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1.
Eur J Neurol ; 29(3): 895-900, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34662474

RESUMO

BACKGROUND AND PURPOSE: Short-chain fatty acids (SCFAs) can have pro- or anti-inflammatory properties, but their relationship with multiple sclerosis (MS) relapses during pregnancy remains unknown. This study aimed to explore SCFA profiles in MS patients during pregnancy and to assess their association with the appearance of relapses during pregnancy and postpartum. METHODS: We prospectively included 53 pregnant MS patients and 21 healthy control women. Patients were evaluated during pregnancy and puerperium. SCFAs were measured by liquid chromatography-mass spectrometry. RESULTS: Sixteen patients (32%) had relapses during pregnancy or puerperium, and 37 (68%) did not. All MS patients showed significant increases in acetate levels during pregnancy and the postpartum period compared to non-MS women. However, propionate and butyrate values were associated with disease activity. Their values were higher in nonrelapsing patients and remained similar to the control group in relapsing patients. The variable that best identified active patients was the propionate/acetate ratio. Ratios of <0.36 during the first trimester were associated with higher inflammatory activity (odds ratio = 165, 95% confidence interval = 10.2-239.4, p < 0.01). Most nonrelapsing patients showed values of >0.36, which were similar to those in healthy pregnant women. CONCLUSIONS: Low propionate/acetate ratio values during the first trimester of gestation identified MS patients at risk of relapses during pregnancy and the postpartum period.


Assuntos
Esclerose Múltipla , Ácidos Graxos Voláteis , Feminino , Humanos , Razão de Chances , Gravidez , Estudos Prospectivos , Recidiva
2.
Eur J Clin Invest ; 47(2): 158-166, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28036121

RESUMO

BACKGROUND: One of the risk factor to develop progressive multifocal leukoencephalopathy (PML) among natalizumab-treated patients is the presence and high levels of anti-JCV antibodies. Our purpose was to test the association of different clinical and demographic variables with the presence and levels of anti-JCV antibodies in a Spanish cohort of patients with multiple sclerosis (MS) during natalizumab treatment. MATERIALS AND METHODS: All patients with MS from two hospitals with at least one measure of the anti-JCV antibodies levels (2011-2014) were recruited, among them were two PML cases. Anti-JCV antibody levels were assessed using two-step ELISA. RESULTS: A total of 1061 patients (16·3% natalizumab-treated) participated in this study. The seropositivity rate of anti-JCV antibodies was 58·2%. It increased with age (Pcorrected = 0·00005) and was lower among HLA-DRB1*15:01 carriers (Pcorrected = 0·049). The two patients with PML were HLA-DRB1*15:01 carriers. We had at least three quarterly anti-JCV antibody measurements (index value) from 137 patients, whose levels did not increase during natalizumab treatment. However, 5·8% of these patients had an increase of the index value higher of one point in a maximum of 6 months, something that was more frequently observed (P = 0·054) among patients treated with immunosuppressant prior to natalizumab onset. CONCLUSIONS: Old age and HLA-DRB1*15:01 were the factors that influence positively and negatively, respectively, our anti-JCV antibody prevalence, although our both PML cases were HLA-DRB1*15:01carriers. Most of our patients showed a stable anti-JCV antibody index values during natalizumab treatment.


Assuntos
Anticorpos Antivirais/metabolismo , Fatores Imunológicos/uso terapêutico , Vírus JC/imunologia , Leucoencefalopatia Multifocal Progressiva/imunologia , Esclerose Múltipla/imunologia , Natalizumab/uso terapêutico , Adulto , Idoso , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/tratamento farmacológico , Espanha
3.
Front Immunol ; 13: 991662, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36189297

RESUMO

Objectives: 1. To analyze the prevalence and levels of anti-EBNA-1 and anti-VCA IgG antibodies of Epstein-Barr virus (EBV) in a Spanish cohort of multiple sclerosis (MS) patients and their interactions with other environmental and genetic risk factors. 2. To analyze the association of the evolution of these antibodies with the clinical response to different disease modifying therapies (DMTs) after two-years of follow-up. 3. To assess their possible correlation with the class II HLA alleles as well as with several SNPs identified in GWAS related to disease susceptibility. Materials and methods: We recruited 325 MS patients without DMT (serum samples were collected 1-3 months before starting a therapy) and 295 healthy controls (HC). For each patient we also collected serum samples 6, 12, 18 and 24 months after starting the DMT. EBNA-1 and VCA IgG titers were analyzed by ELISA; 25(OH)D levels were analyzed by immunoassay; HLA DRB1*15:01 allelic variant was analyzed by Taqman technology. Results: 1. 97.8% (318/325) vs. 87.1% (257/295) positives for EBNA-1 in MS patients and HC, respectively (p<0.0001; O.R. = 6.7); 99.7% (324/325) vs. 94.6% (279/295) for VCA in MS patients and HC, respectively (p=0.0001; O.R. = 18.6). All MS patients were positive for EBNA-1 and/or VCA IgG antibodies vs. 280/295 (94.9%) HC (p<0.0001). IgG titers were also significantly higher in MS patients than in HC. 2. We did not find any statistical correlation in the variation of the EBNA-1 and VCA IgG titers between baseline and 24 month visits with the number of relapses, progression, clinical response, NEDA-3 condition or therapeutic failure. 3. When we compared different epidemiological and clinical variables between those with genetic factors associated with lower EBNA-1 IgG titers and all other MS patients, we found MS started 3.5 years later among the first. Conclusions: These results confirm that MS occurs rarely in absence of EBV. An intriguing association between genetic burden and lower EBNA-1 IgG titers was associated with an earlier age of disease onset. Similar studies with B-cell-targeted therapies should be performed.


