS): median = 3.0, range = 0–6) and 14 adults without disability (WD) (age: 41.9 ± 10.1 years). Intervention Not applicable. Main Outcome Measures PF spasticity and dorsiflexion (DF) and PF maximum voluntary isometric torque (MVIT) were assessed using the Modified Ashworth Scale (MAS) and a computerized dynamometer, respectively. The Timed 25-Foot Walk Test (T25FWT) was the primary outcome measure of walking capacity. Secondary measures included the Six Minute Walk Test (6MWT) and 12-item Multiple Sclerosis Walking Scale (MSWS-12). Results PF strength was the most consistent predictor of the variance in walking capacity (T25FWT: R2 change = 0.23 to 0.29, p ≤ 0.001; 6MWT: R2 change = 0.12 to 0.29, p ≤ 0.012), and self-perceived limitations of walking (MSWS-12: R2 change = 0.04 to 0.14, p < 0.18). There were no significant differences (p > 0.05) between the pwMS with PF spasticity and pwMS without PF spasticity for any of the outcome measures. Conclusions Our study suggests a unique contribution of PF weakness to walking dysfunction in pwMS, and highlights the importance of evaluating PF strength in this clinical population. PMID:24582617

Small-area distribution of multiple sclerosis incidence in western France: in search of environmental triggers.

PubMed

Hammas, Karima; Yaouanq, Jacqueline; Lannes, Morgane; Edan, Gilles; Viel, Jean-François

2017-09-21

Despite intensive research over several decades, the etiology of multiple sclerosis (MS) remains poorly understood, although environmental factors are supposedly implicated. Our goal was to identify spatial clusters of MS incident cases at the small-area level to provide clues to local environmental risk factors that might cause or trigger the disease. A population-based and multi-stage study was performed in the French Brittany region to accurately ascertain the clinical onset of disease during the 2000-2004 period. The municipality of residence at the time of clinical onset was geocoded. To test for the presence of MS incidence clusters and to identify their approximate locations, we used a spatial scan statistic. We adjusted for socioeconomic deprivation, known to be strongly associated with increased MS incident rates, and scanned simultaneously for areas with either high or low rates. Sensitivity analyses (focusing on relapsing-remitting forms and/or places of residence available within the year following clinical onset) were performed. A total of 848 incident cases of MS were registered in Brittany, corresponding to a crude annual incidence rate of 5.8 per 100,000 inhabitants. The spatial scan statistic did not find a significant cluster of MS incidence in either the primary analysis (p value ≥ 0.56) or in the sensitivity analyses (p value ≥ 0.16). The findings of this study indicate that MS incidence is not markedly affected across space, suggesting that in the years preceding the first clinical expression of the disease, no environmental trigger is operative at the small-area population level in the French Brittany region.

Analysis of epididymal sperm maturation by MALDI profiling and top-down mass spectrometry.

PubMed

Labas, Valérie; Spina, Lucie; Belleannee, Clémence; Teixeira-Gomes, Ana-Paula; Gargaros, Audrey; Dacheux, Françoise; Dacheux, Jean-Louis

2015-01-15

The fertilization ability of male gametes is achieved after their transit through the epididymis where important post-gonadal differentiation occurs in different cellular compartments. Most of these maturational modifications occur at the protein level. The epididymal sperm maturation process was investigated using the ICM-MS (Intact Cell MALDI-TOF MS) approach on boar spermatozoa isolated from four different epididymal regions (immature to mature stage). Differential and quantitative MALDI-TOF profiling for whole cells or sub-cellular fractions was combined with targeted top-down MS in order to identify endogenous biomolecules. Using this approach, 172m/z peaks ranging between 2 and 20kDa were found to be modified during maturation of sperm. Using top-down MS, 62m/z were identified corresponding to peptidoforms/proteoforms with post-translational modifications (MS data are available via ProteomeXchange with identifier PXD001303). Many of the endogenous peptides were characterized as N-, C-terminal sequences or internal fragments of proteins presenting specific cleavages, suggesting the presence of sequential protease activities in the spermatozoa. This is the first time that such proteolytic activities could be evidenced for various sperm proteins through quantification of their proteolytic products. ICM-MS/top-down MS thus proved to be a valid approach for peptidome/degradome studies and provided new contributions to understanding of the maturation process of the male gamete involved in the development of male fertility. This peptidomic study (i) characterized the peptidome of epididymal spermatozoa from boar (Sus scrofa); (ii) established characteristic molecular phenotypes distinguishing degrees of maturation of spermatozoa during epididymal transit, and (iii) revealed that protease activities were at the origin of numerous peptides from known and unknown proteins involved in sperm maturation and/or fertility processes. Copyright © 2014 Elsevier B.V. All rights reserved.

Pancreatic cancer counterattack: MUC4 mediates Fas-independent apoptosis of antigen-specific cytotoxic T lymphocyte.

PubMed

Zhu, Yi; Zhang, Jing-Jing; Liang, Wen-Biao; Zhu, Rong; Wang, Bin; Miao, Yi; Xu, Ze-Kuan

2014-04-01

Tumor-associated MUC4 mucin has considerable potential as an immunotherapy target for pancreatic cancer. In previous studies, we developed dendritic cell (DC) vaccines which elicited MUC4 antigen-specific cytotoxic T lymphocyte (MS-CTL) response against tumor cells in vitro. Due to the observation that MS-CTL apoptotic rate increased significantly when co-cultured with MUC4+ tumor cells compared with T2 cells, we investigated whether high expression levels of MUC4 in pancreatic cancer cells would have an effect on the significant increase of apoptosis rate of MS-CTLs. First, the adverse influence of regulatory T cells (Tregs) was eliminated by CD8+ T lymphocyte sorting before the induction of MS-CTLs. Then, we constructed clonal MUC4-knockdown HPAC pancreatic cancer sublines with different MUC4 expression for co-incubation system. By utilizing appropriate control to rule out the possible apoptosis-induced pathway of intrinsic activated cell-autonomous death (ACAD) and analogous antigen-dependent apoptosis of CTL (ADAC) in our study system, further analysis of the effect of MUC4 membrane-expression, supernatants and blockade of CTL surface Fas receptor on MS-CTL apoptosis was carried out. The results demonstrated that the level of MUC4 membrane expression strongly positively correlated with MS-CTL apoptosis and the influence of supernatants and Fas-blockade did not significantly correlate with MS-CTL apoptosis. This evidence suggested that there may be a novel counterattack pathway of pancreatic cancer cells, which is a MUC4-mediated, cell contact-dependent and Fas-independent process, to induce CTL apoptosis. Therefore, further exploration and understanding of the potential counterattack mechanisms is beneficial to enhance the efficacy of MUC4 specific tumor vaccines.

Association of serum 25(OH) vitamin D3 concentration with severity of multiple sclerosis.

PubMed

Harandi, Ali Amini; Shahbeigi, Saeed; Pakdaman, Hosein; Fereshtehnejad, Seyed-Mohammad; Nikravesh, Elham; Jalilzadeh, Roghie

2012-01-01

There is a known inverse association between solar radiation and the prevalence of multiple sclerosis (MS). Some studies have investigated the link between vitamin D and MS. The aim of this study was to investigate the possible association between serum 25(OH) vitamin D3 concentration and the severity of disease in Iranian patients with MS. Patients with relapsing-remitting MS underwent neurological examination, including measurement of Expanded Disability Status Scale (EDSS) score, and were categorized by disease severity into mild (0 ≤ EDSS ≤3), moderate (3.5 ≤ EDSS ≤5.5) and severe (6 ≤ EDSS). Serum concentrations of 25(OH) vitamin D3, calcium, phosphorus, magnesium and parathyroid hormone were also measured. A total of 78 (73.1% female) patients with MS were evaluated. The mean (± standard deviation) of age was 33.9 ± 9.2 years. The mean (± standard error) serum concentrations of 25(OH) vitamin D3 were 36.6 ± 5.1 mg/dL, 50.1 ± 12.6 mg/dL and 19.8 ± 6.5 mg/dL in patients with mild, moderate and severe disease, respectively. There was a statistically significant inverse correlation between 25(OH) vitamin D3 concentration and EDSS score (P = 0.016, r= -0.273 by Spearman rank correlation test), which was observed in women only (P = 0.021, r = -0.305). Receiver operating characteristic curve analysis suggested that a serum 25(OH) vitamin D3 concentration cutoff of 16.5 mg/dL could differentiate patients with mild/moderate MS from severe disease with 74.6% accuracy. Our findings further support the association between vitamin D and disease severity in MS.

Veganism does not reduce the risk of the metabolic syndrome in a Taiwanese cohort.

PubMed

Shang, Penghui; Shu, Zheng; Wang, Yanfang; Li, Na; Du, Songming; Sun, Feng; Xia, Yinyin; Zhan, Siyan

2011-01-01

The purpose of the present study was to assess the risk of the metabolic syndrome (MS) with vegan, pescovegetarian, lactovegetarian and nonvegetarian diets in Taiwan. The design was a retrospective cohort study using secondary data analysis from a Taiwan longitudinal health check-up database provided by MJ Health Screening Center during 1996-2006. A total of 93209 participants were classified as vegans (n=1116), pescovegetarians (n=2461), lactovegetarians (n=4313) and nonvegetarians (n=85319) by food frequency list of self-administered questionnaire at baseline. The association between MS or MS components and different dietary groups was evaluated using Cox proportional-hazards regression models with adjustment for confounders. During the mean 3.75 years of follow up, a total 8006 MS incident cases occurred and the incidence of MS was 229 (95% CI, 224, 234) per 10000 person year. Compared with vegans, hazard ratios of MS for nonvegetarians, pescovegetarians, lactovegetarians were 0.75 (95% CI, 0.64, 0.88), 0.68 (95% CI, 0.55, 0.83) and 0.81 (95% CI, 0.67, 0.97) after adjusting for sex, age, education status, smoking status, drinking status, physical activity at work and leisure, respectively. As for MS components, nonvegetarians and pescovegetarians had 0.72 (95% CI, 0.62, 0.84), 0.70 (95% CI, 0.57, 0.84) times risk of developing low high density lipoprotein cholesterol (HDL-C), while nonvegetarians had 1.16 (95% CI, 1.02, 1.32) times risk of developing high fasting plasma glucose. Our data suggest that the vegan diets did not decrease the risk of metabolic syndrome compared with pescovegetarian, lactovegetarian and nonvegetarian diets in a Taiwanese cohort.

Prevalence of metabolic syndrome in the Brazilian Xavante indigenous population.

PubMed

Soares, Luana Padua; Fabbro, Amaury Lelis Dal; Silva, Anderson Soares; Sartorelli, Daniela Saes; Franco, Luciana Ferreira; Kuhn, Patrícia Chamadoira; Moises, Regina Santiago; Vieira-Filho, João Paulo Botelho; Franco, Laércio Joel

2015-01-01

The raising prevalence of weight excess and of non-communicable diseases in indigenous populations, as well as changes in food consumption and reduction in the frequency and intensity of physical activity, suggest that the prevalence of metabolic syndrome (MS) is also elevated. The objective of this study was to evaluate the prevalence of MS and the frequency of its components in the Xavante adult population living in the Indian reservations of São Marcos and Sangradouro/Volta Grande, in the state of Mato Grosso, Brazil. A cross-sectional study was carried out among 932 Xavante Indians aged 20 years or more, in the 2008-2012 period. The variables analysed were gender, age, weight, height, waist circumference, blood pressure, initial and 2-h capillary glycemia in a 75 g OGTT, levels of triglycerides and HDL-cholesterol. The diagnostic criteria for MS proposed by the IDF and AHA/NHLBI were used. The prevalence of MS was 66.1 % (95 % CI 63.0-69.2), being 76.2 % (95 % CI 72.4-80.0) in women and 55.6 % (95 % CI 51.0-60.2) in men. Women had higher prevalence of MS in all age groups. Elevated waist circumference and lower levels of HDL-cholesterol were the more frequent components in those with MS, and elevated blood pressure was the less frequent. The high prevalence of MS in the Xavante Indians is mainly due to the increased prevalence of weight excess that resulted from an intense change in their life-style, in a short period of time in a population with a genetic predisposition. These findings highlight the magnitude of this health problem and make an alert about the necessity to implement specific preventive interventions.

Prevalence of multiple sclerosis in Health District III, Murcia, Spain.

PubMed

Candeliere-Merlicco, Antonio; Valero-Delgado, Francisco; Martínez-Vidal, Salvadora; Lastres-Arias, María Del Carmen; Aparicio-Castro, Eladio; Toledo-Romero, Francisco; Villaverde-González, Ramón

2016-09-01

The prevalence of multiple sclerosis (MS) varies throughout the world, and available epidemiological data suggest a progressively increasing prevalence of MS in Spain. The objective of this study was to calculate MS prevalence in Health District III of the autonomous community of Murcia in Spain. This is an observational, cross-sectional, descriptive study. The prevalence of MS in Health District III in the Region of Murcia, which includes the municipalities of Lorca, Totana, Águilas, Puerto Lumbreras and Aledo, was calculated from the total population (171,040 inhabitants), and among native Spanish citizens only (137,659 persons). Healthcare and demographic data were obtained from three sources: 1) OMI-AP: the local primary care computer system containing the medical records of all subscribers; 2) the medical record database of the Hospital Rafael Mendez (the single hospital in the district); and 3) the records of the AEMA III Multiple Sclerosis Association to which patients from this healthcare district belong. Data from these three sources were combined to check the accuracy and completeness of the patient records. The prevalence of MS among the general population of this district, including non-Spanish individuals, was 71.9 per 100,000 inhabitants (95% CI=60-85). Prevalence among the native Spanish population was 82.0 per 100,000 (95% CI=68-98). Considering prevalence by sex, it was 118.1 per 100,000 (95% CI: 95-146) in the female native Spanish population, and 45.4 per 100,000 (95% CI: 31-64) in the male native Spanish population. The prevalence in the native Spanish population in this district was calculated by sex and age (grouped by decades). A peak was observed among women aged between 20 and 29 years: 234.2 per 100,000 inhabitants (95% CI: 151-361). Our results suggest that the population in this healthcare district presents a risk of MS similar to that recently reported in other regions of Spain, which is higher than in previous decades. Copyright © 2016 Elsevier B.V. All rights reserved.

Serum uric acid concentrations are directly associated with the presence of benign multiple sclerosis.

