Publications

The objectives of this study were to describe a new spinal cord injury scale for dogs, evaluate repeatability through determining inter-rater variability of scores, compare these scores to another established system (a modified Frankel scale), and determine if the modified Frankel scale and the newly developed scale were useful as prognostic indicators for return to ambulation. A group of client-owned dogs with spinal cord injury were examined by 2 independent observers who applied the new Texas Spinal Cord Injury Score (TSCIS) and a modified Frankel scale that has been used previously. The newly developed scale was designed to describe gait, postural reactions and nociception in each limb. Weighted kappa statistics were utilized to determine inter-rater variability for the modified Frankel scale and individual components of the TSCIS. Comparisons were made between raters for the overall TSCIS score and between scales using Spearman's rho. An additional group of dogs with surgically treated thoracolumbar disk herniation was enrolled to look at correlation of both scores with spinal cord signal characteristics on magnetic resonance imaging (MRI) and ambulatory outcome at discharge. The actual agreement between raters for the modified Frankel scale was 88%, with a weighted kappa value of 0.93. The TSCIS had weighted kappa scores for gait, proprioceptive positioning and nociception components that ranged from 0.72 to 0.94. Correlation between raters for the overall TSCIS score was Spearman's rho=0.99 (P<0.001). Comparison of the overall TSCIS score to the modified Frankel score resulted in a Spearman's rho value of 0.90 (P<0.001). The modified Frankel score was weakly correlated with the length of hyperintensity of the spinal cord: L2 vertebral body length ratio on mid-sagittal T2-weighted MRI (Spearman's rho=-0.45, P=0.042) as was the overall TSCIS score (Spearman's rho=-0.47, P=0.037). There was also a significant difference in admitting modified Frankel scores (P=0.029) and admitting overall TSCIS scores (P=0.02) between dogs that were ambulatory at discharge and those that were not. Results from this study suggest that the TSCIS is an easy to administer scale for evaluating canine spinal cord injury based on the standard neurological exam and correlates well with a previously described modified Frankel scale.

Following neuronal injury, microglia initiate repair by phagocytosing dead neurons without eliciting inflammation. Prior evidence indicates triggering receptor expressed by myeloid cells-2 (TREM2) promotes phagocytosis and retards inflammation. However, evidence that microglia and neurons directly interact through TREM2 to orchestrate microglial function is lacking. We here demonstrate that TREM2 interacts with endogenous ligands on neurons. Staining with TREM2-Fc identified TREM2 ligands (TREM2-L) on Neuro2A cells and on cultured cortical and dopamine neurons. Apoptosis greatly increased the expression of TREM2-L. Furthermore, apoptotic neurons stimulated TREM2 signaling, and an anti-TREM2 mAb blocked stimulation. To examine the interaction between TREM2 and TREM2-L in phagocytosis, we studied BV2 microglial cells and their engulfment of apoptotic Neuro2A. One of our anti-TREM2 mAb, but not others, reduced engulfment, suggesting the presence of a functional site on TREM2 interacting with neurons. Further, Chinese hamster ovary cells transfected with TREM2 conferred phagocytic activity of neuronal cells demonstrating that TREM2 is both required and sufficient for competent uptake of apoptotic neuronal cells. Finally, while TREM2-L are expressed on neurons, TREM2 is not; in the brain, it is found on microglia. TREM2 and TREM2-L form a receptor-ligand pair connecting microglia with apoptotic neurons, directing removal of damaged cells to allow repair.

AIMS

The aim of this study was to examine the association between socioeconomic status, blood pressure (BP) progression, and incident hypertension.