Assuntos
Infecções por Vírus Epstein-Barr , Esclerose Múltipla , Anticorpos Antivirais , Cadeias HLA-DRB1/genética , Herpesvirus Humano 4 , Humanos , Imunoglobulina G , Estudos Longitudinais
4.
Biomedicines ; 10(2)2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-35203596

RESUMO

pHERV-W ENV and syncytin-1, the envelope proteins of the human endogenous retrovirus W family (HERV-W), have been proposed as etiological factors for MS development. In addition, herpesviruses, such as the Epstein-Barr virus (EBV) and the human herpesvirus 6A/B (HHV-6A/B), have been also strongly associated with the disease. This work aims to study the possible link between viral loads and antibody titers against EBV and HHV-6A/B and the pHERV-W ENV/syncytin-1 protein/gene expression. For this purpose, we conducted a 12-month longitudinal study involving 98 RRMS patients. Peripheral blood samples were obtained from each patient. Serum antibody titers against EBV and HHV-6A/B were determined by ELISA, while viral loads were analyzed using qPCR. HLA MS-related alleles were also genotyped. pHERV-W ENV/syncytin-1 protein and gene expression levels in immune cells were assessed by flow cytometry and qPCR, respectively. We found that the 12-month variation of the pHERV-W ENV gene expression levels positively correlated with the variation of the EBV viral load, especially in those patients with high baseline EBV loads. Therefore, these results could support previous studies pointing to the transactivation of pHERV-W ENV by EBV. However, further studies are needed to better understand this possible relationship.

5.
Biology (Basel) ; 11(11)2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36358334

RESUMO

Although impaired mitochondrial function has been proposed as a hallmark of multiple sclerosis (MS) disease, few studies focus on the mitochondria of immune cells. We aimed to compare the mitochondrial function of the peripheral blood mononuclear cells (PBMCs) from MS patients with (M+) and without (M-) lipid-specific oligoclonal immunoglobulin M bands (LS-OCMB), and healthydonors (HD). We conducted an exploratory cross-sectional study with 19 untreated MS patients (M+ = 9 and M- = 10) and 17 HDs. Mitochondrial superoxide anion production and mitochondrial mass in PBMCs were assessed without and with phytohemagglutinin by flow cytometry. The PBMCs' mitochondrial function was analyzed using Seahorse technology. Superoxide anion production corrected by the mitochondrial mass was higher in MS patients compared with HDs (p = 0.011). Mitochondrial function from M+ patients showed some impairments compared with M- patients. Without stimulus, we observed higher proton leak (p = 0.041) but lower coupling efficiency (p = 0.041) in M+ patients; and under stimulation, lower metabolic potential ECAR (p = 0.011), and lower stressed OCR/ECAR in the same patients. Exclusively among M+ patients, we described a higher mitochondrial dysfunction in the oldest ones. The mitochondrial impairments found in the PBMCs from MS patients, specifically in M+ patients, could help to better understand the disease's physiopathology.

6.
Front Immunol ; 13: 904683, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35774792

RESUMO

Background: MicroRNAs are small non-coding RNA that regulate gene expression at a post-transcriptional level affecting several cellular processes including inflammation, neurodegeneration and remyelination. Different patterns of miRNAs expression have been demonstrated in multiple sclerosis compared to controls, as well as in different courses of the disease. For these reason they have been postulated as promising biomarkers candidates in multiple sclerosis. Objective: to correlate serum microRNAs profile expression with disability, cognitive functioning and brain volume in patients with remitting-relapsing multiple sclerosis. Methods: cross-sectional study in relapsing-remitting multiple sclerosis patients treated with glatiramer acetate. Disability was measured with Expanded Disability Status Scale (EDSS) and cognitive function was studied with Symbol Digit Modalities Test (SDMT). Brain volume was analyzed with automatic software NeuroQuant®. Results: We found an association between miR.146a.5p (rs:0.434, p=0.03) and miR.9.5p (rs:0.516, p=0.028) with EDSS; and miR-146a.5p (rs:-0.476, p=0.016) and miR-126.3p (rs:-0.528, p=0.007) with SDMT. Regarding to the brain volume, miR.9.5p correlated with thalamus (rs:-0.545, p=0.036); miR.200c.3p with pallidum (rs:-0.68, p=0.002) and cerebellum (rs:-0.472, p=0.048); miR-138.5p with amygdala (rs:0.73, p=0.016) and pallidum (rs:0.64, p=0.048); and miR-223.3p with caudate (rs:0.46, p=0.04). Conclusions: These data support the hypothesis of microRNA as potential biomarkers in this disease. More studies are needed to validate these results and to better understand the role of microRNAs in the pathogenesis, monitoring and therapeutic response of multiple sclerosis.


