Cystic Fibrosis is caused by mutations in CFTR, with a deletion of a phenylalanine at position 508 (F508del-CFTR) representing the most common mutation. The F508del-CFTR protein exhibits a trafficking defect and is retained in the endoplasmic reticulum. Here we describe the development of a high-content screen based on a functional assay to identify proteins that correct the F508del-CFTR defect. Using a HEK293 MSR GripTite cell line that stably expresses F508del-CFTR, we individually co-expressed ϳ450 unique proteins fused to the Cl ؊ -sensitive YFP(H148Q/I152L) mutant. We then tested correction of F508del-CFTR function by the CI ؊ /l ؊ exchange method following stimulation with forskolin/IBMX/genistein, using quantitative recordings in multiple individual cells with a high-content (high-throughput) Cellomics KSR imaging system. Using this approach, we identified several known and novel proteins that corrected F508del-CFTR function, including STAT1, Endothelin 1, HspA4, SAPK substrate protein 1, AP2M1, LGALS3/galectin-3, Trkfused gene, Caveolin 2, PAP/REG3␣, and others. The ability of these correctors to rescue F508del-CFTR trafficking was then validated by demonstrating their enhancement of maturation (appearance of band C) and by cell surface expression of F508del-CFTR bearing HA tag at the ectodomain using confocal microscopy and flow cytometry. These data demonstrate the utility of highcontent analyses for identifying proteins that correct mutant CFTR and discover new proteins that stimulate this correction. This assay can also be utilized for RNAi screens to identify inhibitory proteins that block

BackgroundWith an ever increasing number of individuals living with chronic and terminal illnesses, palliative care as an emerging field is poised for unprecedented expansion. Today’s rising recognition of its key role in patients’ illnesses has led to increased interest in access to palliative care. It is known that homelessness as a social determinant of health has been associated with decreased access to health resources in spite of poorer health outcomes and some would argue, higher need. This article aims to discuss the current state of affairs with regards to accessing palliative care for the homeless in Canada.DiscussionRecent review of the literature reveals differential access to palliative care services and outcomes with differing socio-economic status (SES). Notably, individuals of lower SES and in particular, those who are homeless have poorer health outcomes in addition to poor access to quality palliative care. Current palliative care services are ill equipped to care for this vulnerable population and most programs are built upon an infrastructure that is prohibitive for the homeless to access its services. A preliminary review of existing Canadian programs in place to address this gap in access identified a paucity of sporadic palliative care programs across the country with a focus on homeless and vulnerably-housed individuals. It is apparent that there is no unified national strategy to address this gap in access.SummaryThe changing landscape of the Canadian population calls for an expansion of palliative care as a field and as many have put it, as a right. The right to access quality palliative and end of life care should not be confined to particular population groups. This article calls for the development of a unified national strategy to address this glaring gap in our healthcare provision and advocates for attention to and adoption of policy and processes that would support the homeless populations’ right to quality palliative care.

Even in a developed country such as Canada, there are disparities in just access to adequate health care-and, more specifically, palliative care. That inequality is most notable in an underserved group such as the homeless population. Even the word "homeless" has become both a negative descriptor and a stereotype in our society. We posit that the provision of hospice palliative care is structured on several problematic assumptions: an expectation that patients will have an informal support network (family and friends), a stable and secure residence, a predictive terminal illness trajectory, and reasonable access to health care. Those assumptions create structural inequality within the system.Homeless individuals have considerable experience with death and dying, and qualitative research has shown them to hold the expectation that their death will be both sudden and violent. Here, we look at the current data concerning known disparities in access to good palliative care services experienced by the homeless population, based on a stakeholder analysis of the available literature. That information, coupled with the use of a public health ethics decision-making tool, such as the Good Decision Making in Real Time framework, is used to explore the common ethics challenges that can arise in public health interventions aimed at the provision of end-of-life care to homeless adults. A broad exploration of the system that underlies our care is critical to the proper and appropriate provision of care for homeless individuals.

Decreased mortality, decreased risk of vertical HIV transmission, and many people living with HIV (PLWHIV) being of reproductive age have led many PLWHIV to consider pregnancy. However, scarce data exist regarding the conception planning resources required and available for PLWHIV to have safe and healthy pregnancies. This study aimed to identify gaps between the need for, knowledge of, and access to conception planning information and services among PLWHIV in Ontario, Canada. PLWHIV from three large and two small urban sites in Ontario were recruited (n = 63). Participants completed a cross-sectional survey assessing demographics, expectations and plans for conception, and knowledge about and access to existing conception information and services for PLWHIV. Univariate correlations and ranked analyses were used to assess the associations between the need for, knowledge of, and access to conception planning resources with various demographic variables. Participants' median age was 40 years (interquartile range = 33-45) with 52% being female, 73% identified as heterosexual, and 27% as lesbian, gay, bisexual, queer, transgender, two-spirited, or other. Univariable analysis indicated that male PLWHIV and those from small urban areas were less likely to expect children in the future and less likely to speak to healthcare providers about conception planning. Although 63% of all participants intended to conceive and 44% had a plan for conception in the near future, only 30% had spoken to a healthcare provider about pregnancy and only 30% had some knowledge about conception planning and assisted reproductive services for safer conception for PLWHIV. Knowledge of and access to resources on conception planning for PLWHIV varied by sexual orientation and geographic location in Ontario. Our results show a gap between the need for conception information and knowledge of and access to adequate information and resources among PLWHIV in Ontario, which may impact the psychosocial well-being of PLWHIV and their children.

Purpose of review Despite established benefits of palliative care in the oncology population, it remains an underutilized resource particularly among older adults. The illness trajectory and needs of an older adult with cancer are unique. The purpose of this paper is to review the current literature on providing comprehensive palliative and end-of-life care for the older adult with cancer. Recent findings Though the difficulties of applying traditional palliative care principles in the older patients with cancer have been discussed, this review reveals a clear gap in the literature in discussing the provision of comprehensive palliative and end-of-life care in this population. Very few articles have been published in this domain with even fewer published within the past 18 months. Summary As such, this article reviews key aspects of palliative and geriatric medicine that need to be considered and integrated in order to provide comprehensive palliative care to the older adult with cancer. This includes a discussion of proper pain and symptoms assessment, performance status assessment, advance care planning, and end-of-life care while considering the nuances of geriatric syndromes.

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