Background and Purpose: Diffusion-weighted imaging (DWI) and perfusion MRI were used to examine the spatiotemporal evolution of stroke lesions in adult macaques with ischemic occlusion. Methods: Permanent MCA occlusion was induced with silk sutures through an interventional approach via the femoral artery in adult rhesus monkeys (n = 8, 10-21 years old). The stroke lesions were examined with high-resolution DWI and perfusion MRI, and T2-weighted imaging (T2W) on a clinical 3T scanner at 1-6, 48, and 96 hours post occlusion and validated with H&E staining. Results: The stroke infarct evolved via a natural logarithmic pattern with the mean infarct growth rate = 1.38 ± 1.32 ml per logarithmic time scale (hours) (n = 7) in the hyperacute phase (1-6 hours). The mean infarct volume after 6 hours post occlusion was 3.6±2.8 ml (n = 7, by DWI) and increased to 3.9±2.9 ml (n = 5, by T2W) after 48 hours, and to 4.7±2.2ml (n = 3, by T2W) after 96 hours post occlusion. The infarct volumes predicted by the natural logarithmic function were correlated significantly with the T2W-derived lesion volumes (n = 5, r = 0.92, p = 0.01) at 48 hours post occlusion. The final infarct volumes derived from T2W were correlated significantly with those from H&E staining (r = 0.999, p < 0.0001, n = 4). In addition, the diffusion-perfusion mismatch was visible generally at 6 hours but nearly diminished at 48 hours post occlusion. Conclusion: The infarct evolution follows a natural logarithmic pattern in the hyperacute phase of stroke. The logarithmic pattern of evolution could last up to 48 hours after stroke onset and may be used to predict the infarct volume growth during the acute phase of ischemic stroke. The nonhuman primate model, MRI protocols, and post data processing strategy may provide an excellent platform for characterizing the evolution of acute stroke lesion in mechanistic studies and therapeutic interventions of stroke disease.
The present study examined the unique impact of perceived negativity in multiple social relationships on endocrine and inflammatory responses to a laboratory stressor. Via hierarchical cluster analysis, those who reported negative social exchanges across relationships with a romantic partner, family, and their closest friend had higher mean IL-6 across time and a greater increase in TNF-α from 15 min to 75 min post stress. Those who reported negative social exchanges across relationships with roommates, family, and their closest friend showed greater IL-6 responses to stress. Differences in mean IL-6 were accounted for by either depressed mood or hostility, whereas differences in the cytokine stress responses remained significant after controlling for those factors. Overall, this research provides preliminary evidence to suggest that having multiple negative relationships may exacerbate acute inflammatory responses to a laboratory stressor independent of hostility and depressed mood.
by
David H. Chae;
Sean Clouston;
Mark L. Hatzenbuehler;
Michael Kramer;
Hannah Cooper;
Sacoby M. Wilson;
Seth I. Stephens-Davidowitz;
Robert S. Gold;
Bruce G. Link
Racial disparities in health are well-documented and represent a significant public health concern in the US. Racism-related factors contribute to poorer health and higher mortality rates among Blacks compared to other racial groups. However, methods to measure racism and monitor its associations with health at the population-level have remained elusive. In this study, we investigated the utility of a previously developed Internet search-based proxy of area racism as a predictor of Black mortality rates. Area racism was the proportion of Google searches containing the "N-word" in 196 designated market areas (DMAs). Negative binomial regression models were specified taking into account individual age, sex, year of death, and Census region and adjusted to the 2000 US standard population to examine the association between area racism and Black mortality rates, which were derived from death certificates and mid-year population counts collated by the National Center for Health Statistics (2004-2009). DMAs characterized by a one standard deviation greater level of area racism were associated with an 8.2% increase in the all-cause Black mortality rate, equivalent to over 30,000 deaths annually. The magnitude of this effect was attenuated to 5.7% after adjustment for DMA-level demographic and Black socioeconomic covariates. A model controlling for the White mortality rate was used to further adjust for unmeasured confounders that influence mortality overall in a geographic area, and to examine Black-White disparities in the mortality rate. Area racism remained significantly associated with the allcause Black mortality rate (mortality rate ratio = 1.036; 95% confidence interval = 1.015, 1.057; p = 0.001). Models further examining cause-specific Black mortality rates revealed significant associations with heart disease, cancer, and stroke. These findings are congruent with studies documenting the deleterious impact of racism on health among Blacks. Our study contributes to evidence that racism shapes patterns in mortality and generates racial disparities in health.
DICER1 is an enzyme that generates mature microRNAs (miRNAs), which regulate gene expression post-transcriptionally in brain and other tissues and is involved in synaptic maturation and plasticity. Here, through genome-wide differential gene expression survey of post-traumatic stress disorder (PTSD) with comorbid depression (PTSD&Dep), we find that blood DICER1 expression is significantly reduced in cases versus controls, and replicate this in two independent cohorts. Our follow-up studies find that lower blood DICER1 expression is significantly associated with increased amygdala activation to fearful stimuli, a neural correlate for PTSD. Additionally, a genetic variant in the 3′ un-translated region of DICER1, rs10144436, is significantly associated with DICER1 expression and with PTSD&Dep, and the latter is replicated in an independent cohort. Furthermore, genome-wide differential expression survey of miRNAs in blood in PTSD&Dep reveals miRNAs to be significantly downregulated in cases versus controls. Together, our novel data suggest DICER1 plays a role in molecular mechanisms of PTSD&Dep through the DICER1 and the miRNA regulation pathway.
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Recent evidence suggests that grammatical aspect can bias how individuals perceive criminal intentionality during discourse comprehension. Given that criminal intentionality is a common criterion for legal definitions (e.g., first-degree murder), the present study explored whether grammatical aspect may also impact legal judgments. In a series of four experiments participants were provided with a legal definition and a description of a crime in which the grammatical aspect of provocation and murder events were manipulated. Participants were asked to make a decision (first- vs. second-degree murder) and then indicate factors that impacted their decision. Findings suggest that legal judgments can be affected by grammatical aspect but the most robust effects were limited to temporal dynamics (i.e., imperfective aspect results in more murder actions than perfective aspect), which may in turn influence other representational systems (i.e., number of murder actions positively predicts perceived intentionality). In addition, findings demonstrate that the influence of grammatical aspect on situation model construction and evaluation is dependent upon the larger linguistic and semantic context. Together, the results suggest grammatical aspect has indirect influences on legal judgments to the extent that variability in aspect changes the features of the situation model that align with criteria for making legal judgments.
Neural stem cells (NSCs) in the adult mammalian central nervous system (CNS) hold the key to neural regeneration through proper activation, differentiation, and maturation, to establish nascent neural networks, which can be integrated into damaged neural circuits to repair function. However, the CNS injury microenvironment is often inhibitory and inflammatory, limiting the ability of activated NSCs to differentiate into neurons and form nascent circuits. Here we report that neurotrophin-3 (NT3)-coupled chitosan biomaterial,when inserted into a 5-mm gap of completely transected and excised rat thoracic spinal cord, elicited robust activation of endogenous NSCs in the injured spinal cord. Through slow release of NT3, the biomaterial attracted NSCs to migrate into the lesion area, differentiate into neurons, and form functional neural networks, which interconnected severed ascending and descending axons, resulting in sensory and motor behavioral recovery. Our study suggests that enhancing endogenous neurogenesis could be a novel strategy for treatment of spinal cord injury.