Acculturation Stress Magnifies Child Depression Effect of Stressful Life Events for Latinx Youth 3 Years Later.

Introduction: Experiences of stressful life events (SLEs) during childhood are associated with greater risk for youth psychopathology. Although SLEs are reported in greater frequency by Latinx families, Latinx populations remain largely absent in the SLE literature. Furthermore, Latinx populations face added stressors related to socio-political climate, acculturation, and racism and discrimination. The purpose of this study was to explore the intersection between parent-reported SLEs and acculturation (i.e., socio-political climate-related) stressors for Latinx youth. Greater frequency of caregiver reported SLEs were hypothesized to predict higher depressive symptoms in their children three years later, and acculturation stress was hypothesized to amplify these effects. Method: The community-recruited, low-income sample for this study consisted of 198 Latinx caregivers (98.5% mothers, 77.3% foreign-born) and their children (M age = 7.4, 47.5% female). Study hypotheses were tested using MPlus. Results: Consistent with prior literature, more SLEs reported at age 7 by parents were associated with more child-reported depressive symptoms at age 10 but only among boys. However, for both boys and girls, there was a significant interaction between acculturation stress and family SLEs. Specifically, as the amount of acculturation stress reported at age 7 increased, the negative impact of family SLEs on child-reported depressive symptoms at age 10 was magnified, regardless of gender. Conclusion: Adding to the literature on SLEs within Latinx families, these results indicate that acculturation and socio-political climate stressors need be considered in discussions of the effects of life stress on Latinx youth and their families.

Stressful Work Trajectories and Depressive Symptoms in Middle-Aged Couples: Moderating Effect of Marital Warmth.

OBJECTIVES: The present study investigated the decade-long actor and partner infleunces between husbands' and wives' trajectories of stressful work conditions (SWCs) and their depressive symptoms while also considering the moderation of these influences by spousal warmth. METHODS: Participants were 330 middle-aged dual-earner couples from the Iowa Midlife Transitions Project. Husbands and wives reported on own SWCs and reported on parenter's warmth in the years of 1991, 1992, and 1994. Depressive symptoms for husbands and wives were measured by the SCL-90-R in 1994 and 2001. Structural equation models, growth curves, and longitudinal data were used to perform our analyses. RESULTS: For husbands and wives, trajectories of SWCs over early middle years (1991-1994) contributed to depressive symptoms in 1994. Notably, for husbands and wives, the severity (level) of SWCs in 1991 had a persistent influence on depressive symptoms a decade later (2001). For husbands, under conditions of wives' low warmth, SWCs exerted a relatively strong influence on their depressive symptoms. However, under conditions of high warmth from wives, most of these influences were greatly diminished. DISCUSSION: Results from the current study indicate that contextual life experiences can have a persistent health influences over the life course.

Derivatives of the pyrazolo[1,5-a]pyrimidine acetamide DPA-713 as translocator protein (TSPO) ligands and pro-apoptotic agents in human glioblastoma.

The 18kDa translocator protein (TSPO) is a target for novel glioblastoma therapies due to its upregulation in this cancer and relatively low levels of expression in the healthy cortex. The pyrazolo[1,5-a]pyrimidine acetamides, exemplified by DPA-713 and DPA-714, are a class of high affinity TSPO ligands with selectivity over the central benzodiazepine receptor. In this study we have explored the potential anti-glioblastoma activity of a library of DPA-713 and DPA-714 analogues, and investigated the effect of amending the alkyl ether chain on TSPO affinity and functional potential. All ligands demonstrated nanomolar affinity for TSPO, but showed diverse functional activity, for example DPA-713 and DPA-714 did not affect the proliferation or viability of human T98G glioblastoma cells, while the hexyl ether and benzyl ether derivatives decreased proliferation of T98G cells without affecting proliferation in human fetal glial SVGp12 cells. These ligands also induced apoptosis and dissipated T98G mitochondrial membrane potential. This suggests that the nature of the alkyl ether chain of pyrazolo[1,5-a]pyrimidine acetamides has little influence on TSPO affinity but is important for functional activity of this class of TSPO ligands.

First Demonstration of Positive Allosteric-like Modulation at the Human Wild Type Translocator Protein (TSPO).

We show that changing the number and position of nitrogen atoms in the heteroatomic core of a pyrazolopyrimidine acetamide is sufficient to induce complex binding to wild type human TSPO. Only compounds with this complex binding profile lacked intrinsic effect on glioblastoma proliferation but positively modulated the antiproliferative effects of a synthetic TSPO ligand. To the best of our knowledge this is the first demonstration of allosteric-like interaction at the wild type human TSPO.