Research on Race/Ethnicity and Health Care Discrimination: Where We Are and Where We Need to Go

https://ajph.aphapublications.org/doi/pdf/10.2105/AJPH.2012.30070

Propofol inhibits the voltage-gated sodium channel NaChBac at multiple sites.

Voltage-gated sodium (NaV) channels are important targets of general anesthetics, including the intravenous anesthetic propofol. Electrophysiology studies on the prokaryotic NaV channel NaChBac have demonstrated that propofol promotes channel activation and accelerates activation-coupled inactivation, but the molecular mechanisms of these effects are unclear. Here, guided by computational docking and molecular dynamics simulations, we predict several propofol-binding sites in NaChBac. We then strategically place small fluorinated probes at these putative binding sites and experimentally quantify the interaction strengths with a fluorinated propofol analogue, 4-fluoropropofol. In vitro and in vivo measurements show that 4-fluoropropofol and propofol have similar effects on NaChBac function and nearly identical anesthetizing effects on tadpole mobility. Using quantitative analysis by 19F-NMR saturation transfer difference spectroscopy, we reveal strong intermolecular cross-relaxation rate constants between 4-fluoropropofol and four different regions of NaChBac, including the activation gate and selectivity filter in the pore, the voltage sensing domain, and the S4-S5 linker. Unlike volatile anesthetics, 4-fluoropropofol does not bind to the extracellular interface of the pore domain. Collectively, our results show that propofol inhibits NaChBac at multiple sites, likely with distinct modes of action. This study provides a molecular basis for understanding the net inhibitory action of propofol on NaV channels. © 2018 Wang et al

Spontaneous self-affirmation is associated with psychological well-being: evidence from a US national adult survey sample

Emerging evidence suggests that individuals spontaneously self-affirm, by reflecting on values and strengths, in response to daily threats. We examined the prevalence and demographic and well-being correlates of spontaneous self-affirmation in the general population. Participants (n = 3185) completed the cross-sectional, nationally representative 2013 Health Information National Trends Survey (HINTS 4, Cycle 3), and answered questions about spontaneous self-affirmation, demographic factors, well-being, and affect. The majority of the population reported spontaneously self-affirming. Black and Hispanic respondents reported engaging in more spontaneous self-affirmation. Engaging in spontaneous self-affirmation was related to greater happiness, hopefulness, optimism, subjective health, and personal health efficacy, and less anger and sadness

Neural mechanisms of self-affirmation's stress buffering effects

Self-affirmation can buffer stress responses across different contexts, yet the neural mechanisms for these effects are unknown. Self-affirmation has been shown to increase activity in reward-related neural regions, including the ventral striatum and ventromedial prefrontal cortex (VMPFC). Given that reward-related prefrontal cortical regions such as the VMPFC are involved in reducing neurobiological and behavioral responses to stress, we hypothesized that self-affirmation would activate VMPFC and also reduce neural responses to stress in key neural threat system regions such as the dorsal anterior cingulate cortex (dACC) and anterior insula (AI). We explored this hypothesis using self-affirmation and evaluative stress tasks following a within-subjects design in the fMRI scanner. Consistent with prior work, self-affirmation blocks led to lower self-reported stress and improved performance. With respect to neural activity, compared to control blocks, self-affirmation blocks led to greater VMPFC activity, and subsequently less left AI (but not dACC) activity during stress task blocks. Functional connectivity analyses revealed greater connectivity between the VMPFC and left and right AI during self-affirmation compared to control. These findings begin to articulate the neural circuits involved in self-affirmation's effects during exposure to stressors, and more broadly specify neural reward-based responses to stressful situations

The impact of changing attitudes, norms, and self-efficacy on health-related intentions and behavior: a meta-analysis

Objective: Several health behavior theories converge on the hypothesis that attitudes, norms, and self-efficacy are important determinants of intentions and behavior. Yet inferences regarding the relation between these cognitions and intention or behavior rest largely on correlational data that preclude causal inferences. To determine whether changing attitudes, norms, or self-efficacy leads to changes in intentions and behavior, investigators need to randomly assign participants to a treatment that significantly increases the respective cognition relative to a control condition, and test for differences in subsequent intentions or behavior. The present review analyzed findings from 204 experimental tests that met these criteria. Methods: Studies were located using computerized searches and informal sources and meta-analyzed using STATA Version 11. Results: Experimentally induced changes in attitudes, norms, and self-efficacy all led to medium-sized changes in intention (d+ = .48, .49, and .51, respectively), and engendered small to medium-sized changes in behavior (attitudes-d+ = .38; norms-d+ = .36; self-efficacy-d+ = .47). These effect sizes generally were not qualified by the moderator variables examined (e.g., study quality, theoretical basis of the intervention, methodological characteristics, features of the targeted behavior), although effects were larger for interventions designed to increase (vs. decrease) behavioral performance. Conclusion: The present review lends novel, experimental support for key predictions from health behavior theories, and demonstrates that interventions that modify attitudes, norms, and self-efficacy are effective in promoting health behavior change

CCL2 Accelerates Microglia-Mediated Aβ Oligomer Formation and Progression of Neurocognitive Dysfunction

The linkages between neuroinflammation and Alzheimer's disease (AD) pathogenesis are well established. What is not, however, is how specific immune pathways and proteins affect the disease. To this end, we previously demonstrated that transgenic over-expression of CCL2 enhanced microgliosis and induced diffuse amyloid plaque deposition in Tg2576 mice. This rodent model of AD expresses a Swedish beta-amyloid (Abeta) precursor protein mutant.We now report that CCL2 transgene expression accelerates deficits in spatial and working memory and hippocampal synaptic transmission in beta-amyloid precursor protein (APP) mice as early as 2-3 months of age. This is followed by increased numbers of microglia that are seen surrounding Abeta oligomers. CCL2 does not suppress Abeta degradation. Rather, CCL2 and tumor necrosis factor-alpha directly facilitated Abeta uptake, intracellular Abeta oligomerization, and protein secretion.We posit that CCL2 facilitates Abeta oligomer formation in microglia and propose that such events accelerate memory dysfunction by affecting Abeta seeding in the brain