Perceived risk and risk reduction behaviours of female first-degree relatives of breast cancer patients attending care at Uganda cancer institute.

OBJECTIVE: The objective of this study was to assess the perceived risk of breast cancer (BC) and adoption of risk reduction behaviours among female first-degree relatives (FDRs) of BC patients attending care at the Uganda Cancer Institute (UCI). METHODS: A cross-sectional study was performed using a questionnaire to collect data between March to October 2019. Adult female FDRs of patients attending care at UCI were recruited consecutively. Breast cancer perceived risk was assessed using a verbal measure; 'My chances of getting BC are great' on a Likert scale with 5 response alternatives. Chi square tests and modified Poisson regression using generalised estimating equations model were used to determine associations and examine factors associated with perceived risk of BC. RESULTS: We enrolled 296 FDRs from 186 female BC patients. Few participants 118/296 (40%) had high perceived risk of BC. Majority 165/296 (56%), had ever practiced breast self-examination. At the multivariable modified Poisson GEE model, women aged 36-45 years were more likely to perceive themselves to be at high risk of developing BC compared to women aged 18-25 years (adjusted prevalence ratio: 1.174; 95% confidence interval [95%CI] = 1.05-2.88; p value = 0.030) after adjusting for age, religion, educational level and residence. CONCLUSION: Few FDRs of BC patients perceived themselves to be at high risk of developing BC and do not seek risk reduction measures including screening and early diagnosis approaches. Breast cancer health education especially targeting younger women should emphasize the increased risk of BC in FDRs.

Employers' and Employees' Perspectives of HIV Self-Testing at Male-Dominated Work Sites and Linkage to Posttest Services in Uganda.

This study explored men's views of workplace-based HIV self-testing and the barriers and facilitators of linkage to posttest services. Six focus group discussions and individual in-depth interviews were held with employers and employees in private security companies in Uganda (N = 70). Using content analysis, five categories emerged. The first category was the mitigation of potential harm, including reduction of stigma and discrimination, and the need for posttest support. The second category was a perceived need for on-site services where the men proposed on-site prevention services and HIV treatment and care. In the third category, which was strengthening linkage mechanisms, participants proposed expanded clinic hours, improved health facility efficiency, and provision of referral documentation. The fourth and fifth categories were organizational support and social support, respectively. There is need for employers and employees to work together for the success of workplace-based HIV initiatives.

Acceptability of HIV testing for men attending televised football venues in Uganda.

BACKGROUND: Worldwide, HIV remains a major public health challenge, especially in Sub-Saharan Africa. Literature indicates that men's involvement in HIV testing, care, and treatment services is lower compared to women, therefore novel approaches are required to engage men in the cascade of HIV care. This study aimed to explore men's perception on the provision of HIV testing services in venues where English Premier League football games are televised. METHODS: An exploratory qualitative study was conducted between February and May 2018. Six focus group discussions were conducted with 50 conveniently selected men aged 18 years and older using a pre-tested discussion guide. All focus group discussions were audio recorded, transcribed verbatim, and analyzed thematically. RESULTS: Overall, HIV testing at venues telecasting English Premier League football games was acceptable to men. There was a very strong preference for health workers providing testing and counseling services be external or unknown in the local community. Possible motivators for testing services provided in these settings include subsidizing or eliminating entrance fee to venues telecasting games, integrating testing and counseling with health promotion or screening for other diseases, use of local football games as mobilization tools and use of expert clients as role models. CONCLUSIONS: This study suggests that HIV testing services at venues where EPL football games are televised is generally acceptable to men. In implementing such services, consideration should be given to preferences for external or unknown health workers and the motivating factors contributing to the use of these services. Given that HIV testing is currently not conducted in these settings, further research should be conducted to evaluate the feasibility of this approach as a means of enhancing HIV testing among Ugandan men.

Assessment of Compressive Raman versus Hyperspectral Raman for Microcalcification Chemical Imaging.

We experimentally implement a compressive Raman technology (CRT) that incorporates chemometric analysis directly into the spectrometer hardware by means of a digital micromirror device (DMD). The DMD is a programmable optical filter on which optimized binary filters are displayed. The latter are generated with an algorithm based on the Cramer-Rao lower bound. We compared the developed CRT microspectrometer with two conventional state-of-the-art Raman hyperspectral imaging systems on samples mimicking microcalcifications relevant for breast cancer diagnosis. The CRT limit of detection significantly improves, when compared to the CCD based system, and CRT ultimately allows 100× and 10× faster acquisition speeds than the CCD- and EMCCD-based systems, respectively.

