Realist evaluation of maternity waiting home intervention models in Inhambane, Mozambique: protocol for a comparative embedded case study, the Mozambique-Canada Maternal Health Project.

INTRODUCTION: This is a study protocol that tests and refines realist theories regarding the uptake and scale-up of the linked maternity waiting home (hereafter MWH) and facility birth intervention in the Mozambican context. The theories were developed through a realist review of MWH-facility birth literature from low-income and middle-income countries. The aim of the proposed study is to contribute to a contextually refined understanding of the causal chains underlying MWH-facility birth adoption by pregnant women and their families, communities, the health system and donors. METHODS AND ANALYSIS: The overarching methodology is mixed-methods realist evaluation. The study will adopt a comparative embedded case study design comparing three new masonry MWHs built by the Mozambique-Canada Maternal Health Project in Inhambane province with three older MWHs selected based on variation in the built environment. Baseline data on participating MWH-facility birth interventions will be collected through observations, reviews of routine data and analysis of statistics and reports from provincial and district health authorities and the Mozambique-Canada Maternal Health project. Realist interviews will be conducted with MWH users and non-users, companions of MWH users and non-users, partners of MWH users and non-users, and stakeholders within the health system and the non-governmental organisation sector. Realist focus groups will be used to collect data from community-level implementers. The analysis will be retroductive and use the context-mechanism-outcome configuration heuristic tool to represent generative causation. We will analyse data from intervention and comparator MWHs independently and compare the resulting refined programme theories. Data analysis will be done in NVivo 12. ETHICS AND DISSEMINATION: Ethics approval for the project has been obtained from the Mozambique National Bioethics Committee (CNBS-Comité Nacional de Bioética para a Saúde) and the University of Saskatchewan Bioethical Research Ethics Board. The evaluation will adhere to the International Ethical Guidelines for Biomedical Research Involving Human Subjects and the African adaptation of evaluation ethics and principles. Evaluation results will be disseminated to stakeholders' practice audiences through peer-reviewed publications, plain-language briefs, theory validation/feedback meetings and conference presentations.

Theoretical studies of the role of C-terminal cysteines in the process of S-nitrosylation of human Src kinases.

Src tyrosine kinases are a family of non-receptor proteins that are responsible for the growth process, cellular proliferation, differentiation and survival. Lack of Src kinase control has been associated with the development of certain human cancers. This family of proteins is constituted of four domains, with SH1 being the kinase or catalytic domain. SH1 also presents three important regulatory sites. Two residues, Tyr416 and Tyr527, are responsible for important phosphorylation processes that lead to, respectively, activation and deactivation of these kinases. More recently, however, a set of four cysteine residues located near the C-terminus-Cys483, Cys487, Cys496 and Cys498-has been associated with the activation of the Src kinases through S-nitrosylation reactions. Particularly, the Cys498 has been specified as a fundamental residue when considering this regulatory mechanism. Aiming to understand the role of these four cysteines in S-nitrosylation, theoretical studies of electrostatic, steric and hydrophobic properties were performed with a sequence of 20 amino acids, enclosing the four cysteine residues under study, extracted from the PDB coordinates of the crystal obtained from the inactive state of Src kinase. Results indicate that Cys498 is buried deeply in the protein, in hydrophobic surroundings in which NO is more likely to suffer decomposition into the electrophilic intermediates known to be responsible for S-nitrosylation reactions. Electronic calculated properties, such as punctual atomic charges, electrostatic potentials and molecular orbital energy, also demonstrated the good nucleophilic potential of Cys498. Graphical Abstract Structure of Src kinase with zoomed area representing the 20 amino acids comprising the CC motif extracted from the whole protein structure. Right upper panel Electrostatic potential map, right lower panel hydrophilic map in anterior view.