Influence of natalizumab on resting-state connectivity in patients with multiple sclerosis.

Background: Changes in brain connectivity occur in patients with multiple sclerosis (MS), even in patients under disease-modifying therapies. Using magnetic resonance imaging (MRI) to asses patients treated with disease-modifying therapies, such as natalizumab, can elucidate the mechanisms involved in clinical deterioration in MS. Objectives: To evaluate differences in resting-state functional connectivity among MS patients treated with natalizumab, MS patients not treated with natalizumab, and controls. Design: Single-center retrospective cross-sectional study. Methods: Twenty-three MS patients being treated with natalizumab were retrospectively compared with 23 MS patients who were naïve for natalizumab, and were using first-line medications (interferon-ß and/or glatiramer acetate), and 17 gender- and age-matched control subjects. The MS patient groups were also matched for time since diagnosis and hyperintense lesion volume on FLAIR. All participants underwent brain MRI using a 3 Tesla scanner. Independent component analysis and dual regression were used to identify resting-state functional connectivity using the FMRIB Software Library. Results: In comparison to controls, the MS patients treated with natalizumab presented decreased connectivity in the left orbitofrontal cortex, in the anterior cingulate and orbitofrontal cortex network. The patients not treated with natalizumab presented increased connectivity in the secondary visual, sensorimotor, and ventral attention networks in comparison to controls.Compared to patients treated with natalizumab, the patients not using natalizumab presented increased connectivity in the left Heschl's gyrus and in the right superior frontal gyrus in the ventral attention network. Conclusion: Differences in brain connectivity between MS patients not treated with natalizumab, healthy controls, and patients treated with natalizumab may be secondary to suboptimal neuronal compensation due to prior less efficient treatments, or due to a compensation in response to maladaptive plasticity.

Nasal carriage of resistant Staphylococcus aureus in a medical student community.

Staphylococcus aureus can cause a variety of infections due to its high transmissibility, high pathogenic potential and resistance to multiple drugs, factors that contribute to the relevance of infections in healthcare services. The aim of this study was to document phenotypic and genotypic resistance factors of Staphylococcus aureus strains, isolated from nasal mucosa of medical students. A nasal swab was collected from the nares (nostrils) of 222 medical students. After collection, the samples were submitted to isolation and identification procedures. From 204 valid samples, 20.6% (42 samples) were positive for S. aureus. For the assessment of phenotypic resistance by disk-diffusion technique, from 42 samples, 95.2% showed resistance to erythromycin, 42.8% to clindamycin, 16.6% to cephoxitin and 9.5% to oxacillin. The D test showed that 26.2% of samples were resistant to macrolides, lincosamides and streptogramin B. A PCR assay allowed for the evaluation of a genotypic resistance profile, in which 16.6% of the samples were positive for the mecA gene, 35.7% positive for the ermC gene or ermA gene and 28.5% were positive for both genes. These results demonstrate that medical students can enter the healthcare service previously colonized by multidrug resistant strains and become potential spreaders in the hospital environment.

Influence of biological fluids in bacterial viability on different hospital surfaces and fomites.

BACKGROUND: The hospital environment is susceptible to bacterial contamination along with survival in fomites and surfaces, allowing dissemination of potential pathogenic strains. The present research aimed to evaluate the influence of biological fluids in bacterial viability on fomites and surfaces commonly present in nosocomial environment. METHODS: Four different fomites and surfaces (ceramic floor, cotton fabric fragments and synthetic fibers, and eggcrate foam mattress) were contaminated with potential pathogens (Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, and Klebsiella pneumoniae), then submitted to influence of biological fluids (blood, urine, artificial saliva). The viability of strains was evaluated at 24 hours after contamination and then in intervals of 7 days, by the colony-forming unit count technique. RESULTS: S aureus presented viability (>70 days) in all conditions tested, E faecalis and K pneumoniae had decreased viability over time, and E coli did not exhibit a growth relationship with surfaces or fluids. Persistence and adaptability capacity of potential pathogens in fomites and surfaces exposed to the patient are important for guidance, planning, and outlining of protocols for microorganism dissemination control and prevention in the health care environment.

Genetic association study of the HLA class II alleles DRB1, DQA1, and DQB1 in patients with pharmacoresistant temporal lobe epilepsy associated with mesial hippocampal sclerosis.

