Conectar
by Nathanael J. Kuzio, Marco Tonelli, Jasna Fejzo, Jeanne A. Hardy
Proteases represent a difficult family of proteins to purify, concentrate and store at homogeneity due to their toxicity during overexpression and their propensity to self-cleave, leading to the loss of sample stability and function. A protease of interest, caspase-6, is a member of the apoptotic family of caspases, and has been shown to be involved in human neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Previous studies have elucidated key structural aspects and potential inhibition mechanisms of caspase-6 through various structural biology techniques such as x-ray crystallography and hydrogen-deuterium exchange mass spectrometry. However, caspase-6 undergoes a structural transition that requires atomic-resolution insight in solution to understand the conformational transitions and ensemble. This can be most optimally achieved using multi-dimensional biomolecular NMR. Prior attempts to study caspase-6 by NMR have failed due to challenges in sample preparation and insufficient protein concentration. Here, we document our exploratory strategy, which ultimately led to the refinement of crucial sample preparation steps and enabled us to obtain isotopically-labeled caspase-6 in yields suitable for heteronuclear NMR studies. We present this work in the hope that it will assist others in the preparation of difficult protein samples, particularly proteases.An estimated 262 million people lived with asthma globally in 2019. Similarly, in 2021, chronic obstructive pulmonary disease (COPD) was responsible for 3.5% million global deaths. They are usually distinct disorders, but the Global Initiative Chronic Obstructive Lung Disease (GOLD) 2024 strategy document asserts that asthma and COPD are conditions that may coexist in an individual and may require specific personalised approaches and treatments. It is acknowledged that they may share some common treatable traits and clinical features There are many challenges to manage asthma and COPD in the older population, including poor adherence to prescribed medications and poor inhaler techniques. The overall aim of this systematic review is to identify, appraise and synthesise available evidence around digital health interventions used to improve medication adherence in older people with asthma or COPD.
This systematic review will examine studies that evaluated digital health interventions for asthma or COPD in any setting (eg, primary or secondary care). To be included, studies must be reported in English, Arabic or French and published from the year 2000 onwards. A literature search will be performed in MEDLINE via Ovid, Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, EMBASE and PsycINFO via Ovid to identify relevant articles published since 2000 and up to December 2024. No language restrictions will be applied.
The Cochrane risk-of-bias tool for randomised trials will be used to assess the quality of retrieved randomised controlled trials and quasi-experimental studies. The quality of cross-sectional, cohort and case-control studies will be assessed using the Newcastle Ottawa Scale. Mixed-methods studies will be assessed using the Mixed Methods Appraisal Tool (MMAT). The quality of qualitative studies will be assessed using the Critical Appraisal Skills Programme (CASP) qualitative checklist.
Data will be synthesised using a convergent segregated approach, which involves an independent synthesis of quantitative and qualitative data leading to the generation of quantitative and qualitative evidence, which will then be integrated.
Ethics approval is not applicable for this study since no original data will be collected. The results will be disseminated through a peer-reviewed publication and conference presentations. Findings will be used in a bigger project aimed to answer the question on how to embed a pharmacist-led digital health service to support older people with asthma or COPD into the NHS (National Health Service) usual care.
CRD42024575924.
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