Leptin plays a crucial role in regulating energy homoeostasis, neuroendocrine function, metabolism, and immune and inflammatory responses. The adipose tissue is a main source of leptin, but during pregnancy, leptin is also secreted primarily by the placenta. Circulating leptin levels peak during the second trimester of human pregnancy and fall after labor. Several studies indicated a strong association between elevated placental leptin levels and preeclampsia (PE) pathogenesis and elevated serum interleukin-6 (IL-6) levels in PE patients. Therefore, we hypothesized that a local increase in placental leptin production induces IL-6 production in Hofbauer cells (HBCs) to contribute to PE-associated inflammation. We first investigated HBCs-specific IL-6 and leptin receptor (LEPR) expression and compared their immunoreactivity in PE vs. gestational age-matched control placentas. Subsequently, we examined the in vitro regulation of IL-6 as well as the phosphorylation levels of intracellular signaling proteins STAT3, STAT5, NF-κB, and ERK1/2 by increasing recombinant human leptin concentrations (10 to 1000 ng/mL) in primary cultured HBCs. Lastly, HBC cultures were incubated with leptin ± specific inhibitors of STAT3 or STAT5, or p65 NF-κB or ERK1/2 MAPK signaling cascades to determine relevant cascade(s) involved in leptin-mediated IL-6 regulation. Immunohistochemistry revealed ~three- and ~five-fold increases in IL-6 and LEPR expression, respectively, in HBCs from PE placentas. In vitro analysis indicated that leptin treatment in HBCs stimulate IL-6 in a concentration-dependent manner both at the transcriptional and secretory levels (p < 0.05). Moreover, leptin-treated HBC cultures displayed significantly increased phosphorylation levels of STAT5, p65 NF-κB, and ERK1/2 MAPK and pre-incubation of HBCs with a specific ERK1/2 MAPK inhibitor blocked leptin-induced IL-6 expression. Our in situ results show that HBCs contribute to the pathogenesis of PE by elevating IL-6 expression, and in vitro results indicate that induction of IL-6 expression in HBCs is primarily leptin-mediated. While HBCs display an anti-inflammatory phenotype in normal placentas, elevated levels of leptin may transform HBCs into a pro-inflammatory phenotype by activating ERK1/2 MAPK to augment IL-6 expression.

One in four American patients now identify as religiously unaffiliated. This study utilizes thematic analysis to deliver qualitative results from in-depth interviews conducted with five chaplains at a premier cancer research institution in Florida to envision what care for their spiritual dimension should look like in practice. It demonstrates why the chaplains interviewed suggested that spiritual caregiving still contributes to their holistic wellbeing, and it suggests how spiritual care and assessments may be provided to so-called religious ‘nones’—or those who identify as spiritual but not religious, not religiously affiliated, secular humanist, atheist, agnostic, and so on. We conclude with a novel spirituality assessment for use while serving this patient population.

Prenatal stress (PNS) impairs offspring ovarian development by exerting negative long-term effects on postnatal ovarian function and folliculogenesis. FKBP51 is a stress-responsive protein that inhibits glucocorticoid and progesterone receptors. We hypothesize that FKBP51 contributes to impaired ovarian development and folliculogenesis induced by PNS. Timed-pregnant Fkbp5^+/+ (wild-type) and Fkbp5^−/− (knockout) mice were randomly assigned to either the undisturbed (nonstress) or PNS group, with exposure to maternal restraint stress from embryonic days 8 to 18. Ovaries from the offspring were harvested and stained, and follicles were counted according to their stages. Ovarian expressions of FKBP51 were evaluated by immunohistochemistry and Fkbp5 and steroidogenic enzymes were evaluated by qPCR. Compared to controls, Fkbp5^+/+ PNS offspring had increased peripubertal primordial follicle atresia and fewer total follicles in the adult and middle-aged groups. In adult Fkbp5^+/+ offspring, PNS elevated FKBP51 levels in granulosa cells of primary to tertiary follicles. Our results suggest that PNS administration increased FKBP51 levels, depleted the ovarian reserve, and dysregulated ovarian steroid synthesis. However, these PNS effects were tolerated in Fkbp5^−/− mice, supporting the conclusion that FKBP51 contributes to reduced ovarian reserve induced by PNS.