Suicidal ideation, anxiety, and depression in patients with multiple sclerosis / Ideação suicida, ansiedade e depressão em pacientes com esclerose múltipla

ABSTRACT Psychiatric disorders frequently occur in patients with multiple sclerosis (MS); however, limited reports are available on these comorbidities. We aimed to investigate the relationships among MS, anxiety, depression, and suicidal ideation. Methods: One hundred and thirty two patients with relapsing-remitting MS were evaluated using the Expanded Disability Status Scale, Beck Depression Inventory-II (BDI-II), Beck Scale for Suicide Ideation (BSI), and Hospital Anxiety and Depression Scale. Results: A hierarchical regression analysis was performed to evaluate the variables. The regression equation significantly predicted the BSI score (R2 = 0.306; adjusted R2 = 0.273; F (9, 125) = 9.18; p < 0.0005), and the BDI-II score was the only variable that contributed significantly to this model (p < 0.0005). Conclusions: A high prevalence of depression and anxiety, and a higher rate of suicidal ideation were identified in MS patients compared to the general population. The presence of depressive symptoms appeared to have a direct influence on the risk of suicide.

RESUMO Transtornos psiquiátricos frequentemente ocorrem em pacientes com esclerose múltipla (EM). No entanto, os artigos sobre estas comorbidades são limitados. Pretendemos investigar as relações entre EM, ansiedade, depressão e ideação suicida. Métodos: Cento e trinta e dois pacientes com EM remitente-recorrente foram avaliados usando a Escala de Estado de Incapacidade Expandida, Inventário de Depressão de Beck-II (IDB-II), Escala de Beck para Ideação de Suicídio (BSI) e Escala de Ansiedade e Depressão. Resultados: Uma análise de regressão hierárquica foi realizada para avaliar as variáveis. A equação de regressão previu significativamente o escore BSI (R2 = 0,306; R2 ajustado = 0,273; F (9,125) = 9,18; p < 0,0005) e o escore no IDB-II foi a única variável que contribuiu significativamente para este modelo (p < 0,0005). Conclusões: Uma alta prevalência de depressão e ansiedade e uma maior taxa de ideação suicida foram identificadas em pacientes com EM em comparação com a população em geral. A presença de sintomas depressivos pareceu ter uma influência direta no risco de suicídio.

Characterization of the first symptoms of multiple sclerosis in a Brazilian center: cross-sectional study / Caracterização dos primeiros sintomas de esclerose múltipla em um centro brasileiro: estudo transversal

ABSTRACT CONTEXT AND OBJECTIVE: Multiple sclerosis (MS) is a chronic, immune-mediated and degenerative central nervous system (CNS) disease with well-established diagnostic criteria. Treatment can modify the course of the disease. The objective of this study was to describe the initial symptoms of multiple sclerosis in a Brazilian medical center. DESIGN AND SETTING: Descriptive study, conducted in a Brazilian reference center for multiple sclerosis treatment. METHODS: Data on 299 patients with confirmed diagnoses of MS were included in the study. Their medical files were evaluated and the data were analyzed. RESULTS: The most common symptom involved the cranial nerves (50.83%) and unifocal manifestation was presented by the majority of this population (73.91%). The mean time between the first symptom and the diagnosis was 2.84 years. Unifocal symptoms correlated with longer time taken to establish the diagnosis, with an average of 3.20 years, while for multifocal symptoms the average time taken for the diagnosis was 1.85 years. Unifocal onset was related to greater diagnostic difficulty. CONCLUSIONS: MS is a heterogeneous disease and its initial clinical manifestation is very variable.

RESUMO CONTEXTO E OBJETIVO: A esclerose múltipla (EM) é uma doença crônica do sistema nervoso central (SNC) imunomediada e degenerativa, com critérios diagnósticos bem estabelecidos. O tratamento pode modificar o curso da doença. O objetivo deste estudo foi descrever os sintomas iniciais da esclerose múltipla em um centro médico brasileiro. TIPO DE ESTUDO E LOCAL: Estudo descritivo, conduzido em um centro médico de referência no tratamento de EM no Brasil. MÉTODOS: Foram incluídos no estudo dados de 299 pacientes com diagnóstico confirmado de EM. Seus prontuários foram avaliados e os dados foram analisados. RESULTADOS: O sintoma mais comum encontrado envolveu nervos cranianos (50,83%) e a manifestação unifocal foi apresentada pela maioria da população estudada (73,91%). O tempo médio entre o primeiro sintoma e o diagnóstico foi de 2,84 anos. O sintoma unifocal foi relacionado com maior tempo para o estabelecimento do diagnóstico, com uma média de 3,20 anos; enquanto para os sintomas multifocais, a média foi de 1,85 anos para o diagnóstico. O início unifocal foi relacionado a maior dificuldade de diagnóstico. CONCLUSÕES: EM é uma doença heterogênea e sua manifestação clínica inicial é muito variável.