PubMed

Simental-Mendía, Esteban; Simental-Mendía, Luis E; Guerrero-Romero, Fernando

2017-09-01

It has been reported that patients with multiple sclerosis (MS) exhibit lower serum uric acid levels; however, the association between uric acid concentrations and benign MS (BMS) has not been assessed. Hence, the objective of the present study was to determine whether the serum concentrations of uric acid are associated with the presence of BMS. Men and non-pregnant women over 16 years of age with diagnosis of MS were enrolled in a cross-sectional study. Expanded Disability Status Scale score < 3, progression of disease ≤10 years, diabetes, renal or hepatic diseases, gout, malignancy, alcohol intake, and treatment with thiazide diuretics and/or acetylsalicylic acid were exclusion criteria. According to subtype of disease, the eligible patients were allocated into groups with BMS and other varieties of MS. A logistic regression analysis was conducted in order to evaluate the association between serum concentrations of uric acid and BMS. A total of 106 patients were included, 39 in the group with BMS and 67 in the group with other varieties of MS. The logistic regression analysis adjusted by age, sex, and disease duration showed that increased concentrations of uric acid, indeed within the physiological levels, are significantly associated with the presence of BMS (OR = 2.60; 95% CI: 1.55-4.38, p < 0.001). The results of the present study suggest that elevated concentrations of uric acid, indeed within the physiological range, are likely linked to the presence of BMS.

White matter microstructural alterations in clinically isolated syndrome and multiple sclerosis.

PubMed

Huang, Jing; Liu, Yaou; Zhao, Tengda; Shu, Ni; Duan, Yunyun; Ren, Zhuoqiong; Sun, Zheng; Liu, Zheng; Chen, Hai; Dong, Huiqing; Li, Kuncheng

2018-07-01

This study aims to determine whether and how diffusion alteration occurs in the earliest stage of multiple sclerosis (MS) and the differences in diffusion metrics between CIS and MS by using the tract-based spatial statistics (TBSS) method based on diffusion tensor imaging (DTI). Thirty-six CIS patients (mean age ± SD: 34.0 years ± 12.6), 36 relapsing-remitting multiple sclerosis (RRMS) patients (mean age ± SD: 35.0 years ± 9.4) and 36 age- and gender-matched normal controls (NCs) were included in this study. Voxel-wise analyses were performed with TBSS using multiple diffusion metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ 1 ) and radial diffusivity (λ 23 ). In the CIS patients, TBSS analyses revealed diffusion alterations in a few white matter (WM) regions including the anterior thalamic radiation, corticospinal tract, inferior fronto-occipital fasciculus, superior longitudinal fasciculus, body and splenium of the corpus callosum, internal capsule, external capsule, and cerebral peduncle. MS patients showed more widespread diffusion changes (decreased FA, increased λ 1 , λ 23 and MD) than CIS. Exploratory analyses also revealed the possible associations between WM diffusion metrics and clinical variables (Expanded Disability Status Scale and disease duration) in the patients. This study provided imaging evidence for DTI abnormalities in CIS and MS and suggested that DTI can improve our knowledge of the path physiology of CIS and MS and clinical progression. Copyright © 2018 Elsevier Ltd. All rights reserved.

Collagen-based proteinaceous binder-pigment interaction study under UV ageing conditions by MALDI-TOF-MS and principal component analysis.

PubMed

Romero-Pastor, Julia; Navas, Natalia; Kuckova, Stepanka; Rodríguez-Navarro, Alejandro; Cardell, Carolina

2012-03-01

This study focuses on acquiring information on the degradation process of proteinaceous binders due to ultra violet (UV) radiation and possible interactions owing to the presence of historical mineral pigments. With this aim, three different paint model samples were prepared according to medieval recipes, using rabbit glue as proteinaceus binders. One of these model samples contained only the binder, and the other two were prepared by mixing each of the pigments (cinnabar or azurite) with the binder (glue tempera model samples). The model samples were studied by applying Principal Component Analysis (PCA) to their mass spectra obtained with Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF-MS). The complementary use of Fourier Transform Infrared Spectroscopy to study conformational changes of secondary structure of the proteinaceous binder is also proposed. Ageing effects on the model samples after up to 3000 h of UV irradiation were periodically analyzed by the proposed approach. PCA on MS data proved capable of identifying significant changes in the model samples, and the results suggested different aging behavior based on the pigment present. This research represents the first attempt to use this approach (PCA on MALDI-TOF-MS data) in the field of Cultural Heritage and demonstrates the potential benefits in the study of proteinaceous artistic materials for purposes of conservation and restoration. Copyright © 2012 John Wiley & Sons, Ltd.

Identification of the major tamoxifen-DNA adducts in rat liver by mass spectroscopy.

PubMed

Rajaniemi, H; Rasanen, I; Koivisto, P; Peltonen, K; Hemminki, K

1999-02-01

We present here the first mass spectroscopic (MS) identification of the main tamoxifen-induced DNA adducts in rat liver. The two main adducts were isolated by high-performance liquid chromatography (HPLC) and identified by MS, MS-MS and ultraviolet spectroscopy. Adduct 1 was the N-desmethyltamoxifen-deoxyguanosine adduct in which the alpha-position of the metabolite N-desmethyltamoxifen is linked covalently to the amino group of deoxyguanosine. Adduct 2 was confirmed to be the trans isomer of alpha-(N2-deoxyguanosinyl)tamoxifen, as previously suggested by co-chromatography.

A novel isoflavone profiling method based on UPLC-PDA-ESI-MS.

PubMed

Zhang, Shuang; Zheng, Zong-Ping; Zeng, Mao-Mao; He, Zhi-Yong; Tao, Guan-Jun; Qin, Fang; Chen, Jie

2017-03-15

A novel non-targeted isoflavone profiling method was developed using the diagnostic fragment-ion-based extension strategy, based on ultra-high performance liquid chromatography coupled with photo-diode array detector and electrospray ionization-mass spectrometry (UPLC-PDA-ESI-MS). 16 types of isoflavones were obtained in positive mode, but only 12 were obtained in negative mode due to the absence of precursor ions. Malonyldaidzin and malonylgenistin glycosylated at the 4'-O position or malonylated at the 4″-O position of glucose were indicated by their retention behavior and fragmentation pattern. Three possible quantification methods in one run based on UPLC-PDA and UPLC-ESI-MS were validated and compared, suggesting that methods based on UPLC-ESI-MS possess remarkable selectivity and sensitivity. Impermissible quantitative deviations induced by the linearity calibration with 400-fold dynamic range was observed for the first time and was recalibrated with a 20-fold dynamic range. These results suggest that isoflavones and their stereoisomers can be simultaneously determined by positive-ion UPLC-ESI-MS in soymilk. Copyright © 2016. Published by Elsevier Ltd.

Over 2,300 phosphorylated peptide identifications with single-shot capillary zone electrophoresis-tandem mass spectrometry in a 100 min separation

PubMed Central

Ludwig, Katelyn R.; Sun, Liangliang; Zhu, Guijie; Dovichi, Norman J.; Hummon, Amanda B.

2015-01-01

Ultra-performance liquid chromatography (UPLC)-electrospray ionization (ESI)-tandem mass spectrometry (MS/MS) is typically employed for phosphoproteome analysis. Alternatively, capillary zone electrophoresis (CZE) - ESI-MS/MS has great potential for phosphoproteome analysis due to the significantly different migration times of phosphorylated and unphosphorylated forms of peptides. In this work, we systematically compared UPLC-MS/MS and CZE-MS/MS for phosphorylated peptide identifications (IDs) using an enriched phosphoproteome from the MCF-10A cell line. When the sample loading amount of UPLC was 10 times higher than that of CZE (2 μg vs. 200 ng), UPLC generated more phosphorylated peptide IDs than CZE (3,313 vs. 1,783). However, when the same sample loading amounts were used for CZE and UPLC (2–200 ng), CZE-MS/MS consistently and significantly outperformed UPLC-MS/MS in terms of phosphorylated peptide and total peptide IDs. This superior performance is most likely due to the higher peptide intensity generated by CZE-MS/MS. More importantly, compared with UPLC data from 2 μg sample, CZE-MS/MS can identify over 500 unique phosphorylated peptides from 200 ng sample, suggesting that CZE and UPLC are complementary for phosphorylated peptide IDs. With further improved loading capacity via a dynamic pH junction method, 2,313 phosphorylated peptides were identified with single-shot CZE-MS/MS in a 100 min analysis. This number of phosphorylated peptide IDs is over one order of magnitude higher than the number of phosphorylated peptide IDs previously reported by single-shot CZE-MS/MS. PMID:26399161

Non-selective His bundle pacing with a biphasic waveform: enhancing septal resynchronization.

PubMed

Ortega, Daniel F; Barja, Luis D; Logarzo, Emilio; Mangani, Nicolas; Paolucci, Analia; Bonomini, Maria P

2018-05-01

His bundle pacing has shown to prevent detrimental effects from right ventricular apical pacing (RVA) and proved to resynchronize many conduction disturbances cases. However, the extent of His bundle pacing resynchronization is limited. An optimized stimulation waveform could expand this limit when implemented in His bundle pacing sets. In this work, we temporarily implemented RVA and Non-selective His bundle pacing with a biphasic anodal-first waveform (AF-nHB) and compared their effects against sinus rhythm (SR). Fifteen patients referred for electrophysiologic study with conduction disturbances, cardiomyopathy and ejection fraction below 35% were enrolled for the study. The following acute parameters were measured: QRS duration, left ventricular activation (RLVT), time of isovolumic contraction (IVCT), ejection fraction (EF), and dP/dtmax. QRS duration and RLVT decreased markedly under AF-nHB (SR: 169 ± 34 ms vs. nHB: 116 ± 31 ms, P < 0.0005) while RVA significantly increased QRS duration (SR: 169 ms vs. RVA: 198 ms, P < 0.05) and did not change RLVT (P = NS). Consistently, IVCT moderately decreased under AF-nHB (SR: 238 ms vs. RVA: 184 ms, P < 0.05 vs. SR) and dP/dtmax showed a 93.35 [mmHg] average increase under AF-nHB against SR. Also, T-wave inversions were observed during AF-nHB immediately after SR and RVA pacing suggesting the occurrence of cardiac memory. AF-nHB corrected bundle branch blocks in patients with severe conduction disturbances, even in those with dilated cardiomiopathy, outstanding from RVA. Also, the occurrence of cardiac memory during AF-nHB turned up as an observational finding of this study.

Use of high-resolution mass spectrometry to investigate a metabolite interference during liquid chromatography/tandem mass spectrometric quantification of a small molecule in toxicokinetic study samples.

PubMed

Furlong, Michael; Bessire, Andrew; Song, Wei; Huntington, Christopher; Groeber, Elizabeth

2010-07-15

During routine liquid chromatography/tandem mass spectrometric (LC/MS/MS) bioanalysis of a small molecule analyte in rat serum samples from a toxicokinetic study, an unexpected interfering peak was observed in the extracted ion chromatogram of the internal standard. No interfering peaks were observed in the extracted ion chromatogram of the analyte. The dose-dependent peak area response and peak area response versus time profiles of the interfering peak suggested that it might have been related to a metabolite of the dosed compound. Further investigation using high-resolution mass spectrometry led to unequivocal identification of the interfering peak as an N-desmethyl metabolite of the parent analyte. High-resolution mass spectrometry (HRMS) was also used to demonstrate that the interfering response of the metabolite in the multiple reaction monitoring (MRM) channel of the internal standard was due to an isobaric relationship between the (13)C-isotope of the metabolite and the internal standard (i.e., common precursor ion mass), coupled with a metabolite product ion with identical mass to the product ion used in the MRM transition of the internal standard. These results emphasize (1) the need to carefully evaluate internal standard candidates with regard to potential interferences from metabolites during LC/MS/MS method development, validation and bioanalysis of small molecule analytes in biological matrices; (2) the value of HRMS as a tool to investigate unexpected interferences encountered during LC/MS/MS analysis of small molecules in biological matrices; and (3) the potential for interference regardless of choice of IS and therefore the importance of conducting assay robustness on incurred in vitro or in vivo study samples. Copyright 2010 John Wiley & Sons, Ltd.

Measurement of macrocyclic trichothecene in floor dust of water-damaged buildings using gas chromatography/tandem mass spectrometry—dust matrix effects

PubMed Central

Saito, Rena; Park, Ju-Hyeong; LeBouf, Ryan; Green, Brett J.; Park, Yeonmi

2017-01-01

Gas chromatography-tandem mass spectrometry (GC-MS/MS) was used to detect fungal secondary metabolites. Detection of verrucarol, the hydrolysis product of Stachybotrys chartarum macrocyclic trichothecene (MCT), was confounded by matrix effects associated with heterogeneous indoor environmental samples. In this study, we examined the role of dust matrix effects associated with GC-MS/ MS to better quantify verrucarol in dust as a measure of total MCT. The efficiency of the internal standard (ISTD, 1,12-dodecanediol), and application of a matrix-matched standard correction method in measuring MCT in floor dust of water-damaged buildings was additionally examined. Compared to verrucarol, ISTD had substantially higher matrix effects in the dust extracts. The results of the ISTD evaluation showed that without ISTD adjustment, there was a 280% ion enhancement in the dust extracts compared to neat solvent. The recovery of verrucarol was 94% when the matrix-matched standard curve without the ISTD was used. Using traditional calibration curves with ISTD adjustment, none of the 21 dust samples collected from water damaged buildings were detectable. In contrast, when the matrix-matched calibration curves without ISTD adjustment were used, 38% of samples were detectable. The study results suggest that floor dust of water-damaged buildings may contain MCT. However, the measured levels of MCT in dust using the GC-MS/MS method could be significantly under- or overestimated, depending on the matrix effects, the inappropriate ISTD, or combination of the two. Our study further shows that the routine application of matrix-matched calibration may prove useful in obtaining accurate measurements of MCT in dust derived from damp indoor environments, while no isotopically labeled verrucarol is available. PMID:26853932

Measurement of macrocyclic trichothecene in floor dust of water-damaged buildings using gas chromatography/tandem mass spectrometry-dust matrix effects.

PubMed

Saito, Rena; Park, Ju-Hyeong; LeBouf, Ryan; Green, Brett J; Park, Yeonmi

2016-01-01

Gas chromatography-tandem mass spectrometry (GC-MS/MS) was used to detect fungal secondary metabolites. Detection of verrucarol, the hydrolysis product of Stachybotrys chartarum macrocyclic trichothecene (MCT), was confounded by matrix effects associated with heterogeneous indoor environmental samples. In this study, we examined the role of dust matrix effects associated with GC-MS/MS to better quantify verrucarol in dust as a measure of total MCT. The efficiency of the internal standard (ISTD, 1,12-dodecanediol), and application of a matrix-matched standard correction method in measuring MCT in floor dust of water-damaged buildings was additionally examined. Compared to verrucarol, ISTD had substantially higher matrix effects in the dust extracts. The results of the ISTD evaluation showed that without ISTD adjustment, there was a 280% ion enhancement in the dust extracts compared to neat solvent. The recovery of verrucarol was 94% when the matrix-matched standard curve without the ISTD was used. Using traditional calibration curves with ISTD adjustment, none of the 21 dust samples collected from water damaged buildings were detectable. In contrast, when the matrix-matched calibration curves without ISTD adjustment were used, 38% of samples were detectable. The study results suggest that floor dust of water-damaged buildings may contain MCT. However, the measured levels of MCT in dust using the GC-MS/MS method could be significantly under- or overestimated, depending on the matrix effects, the inappropriate ISTD, or combination of the two. Our study further shows that the routine application of matrix-matched calibration may prove useful in obtaining accurate measurements of MCT in dust derived from damp indoor environments, while no isotopically labeled verrucarol is available.

