Institutional Development Award Research Articles

Efficacy of Centers of Biomedical Research Excellence (CoBRE) grants to build research capacity in underrepresented states.

Federal funding for research has immediate and long-term economic impact. Since federal research funding is regionally concentrated and not geographically distributed, the benefits are not fully realized in some regions of the country. The Established (previously Experimental) Program to Stimulate Competitive Research (EPSCoR) programs at several agencies, for example, the National Science Foundation, and the Institutional Development Award (IDeA) program at the National Institutes of Health were created to increase competitiveness for funding in states with historically low levels of federal funding. The Centers of Biomedical Research Excellence (CoBRE) award program is a component of the IDeA program. The CoBRE grants support research core facilities to develop research infrastructure. These grants also support the research projects of junior investigators, under the guidance of mentoring teams of senior investigators, to develop human resources at these institutions. Few studies have assessed the effectiveness of these programs. This study examines the investment and outcomes of the CoBRE grants from 2000 through 2022. The maturation of junior investigators into independently funded principal investigators is comparable to other mentoring programs supported by NIH. The investment in research cores resulted in substantial research productivity, measured by publications. Despite the successes of individual investigators and increased research infrastructure and productivity, the geographic distribution of federal and NIH research dollars has not changed. These results will be informative in consideration of policies designed to enhance the geographic distribution of federal research dollars.

Bibliometric and social network analysis of a Clinical and Translational Resource awardee: An Oklahoma experience 2014-2021.

Social Network Analysis is a method of analyzing coauthorship networks or relationships through graph theory. Institutional Development Award (IDeA) Networks for Clinical and Translational Research (IDeA-CTR) was designed to expand the capability for clinical and translational research to enhance National Institutes of Health funding. All publications from a cohort of clinical and translational scientists in Oklahoma were collected through a PubMed search for 2014 through 2021 in October 2022. For this study's bibliometric portion, we pulled the citations from iCite in November of 2022. There were 2,391 articles published in 1,019 journals. The number of papers published by year increased from 56 in 2014 to 448 in 2021. The network had an average of 6.4 authors per paper, with this increasing by year from 5.3 in 2014 to 6.9 in 2021. The average journal impact factor for the overall network was 7.19, with a range from 0.08 to 202.73. The Oklahoma Shared Clinical and Translational Resources (OSCTR) network is a small world network with relatively weak ties. This study provides an overview of coauthorship in an IDeA-CTR collaboration. We show the growth and structure of coauthorship in OSCTR, highlighting the importance of understanding and fostering collaboration within research networks.

Expanding Our Cyclodextrin-Based Sensors with Automation and New Surfaces

We have had significant success in building cyclodextrin mediated sensors. We initially started with a gold surface, being able to detect analyte up to three times post modification [1]. Afterwards, we improved the stability and reusability by moving to a phenyl-modified carbon electrode via diazonium salt chemistry [2]. With his new surface, we were able to detect cortisol up to 10 different times with high accuracy, repeatability, and sensitivity in buffer, urine, and artificial saliva. We were limited by manually manipulating the electrode; therefore, we were not able to test the electrode for greater than 10 measurements. Within this poster, we intend to present our ideas and progress towards developing an automated detection system that can be preprogrammed to clean, reset, and test the cyclodextrin-mediated surface with target analytes. Further, we will share our various target analytes and our strategy to expand our sensor surface to include multiple cyclodextrin derivatives.Research supported by New Hampshire- INBRE through an Institutional Development Award (IDeA), P20GM103506, from the National Institute of General Medical Sciences of the NIH.[1] Z. Panahi, M. A. Merrill, and J. M. Halpern, “Reusable Cyclodextrin-Based Electrochemical Platform for Detection of trans -Resveratrol,” ACS Appl. Polym. Mater., vol. 2, no. 11, pp. 5086–5093, Nov. 2020.[2] Z. Panahi, T. Ren, and J. M. Halpern, “Nanostructured Cyclodextrin-Mediated Surface for Capacitive Determination of Cortisol in Multiple Biofluids,” ACS Appl. Mater. Interfaces, Aug. 2022.

Impairment of endothelial Kir channels in response to elevated glucose is independent of changes in channel expression

Background and Objective. Obesity comprises a complex metabolic pathophysiology often associated with poor glycemic control. Our past studies detailed that impairment of inward rectifying potassium channels (Kir2.1) is a contributing factor to obesity-induced endothelial dysfunction, however, the major obesity-associated factors driving Kir2.1 impairment are unknown. As obesity is often associated with hyperglycemia, we aimed to determine the effect of elevated glucose on endothelial Kir2.1 channel function and expression in vitro. Method. We treated human adipose microvascular endothelial cells (HAMECs) with high glucose (200mg/dL), mannitol (200 mg/dL), or NaCl (300 mOsm/kg) for 72 hours. Control cells were maintained in standard media containing 100 mg/dL glucose. Following treatments, Kir currents were measured using whole-cell patch clamp electrophysiology and Kir2.1 expression was assessed using qPCR, Western immunoblotting, and immunocytochemistry (ICC). ICC was performed on nonpermeabilized HAMECs to detect membrane expression. Statistics: A Kruskal-Wallis one-way analysis of variance (p < 0.05) followed by Dunn Sidak post hoc analysis (*) was used to determine significant differences. Result. HAMECs exposed to elevated glucose exhibited reduced Kir current compared to control. Surprisingly, mannitol induced similar decreases in Kir current. As mannitol originally served as the osmotic control, we next tested the effect of osmotic stress on endothelial Kir current by exposing cells to elevated NaCl, which had no effect. Furthermore, increased glucose or mannitol did not influence channel KCNJ2 gene or total Kir2.1 protein expression, however, preliminary experiments indicate that the membrane expression of Kir2.1 may be increased following exposure to elevated sugars. Discussion and Conclusions. