Thwarted Belonging and Perceived Burdensomeness During Middle and Older Adulthood: The Role of Generativity.

Using a sample of middle-aged and older adults, this research explores associations between generativity and two key risk factors for suicide: thwarted belonging (T.B.) and perceived burdensomeness (P.B.). These variables are typically studied as predictors of suicide; the current study is unique in examining their psychosocial correlates. Erikson described, generativity as a psychosocial construct that characterizes adult well-being in mid-life, conceptualized as the sense one has successfully guided and contributed to the younger generation through mentoring. Using the Midlife in the United States Survey (MIDUS), the current analyses indicate that generativity is associated with lower levels of P.B. and T.B., even after accounting for measures of hopelessness, depressive symptoms, financial stability, perceived neighborhood quality, chronic health conditions, and respondent's demographic characteristics including gender and age. Results are discussed in terms of applications for suicide-risk prevention, and with regard to the promotion of positive psychosocial development across the lifespan.

Evaluation of an in vitro toxicogenetic mouse model for hepatotoxicity.

Numerous studies support the fact that a genetically diverse mouse population may be useful as an animal model to understand and predict toxicity in humans. We hypothesized that cultures of hepatocytes obtained from a large panel of inbred mouse strains can produce data indicative of inter-individual differences in in vivo responses to hepato-toxicants. In order to test this hypothesis and establish whether in vitro studies using cultured hepatocytes from genetically distinct mouse strains are feasible, we aimed to determine whether viable cells may be isolated from different mouse inbred strains, evaluate the reproducibility of cell yield, viability and functionality over subsequent isolations, and assess the utility of the model for toxicity screening. Hepatocytes were isolated from 15 strains of mice (A/J, B6C3F1, BALB/cJ, C3H/HeJ, C57BL/6J, CAST/EiJ, DBA/2J, FVB/NJ, BALB/cByJ, AKR/J, MRL/MpJ, NOD/LtJ, NZW/LacJ, PWD/PhJ and WSB/EiJ males) and cultured for up to 7 days in traditional 2-dimensional culture. Cells from B6C3F1, C57BL/6J, and NOD/LtJ strains were treated with acetaminophen, WY-14,643 or rifampin and concentration-response effects on viability and function were established. Our data suggest that high yield and viability can be achieved across a panel of strains. Cell function and expression of key liver-specific genes of hepatocytes isolated from different strains and cultured under standardized conditions are comparable. Strain-specific responses to toxicant exposure have been observed in cultured hepatocytes and these experiments open new opportunities for further developments of in vitro models of hepatotoxicity in a genetically diverse population.