Enxaqueca em 746 pacientes com esclerose múltipla

Enxaqueca piora o sofrimento do paciente que tem esclerose múltipla (EM). ID-migraine é uma ferramenta útil para seleção de pacientes com enxaqueca e Migraine Disability Assessment (MIDAS) é um questionário que avalia o impacto da doença. O objetivo do presente estudo foi avaliar a presença e impacto de enxaqueca em pacientes com EM. Métodos: Pacientes diagnosticados com EM e tratados em clínicas especializadas foram convidados a responder um questionário online se também apresentassem cefaleia. Resultados: O estudo incluiu 746 participantes com cefaleia e EM que preencheram completamente as respostas. Foram 625 mulheres e 121 homens, sendo 69% dos pacientes com idade entre 20 e 40 anos. Enxaqueca foi identificada em 404 pacientes (54,1%) e moderado a grave impacto da doença foi observado em 68,3% dos casos. Conclusão: Enxaqueca é uma cefaleia primária frequente e incapacitante relatada por pacientes com EM.Migraine adds to the burden of patients suffering from multiple sclerosis (MS). The ID-migraine is a useful tool for screening migraine, and the Migraine Disability Assessment questionnaire can evaluate disease burden. The aim of the present study was to assess the presence and burden of migraine in patients with MS. Methods: Patients diagnosed with MS attending specialized MS units were invited to answer an online survey if they also experienced headache. Results: The study included 746 complete responses from patients with MS and headache. There were 625 women and 121 men, and 69% of all the patients were aged between 20 and 40 years. Migraine was identified in 404 patients (54.1%) and a moderate-to-high burden of disease was observed in 68.3% of the patients. Conclusion: Migraine is a frequent and disabling type of primary headache reported by patients with MS

Demographic and Genetic Structures of Two Partially Isolated Communities of Santa Catarina Island, Southern Brazil

The objectives of this study were to analyze the population structure and genetic variability of two communities, Costa da Lagoa (CLG) and São João do Rio Vermelho (SJRV), located on Santa Catarina Island in southern Brazil. The two populations descend from Azores Archipelago immigrants (Portuguese), with a minor contribution of sub-Saharan Africans and Amerindians. To estimate the relative contribution of the different ethnic groups to the current gene pool of the two communities, values of admixture were obtained using the weighted least-squares method based on allelic frequencies of the loci ABO, RHD-RHCE, GPA-GPB (MNSs), HBB, HP, TF, CP, AK, and ACP1. The origins of the studied populations can be quantified as follows: for CLG, sub-Saharan Africans (A) = 17.3%, Iberian Europeans (P) = 75.0%, and Southern Amerindians (I) = 7.7%; for SJRV, A = 48.8%, P = 44.5%, and I = 6.7%. Because haplotype frequencies of the GPA-GPB loci in SJRV were unusual, possibly as a consequence of random genetic drift, the values of admixture were recalculated after exclusion of GPA-GPB, as follows: A = 28.0%; P = 53.3%, and I = 18.7%. The total diversity (HT) was estimated as 42.29%, of which 99.6% can be attributed to the intrapopulational variability (HS). The interpopulational genetic variation (or standard distance, DST) corresponds to 0.19%, while the gene differentiation coefficient is 0.28%, indicative of low genetic difference. These results led to the conclusion that random genetic drift may have had an important effect on the Costa da Lagoa community, while presently gene flow might be the predominant evolutionary factor potentially capable of changing allele frequencies in SJRV

Silver Nanoparticles In Situ Synthesized and Incorporated in Uniaxial and Core–Shell Electrospun Nanofibers to Inhibit Coronavirus