PURPOSE: Temporal lobe epilepsy (TLE) is the most common variety of focal epilepsy among adults. The neuroinflammatory mechanisms of epilepsies may be involved in the genesis of seizures and refractory epilepsies, particularly in the case of progressive syndromes such as TLE associated with mesial hippocampal sclerosis (TLE-HS). The goal of the present study is investigate the genetic profile of susceptibility of individuals with TLE-HS by analyzing the possible association of TLE-HS with human leukocyte antigen (HLA) DRB1, DQA1 and DQB1 alleles. METHODS: Peripheral blood samples were collected from 42 individuals with pharmacoresistant TLE-HS and 89 healthy controls. The typing of the HLA class II alleles from DRB1, DQB1, and DQA1 loci were analyzed using sequence-specific primer-polymerase chain reaction (SSP-PCR) and identified through sequencing. Statistical analysis of relative allele frequencies was performed using an Excel spreadsheet; p-value, relative risk (RR), and odds ratio (OR) were calculated using the software Epi Info 6.0. p-values <0.05 following Bonferroni's method correction were considered statistically significant. RESULTS: HLA-DRB1*13:02 was the only allele with a statistically significant difference (p=0.01) in frequency between patients and controls. However, the significance was lost following Bonferroni's method correction (p=0.44). The remainder of the alleles in the HLA-DRB1, HLA-DQB1 and HLA-DQA1 regions did not exhibit any significant association. CONCLUSION: The allele HLA DRB1*13:02 has exhibited a tendency to behave as a susceptibility factor for TLE-HS.

The CIITA genetic polymorphism rs4774*C in combination with the HLA-DRB1*15:01 allele as a putative susceptibility factor to multiple sclerosis in Brazilian females.

The objective of this study was to investigate the association between the HLA alleles at the DQA1, DQB1 and DRB1 loci, the CIITA genetic polymorphisms -168A/G and +1614G/C, and susceptibility to multiple sclerosis (MS) in a sample from Rio de Janeiro State, Brazil. Furthermore, we wished to determine whether any of these associations might be more significant in women compared with men. DNA samples from 52 relapsing-remitting MS (RRMS) patients and 126 healthy controls matched for sex and age were analyzed. We identified a significant HLA-DRB1*15:01-MS association that was female-specific (Odds Ratio (OR) = 4.78; p = 0.001). Furthermore, we observed that the +1614G/C mutation in combination with the HLA-DRB1*15:01 allele increased susceptibility to MS in females (OR = 4.55; p = 0.01). Together, these findings highlight the polygenic nature of MS.

The CIITA genetic polymorphism rs4774*C in combination with the HLA-DRB1*15:01 allele as a putative susceptibility factor to multiple sclerosis in Brazilian females / O polimorfismo rs4774*C no gene CIITA em conjunção com o alelo HLA-DRB1*15:01 é um possível fator de susceptibilidade a esclerose múltipla em mulheres brasileiras

The objective of this study was to investigate the association between the HLA alleles at the DQA1, DQB1 and DRB1 loci, the CIITA genetic polymorphisms -168A/G and +1614G/C, and susceptibility to multiple sclerosis (MS) in a sample from Rio de Janeiro State, Brazil. Furthermore, we wished to determine whether any of these associations might be more significant in women compared with men. DNA samples from 52 relapsing-remitting MS (RRMS) patients and 126 healthy controls matched for sex and age were analyzed. We identified a significant HLA-DRB1*15:01-MS association that was female-specific (Odds Ratio (OR) = 4.78; p = 0.001). Furthermore, we observed that the +1614G/C mutation in combination with the HLA-DRB1*15:01 allele increased susceptibility to MS in females (OR = 4.55; p = 0.01). Together, these findings highlight the polygenic nature of MS.

O objetivo deste estudo foi investigar a associação entre alelos HLA, loci DQA1, DQB1 e DRB1, polimorfismos -168A/G e +1614G/C no gene CIITA, e suscetibilidade à esclerose múltipla (EM) em uma amostra de Rio de Janeiro, Brasil. Além disso, buscou-se determinar se alguma dessas associações pode ser gênero-dependente. Foram analisadas amostras de DNA de 52 pacientes com EM reincidente-remitente (EMRR) e 126 controles saudáveis ​​pareados por sexo e idade. Foi identificada associação significativa HLA-DRB1*15:01-EMRR, que foi específica para o gênero feminino (Odds Ratio (OR) = 4,78, p = 0,001). Além disso, observou-se que o polimorfismo +1614 G/C, em combinação com o alelo HLA-DRB1*15:01 provoca o aumento da susceptibilidade à EM em pacientes do sexo feminino (OR = 4,55, p = 0,01). Juntos, estes resultados destacam a natureza poligênica da EM.

