Harshness and unpredictability: Childhood environmental links with immune and asthma outcomes.

The environment has pervasive impacts on human development, and two key environmental conditions - harshness and unpredictability - are proposed to be instrumental in tuning development. This study examined (1) how harsh and unpredictable environments related to immune and clinical outcomes in the context of childhood asthma, and (2) whether there were independent associations of harshness and unpredictability with these outcomes. Participants were 290 youth physician-diagnosed with asthma. Harshness was assessed with youth-reported exposure to violence and neighborhood-level murder rate. Unpredictability was assessed with parent reports of family structural changes. Youth also completed measures of asthma control as well as asthma quality of life and provided blood samples to assess immune profiles, including in vitro cytokine responses to challenge and sensitivity to inhibitory signals from glucocorticoids. Results indicated that harshness was associated with more pronounced pro-inflammatory cytokine production following challenge and less sensitivity to the inhibitory properties of glucocorticoids. Furthermore, youth exposed to harsher environments reported less asthma control and poorer quality of life. All associations with harshness persisted when controlling for unpredictability. No associations between unpredictability and outcomes were found. These findings suggest that relative to unpredictability, harshness may be a more consistent correlate of asthma-relevant immune and clinical outcomes.

The Relationship Between Disproportionate Social Support and Metabolic and Inflammatory Markers: Moderating Role of Socioeconomic Context.

OBJECTIVE: The present study examines the association of disproportionate social support (the relative balance of support given versus received) on metabolic and inflammatory outcomes and whether effects vary by socioeconomic context. METHODS: We enrolled a sample of 307 parental caregivers living with a child with a chronic illness. Parents were assessed on four dimensions of social support: emotional support received, instrumental support received, emotional support given, and instrumental support given. Disproportionate social support was calculated as the difference between support received and support given. Participants provided sociodemographic information, were interviewed about financial stress, and were assessed on metabolic (systolic blood pressure, diastolic blood pressure, total cholesterol, body fat percent, and body mass index) and inflammatory (interleukin 6 and C-reactive protein) outcomes. RESULTS: More disproportionate instrumental and emotional support was associated with higher inflammation (b = 0.10, SE = 0.04, p = .014; b = 0.0.09, SE = 0.05, p = .042, respectively). We observed significant interactions between disproportionate social support and income (b = -0.04, SE = 0.02, p = .021). Parents from lower-income households who gave more emotional support than they received had higher inflammation compared with those from higher-income households. We also observed a significant interaction between disproportionate instrumental support and income (b = 0.04, SE = 0.02, p = .006). Parents from lower-income households who received more instrumental support than they gave had worse metabolic outcomes compared with parents from higher-income households. Parallel interaction patterns were observed using an interview-based measure of financial stress. CONCLUSIONS: These findings show that disproportionate social support has implications for physical health, particularly for caregivers from socioeconomically disadvantaged households.

Evidence for skin-deep resilience using a co-twin control design: Effects on low-grade inflammation in a longitudinal study of youth.

This study tested the skin-deep resilience hypothesis - that low socioeconomic status (SES) youth who are working hard to succeed in life experience good psychological and educational outcomes but at a cost to their physical health - in a sample of monozygotic (MZ) twins. The National Longitudinal Study of Adolescent Health (Add Health) contained a sample of 226 MZ twin pairs at Wave 1 (M age = 16 years), of whom 141 pairs completed the Wave 4 assessment 13 years later (M age = 29 years). Family SES was measured at Wave 1 via income, education, and occupation. Conscientiousness was measured at Wave 4 as an indicator of those who were working hard to succeed in life. Outcomes measured at Wave 4 included low-grade inflammation (C-reactive protein, CRP), mental health (depression, problematic alcohol use), and academic success (educational attainment). A co-twin control design was utilized which directly compared within-twin differences in the association between conscientiousness and life outcomes. Main effects of between-twin conscientiousness were found such that higher levels of conscientiousness were associated with higher educational attainment, fewer symptoms of depression, and less problematic alcohol use, across all SES groups. An interaction between family SES and within-twin difference in conscientiousness was found for CRP, such that, among twins growing up in lower SES households, the twin with higher levels of conscientiousness had higher levels of CRP. These patterns provide support for the phenomenon of skin-deep resilience using a twin methodology that reduces the possibility of confounding by shared genetic and environmental factors.

Inhibitory effects of SEL201 in acute myeloid leukemia.

MAPK interacting kinase (MNK), a downstream effector of mitogen-activated protein kinase (MAPK) pathways, activates eukaryotic translation initiation factor 4E (eIF4E) and plays a key role in the mRNA translation of mitogenic and antiapoptotic genes in acute myeloid leukemia (AML) cells. We examined the antileukemic properties of a novel MNK inhibitor, SEL201. Our studies provide evidence that SEL201 suppresses eIF4E phosphorylation on Ser209 in AML cell lines and in primary patient-derived AML cells. Such effects lead to growth inhibitory effects and leukemic cell apoptosis, as well as suppression of leukemic progenitor colony formation. Combination of SEL201 with 5'-azacytidine or rapamycin results in synergistic inhibition of AML cell growth. Collectively, these results suggest that SEL201 has significant antileukemic activity and further underscore the relevance of the MNK pathway in leukemogenesis.