Xanthine Oxidase Mediates Axonal and Myelin Loss in a Murine Model of Multiple Sclerosis

PubMed Central

Okuno, Tatsusada; Takata, Kazushiro; Koda, Toru; Tada, Satoru; Shirakura, Takashi; Fujimura, Harutoshi; Mochizuki, Hideki; Sakoda, Saburo; Nakatsuji, Yuji

2013-01-01

Objectives Oxidative stress plays an important role in the pathogenesis of multiple sclerosis (MS). Though reactive oxygen species (ROS) are produced by various mechanisms, xanthine oxidase (XO) is a major enzyme generating ROS in the context of inflammation. The objectives of this study were to investigate the involvement of XO in the pathogenesis of MS and to develop a potent new therapy for MS based on the inhibition of ROS. Methods XO were assessed in a model of MS: experimental autoimmune encephalomyelitis (EAE). The contribution of XO-generated ROS to the pathogenesis of EAE was assessed by treating EAE mice with a novel XO inhibitor, febuxostat. The efficacy of febuxostat was also examined in in vitro studies. Results We showed for the first time that the expression and the activity of XO were increased dramatically within the central nervous system of EAE mice as compared to naïve mice. Furthermore, prophylactic administration of febuxostat, a XO inhibitor, markedly reduced the clinical signs of EAE. Both in vivo and in vitro studies showed infiltrating macrophages and microglia as the major sources of excess XO production, and febuxostat significantly suppressed ROS generation from these cells. Inflammatory cellular infiltration and glial activation in the spinal cord of EAE mice were inhibited by the treatment with febuxostat. Importantly, therapeutic efficacy was observed not only in mice with relapsing-remitting EAE but also in mice with secondary progressive EAE by preventing axonal loss and demyelination. Conclusion These results highlight the implication of XO in EAE pathogenesis and suggest XO as a target for MS treatment and febuxostat as a promising therapeutic option for MS neuropathology. PMID:23951137

Simultaneous determination of cucurbitacin B and cucurbitacin E in rat plasma by UHPLC-MS/MS: A pharmacokinetics study after oral administration of cucurbitacin tablets.

PubMed

Wang, Zhibin; Zhu, Wenbo; Gao, Mingjie; Wu, Chengcui; Yang, Chunjuan; Yang, Jing; Wu, Gaosong; Yang, Bingyou; Kuang, Haixue

2017-10-15

Cucurbitacin B (CuB) and cucurbitacin E (CuE) are tetracyclic triterpene compounds from Cucurbitaceae, and the main bioactive compounds of cucurbitacins tablets that used to treatment of chronic hepatitis. Pharmacological research has been very comprehensive, and there are few studies on pharmacokinetics, especially about CuE. An Ultra High Performance Liquid Chromatography-tandem Mass Spectrometry (UHPLC-MS/MS) method with high selectivity, simplicity and sensitivity has been used for quantitative analysis of Cucurbitacin B (CuB) and cucurbitacin E (CuE). Plasma samples were pretreatment by Liquid-liquid extraction (LLE) method with dichloromethane. The chromatographic separation was achieved on a C 18 column (Agilent Eclipse Plus, 1.8μm, 50×2.1mm) using gradient elution with water - methanol at a flow rate of 0.3mL/min and the column temperature was set at 30°C. The method was validated according to FDA guidelines. Lower limit of quantification (LLOQ) was 1.60ng/mL for CuB and 1.58ng/mL for CuE. Correlation coefficients of CuB and CuE were more than 0.99 in rat plasma. All values of intra-day and inter-day precision (RSD%) were not exceeded 15%, the accuracy (RE%) were within -5.57 to 5.20% for CuB and -3.33 to 7.37% for CuE. The mean extraction recoveries were more than 80%. Pharmacokinetic parameters were also evaluated by UHPLC-MS/MS method. The results suggestion that this method was successfully applied to pharmacokinetic study of CuB and CuE in rat plasma after oral administration cucurbitacin tablets. Published by Elsevier B.V.

New Mechanism of Extractive Electrospray Ionization Mass Spectrometry for Heterogeneous Solid Particles.

PubMed

Kumbhani, S; Longin, T; Wingen, L M; Kidd, C; Perraud, V; Finlayson-Pitts, B J

2018-02-06

Real-time in situ mass spectrometry analysis of airborne particles is important in several applications, including exposure studies in ambient air, industrial settings, and assessing impacts on visibility and climate. However, obtaining molecular and 3D structural information is more challenging, especially for heterogeneous solid or semisolid particles. We report a study of extractive electrospray ionization mass spectrometry (EESI-MS) for the analysis of solid particles with an organic coating. The goal is to elucidate how much of the overall particle content is sampled, and determine the sensitivity of this technique to the surface layers. It is shown that, for NaNO 3 particles coated with glutaric acid (GA), very little of the solid NaNO 3 core is sampled compared to the GA coating, whereas for GA particles coated with malonic acid (MA), significant signals from both the MA coating and the GA core are observed. However, conventional ESI-MS of the same samples collected on a Teflon filter (and then extracted) detects much more core material compared to EESI-MS in both cases. These results show that, for the experimental conditions used here, EESI-MS does not sample the entire particle but, instead, is more sensitive to surface layers. Separate experiments on single-component particles of NaNO 3 , GA, or citric acid show that there must be a kinetics limitation to dissolution that is important in determining EESI-MS sensitivity. We propose a new mechanism of EESI solvent droplet interaction with solid particles that is consistent with the experimental observations. In conjunction with previous EESI-MS studies of organic particles, these results suggest that EESI does not necessarily sample the entire particle when solid, and that not only solubility but also surface energies and the kinetics of dissolution play an important role.

Chemical profiling analysis of Maca using UHPLC-ESI-Orbitrap MS coupled with UHPLC-ESI-QqQ MS and the neuroprotective study on its active ingredients

NASA Astrophysics Data System (ADS)

Zhou, Yanyan; Li, Peng; Brantner, Adelheid; Wang, Hongjie; Shu, Xinbin; Yang, Jian; Si, Nan; Han, Lingyu; Zhao, Haiyu; Bian, Baolin

2017-03-01

Lepidium meyenii (Maca), originated from Peru, has been cultivated widely in China as a popular health care food. However, the chemical and effective studies of Maca were less in-depth, which restricted its application seriously. To ensure the quality of Maca, a feasible and accurate strategy was established. One hundred and sixty compounds including 30 reference standards were identified in 6 fractions of methanol extract of Maca by UHPLC-ESI-Orbitrap MS. Among them, 15 representative active compounds were simultaneously determined in 17 samples by UHPLC-ESI-QqQ MS. The results suggested that Maca from Yunnan province was the potential substitute for the one from Peru. Meanwhile, the neuroprotective effects of Maca were investigated. Three fractions and two pure compounds showed strong activities in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced zebrafish model. Among them, 80% methanol elution fraction (Fr5) showed significant neuroprotective activity, followed by 100% part (Fr6). The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) was a possible mechanism of its neuroprotective effect.

Chemical profiling analysis of Maca using UHPLC-ESI-Orbitrap MS coupled with UHPLC-ESI-QqQ MS and the neuroprotective study on its active ingredients

PubMed Central

Zhou, Yanyan; Li, Peng; Brantner, Adelheid; Wang, Hongjie; Shu, Xinbin; Yang, Jian; Si, Nan; Han, Lingyu; Zhao, Haiyu; Bian, Baolin

2017-01-01

Lepidium meyenii (Maca), originated from Peru, has been cultivated widely in China as a popular health care food. However, the chemical and effective studies of Maca were less in-depth, which restricted its application seriously. To ensure the quality of Maca, a feasible and accurate strategy was established. One hundred and sixty compounds including 30 reference standards were identified in 6 fractions of methanol extract of Maca by UHPLC-ESI-Orbitrap MS. Among them, 15 representative active compounds were simultaneously determined in 17 samples by UHPLC-ESI-QqQ MS. The results suggested that Maca from Yunnan province was the potential substitute for the one from Peru. Meanwhile, the neuroprotective effects of Maca were investigated. Three fractions and two pure compounds showed strong activities in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced zebrafish model. Among them, 80% methanol elution fraction (Fr5) showed significant neuroprotective activity, followed by 100% part (Fr6). The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) was a possible mechanism of its neuroprotective effect. PMID:28304399

Chemical profiling analysis of Maca using UHPLC-ESI-Orbitrap MS coupled with UHPLC-ESI-QqQ MS and the neuroprotective study on its active ingredients.

PubMed

Zhou, Yanyan; Li, Peng; Brantner, Adelheid; Wang, Hongjie; Shu, Xinbin; Yang, Jian; Si, Nan; Han, Lingyu; Zhao, Haiyu; Bian, Baolin

2017-03-17

Lepidium meyenii (Maca), originated from Peru, has been cultivated widely in China as a popular health care food. However, the chemical and effective studies of Maca were less in-depth, which restricted its application seriously. To ensure the quality of Maca, a feasible and accurate strategy was established. One hundred and sixty compounds including 30 reference standards were identified in 6 fractions of methanol extract of Maca by UHPLC-ESI-Orbitrap MS. Among them, 15 representative active compounds were simultaneously determined in 17 samples by UHPLC-ESI-QqQ MS. The results suggested that Maca from Yunnan province was the potential substitute for the one from Peru. Meanwhile, the neuroprotective effects of Maca were investigated. Three fractions and two pure compounds showed strong activities in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced zebrafish model. Among them, 80% methanol elution fraction (Fr 5 ) showed significant neuroprotective activity, followed by 100% part (Fr 6 ). The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) was a possible mechanism of its neuroprotective effect.

Monthly oral methylprednisolone pulse treatment in progressive multiple sclerosis.

PubMed

Ratzer, Rikke; Iversen, Pernille; Börnsen, Lars; Dyrby, Tim B; Romme Christensen, Jeppe; Ammitzbøll, Cecilie; Madsen, Camilla Gøbel; Garde, Ellen; Lyksborg, Mark; Andersen, Birgit; Hyldstrup, Lars; Sørensen, Per Soelberg; Siebner, Hartwig R; Sellebjerg, Finn

2016-06-01

There is a large unmet need for treatments for patients with progressive multiple sclerosis (MS). Phase 2 studies with cerebrospinal fluid (CSF) biomarker outcomes may be well suited for the initial evaluation of efficacious treatments. To evaluate the effect of monthly oral methylprednisolone pulse treatment on intrathecal inflammation in progressive MS. In this open-label phase 2A study, 15 primary progressive and 15 secondary progressive MS patients received oral methylprednisolone pulse treatment for 60 weeks. Primary outcome was changes in CSF concentrations of osteopontin. Secondary outcomes were other CSF biomarkers of inflammation, axonal damage and demyelination; clinical scores; magnetic resonance imaging measures of disease activity, magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI); motor evoked potentials; and bone density scans. We found no change in the CSF concentration of osteopontin, but we observed significant improvement in clinical scores, MTR, DTI and some secondary CSF outcome measures. Adverse events were well-known side effects to methylprednisolone. Monthly methylprednisolone pulse treatment was safe, but had no effect on the primary outcome. However, improvements in secondary clinical and MRI outcome measures suggest that this treatment regimen may have a beneficial effect in progressive MS. © The Author(s), 2015.

Modulation of B cell regulatory molecules CD22 and CD72 in myasthenia gravis and multiple sclerosis.

PubMed

Lu, Jiayin; Li, Jing; Zhu, Tai-qing; Zhang, Longbo; Wang, Yuzhong; Tian, Fa-fa; Yang, Huan

2013-06-01

B cell activation mediated by cluster of differentiation (CD) molecules plays an important role in B cell-related autoimmune diseases. CD22 and CD72 have been demonstrated to act as B cell inhibitory receptors in many autoimmune diseases. Activated B cells are involved in the pathogenesis of myasthenia gravis (MG) by secretion of anti-acetylcholine receptor (AchR) antibodies. However, the roles of CD22 and CD72 on B cells of MG are unknown. In this study, we detected the expression of CD22 and CD72 on B cells of MG, compared to multiple sclerosis (MS) patient controls and healthy controls by flow cytometry and quantitative real-time polymerase transcription chain reaction. Our data demonstrated that aberrant expression of CD72 exists on B cells of MG and MS patients and expression level of CD72 molecule has a significantly negative correlation with anti-AchR antibody levels in MG, which suggests that CD72 may be involved in the pathogenesis of MG and MS. There were no significant differences between study patients (MG, ocular MG, generalized MG, and MS) and healthy controls.

Prevalence of Diabetes and Metabolic Syndrome in a Migrant Mixtec Population, Baja California, Mexico

PubMed Central

Goodman, David; Fraga, Miguel A.; Brodine, Stephanie; Ibarra, Maria-de-la-Luz; Garfein, Richard S.

2016-01-01

This study was conducted to determine the prevalence and correlates of metabolic syndrome (MS) and diabetes among a migrant Mixtec population residing in San Quintin, Baja California, Mexico. A cross-sectional study utilizing data collected during a 2-day clinic in 2008 in a rural farming community with a high prevalence of Mixtec Indians. Interviews and clinical examinations were performed to assess sociodemographic data, medical history and anthropometric measures. Blood samples were obtained to measure glycated hemoglobin, fasting glucose, triglycerides, total cholesterol, HDL and LDL. Of the 107 patients surveyed, 56 % were female and mean age was 38.5 (range: 18–74, SD = 12.6) years. Overall, 41.1 % had MS and 26.2 % had diabetes. Drinking alcohol more than once a week [adjusted OR (AOR) = 16.0, p = 0.008] and being literate (AOR = 0.38, p = 0.035) were independently associated with MS. Only female gender was significantly associated with diabetes (OR = 3.95, p = 0.005). The high prevalence of MS, diabetes and other metabolic abnormalities among migrant farm workers in San Quintin suggest the need for interventions to reduce the risk for these conditions. PMID:22961334

A factor analytic investigation of the Mercy Evaluation of Multiple Sclerosis.

