A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

Bibliometric analyses of physical and occupational therapy faculty across Canada indicate productivity and impact of rehabilitation research

© 2015, University of Toronto Press Inc. All rights reserved. Purpose: This study examines physical and occupational therapy faculty across Canada, using bibliometrics and federal funding as indicators of academic impact, and considers the validity of various bibliometric indices. Methods: Faculty members were identified and their rank, professional designation, and department obtained from faculty Web sites. Bibliometric indicators were determined using Publish or Perish software. An independent author (not a faculty member) inspected the data to remove any incorrectly attributed publications. The h-index, citation years, g-index, and total number of citations for each faculty member were retrieved. The Canadian Institutes of Health Research (CIHR) funding database was used to determine the amount of research funding provided to each faculty member as a principal investigator (PI) and his or her total CIHR funding received. Mean faculty indicators by university, rank, gender, and profession were determined. Analysis of variance (ANOVA) was used to detect differences by rank and gender, and measures of association (Pearson correlation coefficients and multiple regression) were used to identify factors that affected h-index and PI funding received. Results: A total of 347 physical and occupational therapy faculty were identified. The median h-index was 5 (inter-quartile range [IQR] 2–8) for assistant professors, 11 (IQR 7– 15) for associate professors, and 18 (IQR 12–26) for full professors. ANOVA indicated no significant differences between male and female faculty in terms of h-index or funding received. Regression analysis indicated that 58% of h-index variance could be explained by gender (p = 0.039), appointment within a department that provides a (rehabilitation science) PhD programme (p \u3c 0.001), rank (p \u3c 0.001), CIHR PI funding (p = 0.001), or total CIHR funding (p \u3c 0.001). Significant predictors of the amount of CIHR funding received as a PI included h-index (p \u3c 0.001) and total number of citations (p = 0.023), which together explained 27% of the variation in funding received. Conclusion: The h-index, although not without flaws, provides a useful metric that indicates that physical and occupational faculty in Canada are productive scientists having a measurable impact and that this impact increases with rank and greater funding

Do AAO-HNSF CORE Grants Predict Future NIH Funding Success?

Objective. To determine (1) whether academic otolaryngologists who have received an American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF) Centralized Otolaryngology Research Efforts (CORE) grant are more likely to procure future National Institutes of Health (NIH) funding; (2) whether CORE grants or NIH Career Development (K) awards have a stronger association with scholarly impact. Study Design and Setting. Historical cohort. Methods. Scholarly impact, as measured by the h-index, publication experience, and prior grant history, were determined for CORE-funded and non-CORE-funded academic otolaryngologists. All individuals were assessed for NIH funding history. Results. Of 192 academic otolaryngologists with a CORE funding history, 39.6% had active or prior NIH awards versus 15.1% of 1002 non-CORE-funded faculty (P \u3c .0001). Higher proportions of CORE-funded otolaryngologists have received K-series and R-series grants from the NIH (P-values \u3c .05). K-grant recipients had higher h-indices than CORE recipients (12.6 vs 7.1, P \u3c .01). Upon controlling for rank and experience, this difference remained significant among junior faculty. Conclusions. A higher proportion of academic otolaryngologists with prior AAO-HNSF CORE funding have received NIH funding relative to their non-CORE-funded peers, suggesting that the CORE program may be successful in its stated goals of preparing individuals for the NIH peer review process, although further prospective study is needed to evaluate a cause and effect relationship. Individuals with current or prior NIH K-grants had greater research productivity than those with CORE funding history. Both cohorts had higher scholarly impact values than previously published figures among academic otolaryngologists, highlighting that both CORE grants and NIH K-grants awards are effective career development resources

Academic Surgical Oncologists’ Productivity Correlates with Gender, Grant Funding, and Institutional NCI Comprehensive Cancer Center Affiliation

BackgroundA scholar's h-index is defined as the number of h papers published, each of which has been cited at least h times. We hypothesized that the h-index strongly correlates with the academic rank of surgical oncologists.MethodsWe utilized the National Cancer Institute (NCI) website to identify NCI-designated Comprehensive Cancer Centers (CCC) and Doximity to identify the 50 highest-ranked general surgery residency programs with surgical oncology divisions. Demographic data of respective academic surgical oncologists were collected from departmental websites and Grantome. Bibliometric data were obtained from Web of Science.ResultsWe identified 544 surgical oncologists from 64 programs. Increased h-index was associated with academic rank (p < 0.001), male gender (p < 0.001), number of National Institutes of Health (NIH) grants (p < 0.001), and affiliation with an NCI CCC (p = 0.018) but not number of additional degrees (p = 0.661) or Doximity ranking (p = 0.102). H-index was a stronger predictor of academic rank (r = 0.648) than total publications (r = 0.585) or citations (r = 0.450).ConclusionsThis is the first report to assess the h-index within academic surgical oncology. H-index is a bibliometric predictor of academic rank that correlates with NIH grant funding and NCI CCC affiliation. We also highlight a previously unexpected and unappreciated gender disparity in the academic productivity of US surgical oncologists. When academic rank was accounted for, female surgical oncologists had lower h-indices compared with their male colleagues. Evaluation of the etiologies of this gender disparity is needed to address barriers to academic productivity faced by female surgical oncologists as they progress through their careers