The cerebrospinal fluid in multiple sclerosis: far beyond the bands / O líquido cefalorraquidiano na esclerose múltipla: muito além das bandas

ABSTRACT The cerebrospinal fluid analysis has been employed for supporting multiple sclerosis diagnosis and ruling out the differential diagnoses. The most classical findings reflect the inflammatory nature of the disease, including mild pleocytosis, mild protein increase, intrathecal synthesis of immunoglobulin G, and, most typically, the presence of oligoclonal bands. In recent years, new biomarkers have emerged in the context of multiple sclerosis. The search for new biomarkers reflect the need of a better evaluation of disease activity, disease progression, and treatment efficiency. A more refined evaluation of disease and therapy status can contribute to better therapeutic choices, particularly in escalation of therapies. This is very relevant taking into account the availability of a greater number of drugs for multiple sclerosis treatment in recent years. In this review, we critically evaluate the current literature regarding the most important cerebrospinal fluid biomarkers in multiple sclerosis. The determination of biomarkers levels, such as chemokine ligand 13, fetuin A, and mainly light neurofilament has shown promising results in the evaluation of this disease, providing information that along with clinical and neuroimaging data may contribute to better therapeutic decisions.

RESUMO A análise do líquido cefalorraquidiano tem sido empregada para avaliação diagnóstica da esclerose múltipla e a exclusão dos diagnósticos diferenciais. Os achados clássicos refletem a natureza inflamatória da doença, incluindo discreta pleocitose, leve hiperproteinorraquia, aumento da síntese intratecal de imunoglobulina G e, mais tipicamente, a presença de bandas oligoclonais. Nos últimos anos, surgiram novos biomarcadores para esclerose múltipla, e esta busca por marcadores reflete a necessidade de melhor avaliar a atividade e a progressão da doença, bem como a eficácia terapêutica. Uma avaliação mais refinada da atividade da doença e da resposta aos medicamentos pode contribuir para melhores decisões terapêuticas, particularmente no que se refere à troca de medicação. Isto é muito importante nos dias de hoje, quando surgem novas opções medicamentosas. Neste artigo de revisão, avaliamos criticamente a literatura atual referente aos novos marcadores liquóricos na esclerose múltipla. A mensuração destes marcadores, como a quimiocina CXCL13, fetuína A e, principalmente, o neurofilamento de cadeia leve, demonstrou resultados promissores na avaliação da doença, provendo informações que, em conjunto com dados clínicos e de neuroimagem, podem contribuir para melhores decisões terapêuticas.

Polyomavirus detection in multiple sclerosis patients under natalizumab therapy: Profile and frequency of urinary shedding.

Patients undergoing Natalizumab (NTZ) therapy are at risk of progressive multifocal leukoencephalopathy (PML). Besides John Cunningham virus (JCV), BK polyomavirus might represent an additional concern for such patients since it can also infect CNS cells. Currently, data regarding the presence of anti-JCV antibodies added to previous immunosuppressive therapy and prolonged NTZ therapy has been used to classify patients at risk of developing PML. Here, we investigated the profile shedding of JCV and BKV in multiple sclerosis (MS) patients during treatment with NTZ. Serial blood and urine samples from 97 MS patients receiving either NTZ or ß-interferon were investigated for polyomavirus shedding. While all blood samples tested negative, 36% of the patients shed polyomavirus in the urine in at least one time point. From these, 21.7%, 9.3%, and 5.1% shed JCV, BKV, and both polyomavirus, respectively. No difference was observed between the rates of urinary shedding of patients treated with NTZ (38.9%) and patients treated with other drugs (34.5%), also no PML event was diagnosed during the follow-up. Therefore, urinary shedding might not be interfered by therapy condition. In our study, we also observed 14/27 (52%) of anti-JCV antibodies prevalence, and nearly half of them (42%) did not present any event of urinary shedding during the follow-up. J. Med. Virol. 89:528-534, 2017. © 2016 Wiley Periodicals, Inc.

Olfactory alterations in patients with multiple sclerosis / Alterações de olfato em portadores de esclerose múltipla

ABSTRACT This cross-sectional study involves 100 multiple sclerosis (MS) and 100 non-MS patients, under the age of 60 years old, with nasal obstruction, traumatic brain injury, previous rhinoplasty or neurosurgery, and so forth. Objective To assess olfactory function using the Connecticut test and verify correlations between olfactory alteration, disease duration and the Expanded Disability Status Scale (EDSS). Methods One hundred MS patients and 100 healthy control patients responded to a questionnaire. Those with olfactory alteration underwent a facial CT to exclude other causes. Results Thirty-two percent of patients showed alterations, compared with 3% in the healthy control group. Patients having EDSS above 4, showed a 5.2-times increased risk of dysfunction. Patients over 38 years of age have a 2.2-times increased risk over younger patients. Conclusions Because MS patients are likely to experience olfactory alterations, this study is a useful tool in follow-up care, although more studies are necessary to evaluate the correlations in MS evolution.