Resection of the epileptogenic lesion abolishes seizures and reduces inflammatory cytokines of patients with temporal lobe epilepsy.

Persistent neuroinflammation is implicated in the pathogenesis of seizures and neuronal degeneration of temporal lobe epilepsy (TLE). Circulating level of inflammatory cytokines was determined during inter-ictal period of 25 non-operated and 10 patients (OP) submitted to anterior temporal lobectomy. OP patients showed marked reduction of IL-1ß, TNFα, MIP-1α, but not IL-6 and TGF-ß1. Paired analysis done before and after lobectomy showed reduction of inflammatory cytokines but increased TGF-ß1 levels, and lack of seizures for more than 6 months. Maintenance of high TGF-ß1 and IL-6 cytokines in both groups suggests a role in down-regulation of neuroinflammation and promotion of brain tissue remodeling for neuronal reorganization.

Brain MRI abnormalities in Brazilian patients with neuromyelitis optica.

Brain abnormalities in neuromyelitis optica (NMO) have been reported previously, but the pathophysiological mechanism and clinical relevance of these abnormalities are poorly understood. We assessed the prevalence and patterns of brain MRI abnormalities in a Brazilian cohort of patients with NMO. Conventional brain MRI and medical records from 24 Brazilian patients with NMO were retrospectively evaluated. Brain MRI were classified into four subgroups: normal, non-specific lesions, multiple sclerosis (MS)-like lesions, and typical lesions. Brain lesions were detected in 19 patients (79.2%). Fourteen patients (58.3%) had non-specific lesions, three (12.5%) had MS-like lesions, and two (8.3%) had typical lesions. Differences between these subgroups with respect to the Expanded Disability Status Scale (EDSS) scores (p=0.86) were not significant. This study demonstrates a high prevalence of brain abnormalities in Brazilian patients with NMO; however, we did not find a significant relationship between these abnormalities and EDSS scores.

The role of demyelination in neuromyelitis optica damage: diffusion-tensor MR imaging study.

PURPOSE: To test the hypothesis that white matter damage in neuromyelitis optica (NMO) is more extensive than previously described and likely includes involvement of normal-appearing white matter and to explore by using diffusion-tensor (DT) imaging whether white matter lesions are not only related to wallerian degeneration but are also caused by demyelination. MATERIALS AND METHODS: Seventeen patients with NMO (mean age, 45 years; 14 women) were compared with 17 sex- and age-matched control subjects. The institutional review board approved the study, and all subjects gave written informed consent. In addition to conventional magnetic resonance imaging sequences, DT imaging was performed along 30 noncollinear directions by using a 1.5-T imager. For tract-based spatial statistics (TBSS) analysis, the white matter skeleton was created, and a permutation-based inference with 5000 permutations with a threshold of P less than .05 to enable the identification of abnormalities in fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) was used. Partial correlation was applied to identify whether the number of clinical relapses and disease duration were correlated with all TBSS parameters. RESULTS: TBSS showed multiple areas with significant FA decrease in patients with NMO, mainly located in the corona radiata, uncinate fasciculus, corpus callosum, optic radiation, internal and external capsules, and cerebral peduncles. The mean FA, RD, and AD in the abnormal voxels located on the corpus callosum were, respectively, 0.69 ± 0.03 (standard deviation), 0.39 × 10(23) mm(2)/sec ± 0.04, and 1.53 × 10(23) mm(2)/sec ± 0.04 in patients with NMO compared with 0.75 ± 0.02, 0.33 × 10(23) mm(2)/sec ± 0.03, and 1.57 × 10(23) mm(2)/sec ± 0.04 in control subjects (P < .0001, P < .0001, and P = .007, respectively). There was a highly significant inverse correlation between FA and RD (r = 20.976, P < .0001). CONCLUSION: The use of TBSS allowed the identification of extensive white matter damage in patients with NMO. Multiple white matter tracts were involved, including the pyramidal tract, optic radiation, and corpus callosum, likely related to both demyelination and wallerian degeneration.