T cell immunity and caregiving stress in young and older caregivers

Background: The present study aimed to examine the impact of caregiving stress and aging on parameters of T cell immunity using caregivers and controls across two age cohorts. Methods: Seventy-nine young and older caregivers (parents of children with developmental disabilities and spousal dementia caregivers, respectively) were compared to 76 non-caregiving controls. Participants completed questionnaires to provide information about socio-demographics, health behaviour, psychosocial and caregiving variables, and provided a blood sample. T cell senescence and exhaustion markers, thymic output, and serum CMV antibody titre were assessed. Results: Despite greater psychological morbidity (greater depression, anxiety, perceived stress) than controls, caregivers showed robust immunity for most T cell parameters with the exception of KLRG-1 (marker involved in T cell senescence pathway). Conclusions: A higher percentage of KLRG1+ T cells in caregivers could explain the poorer vaccination response that has previously been reported in this group. These data also suggest that the impact of caregiving per se on immunity is not uniform

Circulating steroid hormone variations throughout different stages of prostate cancer

Steroid hormones play a central role in the maintenance and progression of prostate cancer. The androgen receptor is the primary driver of tumor cell proliferation and is activated by the androgens testosterone and 5α-dihydrotestosterone. Inhibition of this pathway through medical or surgical castration improves survival in the majority of advanced prostate cancer patients. However, conversion of adrenal androgen precursors and alternative steroidogenic pathways have been found to contribute to tumor progression and resistance to treatment. The emergence of highly accurate detection methods allows us to study steroidogenic mechanisms in more detail, even after treatment with potent steroidogenic inhibitors such as the CYP17A1 inhibitor abiraterone. A clear overview of steroid hormone levels in patients throughout the local, metastatic and castration-resistant stages of prostate cancer and treatment modalities is key toward a better understanding of their role in tumor progression and treatment resistance. In this review, we summarize the currently available data on steroid hormones that have been implicated in the various stages of prostate cancer. Additionally, this review addresses the implications of these findings, highlights important studies in this field and identifies current gaps in literature

Modelling oral adrenal cortisol support

A simplified mathematical model of oral hydrocortisone delivery in adrenal insufficiency is described; the model is based on three components (gastric hydrocortisone, free serum cortisol and bound serum cortisol) and is formulated in terms of linear kinetics, taking into account the dynamics of glucocorticoid-protein binding. Motivated by the need to optimise cortisol replacement in the situations of COVID-19 infection, the model is fitted to recently-published data on 50 mg dosing and earlier data on 10 mg dosing. The fitted model is used to predict typical responses to standard dosing regimes, which involve a larger dose in the morning and 1 or 2 smaller doses later in the day, and the same regimes with doses doubled. In all cases there is a circadian-like response, with early morning nadir. The model is also used to consider an alternative dosing strategy based on four equal and equally-spaced doses of 10, 20 or 30 mg per 24 h, resulting in a more even response resembling a response to sustained inflammatory stress.Comment: 8 pages, 2 figures 1 tabl