PubMed

Merz, Zachary C; Wright, John D; Vander Wal, Jillon S; Gfeller, Jeffrey D

2018-01-23

Neurocognitive deficits commonly are an accompanying feature of Multiple Sclerosis (MS). A brief, yet comprehensive neuropsychological battery is desirable for assessing the extent of these deficits. Therefore, the present study examined the validity of the Mercy Evaluation of Multiple Sclerosis (MEMS) for use with the MS population. Archival data from individuals diagnosed with MS (N = 378) by independent neurologists was examined. Cognitive domains assessed included processing speed and attention, learning, and memory, visuospatial, language, and executive functioning. A mean battery index was calculated to provide a general indicator of cognitive impairment within the current sample. Overall performance across participants was found to be in the lower limits of the average range. Results of factor analytic statistical procedures yielded a four-factor solution, accounting for 67% of total variance within the MEMS. Four neurocognitive measures exhibited the highest sensitivity in detecting cognitive impairment, constituting a psychometrically established brief cognitive screening battery, which accounted for 83% of total variance within the mean battery index score. Overall, the results of the current study suggest appropriate construct validity of the MEMS for use with individuals with MS, as well as provide support for previously established cognitive batteries.

Development of Multilocus Sequence Typing (MLST) for Mycoplasma synoviae.

PubMed

El-Gazzar, Mohamed; Ghanem, Mostafa; McDonald, Kristina; Ferguson-Noel, Naola; Raviv, Ziv; Slemons, Richard D

2017-03-01

Mycoplasma synoviae (MS) is a poultry pathogen that has had an increasing incidence and economic impact over the past few years. Strain identification is necessary for outbreak investigation, infection source identification, and facilitating prevention and control as well as eradication efforts. Currently, a segment of the variable lipoprotein hemagglutinin A (vlhA) gene (420 bp) is the only target that is used for MS strain identification. A major limitation of this assay is that colonality of typed samples can only be inferred if their vlhA sequences are identical; however, if their sequences are different, the degree of relatedness is uncertain. In this study we propose a multilocus sequence typing (MLST) assay to further refine MS strain identification. After initial screening of 24 housekeeping genes as potential targets, seven genes were selected for the MLST assay. An internal segment (450-711 bp) from each of the seven genes was successfully amplified and sequenced from 58 different MS strains and field isolates (n = 30) or positive clinical samples (n = 28). The collective sequence of all seven gene segments (3960 bp total) was used for MS sequence typing. The 58 tested MS samples were typed into 30 different sequence types using the MLST assay and, coincidentally, all the samples were typed into 30 sequence types using the vlhA assay. However, the phylogenetic tree generated using the MLST data was more congruent to the epidemiologic information than was the tree generated by the vlhA assay. We suggest that the newly developed MLST assay and the vlhA assay could be used in tandem for MS typing. The MLST assay will be a valuable and more reliable tool for MS sequence typing, providing better understanding of the epidemiology of MS infection. This in turn will aid disease prevention, control, and eradication efforts.

Detection of metabolites of lysergic acid diethylamide (LSD) in human urine specimens: 2-oxo-3-hydroxy-LSD, a prevalent metabolite of LSD.

PubMed

Poch, G K; Klette, K L; Hallare, D A; Manglicmot, M G; Czarny, R J; McWhorter, L K; Anderson, C J

1999-03-05

Seventy-four urine specimens previously found to contain lysergic acid diethylamide (LSD) by gas chromatography-mass spectrometry (GC-MS) were analyzed by a new procedure for the LSD metabolite 2-oxo-3-hydroxy-LSD (O-H-LSD) using a Finnigan LC-MS-MS system. This procedure proved to be less complex, shorter to perform and provides cleaner chromatographic characteristics than the method currently utilized by the Navy Drug Screening Laboratories for the extraction of LSD from urine by GC-MS. All of the specimens used in the study screened positive for LSD by radioimmunoassay (Roche Abuscreen). Analysis by GC-MS revealed detectable amounts of LSD in all of the specimens. In addition, isolysergic diethylamide (iso-LSD), a byproduct of LSD synthesis, was quantitated in 64 of the specimens. Utilizing the new LC-MS-MS method, low levels of N-desmethyl-LSD (nor-LSD), another identified LSD metabolite, were detected in some of the specimens. However, all 74 specimens contained O-H-LSD at significantly higher concentrations than LSD, iso-LSD, or nor-LSD alone. The O-H-LSD concentration ranged from 732 to 112 831 pg/ml (mean, 16340 pg/ml) by quantification with an internal standard. The ratio of O-H-LSD to LSD ranged from 1.1 to 778.1 (mean, 42.9). The presence of O-H-LSD at substantially higher concentrations than LSD suggests that the analysis for O-H-LSD as the target analyte by employing LC-MS-MS will provide a much longer window of detection for the use of LSD than the analysis of the parent compound, LSD.

Allergies, antibiotics use, and multiple sclerosis.

PubMed

Ren, Jinma; Ni, Huijuan; Kim, Minchul; Cooley, Kimberly L; Valenzuela, Reuben M; Asche, Carl V

2017-08-01

The associations between allergies, antibiotics use, and multiple sclerosis (MS) remain controversial and their mediating or moderating effects have not yet been examined. We aimed to assess the direct and indirect influences of allergies and antibiotics use on MS development, and their interactions. A 1:3 matched case-control study was performed using the National Ambulatory Medical Care Survey database from 2006 to 2013 in the USA. Multiple sclerosis was identified based on the ICD-9 code (340.0) in any position. Cases were matched to their controls based on survey year, age, gender, race, payer type, region, and tobacco use. Allergy diseases and antibiotics prescriptions were extracted by ICD-9 code and drug classification code, respectively. Both generalized structural equation model and MacArthur approach were used to examine their intrinsic relationships. The weighted prevalence of MS was 133.7 per 100,000 visits. A total of 829 MS patients and 2441 controls were matched. Both respiratory tract allergies (OR = 0.29, 95% CI: 0.18, 0.49) and other allergies (OR = 0.38, 95% CI: 0.19, 0.77) were associated with a reduction of the risk of MS. Patients with respiratory tract allergies were more likely to use penicillin (OR = 8.73, 95% CI: 4.12, 18.53) and other antibiotics (OR = 3.77, 95% CI: 2.72, 5.21), and those with other allergies had a higher likelihood of penicillin use (OR = 4.15, 95% CI: 1.27, 13.54); however, the link between antibiotics use and MS was not confirmed although penicillin use might mediate the relationship between allergies and MS. The findings supported allergy as a protective factor for MS development. We also suggest antibiotics use might not be a suitable indicator of bacterial infection to investigate the cause of MS.

Post hoc interlaboratory comparison of single particle ICP-MS size measurements of NIST gold nanoparticle reference materials.

PubMed

Montoro Bustos, Antonio R; Petersen, Elijah J; Possolo, Antonio; Winchester, Michael R

2015-09-01

Single particle inductively coupled plasma-mass spectrometry (spICP-MS) is an emerging technique that enables simultaneous measurement of nanoparticle size and number quantification of metal-containing nanoparticles at realistic environmental exposure concentrations. Such measurements are needed to understand the potential environmental and human health risks of nanoparticles. Before spICP-MS can be considered a mature methodology, additional work is needed to standardize this technique including an assessment of the reliability and variability of size distribution measurements and the transferability of the technique among laboratories. This paper presents the first post hoc interlaboratory comparison study of the spICP-MS technique. Measurement results provided by six expert laboratories for two National Institute of Standards and Technology (NIST) gold nanoparticle reference materials (RM 8012 and RM 8013) were employed. The general agreement in particle size between spICP-MS measurements and measurements by six reference techniques demonstrates the reliability of spICP-MS and validates its sizing capability. However, the precision of the spICP-MS measurement was better for the larger 60 nm gold nanoparticles and evaluation of spICP-MS precision indicates substantial variability among laboratories, with lower variability between operators within laboratories. Global particle number concentration and Au mass concentration recovery were quantitative for RM 8013 but significantly lower and with a greater variability for RM 8012. Statistical analysis did not suggest an optimal dwell time, because this parameter did not significantly affect either the measured mean particle size or the ability to count nanoparticles. Finally, the spICP-MS data were often best fit with several single non-Gaussian distributions or mixtures of Gaussian distributions, rather than the more frequently used normal or log-normal distributions.

Identification of Lactobacillus from the Saliva of Adult Patients with Caries Using Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry

PubMed Central

Ma, Qingwei; Song, Yeqing; Zhang, Qian; Wang, Xiaoyan; Chen, Feng

2014-01-01

Matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) has been presented as a superior method for the detection of microorganisms in body fluid samples (e.g., blood, saliva, pus, etc.) However, the performance of MALDI-TOF MS in routine identification of caries-related Lactobacillus isolates from saliva of adult patients with caries has not been determined. In the present study, we introduced a new MALDI-TOF MS system for identification of lactobacilli. Saliva samples were collected from 120 subjects with caries. Bacteria were isolated and cultured, and each isolate was identified by both 16S rRNA sequencing and MALDI-TOF MS. The identification results obtained by MALDI-TOF MS were concordant at the genus level with those of conventional 16S rRNA-based sequencing for 88.6% of lactobacilli (62/70) and 95.5% of non-lactobacilli (21/22). Up to 96 results could be obtained in parallel on a single MALDI target, suggesting that this is a reliable high-throughput approach for routine identification of lactobacilli. However, additional reference strains are necessary to increase the sensitivity and specificity of species-level identification. PMID:25166027

Expression of the Antioxidative Enzyme Peroxiredoxin 2 in Multiple Sclerosis Lesions in Relation to Inflammation

PubMed Central

Voigt, David; Scheidt, Uta; Derfuss, Tobias; Brück, Wolfgang; Junker, Andreas

2017-01-01

Multiple sclerosis is a chronic inflammatory disease of the central nervous system, characterized by demyelination and axonal damage as well as neuronal degeneration. Since oxygen-derived free radicals are an important factor leading to tissue damage in inflammatory multiple sclerosis (MS) lesions, research on antioxidative systems is essential to identify endogenous factors which can possibly counteract oxidative damage. As an important scavenging enzyme family, peroxiredoxins (PRDXs) play a crucial role in preventing oxidative damage; however little is known about their expression and function in MS lesions. In the present study we examined the expression of PRDX2 in white matter lesions of MS patients with long-standing, chronic disease. PRDX2 expression was investigated by immunohistochemistry in the context of oxidative stress and inflammation (determined by microglia/macrophage and T cell infiltration) in ten MS autopsy cases as well as seven control autopsy cases. PRDX2 was found to be upregulated in white matter MS lesions mainly in astrocytes, and its expression level was positively correlated with the degree of inflammation and oxidative stress. Our data suggest that PRDX2 expression contributes to the resistance of astrocytes against oxidative damage. PMID:28375164

Proteomic Biomarkers for Acute Interstitial Lung Disease in Gefitinib-Treated Japanese Lung Cancer Patients

PubMed Central

Kawakami, Takao; Nagasaka, Keiko; Takami, Sachiko; Wada, Kazuya; Tu, Hsiao-Kun; Otsuji, Makiko; Kyono, Yutaka; Dobashi, Tae; Komatsu, Yasuhiko; Kihara, Makoto; Akimoto, Shingo; Peers, Ian S.; South, Marie C.; Higenbottam, Tim; Fukuoka, Masahiro; Nakata, Koichiro; Ohe, Yuichiro; Kudoh, Shoji; Clausen, Ib Groth; Nishimura, Toshihide; Marko-Varga, György; Kato, Harubumi

2011-01-01

Interstitial lung disease (ILD) events have been reported in Japanese non-small-cell lung cancer (NSCLC) patients receiving EGFR tyrosine kinase inhibitors. We investigated proteomic biomarkers for mechanistic insights and improved prediction of ILD. Blood plasma was collected from 43 gefitinib-treated NSCLC patients developing acute ILD (confirmed by blinded diagnostic review) and 123 randomly selected controls in a nested case-control study within a pharmacoepidemiological cohort study in Japan. We generated ∼7 million tandem mass spectrometry (MS/MS) measurements with extensive quality control and validation, producing one of the largest proteomic lung cancer datasets to date, incorporating rigorous study design, phenotype definition, and evaluation of sample processing. After alignment, scaling, and measurement batch adjustment, we identified 41 peptide peaks representing 29 proteins best predicting ILD. Multivariate peptide, protein, and pathway modeling achieved ILD prediction comparable to previously identified clinical variables; combining the two provided some improvement. The acute phase response pathway was strongly represented (17 of 29 proteins, p = 1.0×10−25), suggesting a key role with potential utility as a marker for increased risk of acute ILD events. Validation by Western blotting showed correlation for identified proteins, confirming that robust results can be generated from an MS/MS platform implementing strict quality control. PMID:21799770

Effect of HeartMate left ventricular assist device on cardiac autonomic nervous activity.

PubMed

Kim, S Y; Montoya, A; Zbilut, J P; Mawulawde, K; Sullivan, H J; Lonchyna, V A; Terrell, M R; Pifarré, R

1996-02-01

Clinical performance of a left ventricular assist device is assessed via hemodynamic parameters and end-organ function. This study examined effect of a left ventricular assist device on human neurophysiology. This study evaluated the time course change of cardiac autonomic activity of 3 patients during support with a left ventricular assist device before cardiac transplantation. Cardiac autonomic activity was determined by power spectral analysis of short-term heart rate variability. The heart rate variability before cardiac transplantation was compared with that on the day before left ventricular assist device implantation. The standard deviation of the mean of the R-R intervals of the electrocardiogram, an index of vagal activity, increased to 27 +/- 7 ms from 8 +/- 0.6 ms. The modulus of power spectral components increased. Low frequency (sympathetic activity) and high frequency power (vagal activity) increased by a mean of 9 and 22 times of each baseline value (low frequency power, 5.2 +/- 3.0 ms2; high frequency power, 2.1 +/- 0.7 ms2). The low over high frequency power ratio decreased substantially, indicating an improvement of cardiac sympatho-vagal balance. The study results suggest that left ventricular assist device support before cardiac transplantation may exert a favorable effect on cardiac autonomic control in patients with severe heart failure.

Early Parallel Activation of Semantics and Phonology in Picture Naming: Evidence from a Multiple Linear Regression MEG Study

PubMed Central

Miozzo, Michele; Pulvermüller, Friedemann; Hauk, Olaf

2015-01-01

The time course of brain activation during word production has become an area of increasingly intense investigation in cognitive neuroscience. The predominant view has been that semantic and phonological processes are activated sequentially, at about 150 and 200–400 ms after picture onset. Although evidence from prior studies has been interpreted as supporting this view, these studies were arguably not ideally suited to detect early brain activation of semantic and phonological processes. We here used a multiple linear regression approach to magnetoencephalography (MEG) analysis of picture naming in order to investigate early effects of variables specifically related to visual, semantic, and phonological processing. This was combined with distributed minimum-norm source estimation and region-of-interest analysis. Brain activation associated with visual image complexity appeared in occipital cortex at about 100 ms after picture presentation onset. At about 150 ms, semantic variables became physiologically manifest in left frontotemporal regions. In the same latency range, we found an effect of phonological variables in the left middle temporal gyrus. Our results demonstrate that multiple linear regression analysis is sensitive to early effects of multiple psycholinguistic variables in picture naming. Crucially, our results suggest that access to phonological information might begin in parallel with semantic processing around 150 ms after picture onset. PMID:25005037

EIA and GC/MS analysis of 8-isoprostane in EBC of children with problematic asthma.