Assuntos
Doenças do Sistema Nervoso Central , MicroRNAs , Esclerose Múltipla , Doenças Neurodegenerativas , Atrofia , Biomarcadores , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Estudos Transversais , Acetato de Glatiramer/uso terapêutico , Humanos , MicroRNAs/metabolismo , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/genética
7.
Front Immunol ; 12: 798003, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34912348

RESUMO

Human endogenous retrovirus W family envelope proteins (pHERV-W ENV/syncytin-1) have been repeatedly associated with multiple sclerosis (MS). Here, we have focused on the study of pHERV-W ENV/syncytin-1 expression levels in MS patients (relapsing and progressive forms) and in healthy donors (HD) and on exploring their possible relationship with Epstein-Barr virus (EBV) and human herpesvirus-6A/B (HHV-6A/B). We included blood samples from 101 MS patients and 37 HD to analyze antiviral antibody titers by ELISA and pHERV-W ENV/syncytin-1 expression levels by flow cytometry as well as by qPCR. Patients with relapsing MS forms showed significantly higher pHERV-W ENV/syncytin-1 protein and gene expression levels than HD. Progressive MS patients also showed significantly higher protein and gene expression levels than both HD and relapsing MS patients. Regarding antiviral antibodies titers, anti-HHV-6A/B IgM levels were positively correlated with pHERV-W ENV/syncytin-1 protein expression levels in patients with relapsing MS, while in the progressive forms patients this correlation was found with anti-HHVA/B IgG levels. Therefore, pHERV-W ENV could be involved in MS pathogenesis, playing a role in relapsing and progressive forms. Besides, anti-HHV-6A/B antibodies positively correlated with pHERV-W ENV expression. Further studies are needed to better understand this possible relationship.


Assuntos
Retrovirus Endógenos/fisiologia , Infecções por Vírus Epstein-Barr/imunologia , Herpesvirus Humano 4/fisiologia , Herpesvirus Humano 6/fisiologia , Esclerose Múltipla/imunologia , Infecções por Roseolovirus/imunologia , Adulto , Anticorpos Antivirais/sangue , Progressão da Doença , Feminino , Regulação Viral da Expressão Gênica , Produtos do Gene env/genética , Produtos do Gene env/metabolismo , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/virologia , Proteínas da Gravidez/genética , Proteínas da Gravidez/metabolismo
8.
Cells ; 10(1)2021 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-33435197

RESUMO

Although the etiology of multiple sclerosis (MS) is still unknown, it is commonly accepted that environmental factors could contribute to the disease. The objective of this study was to analyze the humoral response to Epstein-Barr virus, human herpesvirus 6A/B and cytomegalovirus, and the levels of 25-hydroxyvitamin D (25(OH)D) and the three main short-chain fatty acids (SCFA), propionate (PA), butyrate (BA) and acetate (AA), in MS patients and healthy controls (HC) to understand how they could contribute to the pathogenesis of the disease. With this purpose, we analyzed the correlations among them and with different clinical variables and a wide panel of cell subsets. We found statistically significant differences for most of the environmental factors analyzed when we compared MS patients and HC, supporting their possible involvement in the disease. The strongest correlations with the clinical variables and the cell subsets analyzed were found for 25(OH)D and SCFAs levels. A correlation was also found between 25(OH)D and PA/AA ratio, and the interaction between these factors negatively correlated with interleukin 17 (IL-17)-producing CD4+ and CD8+ T cells in untreated MS patients. Therapies that simultaneously increase vitamin D levels and modify the proportion of SCFA could be evaluated in the future.


Assuntos
Anticorpos Antivirais/imunologia , Ácidos Graxos Voláteis/imunologia , Herpesvirus Humano 4/imunologia , Esclerose Múltipla/imunologia , Esclerose Múltipla/virologia , Vitamina D/metabolismo , Adulto , Estudos de Casos e Controles , Meio Ambiente , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Vitamina D/análogos & derivados
9.
Sci Rep ; 11(1): 8441, 2021 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-33875702

RESUMO

Epstein-Barr virus (EBV), human herpesvirus 6A/B (HHV-6A/B) and multiple sclerosis (MS)-associated retrovirus (MSRV) have been described as possible MS triggers. We analysed antibody titres against EBV and HHV-6, and MSRV envelope (env) mRNA expression, in the serum of pregnant multiple sclerosis patients (P-MS) to study their possible link to the clinical activity of MS during pregnancy and postpartum and their possible role as relapse predictors. For that purpose, serum samples were collected from 71 pregnant women (50 pregnant MS and 21 pregnant healthy controls-P-HC) during pregnancy and postpartum. Relating to antibody titres, IgM antibody titres against HHV-6A/B were significantly higher in P-MS than in P-HC both in each pregnancy trimester and in the postpartum period. Moreover, IgM antibody titres against HHV-6A/B were higher in P-MS who suffered a relapse during the postpartum. Regarding MSRV env mRNA expression, the prevalence in the first trimester of pregnancy was significantly higher in P-MS who suffered relapses during pregnancy. Summing it up, high IgM antibody titres against HHV-6A/B and MSRV env mRNA expression during the first trimester of pregnancy could act as relapse predictors for the gestation/postpartum periods.