METHODS AND RESULTS

We included 27 207 female health professionals free of hypertension and cardiovascular disease at baseline. Participants were classified into five education and six income categories. The main outcome variables were BP progression at 48 months of follow-up and incident hypertension during the entire study period. At 48 months, 48.1% of women had BP progression. The multivariable adjusted relative risks [95% confidence intervals (CIs)] for BP progression were 1.0 (referent), 0.96 (0.92-1.00), 0.92 (0.88-0.96), 0.90 (0.85-0.94), and 0.84 (0.78-0.91) (P for trend <0.0001) across increasing education categories and 1.0 (referent), 1.01 (0.94-1.08), 0.99 (0.93-1.06), 0.97 (0.91-1.04), 0.96 (0.90-1.03), and 0.89 (0.83-0.96) across increasing income categories (P for trend = 0.0001). During a median follow-up of 9.8 years, 8248 cases of incident hypertension occurred. Multivariable adjusted hazard ratios (95% CI) were 1.0 (referent), 0.92 (0.86-0.99), 0.85 (0.79-0.92), 0.87 (0.80-0.94), and 0.74 (0.65-0.84) (P for trend <0.0001) across increasing education categories and 1.0 (referent), 1.07 (0.95-1.21), 1.07 (0.95-1.20), 1.06 (0.94-1.18), 1.04 (0.93-1.16), and 0.93 (0.82-1.06) (P for trend 0.08) across increasing income categories. In joint analyses, education but not income remained associated with BP progression and incident hypertension.

CONCLUSION

Socioeconomic status, as determined by education but not by income, is a strong independent predictor of BP progression and incident hypertension in women.

BACKGROUND

Despite increasing recognition of the importance of human rights in the protection and promotion of health, formal human rights education has been lacking in schools of medicine and public health. Our objectives were: 1) to determine the nature and extent of health and human rights (HHR) education among schools of medicine (SOMs) and public health (SPHs); 2) to identify perceived barriers to implementing HHR curricula; 3) to learn about deans' interests and attitudes toward HHR education, and; 4) to identify factors associated with offering HHR education.

METHODS AND PRINCIPAL FINDINGS

We conducted a cross-sectional survey among deans of all accredited allopathic SOMs and SPHs in the United States and Puerto Rico. Seventy-one percent of U.S. SOMs and SPHs responded. Thirty-seven percent of respondents indicated that their schools offered some form of HHR education. Main barriers to offering HHR education included competition for time, lack of qualified instructors and lack of funding. Among schools not offering HHR education, 35% of deans were interested in offering HHR education. Seventy-six percent of all deans believed that it was very important or important to offer HHR education. Multiple regression analysis revealed that deans' attitudes were the most important factor associated with offering any HHR education.

CONCLUSION

Findings indicate that though a majority of deans of SOMs and SPHs believe that knowledge about human rights is important in health practice and support the inclusion of HHR studies in their schools, HHR education is lacking at most of their institutions. These results and the growing recognition of the critical interdependence between health and human rights indicate a need for SOMs and SPHs to work towards formal inclusion of HHR studies in their curricula, and that HHR competency requirements be considered to overcome barriers to its inclusion.

Pharmacologic remedy of many brain diseases is difficult because of the powerful drug exclusion properties of the blood-brain barrier (BBB). Chemical isolation of the vertebrate brain is achieved through the highly integrated, anatomically compact and functionally overlapping chemical isolation processes of the BBB. These include functions that need to be coordinated between tight diffusion junctions and unidirectionally acting xenobiotic transporters. Understanding of many of these processes has been hampered, because they are not well mimicked by ex vivo models of the BBB and have been experimentally difficult and expensive to disentangle in intact rodent models. Here we show that the Drosophila melanogaster (Dm) humoral/CNS barrier conserves the xenobiotic exclusion properties found in the vertebrate vascular endothelium. We characterize a fly ATP binding cassette (ABC) transporter, Mdr65, that functions similarly to mammalian xenobiotic BBB transporters and show that varying its levels solely in the Dm BBB changes the inherent sensitivity of the barrier to cytotoxic pharmaceuticals. Furthermore, we demonstrate orthologous function between Mdr65 and vertebrate ABC transporters by rescuing chemical protection of the Dm brain with human MDR1/Pgp. These data indicate that the ancient origins of CNS chemoprotection extend to both conserved molecular means and functionally analogous anatomic spaces that together promote CNS selective drug partition. Thus, Dm presents an experimentally tractable system for analyzing physiological properties of the BBB in an intact organism.