PubMed

Carraro, S; Cogo, P E; Isak, I; Simonato, M; Corradi, M; Carnielli, V P; Baraldi, E

2010-06-01

Asthmatic airways are characterised by enhanced oxidative stress, which can be studied by measuring biomarkers, such as 8-isoprostane. The aims of the present study were: 1) to measure the concentrations of 8-isoprostane in exhaled breath condensate (EBC) and urine of children with problematic and well-controlled asthma; 2) to compare the concentrations of 8-isoprostane measured by gas chromatographic/negative ion chemical ionisation mass spectrometry (GC/NICI-MS) and by an enzymatic immunoassay (EIA). We recruited 20 asthmatic allergic children, 13 with well-controlled asthma and seven with problematic asthma. They underwent exhaled nitric oxide measurements and spirometry, and both EBC and urine samples were collected. 8-isoprostane was measured in EBC by GC/NICI-MS and EIA. 8-isoprostane concentrations in EBC were significantly higher in children with problematic asthma than in children with well-controlled asthma (p = 0.01). An acceptable reproducibility emerged between GC/NICI-MS and EIA (coefficient of reproducibility 11.5 pg x mL(-1)). 8-isoprostane levels measured in urine did not correlate with those measured in EBC. We showed that 8-isoprostane in EBC was significantly increased in children with problematic asthma, suggesting a role for oxidative stress in this asthma phenotype. In addition we found an acceptable reproducibility of EIA compared to GC/NICI-MS, even if the latter method had higher accuracy.

Detection of protonated non-Watson-Crick base pairs using electrospray ionization mass spectrometry.

PubMed

Ishida, Riyoko; Iwahashi, Hideo

2018-03-01

Many studies have shown that protonated nucleic acid base pairs are involved in a wide variety of nucleic acid structures. However, little information is available on relative stability of hemiprotonated self- and non-self-dimers at monomer level. We used electrospray ionization mass spectrometry (ESI-MS) to evaluate the relative stability under various concentrations of hydrogen ion. These enable conjecture of the formation of protonated non-Watson-Crick base pairs based on DNA and RNA base sequence. In the present study, we observed that ESI-MS peaks corresponded to respective self-dimers for all examined nucleosides except for adenosine. Peak heights depended on the concentration of hydrogen ion. The ESI-MS peak heights of the hemiprotonated cytidine dimers and the hemiprotonated thymidine dimer sharply increased with increased concentration of hydrogen ion, suggesting direct participation of hydrogen ion in dimer formations. In ESI-MS measurements of the solutions containing adenosine, cytidine, thymidine and guanosine, we observed protonated cytidine-guanosine dimer (CH+-G) and protonated cytidine-thymidine dimer (CH+-T) in addition to hemiprotonated cytidine-cytidine dimer (CH+-C) with following relative peak height, (CH+-C) > (CH+-G) ≈ (CH+-T) > (CH+-A). Additionally, in the ESI-MS measurements of solutions containing adenosine, thymidine and guanosine, we observed a considerable amount of protonated adenosine-guanosine (AH+-G) and protonated adenosine-thymidine (AH+-T).

Goal attainment in cognitive rehabilitation in MS patients.

PubMed

Hanssen, Kjersti Træland; Saltytė Benth, Jūratė; Beiske, Antonie Giæver; Landrø, Nils Inge; Hessen, Erik

2015-01-01

The aim of the study was to investigate the predictive value of important disease-related variables on goal attainment in cognitive rehabilitation in multiple sclerosis (MS). The possible predictive value of executive functions, neurological disability, depression and general cognitive ability was assessed, employing Goal Attainment Scaling (GAS). Fifty-seven patients with MS were assessed for executive functions, neurological disability, depression and general cognitive ability, and guided through the process of formulating GAS-goals for coping with cognitive challenges in everyday life during a four week in-patient cognitive rehabilitation programme. GAS-goal attainment was scored during biweekly follow-up calls in the first three months post-discharge from the rehabilitation centre, and finally at seven months after the start of the rehabilitation. Consistent with the first study hypothesis MS patients succeeded in formulating and achieving GAS goals for coping with cognitive problems in everyday life. The patients were able to maintain a satisfactory level of goal attainment from the first measurement point after six weeks to seven months after the start of the rehabilitation. However, contrary to the second hypothesis, attainment of GAS goals was not predicted by executive functions. Neither was it predicted by neurological disability, depression or general cognitive ability. The findings suggest that GAS may be a practical and robust method in cognitive rehabilitation in MS patients, regardless of important disease-related characteristics.

Anterolateral minithoracotomy versus median sternotomy for mitral valve disease: a meta-analysis.

PubMed

Ding, Chao; Jiang, Da-ming; Tao, Kai-yu; Duan, Qun-jun; Li, Jie; Kong, Min-jian; Shen, Zhong-hua; Dong, Ai-qiang

2014-06-01

Mitral valve disease tends to be treated with anterolateral minithoracotomy (ALMT) rather than median sternotomy (MS), as ALMT uses progressively smaller incisions to promote better cosmetic outcomes. This meta-analysis quantifies the effects of ALMT on surgical parameters and post-operative outcomes compared with MS. One randomized controlled study and four case-control studies, published in English from January 1996 to January 2013, were identified and evaluated. ALMT showed a significantly longer cardiopulmonary bypass time (P=0.001) and aortic cross-clamp time (P=0.05) compared with MS. However, the benefits of ALMT were evident as demonstrated by a shorter length of hospital stay (P<0.00001). According to operative complications, the onset of new arrhythmias following ALMT decreased significantly as compared with MS (P=0.05); however, the incidence of peri-operative mortality (P=0.62), re-operation for bleeding (P=0.37), neurologic events (P=0.77), myocardial infarction (P=0.84), gastrointestinal complications (P=0.89), and renal insufficiency (P=0.67) were similar to these of MS. Long-term follow-up data were also examined, and revealed equivalent survival and freedom from mitral valve events. Current clinical data suggest that ALMT is a safe and effective alternative to the conventional approach and is associated with better short-term outcomes and a trend towards longer survival.

Anterolateral minithoracotomy versus median sternotomy for mitral valve disease: a meta-analysis

PubMed Central

Ding, Chao; Jiang, Da-ming; Tao, Kai-yu; Duan, Qun-jun; Li, Jie; Kong, Min-jian; Shen, Zhong-hua; Dong, Ai-qiang

2014-01-01

Objective: Mitral valve disease tends to be treated with anterolateral minithoracotomy (ALMT) rather than median sternotomy (MS), as ALMT uses progressively smaller incisions to promote better cosmetic outcomes. This meta-analysis quantifies the effects of ALMT on surgical parameters and post-operative outcomes compared with MS. Methods: One randomized controlled study and four case-control studies, published in English from January 1996 to January 2013, were identified and evaluated. Results: ALMT showed a significantly longer cardiopulmonary bypass time (P=0.001) and aortic cross-clamp time (P=0.05) compared with MS. However, the benefits of ALMT were evident as demonstrated by a shorter length of hospital stay (P<0.00001). According to operative complications, the onset of new arrhythmias following ALMT decreased significantly as compared with MS (P=0.05); however, the incidence of peri-operative mortality (P=0.62), re-operation for bleeding (P=0.37), neurologic events (P=0.77), myocardial infarction (P=0.84), gastrointestinal complications (P=0.89), and renal insufficiency (P=0.67) were similar to these of MS. Long-term follow-up data were also examined, and revealed equivalent survival and freedom from mitral valve events. Conclusions: Current clinical data suggest that ALMT is a safe and effective alternative to the conventional approach and is associated with better short-term outcomes and a trend towards longer survival. PMID:24903989

Abdominal massage for neurogenic bowel dysfunction in people with multiple sclerosis (AMBER - Abdominal Massage for Bowel Dysfunction Effectiveness Research): study protocol for a randomised controlled trial.

PubMed

McClurg, Doreen; Goodman, Kirsteen; Hagen, Suzanne; Harris, Fional; Treweek, Sean; Emmanuel, Anton; Norton, Christine; Coggrave, Maureen; Doran, Selina; Norrie, John; Donnan, Peter; Mason, Helen; Manoukian, Sarkis

2017-03-29

Multiple sclerosis (MS) is a life-long condition primarily affecting younger adults. Neurogenic bowel dysfunction (NBD) occurs in 50-80% of these patients and is the term used to describe constipation and faecal incontinence, which often co-exist. Data from a pilot study suggested feasibility of using abdominal massage for the relief of constipation, but the effectiveness remains uncertain. This is a multi-centred patient randomised superiority trial comparing an experimental strategy of once daily abdominal massage for 6 weeks against a control strategy of no massage in people with MS who have stated that their constipation is bothersome. The primary outcome is the Neurogenic Bowel Dysfunction Score at 24 weeks. Both groups will receive optimised advice plus the MS Society booklet on bowel management in MS, and will continue to receive usual care. Participants and their clinicians will not be blinded to the allocated intervention. Outcome measures are primarily self-reported and submitted anonymously. Central trial staff who will manage and analyse the trial data will be unaware of participant allocations. Analysis will follow intention-to-treat principles. This pragmatic randomised controlled trial will demonstrate if abdominal massage is an effective, cost-effective and viable addition to the treatment of NBD in people with MS. ClinicalTrials.gov, ISRCTN85007023 . Registered on 10 June 2014.

Identification of prohibitin 1 as a potential prognostic biomarker in human pancreatic carcinoma using modified aqueous two-phase partition system combined with 2D-MALDI-TOF-TOF-MS/MS.

PubMed

Zhong, Ning; Cui, Yazhou; Zhou, Xiaoyan; Li, Tianliang; Han, Jinxiang

2015-02-01

Membrane proteins are an important source of potential targets for anticancer drugs or biomarkers for early diagnosis. In this study, we used a modified aqueous two-phase partition system combined with two-dimensional (2D) matrix-assisted laser desorption ionization (MALDI) time of flight (TOF) mass spectrometry (MS, 2D-MALDI-TOF-TOF-MS/MS) analysis to isolate and identify membrane proteins in PANC-1 pancreatic cancer cells. Using this method, we identified 55 proteins, of which 31 (56.4 %) were membrane proteins, which, according to gene ontology annotation, are associated with various cellular processes including cell signal transduction, differentiation, and apoptosis. Immunohistochemical analysis showed that the expression level of one of the identified mitochondria membrane proteins, prohibitin 1 (PHB1), is correlated with pancreatic carcinoma differentiation; PHB1 is expressed at a higher level in normal pancreatic tissue than in well-differentiated carcinoma tissue. Further studies showed that PHB1 plays a proapoptotic role in human pancreatic cancer cells, which suggests that PHB1 has antitumorigenic properties. In conclusion, we have provided a modified method for isolating and identifying membrane proteins and demonstrated that PHB1 may be a promising biomarker for early diagnosis and therapy of pancreatic (and potentially other) cancers.

Physiological Stress Responses to Prolonged Exposure to MS-222 and Surgical Implantation in Juvenile Chinook Salmon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wagner, Katie A.; Woodley, Christa M.; Seaburg, Adam

While many studies have investigated the effects of transmitters on fish condition, behavior, and survival, to our knowledge, no studies have taken into account anesthetic exposure time in addition to tag and surgery effects. We investigated stress responses to prolonged MS-222 exposure after stage 4 induction in surgically implanted juvenile Chinook salmon (Oncorhynchus tshawytscha). Survival, tag loss, plasma cortisol concentration, and blood Na +, K +, Ca 2+, and pH were measured immediately following anesthetic exposure and surgical implantation and 1, 7, and 14 days post-treatment. Despite the prolonged anesthetic exposure, 3-15 minutes post Stage 4 induction, there were nomore » mortalities or tag loss in any treatment. MS-222 was effective at delaying immediate cortisol release during surgical implantation; however, osmotic disturbances resulted, which were more pronounced in longer anesthetic time exposures. From day 1 to day 14, Na +, Ca 2+, and pH significantly decreased, while cortisol significantly increased. The cortisol increase was exacerbated by surgical implantation. There was a significant interaction between MS-222 time exposure and observation day for Na +, Ca 2+, K +, and pH; variations were seen in the longer time exposures, although not consistently. In conclusion, stress response patterns suggest stress associated with surgical implantation is amplified with increased exposure to MS-222.« less

Magnetic properties of black mud turbidites from ODP Leg 116, distal Bengal Fan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sager, W.W.; Hall, S.A.

1991-03-01

Turbidites from the distal Bengal Fan cored on ODP Leg 116 showed large magnetic susceptibility (MS) variations. MS peaks were traced to individual turbidites, the most magnetic being dark gray mud turbidites. In addition to large MS values, the turbidites stand out from surrounding layers because of high NRMs, ARMs, SIRMs, and ratios of ARM and SIRM to susceptibility. Alternating field and thermal demagnetization properties and IRM acquisition curves suggest titanomagnetite grains as the primary magnetic mineral with some amount of hematite present. These properties are similar to those of Deccan flood basalts and suggest this formation as a sourcemore » of magnetic grains. Magnetic granulometry tests implied that the magnetic particles behave as single-domain and pseudo single-domain grains. They also indicate that the large susceptibility peaks result from a tenfold increase in the concentration of titanomagnetite grains. Electron microscope, EDX, and SIRM analyses revealed detrital titanomagnetites with typical sizes around 8-10 {mu}m, but as large as 20-25 {mu}. These are probably the dominant magnetic grains in the black mud turbidites; however, ARM and susceptibility frequency-dependence suggested that there may also be a submicrometer fraction present. Most of the observed titanomagnetite grains are tabular and some display exsolution lamellae, accounting for the pseudo single-domain behavior despite their moderate sizes. Variations in individual MS peak shapes may reflect sedimentological factors such as current velocity changes. Moreover, downhole variations in the amplitudes of turbidite MS peaks suggest a tectonic or environmental influence.« less

Quality of life in multiple sclerosis (MS) and role of fatigue, depression, anxiety, and stress: A bicenter study from north of Iran.