Assuntos
Herpesvirus Cercopitecino 1/imunologia , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 6/imunologia , Esclerose Múltipla , Viroses/diagnóstico , Adulto , Anticorpos Antivirais/sangue , Biomarcadores , Retrovirus Endógenos/isolamento & purificação , Retrovirus Endógenos/metabolismo , Infecções por Vírus Epstein-Barr/complicações , Feminino , Herpes Zoster , Humanos , Imunoglobulina M/sangue , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/etiologia , Esclerose Múltipla/virologia , Gravidez , RNA Mensageiro/sangue , RNA Viral/sangue , Proteínas do Envelope Viral/sangue , Proteínas do Envelope Viral/genética , Viroses/complicações , Viroses/imunologia
10.
Front Immunol ; 11: 2142, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072077

RESUMO

Human herpesvirus-6A (HHV-6A) and -6B (HHV-6B) might be involved in the etiopathogenesis of multiple sclerosis (MS), especially the HHV-6A. We aim at assessing, for the first time in the scientific literature, the HHV-6A/B microRNAs in MS patients. We analyzed the miRNAs of HHV-6A: miR-U86, and -6B: hhv6b-miR-Ro6-1, -2, -3-3p, -3-5p, and -4 in paired samples of serum and CSF of 42 untreated MS patients and 23 patients with other neurological diseases (OND), using Taqman MicroRNA Assays. Intrathecal HHV-6A/B antibody production and anti-HHV-6A/B IgG/IgM levels in serum were measured. MS clinical data were available. We detected the following miRNAs: hhv6b-miR-Ro6-2 (serum: MS:97.7%, OND:95.7%; CSF: MS:81%, OND:86.4%), 3-3p (serum: MS:4.8%, OND:0%; CSF: MS:2.4%, OND:4.5%), -3-5p (serum: MS:95.2%, OND:91.3%; CSF: MS:50%, OND:54.5%), and miR-U86 (serum: MS:54.8%, OND:47.8%; CSF: MS:11.9%, OND:9.1%). In the serum of the whole population (MS and OND patients) we found a significant correlation between the levels of hhv6b-miR-Ro6-2 and -3-5p (Spearman r = 0.839, pcorr = 3E-13), -2 and miR-U86 (Spearman r = 0.578, pcorr = 0.001) and -3-5p and miR-U86 (Spearman r = 0.698, pcorr = 1.34E-5); also in the CSF, between hhv6b-miR-Ro6-2 and -3-5p (Spearman r = 0.626, pcorr = 8.52E-4). These correlations remained statistically significant when both populations were considered separately. The anti-HHV-6A/B IgG levels in CSF and the intrathecal antibody production in positive MS patients for hhv6b-miR-Ro6-3-5p were statistically significant higher than in the negative ones (pcorr = 0.006 and pcorr = 0.036). The prevalence of miR-U86 (30.8%) in the CSF of individuals without gadolinium-enhancing lesions was higher (p = 0.035) than in the ones with these lesions (0%); however, the difference did not withstand Bonferroni correction (pcorr = 0.105). We propose a role of HHV-6A/B miRNAs in the maintenance of the viral latency state. Further investigations are warranted to validate these results and clarify the function of these viral miRNAs.


Assuntos
Herpesvirus Humano 6/isolamento & purificação , MicroRNAs/sangue , MicroRNAs/líquido cefalorraquidiano , Esclerose Múltipla/virologia , RNA Viral/sangue , Adulto , Anticorpos Antivirais/sangue , Anticorpos Antivirais/líquido cefalorraquidiano , Estudos de Casos e Controles , Feminino , Herpesvirus Humano 6/genética , Herpesvirus Humano 6/imunologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/líquido cefalorraquidiano , Imunoglobulina M/sangue , Imunoglobulina M/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/sangue , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/diagnóstico por imagem , Doenças do Sistema Nervoso/sangue , Doenças do Sistema Nervoso/líquido cefalorraquidiano , RNA Viral/líquido cefalorraquidiano , Estudos Retrospectivos , Latência Viral/genética
11.
Front Immunol ; 11: 771, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32431704

RESUMO

Myelin basic protein (MBP) is thought to be one of the key autoantigens in multiple sclerosis (MS) development. A recent study described the association of the single nucleotide polymorphism (SNP) rs12959006, within the MBP gene, with a higher risk of relapse and worse prognosis. We aim at studying potential associations of this SNP to MS in an independent population. Clinical data of the first 5 years of the disease were collected retrospectively from 291 MS confirmed patients. MBP polymorphism rs12959006 was genotyped in all patients. Associations with EDSS, number of relapses and serology for Herpesvirus 6 (HHV-6) and Epstein Barr (EBV) viruses were studied. Lymphocyte activation measured by CD69 expression was also analyzed according to sex and rs12959006 genotype. The rs12959006 polymorphism contributed significantly to a higher number of relapses at 5 years after onset only in male patients (rs12959006∗TT ß = 0.74 [0.36-1.09]; p = 7 × 10-5). Titers of anti-HHV6 IgG antibodies showed also a mild association with relapses, both in male and female patients (ß = 0.01 [0.01-0.02]; p = 3.7 × 10-8). Both the genetic variation in MBP and HHV-6 infection aid in predicting a higher number of relapses during the first years of MS. The association described in MBP rs12959006∗T is exclusive to male patients.


