Biology subjects

Martins da Silva, A.

Publications and source records attributed to Martins da Silva, A..

3 recordsLinked to original sources

bioRxiv2023

Distinct disease-modifying therapies are associated with different blood immune cell profiles in people with relapsing-remitting multiple sclerosis

Disease modifying therapies (DMTs) used for treating people with relapsing-remitting multiple sclerosis (pwRRMS) target the immune system by different mechanisms of action. However, there is a lack of a comprehensive comparison of their effects on the immune system. Herein, we evaluated the numbers of circulating B cells, CD4+ and CD8+ T cells, regulatory T cells (Tregs), natural killer (NK) cells and NKT cells, and their subsets, in pwRRMS who were treatment-naive or treated with different DMTs. Compared to treatment-naive pwRRMS, common and divergent effects on immune system cells were observed on pwRRMS treated with different DMTs, with no consistent pattern across all therapies in any of the cell populations analysed. PwRRMS treated with fingolimod, dimethyl fumarate (DMF), or alemtuzumab have reduced numbers of CD4+ and CD8+ T cells, as well as Treg subsets, with fingolimod causing the most pronounced decrease in T cell subsets. In contrast, teriflunomide and interferon (IFN) {beta} have minimal impact on T cells, and natalizumab marginally increases the number of memory T cells in the blood. The effect of DMTs on the B cell, NKT and NK cell subsets is highly variable with alemtuzumab inducing a strong increase in the number of the most immature NK cells and its subsets. This study highlights the absence of a consistent pattern of the impact of various DMTs on immune system cells, with variations in both direction and magnitude of effect thus reenforcing the notion that distinct immune cell subsets are potential players in MS pathophysiology and/or DMT efficacy.

immunology↗

bioRxiv2023

Purinergic Preconditioning Induces Epigenomic and Transcriptomic Changes Resembling Epilepsy-associated Microglial States

Microglia, as the main immune effector cells in the central nervous system (CNS), play a crucial role in a diverse range of neuropathological conditions through their exacerbated activation. Microglial inflammatory responses can be influenced by prior exposures to noxious stimuli, such as increased levels of extracellular adenosine and ATP. These conditions are characteristic of brain insults like epileptic seizures and could potentially shape subsequent responses through epigenetic regulation. In this study, we investigated DNA methylation and expression changes in microglia-like cells differentiated from monocytes following ATP-mediated preconditioning. First, during differentiation, we demonstrate that microglia-like cells acquire standard microglial features, including whole transcriptomes and methylomes like in vivo profiles. We show a predominant DNA demethylation in genomic sequences enriched in binding motifs of microglia lineage transcription factors like PU.1, consistent with the relevance of this factor in in vivo microglia. TLR-mediated activation, after a first exposure to ATP, promotes exacerbated pro-inflammatory activation compared to cells not pre-exposed to ATP. These changes are accompanied by DNA methylation and transcriptional reprogramming associated with the acquisition of trained immunity and altered immune-related functions such as with antigen presentation, phagocytosis and cytokine signaling. Finally, the reprogramming associated with ATP-mediated preconditioning leads to profiles found in microglial subsets linked to epilepsy. Purine-driven microglia immune preconditioning drives epigenetic and transcriptional changes that could contribute to altered functions of microglia during seizure development and progression, particularly associated with neuroinflammation.

immunology↗

bioRxiv2021

Instruments to assess Evidence-Based Practice among healthcare professionals: a systematic review

The study makes it possible to select the most appropriate instruments to evaluate the use of Evidence-Based Practice (EBP) among health professionals. The objective of this study was to assess the measurement properties, summarize and describe the instruments that evaluate the use of EBP in health professionals, currently available through the update of the systematic review. The study was conducted and reported according to recommendations of the PRISMA checklist. A systematic search was conducted in the databases: PubMed, Embase, CINAHL and ERIC. In addition, three groups of search terms: EBP terms; evaluation; cross-cultural adaptation and measurement proprieties. They included studies that showed assessment tools of EBP in healthcare workers in general publication of full-text scientific articles, which tested the measurement properties and publication of an article in English. Searches included published studies from 2006 until July 2020. Evaluation of the methodological quality of the studies was conducted according to the COSMIN initiative. 92 studies were included. Forty new instruments have been identified to assess EBP. From these, most were developed for nursing professionals and physiotherapists. More than 48% of studies have American and Australian English as their native language. Only 28% of the studies included students in the samples. Reliability was considered appropriate (sufficient) in 76% of the instruments. The COSMIN checklist classified 7 (seven) instruments as being suitable for use in the target audience. However, Fresno Test remains the most appropriate instrument for assessing the use of EBP in healthcare professionals. 40 new instruments that assess EBP have been identified. Most are consistent and reliable for measuring the use of EBP in healthcare professionals. The Fresno Test, in a list of seven reliable and valid instruments for analysis, remains the most used and the one that most assesses the domains of EBP.

scientific communication and education↗