PubMed

Salehpoor, Ghasem; Rezaei, Sajjad; Hosseininezhad, Mozaffar

2014-11-01

Although studies have demonstrated significant negative relationships between quality of life (QOL), fatigue, and the most common psychological symptoms (depression, anxiety, stress), the main ambiguity of previous studies on QOL is in the relative importance of these predictors. Also, there is lack of adequate knowledge about the actual contribution of each of them in the prediction of QOL dimensions. Thus, the main objective of this study is to assess the role of fatigue, depression, anxiety, and stress in relation to QOL of multiple sclerosis (MS) patients. One hundred and sixty-two MS patients completed the questionnaire on demographic variables, and then they were evaluated by the Persian versions of Short-Form Health Survey Questionnaire (SF-36), Fatigue Survey Scale (FSS), and Depression, Anxiety, Stress Scale-21 (DASS-21). Data were analyzed by Pearson correlation coefficient and hierarchical regression. Correlation analysis showed a significant relationship between QOL elements in SF-36 (physical component summary and mental component summary) and depression, fatigue, stress, and anxiety (P < 0.01). Hierarchical regression analysis indicated that among the predictor variables in the final step, fatigue, depression, and anxiety were identified as the physical component summary predictor variables. Anxiety was found to be the most powerful predictor variable amongst all (β = -0.46, P < 0.001). Furthermore, results have shown depression as the only significant mental component summary predictor variable (β = -0.39, P < 0.001). This study has highlighted the role of anxiety, fatigue, and depression in physical dimensions and the role of depression in psychological dimensions of the lives of MS patients. In addition, the findings of this study indirectly suggest that psychological interventions for reducing fatigue, depression, and anxiety can lead to improved QOL of MS patients.

Prevalence and risk factors associated with the metabolic syndrome and dyslipidemia in White, Black, Amerindian and Mixed Hispanics in Zulia State, Venezuela.

PubMed

Florez, Hermes; Silva, Eglé; Fernández, Virginia; Ryder, Elena; Sulbarán, Tulio; Campos, Gilberto; Calmón, Gustavo; Clavel, Emilio; Castillo-Florez, Sumaya; Goldberg, Ronald

2005-07-01

Studies have highlighted the association between insulin resistance (IR) and several cardiovascular (CV) risk factors, including hypertension (HTN), obesity, dyslipidemia (i.e. high triglyceride and low HDL-cholesterol) and glucose intolerance, in a cluster known as the metabolic syndrome (MS). There are few data on the frequency of the MS and dyslipidemia in developing countries, and none in South America. To estimate the prevalence of the MS and its components in Zulia State, Venezuela, and to establish associated demographic and clinical factors, we evaluated 3108 Hispanic men and women aged 20 years or older from a cross-sectional survey of a random representative sample from each health district in Zulia State, Venezuela (1999-2001). Prevalence of the MS and dyslipidemia was defined according to the National Cholesterol Education Program (NCEP)/Adult Treatment Panel III (ATP III) criteria. The age-adjusted prevalence of MS and dyslipidemia was 31.2% and 24.1%, respectively, with higher rates in men than in women. Prevalence rates increased with age and with the degree of obesity. MS prevalence was lower in Amerindian (17.%) compared to Black (27.2%), White (33.3%) and Mixed (37.4%) men, but no differences were found among women. Overall, low HDL-cholesterol (65.3%), abdominal obesity (42.9%) and HTN (38.1%) were the most frequent MS components. After adjusting for age, sex and race groups, family history of diabetes, obesity and HTN were associated with the MS. Sedentary lifestyle also increased the risk of MS, event after adjusting for the same covariates, obesity and the degree of IR. These results suggest that MS is found in approximately one-third of the Venezuelan adult population in Zulia State, with higher prevalence in men related to the presence of dyslipidemia. Lifestyle interventions in MS subjects are needed in Venezuela to halt the burden of CV disease and diabetes.

Adolescence fluoxetine increases serotonergic activity in the raphe-hippocampus axis and improves depression-like behaviors in female rats that experienced neonatal maternal separation.

PubMed

Yoo, Sang Bae; Kim, Bom-Taeck; Kim, Jin Young; Ryu, Vitaly; Kang, Dong-Won; Lee, Jong-Ho; Jahng, Jeong Won

2013-06-01

This study was conducted to examine if fluoxetine, a selective 5-hydroxytryptamine (5-HT) reuptake inhibitor, would reverse adverse behavioral effects of neonatal maternal separation in female rats. Sprague-Dawley pups were separated from dam daily for 3h during postnatal day (PND) 1-14 (maternal separation; MS) or left undisturbed (non-handled; NH). Female NH and MS pups received intraperitoneal injection of fluoxetine (10mg/kg) or vehicle daily from PND 35 until the end of the whole experimental period. Rats were either subjected to behavioral tests during PND 44-54, or sacrificed for neurochemical analyses during PND 43-45. Daily food intake and weight gain of both NH and MS pups were suppressed by fluoxetine, with greater effects in MS pups. MS experience increased immobility and decrease swimming in forced swim test. Swimming was increased, although immobility was not significantly decreased, in MS females by adolescence fluoxetine. However, adolescence fluoxetine increased immobility during forced swim test and decreased time spent in open arms during elevated plus maze test in NH females. Fluoxetine normalized MS-induced decrease of the raphe 5-HT levels and increased 5-HT metabolism in the hippocampus in MS females, and increased the hypothalamic 5-HT both in NH and MS. Fluoxetine decreased the raphe 5-HT and increased the plasma corticosterone in NH females. Results suggest that decreased 5-HTergic activity in the raphe nucleus is implicated in the pathophysiology of depression-like behaviors, and increased 5-HTergic activities in the raphe-hippocampus axis may be a part of anti-depressant efficacy of fluoxetine, in MS females. Also, an extra-hypothalamic 5-HTergic activity may contribute to the increased anorectic efficacy of fluoxetine in MS females. Additionally, decreased 5-HT in the raphe and elevated plasma corticosterone may be related with fluoxetine-induced depression- and/or anxiety-like behaviors in NH females. Copyright © 2012 Elsevier Ltd. All rights reserved.

Brain activation patterns and cognitive processing speed in patients with pediatric-onset multiple sclerosis.

PubMed

Akbar, Nadine; Banwell, Brenda; Sled, John G; Binns, Malcolm A; Doesburg, Sam M; Rypma, Bart; Lysenko, Magdalena; Till, Christine

2016-01-01

This study aimed to determine the extent and pattern of brain activation elicited by a functional magnetic resonance imaging version of the Symbol Digit Modalities Test (fMRI-SDMT), a task of information processing speed, in pediatric-onset multiple sclerosis (MS) patients as compared to sex- and age-matched non-MS self-reported healthy individuals. Participants included 20 right-handed individuals aged 13-24 years with pediatric-onset MS (mean age = 19 years, 15 female) and 16 non-MS self-reported healthy individuals. All participants underwent a 3.0-tesla MRI scan with structural (T1; T2; proton density, PD; fluid-attenuated inversion recovery, FLAIR) and fMRI-SDMT acquisition. Participants were instructed to indicate with a button press whether a single pairing of a symbol to a number matched any of those shown in a key that displays nine possible pairings. Response time (p = .909) and accuracy (p = .832) on the fMRI-SDMT did not differ between groups. However, the MS group demonstrated lower overall activation than the non-MS group in the right middle frontal gyrus (p = .003). Within the MS group, faster response time was associated with greater activation of the right inferior occipital, anterior cingulate, right superior parietal, thalamus, and left superior occipital cortices (all p < .05). A significant interaction effect was demonstrated, indicating that faster response time was associated with greater activation of the left superior occipital region in the pediatric MS group than in the non-MS group (p = .002). Attenuated activation of frontal regions was observed in this cohort of pediatric-onset MS patients when performing the fMRI-SDMT, even in the absence of behaviorally detectable deficits. Within the MS group only, faster response time elicited greater activation, suggesting this to be an adaptive mechanism that may contribute to limiting the impact of disease-related structural pathology.

Behçet's disease patients with multiple sclerosis-like features: discriminative value of Barkhof criteria.

PubMed

Akman-Demir, Gulsen; Mutlu, Melike; Kiyat-Atamer, Asli; Shugaiv, Erkingul; Kurtuncu, Murat; Tugal-Tutkun, Ilknur; Tuzun, Erdem; Eraksoy, Mefkure; Bahar, Sara

2015-01-01

Behçet's disease (BD) is a systemic auto-inflammatory disorder of unknown cause, which may affect the central nervous system in around 5% of the patients [neuro-BD (NBD)], usually causing large lesions encompassing brainstem, diencephalon and basal ganglia regions. Occasionally NBD patients present with white matter lesions necessitating differential diagnosis from multiple sclerosis (MS). In this study, the efficacy of Barkhof criteria was tested in diagnostic differentiation of NBD and MS. Charts and MRIs of 84 NBD patients were retrospectively evaluated. Clinical and radiological features of NBD patients fulfilling (Barkhof+) and not fulfilling Barkhof criteria (Barkhof-) were compared. While the Barkhof- patients (n=73) mostly displayed typical large lesions covering brainstem, diencephalon and basal ganglia regions and neurological findings consistent with brainstem involvement, all Barkhof+ (n=11) patients demonstrated MS-like white matter lesions, fulfilled McDonald's criteria and showed reduced frequency of brainstem symptoms and increased frequency of hemiparesis, hemihypesthesia and spinal cord symptoms. Moreover, the Barkhof+ group had more female patients, increased number of attacks, higher rate of oligoclonal band positivity and less patients with cerebrospinal fluid pleocytosis. A subgroup of BD patients with neurological complaints displays MS-like lesions, fulfills the clinical and radiological criteria of MS and presents with clinical and laboratory features resembling those of MS rather than NBD. These results suggest that Barkhof+ patients are either an overlapping group between NBD and MS, or they represent MS patients with concomitant systemic findings of BD, rather than NBD. Barkhof criteria appear to be effective in discriminating these patients.

How proprioceptive impairments affect quiet standing in patients with multiple sclerosis.

PubMed

Rougier, P; Faucher, M; Cantalloube, S; Lamotte, D; Vinti, M; Thoumie, P

2007-01-01

To assess if multiple sclerosis patients with proprioceptive impairment are specifically affected during quiet standing with eyes open and how they can develop motor compensatory processes, 56 patients, classified from sensory clinical tests as ataxo-spastic (MS-AS) or only having spasticity (MS-S), were compared to 23 healthy adults matched for age. The postural strategies were assessed from the centre-of-pressure trajectories (CP), measured from a force platform in the eyes open standing condition for a single trial lasting 51.2 s. The vertical projection of the centre of gravity (CGv) and its vertical difference from the CP (CP-CGv) were then estimated through a biomechanical relationship. These two movements permit the characterization of the postural performance and the horizontal acceleration communicated to the CG and from that, the global energy expenditure, respectively. Both MS-AS and MS-S groups demonstrate larger CGv and CP-CGv movements than healthy individuals of the same age. Whilst similar CGv values are noticed in both MS subgroups, suggesting similar postural performances, statistically significant differences are observed for the CP-CGv component. Biomechanically, this feature expresses the necessity for the MS-AS group to develop augmented neuro-muscular means to control their body movements, as compared to the MS-S group. By demonstrating for both groups of patients similar postural performance accompanied by a varying degree of energy expenditure to maintain undisturbed upright stance, this study reveals that MS-AS patients which are affected by proprioceptive loss can compensate for this deficit with more efficient control strategies, when standing still with their eyes open.

Epstein-Barr virus in oral shedding of children with multiple sclerosis

PubMed Central

Yea, Carmen; Tellier, Raymond; Chong, Patrick; Westmacott, Garrett; Marrie, Ruth Ann; Bar-Or, Amit

2013-01-01

Objective: To investigate Epstein-Barr virus (EBV) oral shedding frequency and EBV genetic diversity in pediatric patients with multiple sclerosis (MS). Methods: This was a prospective case-control study. We used PCR-based assays to detect viral DNA in the monthly mouth swabs of 22 pediatric patients with MS and 77 age- and sex-matched healthy controls. EBV-positive samples were further analyzed for sequence variation in the EBV BCRF1 (ebvIL-10) gene using direct DNA sequencing methods, and in the EBV LMP1 gene by mass spectrometry. Results: Nineteen of the 22 (86.4%) children with MS were seropositive for remote EBV infection compared to 35 out of 77 (45.5%) healthy controls (p = 0.008). Baseline analysis of mouth swabs revealed a higher proportion of EBV-positive samples from EBV-seropositive patients with MS compared to EBV-seropositive healthy controls (52.6% vs 20%, p = 0.007). Longitudinal analysis of monthly swabs revealed average EBV detection rates of 50.6% in patients with MS and 20.4% in controls (p = 0.01). The oral shedding frequencies of Herpesviruses herpes simplex virus–1, cytomegalovirus, human herpesvirus (HHV)-6, and HHV-7 did not differ between groups. Changes in the predominant EBV genetic variants were detected more frequently in patients with MS; however, no specific EBV genetic variant was preferentially associated with MS. Conclusion: Children with MS demonstrate abnormally increased rates of EBV viral reactivation and a broader range of genetic variants, suggesting a selective impairment in their immunologic control of EBV. PMID:24014504

Molecular cloning and characterization of the MsHSP17.7 gene from Medicago sativa L.

PubMed

Li, Zhen-Yi; Long, Rui-Cai; Zhang, Tie-Jun; Yang, Qing-Chuan; Kang, Jun-Mei

2016-08-01

Heat shock proteins (HSPs) are ubiquitous protective proteins that play crucial roles in plant development and adaptation to stress, and the aim of this study is to characterize the HSP gene in alfalfa. Here we isolated a small heat shock protein gene (MsHSP17.7) from alfalfa by homology-based cloning. MsHSP17.7 contains a 477-bp open reading frame and encodes a protein of 17.70-kDa. The amino acid sequence shares high identity with MtHSP (93.98 %), PsHSP17.1 (83.13 %), GmHSP17.9 (74.10 %) and SlHSP17.6 (79.25 %). Phylogenetic analysis revealed that MsHSP17.7 belongs to the group of cytosolic class II small heat shock proteins (sHSP), and likely localizes to the cytoplasm. Quantitative RT-PCR indicated that MsHSP17.7 was induced by heat shock, high salinity, peroxide and drought stress. Prokaryotic expression indicated that the salt and peroxide tolerance of Escherichia coli was remarkably enhanced. Transgenic Arabidopsis plants overexpressing MsHSP17.7 exhibited increased root length of transgenic Arabidopsis lines under salt stress compared to the wild-type line. The malondialdehyde (MDA) levels in the transgenic lines were significantly lower than in wild-type, although proline levels were similar between transgenic and wild-type lines. MsHSP17.7 was induced by heat shock, high salinity, oxidative stress and drought stress. Overexpression analysis suggests that MsHSP17.7 might play a key role in response to high salinity stress.

The effectiveness of the Permission, Limited Information, Specific suggestions, Intensive Therapy (PLISSIT) model based sexual counseling on the sexual function of women with Multiple Sclerosis who are sexually active.