RESUMO Estudo transversal em que pacientes portadores de esclerose múltipla (EM) do ambulatório do CATEM e controles saudáveis foram submetidos a avaliação de função olfativa. Objetivo Avaliar a função olfativa através do teste de Connecticut (CCCRC) em pacientes com EM e verificar possível correlação entre a alteração de olfato com o tempo de doença e o Expanded Disability Status Scale (EDSS). Métodos No total, 100 pacientes com EM e 100 pacientes controles participaram do estudo. Aqueles que apresentaram alteração de olfato realizaram TC de face para excluir outras possíveis causas para a alteração olfativa. Resultados 32% apresentaram alterações do olfato, enquanto apenas 3% dos controles apresentaram semelhante alteração. Obtendo-se uma correlação entre o EDSS e alteração olfatória para pacientes com EDSS acima de 4. Pacientes com mais de 38 anos apresentam 2,2 vezes mais risco de ter alterações no olfato. Conclusões Neste estudo observou-se que a alteração olfativa está presente nos pacientes portadores de EM e essa alteração pode ser uma ferramenta útil no acompanhamento desses pacientes.

Validation and cross-cultural adaptation of sexual dysfunction modified scale in multiple sclerosis for Brazilian population / Validação e adaptação transcultural da escala modificada de disfunção sexual em esclerose múltipla na população brasileira

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). These patients suffer from various comorbidities, including sexual dysfunction (SD). The lesions of MS may affect regions of the CNS along the pathway of sexual response. The Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19) is a scale that assesses sexual dysfunction. Adapt and validate the MSISQ-19 to Brazilian patients with MS. 204 individuals were evaluated, 134 patients with MS and 70 healthy persons for the control group. It was determined reproducibility, validity, internal consistency and sensitivity of the MSISQ-19-BR. Among patients with MS, 54.3% of male and 71.7% of female presented some kind of SD. In the control group the results were 12.5% and 19.5%, respectively. The MSISQ-19-BR is reproducible, reliable and valid for the Brazilian population and may be used as a tool for assessing the impact of sexual dysfunction in patients with MS.

A esclerose múltipla (EM) é uma doença crônica inflamatória do sistema nervoso central (SNC). Esses pacientes sofrem de várias comorbidades, incluindo a disfunção sexual. As lesões da EM podem afetar varias regiões do SNC inclusive a via de resposta sexual. O Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19) é uma escala de avaliação da disfunção sexual. Adaptar e validar o MSISQ-19 para os pacientes brasileiros com EM. 204 indivíduos foram avaliados, 134 pacientes com EM e 70 controles saudáveis. Foi determinado à reprodutibilidade, validade, consistência interna e a sensibilidade do MSISQ-19BR. Entre os pacientes com EM, 54,3% dos homens e 71,7% das mulheres apresentam algum tipo de DS. No grupo controle os resultados foram 12,5% e 19,5%, respectivamente. O MSISQ-19BR foi reprodutível, confiável e validade para a população brasileira e pode ser usado como uma ferramenta de avaliação do impacto da disfunção sexual nos pacientes com EM.

Diplopia as first symptom of multiple sclerosis / Diplopia como primeiro sintoma de esclerose múltipla

Purpose: To determine the frequency and clinical features of the extrinsic ocular motility changes in patients with multiple sclerosis living in the state of Sao Paulo (Brazil), consecutive cases series from 1996 to 2011. Methods: Eighty-three consecutive multiple sclerosis subjects were enrolled, aged from 17 to 59 years. All patients had a history taking and a comprehensive ocular exam. Results: Extrinsic ocular motility changes was detected in 17 (20,48%) out of 83 individuals. Diplopia as the first symptom of the disease occurred in 11 (13,25%) individuals. Conclusions: Frequency of diplopia as first symptom of multiple sclerosis is relevant. According to this statement, crucial importance should be given concerning spreading of knowledge and skills to internal medicine and general ophthalmology practicing physicians about early diagnosis of multiple sclerosis, which would reduce a delay in diagnosis of the disease and would help patients in the prognosis of the disease which they endure.