In the present study, we sought to develop materials applicable to personal and collective protection equipment to mitigate SARS-CoV-2. For this purpose, AgNPs were synthesized and stabilized into electrospinning nanofiber matrices (NMs) consisting of poly(vinyl alcohol) (PVA), chitosan (CHT), and poly-ε-caprolactone (PCL). Uniaxial nanofibers of PVA and PVA/CHT were developed, as well as coaxial nanofibers of PCL[PVA/CHT], in which the PCL works as a shell and the blend as a core. A crucial aspect of the present study is the in situ synthesis of AgNPs using PVA as a reducing and stabilizing agent. This process presents few steps, no additional toxic reducing agents, and avoids the postloading of drugs or the posttreatment of NM use. In general, the in situ synthesized AgNPs had an average size of 11.6 nm, and the incorporated nanofibers had a diameter in the range of 300 nm, with high uniformity and low polydispersity. The NM’s spectroscopic, thermal, and mechanical properties were appropriate for the intended application. Uniaxial (PVA/AgNPs and PVA/CHT/AgNPs) and coaxial (PCL[PVA/CHT/AgNPs]) NMs presented virucidal activity (log’s reduction ≥ 5) against mouse hepatitis virus (MHV-3) genus Betacoronavirus strains. In addition to that, the NMs did not present cytotoxicity against fibroblast cells (L929 ATCC® CCL-1TM lineage)

Haplotypes of the HLA-G 3' Untranslated Region Respond to Endogenous Factors of HLA-G+ and HLA-G- Cell Lines Differentially.

The immune checkpoint HLA-G prevents maternal rejection of the fetus and contributes in cancer invasion and acceptance of allografts. The 5' and 3' regulatory regions of the HLA-G gene are polymorphic and balancing selection probably maintains this variability. It is proposed that nucleotide variations may affect the level of HLA-G expression. To investigate this issue we aimed to analyze how haplotypes of the 3' untranslated region (3'UTR) with highest worldwide frequencies, namely UTR-1, UTR-2, UTR-3, UTR-4, UTR-5, UTR-18 and UTR-7, impact the expression of a luciferase reporter gene in vitro. Experiments performed with the HLA-G positive cell lines JEG-3 (choricarcinoma) and FON (melanoma), and with the HLA-G negative cell lines M8 (melanoma) and U251MG (glioblastoma) showed that the HLA-G 3'UTR polymorphism influences the response to endogenous cellular factors and may vary according to the cell type. UTR-5 and UTR-7 impact the activity of luciferase the most whereas UTR-2, UTR-3, UTR-4, and UTR-18 have intermediate impact, and UTR-1 has the lowest impact. These results corroborate the previous associations between amounts of plasma sHLA-G levels and 3'UTR haplotypes in healthy individuals and reinforce that 3'UTR typing may be a predictor of the genetic predisposition of an individual to express different levels of HLA-G

Polymorphic Sites at the 3 ' Untranslated Region of the HLA-G Gene Are Associated with Differential hla-g Soluble Levels in the Brazilian and French Population

HLA-G molecule has well-recognized tolerogenic properties, and the encoding gene shows lower frequency of polymorphism at the coding region but higher variability at regulatory 5' and 3' untranslated (3' UTR) regions. At least three 3' UTR polymorphic sites have been associated with HLA-G mRNA regulation, including the 14 base pair (14bp) Insertion/Deletion, +3142C-G and +3187A-G. We studied the association of polymorphic sites at 3' UTR (sequencing analysis, encompassing the 14bp Ins-Del/+3003T-C/+3010C-G/+3027C-A/+3035C-T/+3142C-G/+3187A-G/+3196C-G polymorphic sites) with plasma soluble HLA-G levels (sHLA-G, detected by ELISA) in 187 French and 153 Brazilian healthy individuals. Allele and genotype frequencies were closely similar in both populations; however, Brazilians showed a higher HLA-G 3' UTR haplotype diversity. Considering sHLA-G levels in both populations altogether, individuals presenting 14bp Del/Del showed higher levels compared to 14bpIns/Ins genotype (P < 0.05); those presenting +3010C/G showed higher levels compared to the +3010C-C genotype (P<0.05); those presenting +3027C-C showed higher levels than the +3027A-A genotype (P<0.05); and those bearing +3035C-C showed higher levels compared to the +3035C-T (P < 0.01) and +3035T-T (P < 0.05) genotypes. The analyses of 3' UTR haplotypes showed that UTR-1 (DelTGCCCGC) was associated with higher expression of sHLA-G, whereas UTR-5 (InsTCCTGAC) and UTR-7 (InsTCATGAC) with lower expression and other UTRs (UTR-2/3/4/6) exhibited intermediate levels. Since the differential expression of HLA-G may be beneficial or harmful depending on the underlying condition, the identification of individuals genetically programmed to differentially express HLA-G may help on defining novel strategies to control the immune response against the underlying disorder.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Impact of the 14 bp InDel on the luciferase reporter gene expression when both construction types (1Fter-4R and 1Fter-2R primers) were considered in each cell line independently or in the four cell lines in combination.