Assuntos
Esclerose Múltipla Recidivante-Remitente/genética , Esclerose Múltipla Recidivante-Remitente/imunologia , Proteína Básica da Mielina/genética , Polimorfismo de Nucleotídeo Único , Adulto , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/virologia , Feminino , Seguimentos , Genótipo , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 6/imunologia , Humanos , Masculino , Esclerose Múltipla Recidivante-Remitente/complicações , Esclerose Múltipla Recidivante-Remitente/epidemiologia , Prognóstico , Recidiva , Estudos Retrospectivos , Infecções por Roseolovirus/complicações , Infecções por Roseolovirus/imunologia , Infecções por Roseolovirus/virologia , Fatores Sexuais , Espanha/epidemiologia , Adulto Jovem
12.
PeerJ ; 8: e10220, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33240608

RESUMO

BACKGROUND: Gut microbiota has been related to multiple sclerosis (MS) etiopathogenesis. Short-chain fatty acids (SCFA) are compounds derived from microbial metabolism that have a role in gut-brain axis. OBJECTIVES: To analyse SCFA levels in plasma of MS patients and healthy donors (HD), and the possible link between these levels and both clinical data and immune cell populations. METHODS: Ninety-five MS patients and 54 HD were recruited. Patients were selected according to their score in the Expanded Disability Status Scale (EDSS) (49 EDSS ≤ 1.5, 46 EDSS ≥ 5.0). SCFA were studied in plasma samples by liquid chromatography-mass spectrometry. Peripheral blood mononuclear cells were studied by flow cytometry. Gender, age, treatments, EDSS and Multiple Sclerosis Severity Score (MSSS) were evaluated at the recruitment. RESULTS: Plasma acetate levels were higher in patients than in HD (p = 0.003). Patients with EDSS ≥ 5.0 had higher acetate levels than those with EDSS≤ 1.5 (p = 0.029), and HD (p = 2.97e-4). Acetate levels correlated with EDSS (r = 0.387; p = 1.08e-4) and MSSS (r = 0.265; p = 0.011). In untreated MS patients, acetate levels correlated inversely with CD4+ naïve T cells (r =  - 0.550, p = 0.001) and directly with CD8+ IL-17+ cells (r = 0.557; p = 0.001). CONCLUSIONS: Plasma acetate levels are higher in MS patients than in HD. In MS there exists a correlation between plasma acetate levels, EDSS and increased IL-17+ T cells. Future studies will elucidate the role of SCFA in the disease.

13.
Sci Rep ; 10(1): 14244, 2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32859922

RESUMO

There are an increasing number of treatments available for multiple sclerosis (MS). The early identification of optimal responders to individual treatments is important to achieve individualized therapy. With this aim, we performed a multicenter retrospective longitudinal study including 186 MS patients treated with natalizumab who were followed for 2 years. We analyzed the following variables at recruitment: sex, current age, age at disease onset, disease duration, EDSS, number of T2 and Gd + lesions, IgG and IgM oligoclonal bands, HLA class II (DR, DRB, DQA, DQB, and DRB1*15:01), IgG and IgM antibody titers against human herpesvirus 6 (HHV-6) and the antibody response to Epstein-Barr virus (EBV) through the measurement of the anti-EBNA-1 and anti-VCA IgG titers, in relation to clinical response (no relapses or disability progression), and to NEDA-3 (no evidence of disease activity in terms of clinical response and no changes in MRI scans either) after 2-years follow-up. Baseline EDSS score, baseline EBNA-1 IgG titers and percentage change of HHV6 IgG titers between baseline and 6 month visits were significantly different in clinical responders and in NEDA-3 status (all of them remained significant in the multivariate analysis). We identified three variables for the early identification of natalizumab optimal responders in a rapid and cost-effective approach.


Assuntos
Biomarcadores Farmacológicos/análise , Esclerose Múltipla/tratamento farmacológico , Natalizumab/uso terapêutico , Adulto , Formação de Anticorpos , Biomarcadores Farmacológicos/sangue , Proteínas do Capsídeo/análise , Proteínas do Capsídeo/imunologia , Progressão da Doença , Infecções por Vírus Epstein-Barr/imunologia , Antígenos Nucleares do Vírus Epstein-Barr/análise , Feminino , Antígenos HLA/análise , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 6/imunologia , Humanos , Imunoglobulina G/análise , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia , Natalizumab/metabolismo , Prognóstico , Recidiva , Estudos Retrospectivos , Espanha
14.
PeerJ ; 7: e8235, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31976164

RESUMO

BACKGROUND: Low levels of 25-hydroxyvitamin D (25(OH)D) have been described as one of the possible environmental factors involved in multiple sclerosis (MS) etiopathogenesis. OBJECTIVES: To study epidemiology of MS and 25(OH)D serum levels of patients in Lanzarote (29°02'06″N), a region with high ultraviolet radiation values during the whole year which is located far apart from Iberian Peninsula (36°-43°N), but without genetic/ethnic differences with it. METHODS: Incidence in Lanzarote was assessed according to McDonald 2005 criteria between January 2008 and December 2015 and prevalence date was 12/31/15. For 25(OH)D serum levels analyses, samples from 60 MS patients and 60 healthy donors (HD) were collected monthly in a one-year prospective study. RESULTS: The prevalence of MS in Lanzarote was 50.0/100,000 and the incidence per year was 2.5/100,000. Median 25(OH)D levels values were 29.1 ng/ml for MS patients (maximum = 36.1 ng/ml, minimum = 22.5 ng/ml) and 27.1 ng/ml for HD (maximum = 34.8 ng/ml, minimum = 22.8 ng/ml). There were no significant differences between 25(OH)D serum levels between MS patients and HD. CONCLUSIONS: Lanzarote possesses lower prevalence and incidence values than peninsular Spain. Moreover, 25(OH)D serum levels do not differ between MS patients and HD.