Objetivo:Determinar a frequência e as características clínicas das alterações da motilidade ocular extrínseca em indivíduos portadores de esclerose múltipla, residentes no estado de São Paulo, em série de casos consecutivos de 1996 a 2011.Métodos:Foram selecionados oitenta e três indivíduos com esclerose múltipla, com idade entre 17 e 59 anos. Todos foram submetidos à anamnese e exame ocular completo.Resultados:Alterações da motilidade ocular extrínseca foram encontradas em 17 ( 20,48%) dos 83 indivíduos. A diplopia ocorreu como primeiro sintoma da doença em 11 (13,25%) indivíduos.Conclusão:A frequência de diplopia como primeiro sintoma de esclerose múltipla é relevante. Por esse fato, é fundamental ressaltar a importância da difusão do conhecimento desse achado para a realização de diagnóstico precoce de esclerose múltipla, tanto para o oftalmologista geral, como para o médico generalista, melhorando assim o prognóstico dos pacientes que dela padecem.

A comparative study of bronchoscopic microsample probe versus bronchoalveolar lavage in patients with burns-related inhalational injury, acute lung injury and chronic stable lung disease.

BACKGROUND AND OBJECTIVES: The bronchoscopic microsample (BMS) probe allows direct epithelial lining fluid (ELF) level measurement without saline lavage. We investigated whether cytokine levels in ELF from a BMS differed from those obtained by bronchoalveolar lavage (BAL) in stable and acute lung disease. METHODS: In a single-centre, prospective observational cohort study of 45 patients, a sequential BMS probe procedure and BAL were performed on patients with stable chronic obstructive lung disease, interstitial lung disease, acute lung injury (ALI), burns-related inhalational injury or controls. ELF samples were assayed for IL-1ß, IL-6, IL-8, TNF-α and G-CSF. RESULTS: Both bronchoscopic microsampling and BAL showed significantly higher cytokine levels in the ELF from patients with ALI and burns-related inhalational injury than from those with chronic stable lung disease. The BMS method detected cytokine levels approximately 20- to 80-fold higher than the corresponding BAL (uncorrected for dilution). The ratio of BMS and BAL cytokine levels was as follows: the ratio for IL-1ß [mean 55, 95% confidence interval (CI) 34-88] was higher than that for IL-6 (mean 16, 95% CI 10-23, p = 0.015) and IL-8 (mean 13, 95% CI -5 to 36, p = 0.03). The ratio for G-CSF (mean 43, 95% CI 24-75) was higher than that for IL-6 (mean 16, 95% CI 10-23, p = 0.008). CONCLUSIONS: The BMS probe safely collects ELF with higher equivalent inflammatory cytokine concentrations than via BAL from patients with both acute and chronic lung disease and can be an alternative to saline BAL. Variations in cytokine concentrations between BMS and BAL and sampling-site differences warrant further study.

Validation survey of the impact of urinary incontinence (IIQ-7) and inventory of distress urogenital (UDI-6) – the short scales – in patients with multiple sclerosis / Validação da escala curta do questionário de impacto da incontinência urinária (IIQ-7) e do inventário de angústia urogenital (UDI-6) em pacientes com esclerose múltipla

Cross-cultural adaptation and validation of the Impact Questionnaire of Urinary Incontinence (IIQ-7) and Urogenital Distress Inventory (UDI-6) - short scale - in the Brazilian population with multiple sclerosis. The IIQ-7 and UDI-6 were translated into Portuguese, called IIQ-7-BR and UDI-6-BR. The questionnaires were administered in 211 individuals selected randomly. Of these, 140 had MS according to McDonald criteria and 71 were included in the control group. In both questionnaires, the Cronbach’s alpha coefficient was above 0.7. The IIQ-7-BR showed 94.31% concordance between the evaluated studies and UDI-6-BR, 93.33%. Thus, the instruments of this study were presented according to the standards proposed by the Instrument Review Criteria, reliability, validity and sensitivity, maintaining the original scales characteristics.

Adaptação transcultural e validação da escala curta do Questionário de Impacto de Incontinência Urinária (IIQ-7) e do Inventário da Angústia Urogenital (UDI-6) na população brasileira com esclerose múltipla (EM). O IIQ-7 e o UDI-6 foram traduzidos para a língua portuguesa, obtendo-se IIQ-7-BR e UDI-6-BR. Os questionários foram aplicados em 211 indivíduos selecionados aleatoriamente. Destes, 140 apresentavam EM nos critérios de McDonald, e 71 foram incluídos no grupo controle. Em ambos os questionários aplicados nos grupos, o coeficiente alpha de Cronbach apresentou-se acima de 0,7. O IIQ-7-BR apresentou 94,31% de concordância entre os estudos avaliados e o UDI-6-BR, 93,33%. Sendo assim, os instrumentos desse estudo apresentaram-se, segundo as normas propostas pelo Instrument Review Criteria, confiabilidade, validade e sensibilidade, mantendo as características das escalas originais.