<p>Impact of the 14 bp InDel on the luciferase reporter gene expression when both construction types (1Fter-4R and 1Fter-2R primers) were considered in each cell line independently or in the four cell lines in combination.</p

Significant differences in the modulation of the expression of the luciferase reporter gene considering either the cell type or the status of HLA-G expression, with 1Fter-2R and 1Fter-4R constructions and haplotypes combined.

<p>Points indicate the mean and vertical bars indicate the 95% confidence interval. The number of experiments considering each cell line or the status of HLA-G expression is indicated between parentheses. MW: Mann-whitney test; KW: Kruskal-Wallis test. (A) Modulation of luciferase gene expression in each cell line separately. The decrease in the luciferase gene activity in U251MG (HLA-G-) and FON cells (HLA-G+) was not statistically different. (B) Modulation of luciferase gene expression in the HLA-G- (M8 + U251MG) cells <i>vs</i> HLA-G + (FON + JEG-3) cells combined.</p

Modulation of luciferase reporter gene expression in FON+, JEG-3, M8 and U251MG cells considering the constructions 1Fter-2R <i>vs</i> 1Fter-4R, is not statistically different, regardless of the haplotypes.

<p>Points indicate the means and vertical bars indicate the 95% confidence interval. The number of experiments considering each 1Fter construction is indicated between parentheses. MW: Mann-whitney test; KW: Kruskal-Wallis test. (A) Modulation of luciferase gene expression in the four cell lines combined. (B) Modulation of luciferase gene expression in each cell line independently. P values for Dunn’s multiple comparison test are indicated above and under the horizontal bar for the 1Fter-2R and 1Fter-4R constructions respectively (** p value < 0.01; *** p value < 0.001).</p

Significant differences in the modulation of the expression of the luciferase reporter gene in FON+, JEG-3, M8 and U251MG cells considering each 3’UTR haplotype independently, with the 1Fter-2R and 1Fter-4R constructions combined.

<p>Points indicate the means and vertical bars indicate the 95% confidence interval. The number of experiments considering each 3’UTR haplotype is indicated between parentheses. KW: Kruskal-Wallis test; * p value <0.05; ** p value < 0.01; *** p value < 0.001. (A) Modulation of luciferase expression in the four cell lines combined. (B) Modulation of luciferase expression in the HLA-G+ (FON + JEG-3) cell lines combined. (C) Modulation of luciferase expression in the HLA-G- (M8 + U251MG) cell lines combined. In (A) and (B) luciferase expression is significantly more intensely downregulated by UTR-5 and UTR-7 than by other haplotypes.</p

<i>HLA-G</i> 3’UTR polymorphisms.

<p>(A) Variations in <i>HLA-G</i> mRNA (red) along the 3’UTR. The less frequent variants are positioned below the most frequent one in the nucleotide sequence. Polymorphic sites are framed in bold <u>when the frequency of the</u> minor allele worldwide is higher than 1%. Purple single arrows point to the three predicted polyadenylation signals. Vertical lines with horizontal arrows indicate the 5’ end of the <i>HLA-G</i> nucleotide sequences for 1Fter, 2R and 4R primers used <u>in</u> pMIR-REPORT^™ constructions. (B) Sequence comparison of the most frequent 3’UTR haplotypes (21 worldwide populations; 2n = 3870) [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0169032#pone.0169032.ref025" target="_blank">25</a>] analyzed in the present study. Frequencies are indicated on the right part. UTR-1 and UTR-2 differ at 5 positions (pink rectangles). UTR-6 and UTR-18 (analyzed in the present work) only differ at one position and depending on the UTR typing strategy that was used (i.e., targeting or not +3227 SNP), UTR-18 could be confused with UTR-6 in several studies.</p