Ratiometric imaging of minor groove binders in mammalian cells using Raman microscopy.

Quantitative drug imaging in live cells is a major challenge in drug discovery and development. Many drug screening techniques are performed in solution, and therefore do not consider the impact of the complex cellular environment in their result. As such, important features of drug-cell interactions may be overlooked. In this study, Raman microscopy is used as a powerful technique for semi-quantitative imaging of Strathclyde-minor groove binders (S-MGBs) in mammalian cells under biocompatible imaging conditions. Raman imaging determined the influence of the tail group of two novel minor groove binders (S-MGB-528 and S-MGB-529) in mammalian cell models. These novel S-MGBs contained alkyne moieties which enabled analysis in the cell-silent region of the Raman spectrum. The intracellular uptake concentration, distribution and mechanism were evaluated as a function of the pK a of the tail group, morpholine and amidine, for S-MGB-528 and S-MGB-529, respectively. Although S-MGB-529 had a higher binding affinity to the minor groove of DNA in solution-phase measurements, the Raman imaging data indicated that S-MGB-528 showed a greater degree of intracellular accumulation. Furthermore, using high resolution stimulated Raman scattering (SRS) microscopy, the initial localisation of S-MGB-528 was shown to be in the nucleus before accumulation in the lysosome, which was demonstrated using a multimodal imaging approach. This study highlights the potential of Raman spectroscopy for semi-quantitative drug imaging studies and highlights the importance of imaging techniques to investigate drug-cell interactions, to better inform the drug design process.

Stepping Up and Stepping In: Exploring the Role of Nurses in Supporting Grandparents Raising Grandchildren.

This study focused on the experiences of grandparents raising grandchildren in rural, Prince Edward Island, Canada. Termed grand-families, there are numerous reasons why grandparents must step up and step in to care for their grandchildren. Often these reasons are related to their adult children's struggles with mental illness and substance use disorders. Adopting Clandinin and Connelly's approach to narrative inquiry, we present findings from the conversational interviews conducted with 12 grandparents raising their grandchildren. Interview data were analyzed through the narrative dimensions of time, place, and relationship. Findings are presented as rich narratives which illuminate the evolution and storied experiences of grand-families. Particularly revealing are the challenges grandparents face as they navigate various systems, including health care, that do not acknowledge the uniqueness of their family form. Nurses work with grand-families across varied clinical settings. Grounded within the philosophy of Patient and Family Centered Care and family nursing theory, this article offers recommendations for supportive interventions that nurses can implement when caring for grand-families across clinical settings. This study has the potential to facilitate the development of evidence-based supports and services, which are responsive to the needs, realities, and complexities of grand-families.

Patient healthcare experiences in the Northwest Territories, Canada: an analysis of news media articles.

The factors that influence patient healthcare experiences are complex and connected to place. In northern Canada, the socio-historical context and the inequitable distribution of health services are unique influences on patients. The objective of this study was to examine the characteristics of patient healthcare experiences as reported through news media in the Northwest Territories. We used a case series design to examine patient healthcare experiences reported in news media articles. We conducted a systematic search for articles published between 2008 and 2017 in the online database of a media outlet in the Northwest Territories. We used descriptive statistics to summarise the article characteristics and thematic analysis to understand patient experiences in 128 articles related to 71 cases. Most often, cases involved women, concerned mental health, suicidality, or chronic diseases, and were predominantly negative. Patient experiences included problems associated with medical travel, communication difficulties with providers, lack of cultural safety, and barriers in accessing care resulting in poor-quality care, particularly for Indigenous patients. Broadly, these experiences are rooted in the colonial history in the North. Understanding patient experiences and including Indigenous patients in health system decision-making can help focus policies and clinical care on cultural safety and equity.