The autoantibody repertoire in periodontitis: a role in the induction of autoimmunity to citrullinated proteins in rheumatoid arthritis?

BACKGROUND: Studies suggest that periodontitis may be a risk factor for rheumatoid arthritis (RA). The purpose of this study was to determine whether periodontitis is associated with autoantibodies characteristic of RA. METHODS: Serum samples were tested for anti-cyclic citrullinated peptide (CCP), anti-mutated citrullinated vimentin (MCV), anti-citrullinated α-enolase peptide-1 (CEP-1), anti-citrullinated vimentin (cit-vim), anti-citrullinated fibrinogen (cit-fib) and their uncitrullinated forms anti-CParg (negative control for anti-CCP), anti-arginine-containing α-enolase peptide-1 (REP-1), anti-vimentin and anti-fibrinogen antibodies in patients with and without periodontitis, none of whom had RA. RESULTS: Periodontitis, compared with non-periodontitis, was associated with a normal frequency of anti-CCP and anti-MCV (∼1%) but a higher frequency of positive anti-CEP-1 (12% vs 3%; p=0.02) and its uncitrullinated form anti-REP-1 (16% vs 2%; p<0.001). Positive antibodies against uncitrullinated fibrinogen and CParg were also more common among those with periodontitis compared to non-periodontitis patients (26% vs 3%; p<0.001, and 9% vs 3%; p=0.06). After adjusting for confounders, patients with periodontitis had 43% (p=0.03), 71% (p=0.002) and 114% (p<0.001) higher anti-CEP-1, anti-REP-1 and anti-fibrinogen titres, compared with non-periodontitis. Non-smokers with periodontitis, compared with non-periodontitis, had significantly higher titres of anti-CEP-1 (103%, p<0.001), anti-REP-1 (91%, p=0.001), anti-vimentin (87%, p=0.002), and anti-fibrinogen (124%, p<0.001), independent of confounders, confirming that the autoantibody response in periodontitis was not due to smoking. CONCLUSIONS: We have shown that the antibody response in periodontitis is predominantly directed to the uncitrullinated peptides of the RA autoantigens examined in this study. We propose that this loss of tolerance could then lead to epitope spreading to citrullinated epitopes as the autoimmune response in periodontitis evolves into that of presymptomatic RA.

Smoking, the HLA-DRB1 shared epitope and ACPA fine-specificity in Koreans with rheumatoid arthritis: evidence for more than one pathogenic pathway linking smoking to disease.

OBJECTIVES: Data from North European rheumatoid arthritis (RA) populations has suggested a particularly strong association of gene-environment interaction between smoking and HLA-DRB1 shared epitope (SE) with antibodies to citrullinated α-enolase (CEP-1) and vimentin (cVim) peptides. We investigated this further by examining anticitrullinated peptide/protein antibody (ACPA) fine specificity in a Korean cohort, where there are notable differences in the RA-associated HLA-DRB1 alleles. METHODS: Antibodies to fibrinogen (cFib), α-enolase (CEP-1) and vimentin (cVim) peptides and cyclic citrullinated peptide (CCP) were measured in 513 cases. The Mann-Whitney U test was used to compare antibody levels. Logistic regression generated ORs for RA in a case-control analysis with 1101 controls. Association of ACPA status and erosion in patients with RA was examined by logistic regression. RESULTS: Anti-CCP, CEP-1, cVim and fibrinogen peptides were found in 86.7%, 63.9%, 45.5% and 74.7%, respectively. The number of ACPA and their levels were associated with SE, with evidence of a gene-dosage effect. There was a particular association of smoking with levels of anti-CEP-1. However, a gene-environment interaction was associated with all the ACPA positive subgroups, albeit the highest OR was seen with the anti-CCP+/cVim+ subset. In the absence of SE, smoking only conferred risk for anti-CCP negative subsets. The presence of erosions was not associated with the number of positive ACPA or specificity. CONCLUSIONS: The SE governed the magnitude and diversity of the ACPA response, but its interaction with smoking did not exclusively segregate with any of the ACPA specificities studied here. Smoking was associated with RA by SE-dependent and independent effects.

Multiple sclerosis and herpesvirus interaction / Esclerose multipla e interacao com os herpesvirus

Multiple sclerosis is the most common autoimmune inflammatory demyelinating disease of the central nervous system, and its etiology is believed to have both genetic and environmental components. Several viruses have already been implicated as triggers and there are several studies that implicate members of the Herpesviridae family in the pathogenesis of MS. The most important characteristic of these viruses is that they have periods of latency and exacerbations within their biological sanctuary, the central nervous system. The Epstein-Barr, cytomegalovirus, human herpesvirus 6 and human herpesvirus 7 viruses are the members that are most studied as being possible triggers of multiple sclerosis. According to evidence in the literature, the herpesvirus family is strongly involved in the pathogenesis of this disease, but it is unlikely that they are the only component responsible for its development. There are probably multiple triggers and more studies are necessary to investigate and define these interactions.