15.
Edumecentro ; 162024.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1564491

RESUMO

Fundamento: Moodle rompe las limitaciones de espacio y tiempo en el proceso de enseñanza aprendizaje, fomenta el uso de recursos que posibilitan el desarrollo del proceso de evaluación y la independencia cognoscitiva de los estudiantes. Objetivo: diseñar una metodología para la preparación del docente sobre el uso de la plataforma Moodle en el proceso de evaluación de la disciplina Metodología de la Investigación en Salud. Métodos: se realizó una investigación de desarrollo en la Universidad de Ciencias Médicas de Holguín, curso 2022. Se emplearon métodos teóricos y empíricos. Se calcularon valores absolutos y porcentajes. El Alfa de Cronbach aplicado en el cuestionario a docentes resultó 0.73. Se seleccionaron cinco especialistas para la valoración de la metodología. Resultados: más de 50 % de los docentes expresaron que pocas veces o nunca emplean la plataforma Moodle para la evaluación frecuente y 86,7 % consideró regular el conocimiento que poseen; mientras el 84,4 % de los estudiantes la emplean para descargar materiales docentes. Se propone una metodología para la preparación del docente en la evaluación frecuente utilizando la plataforma, incluye instructivo y entrenamiento, fue estructurada en cinco etapas. Conclusiones: la metodología diseñada facilitó herramientas para la elaboración de la evaluación frecuente mediante la plataforma. Los especialistas la valoraron como aceptada para su aplicación.


Background: Moodle breaks the limitations of space and time in the teaching-learning process, encouraging the use of resources that enable the development of the evaluation process and the cognitive independence of students. Objective: design a methodology for teaching preparation on the use of the Moodle platform in the evaluation process of the Health Research Methodology discipline. Methods: a development investigation was carried out at Holguín University of Medical Sciences, academic year 2022. Theoretical and empirical methods were used. Absolute values and percentages were calculated. Cronbach's Alpha applied to the teacher's questionnaire was 0.73. Five specialists were selected to evaluate the methodology. Results: more than 50% of teachers expressed that they rarely or never use the Moodle platform for frequent evaluation and 86.7% considered they regulate the knowledge they possess; while 84.4% of students use it to download teaching materials. A methodology is proposed for teaching preparation in frequent evaluation using the platform, it includes instructions and training, it was structured in five stages. Conclusions: the designed methodology provided tools for the preparation of frequent evaluation through the platform. The specialists assessed it as accepted for application.

16.
Edumecentro ; 152023.
Artigo em Espanhol | LILACS | ID: biblio-1520834

RESUMO

Fundamento: la evaluación del desempeño profesional y la competencia constituye el eje fundamental del modelo cubano para el análisis y evaluación de la calidad en la educación y práctica médicas. Objetivo: diseñar un modelo de evaluación de la competencia investigativa del licenciado en Imagenología. Métodos: se realizó una investigación de desarrollo en los centros de atención secundaria del municipio Holguín desde 2021 a 2022. Se emplearon métodos teóricos: histórico-lógico, análisis-síntesis, sistémico-estructural-funcional y modelación; y empíricos: análisis documental y cuestionario a licenciados en Imagenología. Para la valoración del modelo se empleó el criterio de 10 especialistas con reconocido prestigio en los centros de atención. Los indicadores fueron la pertinencia, utilidad, factibilidad. Resultados: se constataron insuficiencias en la competencia investigativa evidenciadas en el desempeño profesional. Se elaboró un modelo de evaluación compuesto por dos subsistemas: teórico funcional y contextualización; de sus relaciones deviene una nueva cualidad que se enuncia en la mejora del desempeño profesional investigativo para la solución de problemas tecnológicos y biomédicos. Conclusiones: los dos subsistemas que componen el modelo de evaluación de la competencia investigativa tienen una relación de coordinación. Los especialistas lo valoraron como pertinente, útil y factible de ser aplicado.


Background: the evaluation of professional performance and competence constitutes the fundamental axis of the Cuban model for the analysis and evaluation of quality in medical education and practice. Objective: to design a model for evaluating the research competence of the graduate in Imaging. Methods: a development investigation was carried out in the secondary care centers of the Holguín municipality from 2021 to 2022. Theoretical methods were used: historical-logical, analysis-synthesis, systemic-structural-functional and modeling; and empirical: documentary analysis and questionnaire to graduates in Imaging. To evaluate the model, the criteria of 10 specialists with recognized prestige in care centers were used. The indicators were relevance, usefulness, feasibility. Results: insufficiencies in the researching competence were found, evidenced in professional performance. An evaluation model composed of two subsystems was developed: functional theory and contextualization; from their relationships becomes a new quality that is expressed in the improvement of professional researching performance for the solution of technological and biomedical problems. Conclusions: the two subsystems that make up the research competence evaluation model have a coordination relationship. The specialists valued it as pertinent, useful and feasible to be applied.


