SummaryThe fibromuscular stroma of the prostate regulates normal epithelial differentiation and contributes to carcinogenesis in vivo. We developed and characterized a human 3D prostate organoid co-culture model that incorporates prostate stroma. Primary prostate stromal cells increased organoid formation and directed organoid morphology into a branched acini structure similar to what is observed in vivo. Organoid branching occurred distal to physical contact with stromal cells, demonstrating non-random branching. Stroma-induced phenotypes were similar in all patients examined, yet they maintained inter-patient heterogeneity in the degree of response. Stromal cells expressed growth factors involved in epithelial differentiation, which was not observed in non-prostatic fibroblasts. Organoids derived from areas of prostate cancer maintained differential expression of alpha-methylacyl-CoA racemase and showed increased viability and passaging when co-cultured with stroma. The addition of stroma to epithelial cells in vitro improves the ability of organoids to recapitulate features of the tissue and enhances the viability of organoids.

The results raise questions about what constitutes appropriate levels of occupational therapy service use and how to ensure that these levels are achieved.

This article describes a three-phase project to identify and develop an occupational therapy response to the challenges experienced by caregivers of middle-aged and older adults with multiple sclerosis (MS). In Phase 1 302 caregivers of middle-aged and older adults with MS were interviewed by telephone to identify the care-giving challenges they experienced. A total of eight challenges were identified, with the four most prevalent ones including finding and using formal support services, managing the emotional aspects of caregiving, doing the physical aspects of care-giving and dealing with informal supports. In Phase 2 a comprehensive literature review was conducted to identify existing caregiver education programmes that could be used to address these challenges. None of the 21 programmes that were located addressed all of the challenges identified through the Phase 1 interviews. In response, a new five-session psycho-educational group programme entitled 'Meeting the Challenges of MS' was developed in Phase 3. The programme was empirically grounded in Phase 1 findings, and drew on theory to guide group process and sequencing. The findings from Phases 1 and 2 and the resulting programme cannot be generalized to caregivers of younger adults with MS, although the steps taken to develop this programme have the potential for replication with other populations served by occupational therapists.

Multiple sclerosis (MS) is a chronic neurological disease with numerous symptoms and consequences that does not typically reduce life expectancy. Mental health issues are common in this population, yet few investigations have targeted people aging with this disease (i.e., people aged 45+). This study examined factors contributing to mental health challenges among 1282 people with MS aged 45 to 90 and the extent of mental health service use among those who reported problems. Findings showed that functional abilities, age, years since diagnosis, presence of a helper, and self-rated health are related to mental health challenges. Less than 16% of people with mental health challenges were receiving services.

Vitamin D is an essential steroid hormone that regulates systemic calcium homeostasis and cell fate decisions. The prostate gland is hormonally regulated, requiring steroids for proliferation and differentiation of secretory luminal cells. Vitamin D deficiency is associated with an increased risk of lethal prostate cancer, which exhibits a dedifferentiated pathology, linking vitamin D sufficiency to epithelial differentiation. To determine vitamin D regulation of prostatic epithelial differentiation, patient-derived benign prostate epithelial organoids were grown in vitamin D-deficient or -sufficient conditions. Organoids were assessed by phenotype and single-cell RNA sequencing. Mechanistic validation demonstrated that vitamin D sufficiency promoted organoid growth and accelerated differentiation by inhibiting canonical Wnt activity and suppressing Wnt family member DKK3. Wnt and DKK3 were also reduced by vitamin D in prostate tissue explants by spatial transcriptomics. Wnt dysregulation is a known contributor to aggressive prostate cancer, thus findings further link vitamin D deficiency to lethal disease.