PubMed

Khakbazan, Zohreh; Daneshfar, Fatemeh; Behboodi-Moghadam, Zahra; Nabavi, Seyed Massood; Ghasemzadeh, Sogand; Mehran, Abbas

2016-07-01

This study was conducted to evaluate the effectiveness of sexual counseling based on the Permission, Limited Information, Specific Suggestion, Intensive Therapy (PLISSIT) model on the Sexual Dysfunction (SD) of married sexually active women who suffer from Multiple Sclerosis (MS). This is the first sexual intervention applied by a midwife as a health professional on MS patients in Iran where the cultural and religious limitations are important challenging issues. This randomized clinical trial was carried out in Iranian Community of Support for MS Patients in Tehran, Iran. The participating women who had a definite diagnosis of MS and SD, Expanded Disability Status Scale (EDSS) scores <7, and aged 18-55 years were randomly assigned to experimental (EG, n=43) and control group (CG, n=45). Participants in the EG group received 4 weekly sexual counseling sessions based on the PLISSIT model (90-120min per session). Sexual function was assessed three times (before the intervention, and 2 months and 3 months after the intervention) using the Female Sexual Function Index (FSFI). Chi-square test, Fisher's exact test, and Repeated Measures ANOVA were employed to analyze the data. The mean total FSFI score of the women in EG improved at 2 and 3 months after the intervention when it was compared with the FSFI score before the intervention (p<0.05). There was no significant difference in the total FSFI score when the data of 3 evaluations was compared in CG. A significant increase in the mean score of 6 subgroups was seen in EG (p<0.05) but not in CG. According to this study, utilizing the PLISSIT model as a framework for sexual counseling can improve sexual function in women who are sexually active and suffer from SD due to MS. Copyright © 2016 Elsevier B.V. All rights reserved.

Intensive social cognitive treatment (can do treatment) with participation of support partners in persons with relapsing remitting multiple sclerosis: observation of improved self-efficacy, quality of life, anxiety and depression 1 year later.

PubMed

Jongen, Peter Joseph; Heerings, Marco; Ruimschotel, Rob; Hussaarts, Astrid; Duyverman, Lotte; van der Zande, Anneke; Valkenburg-Vissers, Joyce; van Droffelaar, Maarten; Lemmens, Wim; Donders, Rogier; Visser, Leo H

2016-07-29

In persons with multiple sclerosis (MS) self-efficacy positively affects health-related quality of life (HRQoL) and physical activity. In a previous study we observed that 6 months after an intensive 3-day social cognitive treatment (Can Do treatment) with the participation of support partners, self-efficacy and HRQoL had improved in persons with relapsing remitting MS (RRMS). Given the chronic nature of the disease, it is important to know whether these beneficial changes may last. Can Do treatment was given to 60 persons with MS and their support partners. At baseline and 12 months after treatment self-efficacy control, self-efficacy function, physical and mental HRQoL, anxiety, depression and fatigue were assessed via self-report questionnaires. Differences were tested via a paired t test. Of the 57 persons with MS that completed the baseline assessment and the 3-day treatment, 38 filled in the 12th month questionnaires (response rate 66.7 %), 22 with RRMS and 14 with progressive MS. In the RR group self-efficacy control had increased by 20.2 % and physical HRQoL by 15.0 %, and depression and anxiety had decreased by 29.8 and 25.9 %, respectively (all P < 0.05); the changes in mental HRQoL (+17 %) and fatigue (-20 %) failed to be statistically significant (P = 0.087, P = 0.080, respectively). In the progressive group no changes suggestive of improvement were seen. The findings suggest that a 3-day intensive social cognitive treatment (Can Do treatment) with the participation of support partners may have long lasting beneficial effects on the self-efficacy and HRQoL in persons with RRMS; and that improvements in anxiety and depression, not seen in the 6-month study, may yet develop at 12 months.

Brain atrophy and lesion load measures over 1 year relate to clinical status after 6 years in patients with clinically isolated syndromes.

PubMed

Di Filippo, M; Anderson, V M; Altmann, D R; Swanton, J K; Plant, G T; Thompson, A J; Miller, D H

2010-02-01

Conventional MRI lesion measures modestly predict long term disability in some clinically isolated syndrome (CIS) studies. Brain atrophy suggests neuroaxonal loss in multiple sclerosis (MS) with the potential to reflect disease progression to a greater extent than lesion measures. To investigate whether brain atrophy and lesion load, during the first year in patients presenting with CIS, independently predict clinical outcome (development of MS and disability at 6 years). 99 patients presenting with CIS were included in the study. T1 gadolinium enhanced and T2 weighted brain MRI was acquired at baseline and approximately 1 year later. Percentage brain atrophy rate between baseline and follow-up scans was analysed using SIENA. Mean annual brain atrophy rates were -0.38% for all patients, -0.50% in patients who had developed MS at 6 years and -0.26% in those who had not. Brain atrophy rate (p = 0.005) and baseline T2 lesion load (p<0.001) were independent predictors of clinically definite MS. While brain atrophy rate was a predictor of Expanded Disability Status Scale (EDSS) score in a univariate analysis, only 1 year T2 lesion load change (p = 0.007) and baseline gadolinium enhancing lesion number (p = 0.03) were independent predictors of EDSS score at the 6 year follow-up. T1 lesion load was the only MRI parameter which predicted Multiple Sclerosis Functional Composite score at the 6 year follow-up. The findings confirm that brain atrophy occurs during the earliest phases of MS and suggest that 1 year longitudinal measures of MRI change, if considered together with baseline MRI variables, might help to predict clinical status 6 years after the first demyelinating event in CIS patients, better than measurements such as lesion or brain volumes on baseline MRI alone.

No Difference on Quantitative Magnetic Resonance Imaging in Patellofemoral Cartilage Composition Between Patients With Patellofemoral Pain and Healthy Controls.

PubMed

van der Heijden, Rianne A; Oei, Edwin H G; Bron, Esther E; van Tiel, Jasper; van Veldhoven, Peter L J; Klein, Stefan; Verhaar, Jan A N; Krestin, Gabriel P; Bierma-Zeinstra, Sita M A; van Middelkoop, Marienke

2016-05-01

Retropatellar cartilage damage has been suggested as an etiological factor for patellofemoral pain (PFP), a common knee condition among young and physically active individuals. To date, there is no conclusive evidence for an association between cartilage defects and PFP. Nowadays, advanced quantitative magnetic resonance imaging (MRI) techniques enable estimation of cartilage composition. To investigate differences in patellofemoral cartilage composition between patients with PFP and healthy control subjects using quantitative MRI. Cross-sectional study; Level of evidence, 3. Patients with PFP and healthy control subjects underwent 3.0-T MRI including delayed gadolinium-enhanced MRI of cartilage and T1ρ and T2 mapping. Differences in relaxation times of patellofemoral cartilage were compared between groups by linear regression analyses, adjusted for age, body mass index, sex, sports participation, and time of image acquisition. This case-control study included 64 patients and 70 controls. The mean (±SD) age was 23.2 ± 6.4 years and the mean body mass index was 22.9 ± 3.4 kg/m(2); 56.7% were female. For delayed gadolinium-enhanced MRI of cartilage, the mean T1GD relaxation times of patellar (657.8 vs 669.4 ms) and femoral cartilage (661.6 vs 659.8 ms) did not significantly differ between patients and controls. In addition, no significant difference was found in mean T1ρ relaxation times of patellar (46.9 vs 46.0 ms) and femoral cartilage (50.8 vs 50.2 ms) and mean T2 relaxation times of patellar (33.2 vs 32.9 ms) and femoral cartilage (36.7 vs 36.6 ms) between patients and controls. Analysis of prespecified medial and lateral subregions within the patellofemoral cartilage also revealed no significant differences. There was no difference in composition of the patellofemoral cartilage, estimated with multiple quantitative MRI techniques, between patients with PFP and healthy control subjects. However, clinically relevant differences could not be ruled out for T1ρ in the adolescent population. Retropatellar cartilage damage has long been hypothesized as an important factor in the pathogenesis of PFP, but study findings suggest that diminished patellofemoral cartilage composition is not associated with PFP. © 2016 The Author(s).

Diagnostic Criteria, Classification and Treatment Goals in Multiple Sclerosis: The Chronicles of Time and Space.

PubMed

Ntranos, Achilles; Lublin, Fred

2016-10-01

Multiple sclerosis (MS) is one of the most diverse human diseases. Since its first description by Charcot in the nineteenth century, the diagnostic criteria, clinical course classification, and treatment goals for MS have been constantly revised and updated to improve diagnostic accuracy, physician communication, and clinical trial design. These changes have improved the clinical outcomes and quality of life for patients with the disease. Recent technological and research breakthroughs will almost certainly further change how we diagnose, classify, and treat MS in the future. In this review, we summarize the key events in the history of MS, explain the reasoning behind the current criteria for MS diagnosis, classification, and treatment, and provide suggestions for further improvements that will keep enhancing the clinical practice of MS.

Independent genetic control of early and late stages of chemically induced skin tumors in a cross of a Japanese wild-derived inbred mouse strain, MSM/Ms.

PubMed

Okumura, Kazuhiro; Sato, Miho; Saito, Megumi; Miura, Ikuo; Wakana, Shigeharu; Mao, Jian-Hua; Miyasaka, Yuki; Kominami, Ryo; Wakabayashi, Yuichi

2012-11-01

MSM/Ms is an inbred mouse strain derived from a Japanese wild mouse, Mus musculus molossinus. In this study, we showed that MSM/Ms mice exhibit dominant resistance when crossed with susceptible FVB/N mice and subjected to the two-stage skin carcinogenesis protocol using 7,12-dimethylbenz(a)anthracene (DMBA)/ 12-O-tetradecanoylphorbol-13-acetate (TPA). A series of F1 backcross mice were generated by crossing p53(+/+) or p53(+/-) F1 (FVB/N × MSM/Ms) males with FVB/N female mice. These generated 228 backcross animals, approximately half of which were p53(+/-), enabling us to search for p53-dependent skin tumor modifier genes. Highly significant linkage for papilloma multiplicity was found on chromosomes 6 and 7 and suggestive linkage was found on chromosomes 3, 5 and 12. Furthermore, in order to identify stage-dependent linkage loci we classified tumors into three categories (<2mm, 2-6mm and >6mm), and did linkage analysis. The same locus on chromosome 7 showed strong linkage in groups with <2mm or 2-6mm papillomas. No linkage was detected on chromosome 7 to papillomas >6mm, but a different locus on chromosome 4 showed strong linkage both to papillomas >6mm and to carcinomas. This locus, which maps near the Cdkn2a/p19(Arf) gene, was entirely p53-dependent, and was not seen in p53 (+/-) backcross animals. Suggestive linkage conferring susceptibility to carcinoma was also found on chromosome 5. These results clearly suggest distinct loci regulate each stage of tumorigenesis, some of which are p53-dependent.

Differentiation of subsequent memory effects between retrieval practice and elaborative study.

PubMed

Liu, Yi; Rosburg, Timm; Gao, Chuanji; Weber, Christine; Guo, Chunyan

2017-07-01

Retrieval practice enhances memory retention more than re-studying. The underlying mechanisms of this retrieval practice effect have remained widely unclear. According to the elaborative retrieval hypothesis, activation of elaborative information occurs to a larger extent during testing than re-studying. In contrast, the episodic context account has suggested that recollecting prior episodic information (especially the temporal context) contributes to memory retention. To adjudicate the distinction between these two accounts, the present study used the classical retrieval practice effect paradigm to compare retrieval practice and elaborative study. In an initial behavioral experiment, retrieval practice produced greater retention than elaboration and re-studying in a one-week delayed test. In a subsequent event-related potential (ERP) experiment, retrieval practice resulted in reliably superior accuracy in the delayed test compared to elaborative study. In the ERPs, a frontally distributed subsequent memory effect (SME), starting at 300ms, occurred in the elaborative study condition, but not in the retrieval practice condition. A parietal SME emerged in the retrieval practice condition from 500 to 700ms, but was absent in the elaborative study condition. After 700ms, a late SME was present in the retrieval practice condition, but not in the elaborative study condition. Moreover, SMEs lasted longer in retrieval practice than in elaboration. The frontal SME in the elaborative study condition might be related to semantic processing or working memory-based elaboration, whereas the parietal and widespread SME in the retrieval practice condition might be associated with episodic recollection processes. These findings contradict the elaborative retrieval theory, and suggest that contextual recollection rather than activation of semantic information contributes to the retrieval practice effect, supporting the episodic context account. Copyright © 2017. Published by Elsevier B.V.

Tracking near-surface atmospheric conditions using an infrasound network.

PubMed

Marcillo, O; Johnson, J B

2010-07-01

Continuous volcanic infrasound signal was recorded on a three-microphone network at Kilauea in July 2008 and inverted for near-surface horizontal winds. Inter-station phase delays, determined by signal cross-correlation, vary by up to 4% and are attributable to variable atmospheric conditions. The results suggest two predominant weather regimes during the study period: (1) 6-9 m/s easterly trade winds and (2) lower-intensity 2-5 m/s mountain breezes from Mauna Loa. The results demonstrate the potential of using infrasound for tracking local averaged meteorological conditions, which has implications for modeling plume dispersal and quantifying gas flux.

Lexical access and evoked traveling alpha waves.

PubMed

Zauner, Andrea; Gruber, Walter; Himmelstoß, Nicole Alexandra; Lechinger, Julia; Klimesch, Wolfgang

2014-05-01

Retrieval from semantic memory is usually considered within a time window around 300-600ms. Here we suggest that lexical access already occurs at around 100ms. This interpretation is based on the finding that semantically rich and frequent words exhibit a significantly shorter topographical latency difference between the site with the shortest P1 latency (leading site) and that with the longest P1 latency (trailing site). This latency difference can be described in terms of an evoked traveling alpha wave as was already shown in earlier studies. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Tissue engineering scaffolds of mesoporous magnesium silicate and poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) composite.

PubMed

He, Dawei; Dong, Wei; Tang, Songchao; Wei, Jie; Liu, Zhenghui; Gu, Xiaojiang; Li, Ming; Guo, Han; Niu, Yunfei

2014-06-01

Mesoporous magnesium silicate (m-MS) and poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL) composite scaffolds were fabricated by solvent-casting and particulate leaching method. The results suggested that the incorporation of m-MS into PCL-PEG-PCL could significantly improve the water adsorption of the m-MS/PCL-PEG-PCL composite (m-MPC) scaffolds. The in vitro degradation behavior of m-MPC scaffolds were determined by testing weight loss of the scaffolds after soaking into phosphate buffered saline (PBS), and the result showed that the degradation of m-MPC scaffolds was obviously enhanced by addition of m-MS into PCL-PEG-PCL after soaking for 10 weeks. Proliferation of MG63 cells on m-MPC was significantly higher than MPC scaffolds at 4 and 7 days. ALP activity on the m-MPC was obviously higher than MPC scaffolds at 7 days, revealing that m-MPC could promote cell differentiation. Histological evaluation showed that the introduction of m-MS into PCL-PEG-PCL enhanced the efficiency of new bone formation when the m-MPC scaffolds implanted into bone defect of rabbits. The results suggested that the inorganic/organic composite of m-MS and PCL-PEG-PCL scaffolds exhibited good biocompatibility, degradability and osteogenesis.