Assuntos
Apoio à Pesquisa como Assunto , Desenvolvimento de Pessoal , Educação Médica , Descrição de Cargo
17.
Edumecentro ; 152023.
Artigo em Espanhol | LILACS | ID: biblio-1448174

RESUMO

Fundamento: el sector cubano de salud, además de garantizar una atención médico-social al adulto mayor, tiene la misión de formar los recursos humanos especializados en esta área del conocimiento, desde el pregrado en las carreras de las ciencias médicas, y de forma continua y sostenida hasta el posgrado; por lo que se precisa observar el tratamiento de los contenidos relacionados con la Gerontogeriatría en los planes de estudio. Objetivo: caracterizar la representación de la Gerontogeriatría en el curso propio "Envejecimiento" del Plan de estudios "D" de la carrera de Medicina en Cuba. Métodos: se realizó una investigación educativa observacional, descriptiva. Se desarrolló una amplia revisión documental de los planes de estudio y el diseño del curso propio "Envejecimiento" del Plan de estudios "D", precisando el análisis de sus contenidos y su aporte a la Gerontogeriatría. Resultados: se constató que el curso permite la enseñanza de la Gerontología y Geriatría, diseñado con tres objetivos y cinco temas, y contenidos que favorecen la formación gerontogeriátrica en el desempeño de la función de atención médica integral al particular proceso salud enfermedad que se expresa en el adulto mayor. Conclusiones: la Gerontogeriatría está presente en el curso propio "Envejecimiento", representada fundamentalmente con este diseño académico en todo el vigente Plan de estudios "D".


Background: the Cuban health branch, in addition to guaranteeing medical-social care for the elderly, has the mission of training specialized human resources in this area of knowledge, from undergraduate in medical sciences careers, and continuously and sustained until postgraduate; Therefore, it is necessary to observe the treatment of the contents related to Gerontogeriatrics in the study plans. Objective: to characterize the representation of Gerontogeriatrics in the own course "Aging" of the Study Plan "D" of the Medicine career in Cuba. Methods: an observational, descriptive educational research was carried out. An extensive documentary review of the study plans and the design of the own course "Aging" of the Study Plan "D" was carried out, specifying the analysis of its contents and its contribution to Gerontogeriatrics. Results: it was verified that the course allows the teaching of Gerontology and Geriatrics, designed with three objectives and five topics, and contents that favor gerontology and geriatric training in the performance of the function of comprehensive medical attention to the particular health-disease process that is expressed in the elderly. Conclusions: Gerontogeriatrics is present in the own course "Aging", fundamentally represented with this academic design throughout the current Curriculum "D".


Assuntos
Planos e Programas de Saúde , Dinâmica Populacional , Educação Médica , Geriatria , Programas Governamentais , Programas Nacionais de Saúde
18.
Medisur ; 21(3)jun. 2023.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1448673

RESUMO

Fundamento: e l aula invertida es una modalidad de enseñanza semipresencial, donde los alumnos aprenden los conceptos por sí mismos, usando normalmente videos educativos, archivos de audio y otras tecnologías, mediante la colaboración entre los compañeros en comunidades en línea. Objetivo: proponer un método de aula invertida para la formación en gerontogeriatría de estudiantes de la carrera de Medicina. Métodos: se realizó un estudio de tipo observacional de corte transversal mediante el empleo de métodos científicos: revisión de documentos, observación directa en el terreno, análisis, síntesis, inducción, deducción, sistémico y de estadística descriptiva. Resultados: se aporta un método de aula invertida para la formación gerontogeriátrica de los estudiantes de la carrea de Medicina que combina las modalidades de presencialidad y virtualidad desde la interacción entre las formas de organización de la docencia médica y de la educación en el trabajo en la Atención Primaria en Salud: consulta y visita de terreno domiciliaria. Conclusiones: el aula invertida es un contexto que favorece la formación gerontogeriátrica del estudiante de la carrera de Medicina ya que dinamiza y transforma las concepciones y enfoques tradicionales de la enseñanza - aprendizaje, al lograr un mayor protagonismo estudiantil, aumento de la autonomía, la instantaneidad, interconexión, multimedialidad y la creatividad e innovación del estudiante en la solución de problemas de salud del adulto mayor, así como el aprovechamiento de las potencialidades de los recursos y entornos virtuales de aprendizaje que posee, combinando modalidades de enseñanza presencial y virtual.


Background: the inverted classroom is a blended learning modality, where students learn the concepts by themselves, usually using educational videos, audio files and other technologies, through collaboration among peers in online communities. Objective: to propose an inverted classroom method for gerontogeriatric training in Medicine students. Methods: a cross-sectional observational study was carried out using scientific methods: document review, direct observation in the field, analysis, synthesis, induction, deduction, systemic and descriptive statistics. Results: an inverted classroom method is provided for the gerontogeriatric training of Medicine students that combines face-to-face and virtual modalities from the interaction between the forms of organization of medical teaching and education at work in the Primary Health Care: consultation and home field visit. Conclusions: the inverted classroom is a context that favors the gerontogeriatric training of the Medicine student since it revitalizes and transforms the traditional conceptions and approaches of teaching-learning, by achieving a greater student role, increased autonomy, instantaneous, interconnection, multimedia and the creativity and innovation of the student in the solution of health problems of the elderly, as well as the use of the resources and virtual learning environments' potential that it possesses, combining face-to-face and virtual teaching modalities.

