Socioeconomic, health-care access and clinical determinants of disease severity in Multiple Sclerosis in Chile.

BACKGROUND: MS severity may be affected by genetic, patient-related, disease-related and environmental factors. Socioeconomic status, including income and healthcare access, amongst others, may also have a role in affecting diagnostic delay or therapy prescription. In Chile, two main healthcare systems exist, public-healthcare and private-healthcare, nonetheless universal care laws (e.g., access to High Efficacy Therapy-HET), including both systems, have been recently enacted for people with MS. OBJECTIVE: To assess the role of Socioeconomic Conditions (SEC), clinical variables and public health policies on the impact of disease severity of MS patients in Chile. METHODS: Multicentric, observational, cross-sectional study including patients from two reference centres (1 national reference centre from the private-health system and 1 regional reference centre from the public-health system). SEC and clinical variables included healthcare insurance (private or public), subclassification of health insurance according to monthly income, sex, age at onset, diagnostic delay, disease duration, diagnosis before HET law (as a proxy of HET delay), and current HET treatment. Progression Index (PI), EDSS ≥6.0 and Progressive MS diagnosis were used as outcome measures. Multivariable binary logistic regression was performed. RESULTS: We included 604 patients (460 private-health, 144 public-health), 67% women, 100% white/mestizo, 88% RRMS, mean age 42±12 years, mean age at onset 32±11 years, mean disease duration 10±6 years, median diagnostic delay 0 (0-34) years, 86% currently receiving any DMT, 55% currently receiving HET, median EDSS at last visit of 2.0 (0-10), and median PI 0.17 (0-4.5). Lower monthly income was associated with higher EDSS and higher PI. In the multivariable analysis, public-healthcare (OR 10.2), being diagnosed before HET-law (OR 4.89), longer diagnostic delay (OR 1.26), and older age at onset (OR 1.05) were associated with a higher risk of PI>0.2, while current HET (OR 0.39) was a protective factor. Diagnosis before HET-law (OR 7.59), public-healthcare (OR 6.49), male sex (OR 2.56), longer disease duration (OR 1.2) and older age at onset (OR 1.1) were associated with a higher risk of Progressive MS. Public-healthcare (OR 5.54), longer disease duration (OR 1.14) and older age at onset (OR 1.08) were associated with a higher risk of EDSS ≥6.0 while current treatment with HET had a trend as being a protective factor (OR 0.44, p = 0.05). CONCLUSION: MS severity is impacted by non-modifiable factors such as sex and age at onset. Interventions focused on shortening diagnostic delay and encouraging early access to high-efficacy therapies, as well as initiatives that may reduce the disparities inherent to lower socioeconomic status, may improve outcomes in people with MS.

Ythdf2 regulates cardiac remodeling through its mRNA target transcripts.

m6A mRNA methylation controls cardiomyocyte function and increased overall m6A levels are a stereotyping finding in heart failure independent of the underlying etiology. However, it is largely unknown how the information is read by m6A reader proteins in heart failure. Here we show that the m6A reader protein Ythdf2 controls cardiac function and identified a novel mechanism how reader proteins control gene expression and cardiac function. Deletion of Ythdf2 in cardiomyocytes in vivo leads to mild cardiac hypertrophy, reduced heart function, and increased fibrosis during pressure overload as well as during aging. Similarly, in vitro the knockdown of Ythdf2 results in cardiomyocyte growth and remodeling. Mechanistically, we identified the eucaryotic elongation factor 2 as post-transcriptionally regulated by Ythdf2 using cell type specific Ribo-seq data. Our study expands our understanding on the regulatory functions of m6A methylation in cardiomyocytes and how cardiac function is controlled by the m6A reader protein Ythdf2.

Atividade antimicrobiana in vitro da midecamicina sobre bactérias anaeróbicas / In vitro activity of midecamycin against anaerobic bacteria

Quarenta e oito cepas de bactérias anaeróbias, provenientes de casos clínicos recentes, foram avaliadas quanto à sensibilidade à concentraçäo crítica de midecamicina e de outros quatro antimicrobianaos: eritromicina, rifampicina, clindamicina e cloranfenicol. A eritromicina mostrou-se a menos ativa das drogas estudadas, seguindo-se em ordem crescente de atividade, o cloranfenicol, a rifampicina, a midecamicina e a clindamicina. A midecamicina mostrou 100% de atividade sobre os bacilos e cocos Gram-positivos e foi a mais ativa (92%) sobre os bacilos Gram-positivos esporulados. Pelos resultados no controle da infecçäo anaeróbia

Passivacao do cobre, alternativa para obtencao da condicao de anaerobiose. / Copper oxidation, an alternative for obtaining anaerobiosis conditions

Os metodos empregados, para obtencao da condicao de anaerobiose, foram analizados tomando-se em conta as exigencias fisiologicas dos anaerobios. A monitoracao da condicao de anaerobiose, no interior da jarra, empregando-se um sistema alternativo de isolamento de anaerobios clinicamente significantes, foi feita utilizando-se corantes indicadores de oxi-reducao, indicadores biologicos, e as variacoes manometricas.As provas foram realizadas usando-se como parametros de comparacao, um sistema convencional. A determinacao do potencial oxi-reducao com corantes mostrou que o tempo necessario para obter-se a condicao desejada, na atmosfera interna da jarra(5 horas), e superior ao necessario para o mesmo objetivo nos meios de cultura usados(2,30 horas). Todos os anaerobios empregados como indicadores biologicos tiveram crescimento satisfatorio. O estudo das variacoes manometricas comprovou que o mecanismo proposto para o sistema alternativo apresentado e valido, sendo portando indicado o seu uso por ser simples e barato