Cannabis use by individuals with multiple sclerosis: effects on specific immune parameters.

PubMed

Sexton, Michelle; Cudaback, Eiron; Abdullah, Rehab A; Finnell, John; Mischley, Laurie K; Rozga, Mary; Lichtman, Aron H; Stella, Nephi

2014-10-01

Cannabinoids affect immune responses in ways that may be beneficial for autoimmune diseases. We sought to determine whether chronic Cannabis use differentially modulates a select number of immune parameters in healthy controls and individuals with multiple sclerosis (MS cases). Subjects were enrolled and consented to a single blood draw, matched for age and BMI. We measured monocyte migration isolated from each subject, as well as plasma levels of endocannabinoids and cytokines. Cases met definition of MS by international diagnostic criteria. Monocyte cell migration measured in control subjects and individuals with MS was similarly inhibited by a set ratio of phytocannabinoids. The plasma levels of CCL2 and IL17 were reduced in non-naïve cannabis users irrespective of the cohorts. We detected a significant increase in the endocannabinoid arachidonoylethanolamine (AEA) in serum from individuals with MS compared to control subjects, and no significant difference in levels of other endocannabinoids and signaling lipids irrespective of Cannabis use. Chronic Cannabis use may affect the immune response to similar extent in individuals with MS and control subjects through the ability of phytocannabinoids to reduce both monocyte migration and cytokine levels in serum. From a panel of signaling lipids, only the levels of AEA are increased in individuals with MS, irrespective of Cannabis use or not. Our results suggest that both MS cases and controls respond similarly to chronic Cannabis use with respect to the immune parameters measured in this study.

The computer-based Symbol Digit Modalities Test: establishing age-expected performance in healthy controls and evaluation of pediatric MS patients.

PubMed

Bigi, Sandra; Marrie, R A; Till, C; Yeh, E A; Akbar, N; Feinstein, A; Banwell, B L

2017-04-01

Decreased information processing speed (IPS) is frequently reported in pediatric multiple sclerosis (MS) patients. The computerized version of the Symbol Digit Modalities Test (c-SDMT) measures IPS over eight consecutive trials per session and additionally captures changes in performance within the session. Here, we establish normative c-SDMT performance and test-retest reliability in healthy children (HC) and explore differences in the overall c-SDMT-performance between HC and MS patients. This cross-sectional study included 478 HC (237 female, 49.5%) divided into five age groups (2 years each), and 27 MS patients (22 female, 81.5%) aged 8-18 years. The average time to complete the c-SDMT increased with age (|r| 0.70, 95% CI -0.74, -0.64). Test-retest reliability was high (ICC = 0.91) in HC. The total time to complete the c-SDMT did not differ between children with MS and sex- and age- matched HC (p = 0.23). However, MS patients were less likely to show faster performance across all the successive eight trials compared to HC (p = 0.0001). Healthy children demonstrate faster IPS with increasing age, as well as during successive trials of the c-SDMT. The inability of pediatric MS patients to maintain the increase in processing speed over successive trials suggests a reduced capacity for procedural learning, possibly resulting from cognitive fatigue.

The relationship between extracurricular activities assessed during selection and during medical school and performance.

PubMed

Urlings-Strop, Louise C; Themmen, Axel P N; Stegers-Jager, Karen M

2017-05-01

Several medical schools include candidates' extracurricular activities in their selection procedure, with promising results regarding their predictive value for achievement during the clinical years of medical school. This study aims to reveal whether the better achievement in clinical training of students selected on the basis of their extracurricular activities could be explained by persistent participation in extracurricular activities during medical school (msECAs). Lottery-admitted and selected student admission groups were compared on their participation in three types of msECAs: (1) research master, (2) important board positions or (3) additional degree programme. Logistic regression was used to measure the effect of admission group on participation in any msECA, adjusted for pre-university GPA. Two-way ANCOVA was used to examine the inter-relationships between admission group, participation in msECAs and clerkship grade, with pre-university GPA as covariate. Significantly more selected students compared to lottery-admitted students participated in any msECA. Participation in msECAs was associated with a higher pre-university GPA for lottery-admitted students only, whereas participation in msECAs was associated with higher clerkship grades for selected students only. These results suggest that persistent participation in extracurricular activities of selected students favours better clinical achievement, supporting the inclusion of ECAs in the selection procedure. More insight in the rationale behind participation in extracurricular activities during medical school may explain differences found between lottery-admitted and selected students.

CANNABIS USE BY INDIVIDUALS WITH MULTIPLE SCLEROSIS: EFFECTS ON SPECIFIC IMMUNE PARAMETERS

PubMed Central

Sexton, Michelle; Cudaback, Eiron; Abdullah, Rehab A.; Finnell, John; Mischley, Laurie K; Rozga, Mary; Lichtman, Aron H.; Stella, Nephi

2014-01-01

Cannabinoids affect immune responses in ways that may be beneficial for autoimmune diseases. We sought to determine whether chronic Cannabis use differentially modulates a select number of immune parameters in healthy controls and individuals with multiple sclerosis (MS cases). Subjects were enrolled and consented to a single blood draw, matched for age and BMI. We measured monocyte migration isolated from each subject, as well as plasma levels of endocannabinoids and cytokines. Cases met definition of MS by international diagnostic criteria. Monocyte cell migration measured in control subjects and individuals with MS were similarly inhibited by a set ratio of phytocannabinoids. The plasma levels of CCL2 and IL17 were reduced in non-naïve cannabis users irrespective of the cohorts. We detected a significant increase in the endocannabinoid arachidonoylethanolamine (AEA) in serum from individuals with MS compared to control subjects, and no significant difference in levels of other endocannabinoids and signaling lipids irrespective of Cannabis use. Chronic Cannabis use may affect the immune response to similar extent in individuals with MS and control subjects through the ability of phytocannabinoids to reduce both monocyte migration and cytokine levels in serum. From a panel of signaling lipids, only the levels of AEA are increased in individuals with MS, irrespective from Cannabis use or not. Our results suggest that both MS cases and controls respond similarly to chronic Cannabis use with respect to the immune parameters measured in this study. PMID:25135301

Preclinical and early clinical development of GNbAC1, a humanized IgG4 monoclonal antibody targeting endogenous retroviral MSRV-Env protein

PubMed Central

Curtin, François; Perron, Hervé; Kromminga, Arno; Porchet, Hervé; Lang, Alois B

2015-01-01

Monoclonal antibodies (mAbs) play an increasing important role in the therapeutic armamentarium against multiple sclerosis (MS), an inflammatory and degenerative disorder of the central nervous system. Most of the mAbs currently developed for MS are immunomodulators blocking the inflammatory immune process. In contrast with mAbs targeting immune function, GNbAC1, a humanized IgG4 mAb, targets the multiple sclerosis associated retrovirus envelope (MSRV-Env) protein, an upstream factor in the pathophysiology of MS. MSRV-Env protein is of endogenous retroviral origin, expressed in MS brain lesions, and it is pro-inflammatory and toxic to the remyelination process, by preventing the differentiation of oligodendrocyte precursor cells. We present the preclinical and early clinical development results of GNbAC1. The specificity of GNbAC1 for its endogenous retroviral target is described. Efficacy of different mAb versions of GNbAC1 were assessed in MSRV-Env induced experimental allergic encephalitis (EAE), an animal model of MS. Because the target MSRV-Env is not expressed in animals, no relevant animal model exists for a proper in vivo toxicological program. An off-target 2-week toxicity study in mice was thus performed, and it showed an absence of safety risk. Additional in vitro analyses showed an absence of complement or antibody-dependent cytotoxicity as well as a low level of cross-reactivity to human tissues. The first-in-man clinical study in 33 healthy subjects and a long-term clinical study in 10 MS patients showed that GNbAC1 is well tolerated in humans without induction of immunogenicity and that it induces a pharmacodynamic response on MSRV biomarkers. These initial results suggest that the mAb GNbAC1 could be a safe long-term treatment for patients with MS with a unique therapeutic mechanism of action. PMID:25427053

Prevalence of metabolic syndrome in a north Indian hospital-based population with obstructive sleep apnoea

PubMed Central

Agrawal, Swastik; Sharma, Surendra K.; Sreenivas, Vishnubhatla; Lakshmy, Ramakrishnan

2011-01-01

Background & objectives: Obstructive sleep apnoea (OSA) is known to be associated with cardiovascular risk factors and metabolic syndrome (MS). The burden of MS in patients with OSA in India is unknown. We investigated the prevalence of MS and its components in a cross-sectional study in patients with and without OSA in a hospital-based population of a tertiary health care centre in New Delhi, India. Methods: Consecutive patients undergoing overnight polysomnography in the Sleep Laboratory of the Department of Internal Medicine of All India Institute of Medical Sciences (AIIMS) hospital, New Delhi, were studied. Anthropometry and body composition analysis, blood pressure (BP), fasting blood glucose, insulin resistance by homeostasis model assessment (HOMA-IR) and fasting blood lipid profile were measured. MS was defined using the National Cholesterol Education Program Adult treatment panel III criteria, with Asian cut-off values for abdominal obesity. Results: Of the 272 subjects recruited, 187 (82%) had OSA [apnoea-hypopnoea index (AHI)>5 events/h] while 40 (18%) had a normal sleep study. Prevalence of MS in OSA patients was 79 per cent compared to 48 per cent in non-OSA individuals [OR 4.15, (2.05-8.56), P<0.001]. Prevalence of OSA in mild, moderate and severe OSA was 66, 72 and 86 per cent, respectively (P<0.001). Patients with OSA were more likely to have higher BP [OR: 1.06 (1.02-1.11)], fasting insulin [OR: 1.18 (1.05-1.32)], HOMA-IR [OR: 1.61 (1.11-2.33)] and waist circumference [OR: 1.20 (1.13-1.27)]. Interpretation & conclusions: Our findings suggest that OSA is associated with a 4-fold higher occurrence of MS than patients without OSA. The prevalence of MS increases with increasing severity of OSA, therefore, early detection will be beneficial. PMID:22199102

Anion binding by bambus[6]uril probed in the gas phase and in solution.

PubMed

Révész, Agnes; Schröder, Detlef; Svec, Jan; Wimmerová, Michaela; Sindelar, Vladimir

2011-10-20

Electrospray ionization mass spectrometry (ESI-MS) is used to probe the binding of small anions to the macrocycle of bambus[6]uril. For the halide ions, the experimental patterns suggest F(-) < Cl(-) < Br(-) < I(-), which is consistent with the order of anion binding found in the condensed phase. Parallel equilibrium studies in the condensed phase establish the association constants of halide anions and bambus[6]uril in mixed solvents. A detailed analysis of the mass spectrometric data is used to shed light on the correlations between the binding constants in the condensed phase and the ion abundances observed using ESI-MS. From the analysis it becomes apparent that ESI-MS can indeed represent the situation in solution to some extent, but the sampling in the gas-phase experiment is not 1:1 compared to that in solution.

Ratiometric analysis of in vivo retinal layer thicknesses in multiple sclerosis

NASA Astrophysics Data System (ADS)

Bhaduri, Basanta; Nolan, Ryan M.; Shelton, Ryan L.; Pilutti, Lara A.; Motl, Robert W.; Boppart, Stephen A.

2016-09-01

We performed ratiometric analysis of retinal optical coherence tomography images for the first time in multiple sclerosis (MS) patients. The ratiometric analysis identified differences in several retinal layer thickness ratios in the cohort of MS subjects without a history of optic neuritis (ON) compared to healthy control (HC) subjects, and there was no difference in standard retinal nerve fiber layer thickness (RNFLT). The difference in such ratios between HC subjects and those with mild MS-disability, without a difference in RNFLT, further suggests the possibility of using layer ratiometric analysis for detecting early retinal changes in MS. Ratiometric analysis may be useful and potentially more sensitive for detecting disease changes in MS.

The different oscillation patterns of alpha band in the early and later stages of working memory maintenance.

PubMed

Xie, Yuanjun; Feng, Zhengquan; Xu, Yuanyuan; Bian, Chen; Li, Min

2016-10-28

A putative functional role for alpha oscillations in working memory remains controversial. However, recent evidence suggests that such oscillation may reflect distinct phases of working memory processing. The present study investigated alpha band (8-13Hz) activity during the maintenance stage of working memory using a modified Sternberg working memory task. Our results reveal that alpha power was concentrated primarily in the occipital cortex and was decreased during the early stage of maintenance (0-600ms), and subsequently increased during the later stage of maintenance (1000-1600ms). We suggest that reduced alpha power may be involved in focused attention during the working memory maintenance, whereas increased alpha power may reflect suppression of visual stimuli to facilitate internal processing related to the task. This interpretation is generally consistent with recent reports suggesting that variations in alpha power are associated with the representation and processing of information in the discrete time intervals during the working memory maintenance. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

MIF functional polymorphisms (-794 CATT5-8 and -173 G>C) are associated with MIF serum levels, severity and progression in male multiple sclerosis from western Mexican population.

PubMed

Castañeda-Moreno, V A; De la Cruz-Mosso, U; Torres-Carrillo, N; Macías-Islas, M A; Padilla-De la Torre, O; Mireles-Ramírez, M A; González-Pérez, O; Ruiz-Sandoval, J L; Huerta, M; Trujillo, X; Ortuño-Sahagún, D; Muñoz-Valle, J F

2018-07-15

Macrophage migration inhibitory factor (MIF) is a cytokine associated with tissue damage in multiple autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and psoriatic arthritis. The role of MIF in multiple sclerosis (MS) and the contribution of its polymorphisms are unknown in our population. Therefore, we decided to investigate the genetic association of -794 CATT 5-8 (rs5844572) and -173 G>C (rs755622) MIF polymorphisms with MS, clinical variables and MIF serum levels in the population of western Mexico. 230 MS patients diagnosed according to McDonald criteria and 248 control subjects (CS) were recruited for this study, both polymorphisms were genotyped by PCR and PCR-RFLP and MIF serum levels were measured by ELISA kit. Severity and progression of MS were evaluated by EDSS and MSSS scores, respectively. Genotypes carrying the 5 repeats alleles of -794 CATT 5-8 MIF polymorphism present higher MIF serum levels in comparison with no carriers, and the presence of 5,7 heterozygous genotype contribute to the increase of disease severity and damage progression in MS patients. Notably when we stratified by sex, an effect of risk alleles (7 repeats and -173*C) of both MIF polymorphisms on EDSS and MSSS scores on males was found (p < 0.01). This study suggests that polymorphic alleles of MIF polymorphisms could act as sex-specific disease modifiers that increase the severity and progression of MS in male Mexican-Mestizo western population. Copyright © 2018 Elsevier B.V. All rights reserved.