19.
Arch. méd. Camaguey ; 25(4): e8188, 2021. tab
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1339117

RESUMO

RESUMEN Fundamento: la utilización de las tecnologías de la información y las comunicaciones en el primer año de la carrera de Medicina constituye una herramienta para desarrollar habilidades informáticas en cuanto a la búsqueda y recuperación de la información en salud. Objetivo: diseñar una estrategia de actualización en búsqueda y recuperación de información científica para desarrollar habilidades informáticas en el primer año de la carrera de Medicina. Métodos: se realizó un estudio de desarrollo en la Facultad de Ciencias Médicas de Holguín, se diseñó una estrategia con tres etapas: planificación, ejecución y evaluación. Para el estudio se seleccionó 220 estudiantes por muestreo aleatorio simple y de forma intencionada, a los profesores principales de las diferentes asignaturas que se imparten en el primer año de la carrera y los profesores de la disciplina Metodología de la Investigación en Salud. Resultados: se diseñó una estrategia de actualización en búsqueda y recuperación de información científica para desarrollar habilidades informáticas, en el primer año de la carrera de Medicina. La planificación para transmitir conocimientos básicos en la utilización del portal de Infomed y sus recursos. La ejecución se materializa con actividades teórico-prácticas referentes a la búsqueda y recuperación de información científica. En la tercera etapa se evalúo la actualización en búsqueda y recuperación de la información científica de forma integral. Conclusiones: con la estrategia se prepara a los estudiantes en la búsqueda y recuperación de la información científica, la cual desarrolla conocimientos y habilidades informáticas, según las exigencias del plan de estudio E en la carrera de Medicina.


ABSTRACT Background: the use of information and communication technologies in the first year of the Medicine career constitutes a tool to develop computer skills in search and retrieval of health information. Objective: to design an update strategy in search and retrieval of scientific information to develop computer skills in the first year of the Medicine degree. Methods: a development study was carried out at the Faculty of Medical Sciences of Holguín; a strategy was designed with three stages: planning, execution and evaluation. A sample of 220 students was selected by simple random sampling and intentionally, to the main teachers of the different subjects taught in the first year of the career and teachers of the discipline Health Research Methodology. Results: an update strategy was designed in search and retrieval of scientific information to develop computer skills in the first year of the Medicine degree. With three stages: Planning, execution and evaluation. Planning to transmit basic knowledge in the use of the Infomed portal and its resources. The execution is materialized with theoretical-practical activities related to the search and retrieval of scientific information. In the third stage, the updating in search and recovery of scientific information is evaluated in a comprehensive way. Conclusions: the strategy prepares students in the search and retrieval of scientific information, which develops computer knowledge and skills, according to the demands of study plan E in the Medicine degree.

20.
Rev. cienc. med. Pinar Rio ; 25(5): e5074, 2021. graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1351902

RESUMO

RESUMEN Introducción: el software educativo juega un rol importante en el proceso enseñanza aprendizaje en la Educación Médica Superior en Cuba. Es una valiosa herramienta que contribuirá de manera significativa al desarrollo del auto aprendizaje de la matemática. Objetivo: proponer un software educativo como recurso didáctico para el desarrollo del proceso de enseñanza aprendizaje de la asignatura matemática en la carrera de Vigilancia y Lucha Antivectorial. Métodos: se realizó un estudio de desarrollo tecnológico en el área de recursos para el aprendizaje en la Filial de Ciencias Médicas ¨Lidia Doce Sánchez¨ de Mayarí, en el período de enero del 2018 a junio del 2019. El universo estuvo constituido por 39 estudiantes de las carreras de Tecnología de la Salud y 18 profesores que les imparten docencia a estos estudiantes. La muestra fue de 27 estudiantes y cinco profesores que imparten la asignatura matemática, escogidos de forma intencional, se utilizaron métodos teóricos y dentro de los empíricos, el cuestionario, la técnica de lluvia de ideas y la observación. Se utilizó escala de actitud Likert. Resultados: se identificó la necesidad de la elaboración del recurso de aprendizaje para la asignatura matemática. Se diseñó un software educativo para el aprendizaje de los cuatro temas de la asignatura matemática con orientaciones metodológicas para su uso en las clases. Conclusión: el software educativo motiva el aprendizaje, eleva la calidad del proceso docente y estimulan la participación creadora de los estudiantes. Se recomienda la utilización del mismo y continuar su actualización y perfeccionamiento.


ABSTRACT Introduction: educational software plays an important role in the teaching-learning process in Higher Medical Education in Cuba. It is a valuable tool that will contribute significantly to the development of mathematics self-learning. Objective: to propose educational software as a didactic resource for the development of the teaching-learning process of the subject of mathematics in the profession of Surveillance and Vector Control. Methods: a technological development study was conducted in the area of learning resources at Lidia Doce Sánchez Medical Science Affiliate Institution of Mayarí, in the period from January 2018 to June 2019. The target group comprised 39 students of Health Technology Studies and 18 professors of these students and the sample included 27 students and 5 professors who teach the subject of mathematics, chosen intentionally. Theoretical methods were used, and among the empirical methods, the questionnaire, the brainstorming technique and observation. Likert Attitude Scale was used. Results: the need for the development of a learning resource for the subject of mathematics was identified. The educational software was designed for learning the four topics of the subject with methodological guidelines for its application in the program of study. Conclusion: the educational software motivates learning, raises the quality of the teaching process and stimulates the creative participation of students. It is recommended to use it and to continue its update and improvement.

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