Social support moderates D-dimer and self-rated successful aging within people with HIV and older adults.

Many factors can influence perceptions of successful aging (SA), including social isolation and poor physical health. We hypothesized that social support attenuates the negative effect of plasma D-dimer, a correlate of HIV and aging, on SA. Participants included 230 adults (134 people with HIV; PWH, 96 HIV-), ages 36-65, segregated into age cohorts with up to 5 yearly visits. Multilevel modeling examined longitudinal within-person associations between D-dimer, social support, and SA. Social support moderated the relationship between D-dimer and SA and was significant among PWH and older individuals (ages 56-65), but not HIV- or younger cohorts. This association was significant only at extreme levels of social support, with significant decreases in social support potentiating the negative impact of D-dimer on SA and significant increases in social support facilitating increased SA. Despite declining health, high social support may improve SA in PWH and older adults, and low support may be especially problematic for older adults

The Oxytocin Receptor as an Acute Phase Protein and its Signaling Pathways in Response to Inflammation

Social environment influences the progression of atherosclerosis, a chronic inflammatory process. Oxytocin (OT) has been associated with pro-social behavior; however, plasma OT levels are not elevated in a pro-social environment in animal models of disease. Infusion of exogenous OT in these disease models attenuates inflammation and arterial plaque, which raises the possibility that OT’s anti-inflammatory effects may be regulated at the level of the OT receptor (OTR) rather than by changes in plasma OT titers as a function of social environment. The current study investigated OTR and signaling pathways in human macrophages to understand how inflammation affects the OT/OTR system at the molecular level. We hypothesized that OTR is an acute phase protein, whose expression is increased during the inflammatory response though a nuclear factor κB (NF-κB) mediated pathway. We further evaluated whether inflammation alters OTR signaling pathways, which can occur through either the phosphatidylinositol (PI) (Gαq/11) or the cAMP (Gαs) pathways. Inflammation was induced by treating THP-1 macrophages with lipopolysaccharide (LPS) and monitored by expression of the inflammatory cytokine, interleukin-6 (IL-6). Cells were treated with exogenous IL-6 and NF- κB inhibitor and OTR gene expression was measured by RT-PCR. OTR signaling was evaluated by phosphorylation of downstream targets, ERK1/2 from the PI pathway, and CREB from the cAMP pathway, by immunoblotting after LPS and OT treatments. Induction of inflammation by LPS stimulation of macrophages significantly up-regulated OTR transcription 150-fold relative to control cell, however IL-6 had no effect on OTR expression. Blocking NF-κB activation prevented the increase in OTR transcription. Our data also confirmed OT-treatment of macrophages inhibits LPS stimulated IL-6 secretion. Incubation of LPS-treated cells with OT caused increased phosphorylation of ERK1/2 and CREB. Individual blocking of Gαq/11 and Gαs RNA resulted in a loss of OT’s ability to down-regulate IL-6. Together these results demonstrate receptor function through both Gαq/11 and Gαs signaling pathways during inflammation. OTR is an acute phase protein, whose expression can be regulated by NF-κB. Current data suggest both the PI and cAMP signaling pathways are activated by OTR during an inflammatory response and that the receptor may be responsible for attenuating the inflammatory response of the macrophage. This study is the first to demonstrate OT\u27s effect on the non-conventional cAMP signaling pathway in this cell line and the importance of OTR in regulating inflammation. This suggests OTR regulation/function should be considered in addition to measurement of plasma OT

Associations Between Physical Frailty and Cognitive Functioning Using Factor Analysis

While there are several proposed definitions, Fried et al. (2001) is the first study to define the physical characteristics of frailty. To date there have been few attempts to validate this criterion. Further, there is a long-standing and growing interest in the relationship between frailty and cognitive impairment. Few studies have investigated this relationship using an unmodified Fried criterion and cognitive measures beyond a mental status screener. We first examined whether the physical indicators of Fried phenotype cluster together to describe frailty syndrome using confirmatory factor analysis (CFA) and we further explored the association between frailty as a latent variable and as individual indicators with specific cognitive domains. Participants (n=214) were recruited from the University of Miami Memory Disorders Clinic and the Miami community. All participants underwent frailty and comprehensive neuropsychological assessments. A five-factor confirmatory model was tested and latent and multiple regression were used to determine associations between frailty and cognition. We found the five-factor model of frailty fit the data. The frailty latent variable was negatively associated with verbal and visual memory. Walking speed was negatively associated with verbal memory and demonstrated marginal significant association with visual memory. The data support the existence of a latent construct consistent with frailty syndrome. Frailty syndrome was associated with memory dysfunction, but not with other cognitive domains. This contrasts with literature showing more widespread cognitive dysfunction among frail individuals. Understanding the relationship between frailty and memory may encourage clinicians to consider additional screens/referrals, which ultimately will improve caring for older adults.</p