A esclerose múltipla é a doença inflamatória auto-imune mais comum do sistema nervoso central. Sua etiologia já foi creditada apresentar tanto causas genéticas quanto ambientais. Vários vírus já foram implicados como desencadeadores desta doença e existem inúmeros trabalhos fazendo correlação entre a família Herpesviridae e a patogênese da esclerose múltipla. As características mais importantes dos Herpesviridae são as de apresentarem períodos de latência e exacerbação e terem como seu principal santuário biológico o sistema nervoso central. O vírus Epstein-Barr, o citomegalovírus, o herpesvirus tipo 6 e herpesvirus tipo 7 são os membros mais estudados como desencadeadores da esclerose múltipla. Conforme as evidencias que a literatura apresenta a família Herpesviridae está fortemente envolvida na patogênese da esclerose múltipla, porém é pouco provável que sejam os únicos responsáveis pelo seu início. É provável que esta doença apresente inúmeros desencadeadores e mais estudos são necessários para determinar estas interações.

Central nervous system infectious diseases mimicking multiple sclerosis: recognizing distinguishable features using MRI / Doencas infecciosas do sistema nervoso central mimetizando esclerose multipla: reconhecendo as caracteristicas de imagem por RM que as distinguem

The current diagnostic criteria for multiple sclerosis (MS) confirm the relevant role of magnetic resonance imaging (MRI), supporting the possibility of characterizing the dissemination in space (DIS) and the dissemination in time (DIT) in a single scan. To maintain the specificity of these criteria, it is necessary to determine whether T2/FLAIR visible lesions and the gadolinium enhancement can be attributed to diseases that mimic MS. Several diseases are included in the MS differential diagnosis list, including diseases with exacerbation, remitting periods and numerous treatable infectious diseases, which can mimic the MRI features of MS. We discuss the most relevant imaging features in several infectious diseases that resemble MS and examine the primary spatial distributions of lesions and the gadolinium enhancement patterns related to MS. Recognizing imaging "red flags" can be useful for the proper diagnostic evaluation of suspected cases of MS, facilitating the correct differential diagnosis by assessing the combined clinical, laboratory and MR imaging information.

Os critérios diagnósticos atuais para a esclerose múltipla (EM) destacam a ressonância magnética (RM) e reforçam a caracterização de disseminação no espaço e no tempo, mesmo em um único exame. Para preservar a especificidade desses critérios é necessário determinar se as lesões identificadas em T2/FLAIR e o realce pelo gadolínio não são devidos a doenças que mimetizam EM. Várias doenças compõem a lista de diagnósticos diferenciais da EM, incluindo algumas com períodos de exacerbação e remissão, além de doenças infecciosas tratáveis, que podem imitar suas características de RM. Discutiremos as características de imagem mais relevantes de diversas neuroinfecções que mimetizam EM, examinando a distribuição espacial das lesões e os padrões de realce pelo gadolínio. O reconhecendo dos sinais de alerta por imagem pode ser útil para a avaliação diagnóstica de casos suspeitos de EM, conduzindo ao diagnóstico diferencial correto através de uma avaliação combinada da clínica, laboratório e imagem.

Medication withdrawal may be an option for a select group of patients in relapsing-remitting multiple sclerosis.

This article describes the clinical and radiological evolution of a stable group of patients with relapsing-remitting multiple sclerosis that had their disease-modifying therapy (DMT) withdrawn. Forty patients, which had made continuous use of one immunomodulator and had remained free of disease for at least 5 years, had their DMT withdrawn and were observed from 13 to 86 months. Out of the followed patients, 4 (10%) patients presented with new attacks. In addition to these patients, 2 (5%) patients had new lesions revealed by magnetic resonance imaging that did not correspond to clinical attacks. Despite these results, the difficult decision to withdraw medication requires careful analysis. Withdrawal, however, should not be viewed as simply the suspension of treatment because these patients should be evaluated periodically, and the immunomodulators should be readily reintroduced if new attacks occur. Nonetheless, medication withdrawal is an option for a select group of patients.

Disfagia orofaríngea em pacientes com esclerose múltipla: as escalas de classificação da doença refletem a gravidade da disfagia? / Oropharyngeal dysphagia in patients with multiple sclerosis: do the disease classification scales reflect dysphagia severity?

A esclerose múltipla é uma afecção neurológica que envolve distúrbios da deglutição. Muitos estudos têm mostrado associação entre o comprometimento neurológico e o desempenho da deglutição, porém, os resultados têm sido conflitantes. OBJETIVO: Identificar a frequência de disfagia nos pacientes com esclerose múltipla e os indicadores neurológicos que podem representar o desempenho da deglutição. MÉTODO: Neste estudo (estudo transversal), 120 pacientes com esclerose múltipla foram submetidos à avaliação funcional da deglutição por fibronasofaringolaringoscopia, cujos resultados foram comparados com a pontuação das escalas de classificação (Formas Clínicas Evolutivas da Doença, Escala de Incapacidade Funcional por Sistemas e Escala Ampliada de Incapacidade Funcional [Kurtzke Expanded Disability Status Scale]). RESULTADOS: A disfagia foi identificada em 90% dos pacientes. Dentre as formas clínicas, as formas progressivas (primária progressiva e secundária progressiva) apresentaram com maior frequência disfagia grave, enquanto a forma remitente-recorrente apresentou mais frequentemente disfagia leve e moderada. Em relação à Escala de Incapacidade Funcional por Sistemas, as funções cerebelares, do tronco encefálico e mental tiveram associação com a disfagia, especialmente na forma grave. Quanto à Escala Ampliada de Incapacidade Funcional, pontuações mais altas se associaram aos quadros graves de disfagia. CONCLUSÃO: A disfagia é frequente em pacientes com esclerose múltipla, especialmente naqueles com maior comprometimento das funções neurológicas.

Multiple sclerosis is a neurological disease that involves swallowing disorders. Many studies have shown an association between neurological and swallowing performance, but results have been conflicting. OBJECTIVE: To identify the frequency of dysphagia in patients with multiple sclerosis and neurological indicators that can represent the performance of swallowing. METHOD: In this study (cross-sectional) 120 Multiple Sclerosis patients underwent Functional Assessment of Swallowing by flexible nasal-pharyngo-laryngoscopy and the results were compared with the scores of the rating scales: (Clinical Evolving Forms of Disease, Functional Disability Scale for and Scale Systems Extended Functional Disability [Kurtzke Expanded Disability Status Scale]). RESULTS: Dysphagia was found in 90% of patients. Among the clinical forms of the disease, the progressive forms (primary progressive and secondary progressive) were more frequently associated with severe dysphagia, while the relapsing-remitting form presented more often mild and moderate dysphagia. Regarding the Disability Scale for Functional Systems, cerebellar function, brainstem function and mental health were associated with dysphagia, especially in the severe form. Regarding the Extended Functional Disability Scale, higher scores were associated with severe dysphagia. CONCLUSION: Dysphagia is common in MS patients, especially in those with greater impairment of neurological functions.

Medication withdrawal may be an option for a select group of patients in relapsing-remitting multiple sclerosis / Retirada de medicacao pode ser uma opcao para um grupo selecionado de pacientes com esclerose multipla remitente-recorrente

This article describes the clinical and radiological evolution of a stable group of patients with relapsing-remitting multiple sclerosis that had their disease-modifying therapy (DMT) withdrawn. Forty patients, which had made continuous use of one immunomodulator and had remained free of disease for at least 5 years, had their DMT withdrawn and were observed from 13 to 86 months. Out of the followed patients, 4 (10%) patients presented with new attacks. In addition to these patients, 2 (5%) patients had new lesions revealed by magnetic resonance imaging that did not correspond to clinical attacks. Despite these results, the difficult decision to withdraw medication requires careful analysis. Withdrawal, however, should not be viewed as simply the suspension of treatment because these patients should be evaluated periodically, and the immunomodulators should be readily reintroduced if new attacks occur. Nonetheless, medication withdrawal is an option for a select group of patients.

Esse artigo descreve a evolução clínica e radiológica de um grupo de pacientes com esclerose múltipla estável, forma recorrente-remitente, nos quais foi retirada a terapia modificadora da doença (DMT). Quarenta pacientes, que faziam uso contínuo de um imunomodulador e permaneceram livres da doença pelo menos por 5 anos, tiveram sua DMT retirada e foram observados de 13 a 86 meses. Dos pacientes seguidos, 4 (10%) apresentaram novos surtos. Além destes, 2 (5%) pacientes apresentavam novas lesões na ressonância magnética, sem sintomas clínicos. Apesar destes resultados, a retirada da medicação é uma decisão difícil, requer análise cuidadosa e não deve ser considerada como sinônimo de suspender o tratamento, já que estes pacientes devem ser avaliados periodicamente e o uso de imunomoduladores tem de ser prontamente reiniciado no caso do aparecimento de novos surtos. Não obstante, a retirada do medicamento é uma opção para um grupo selecionado de pacientes.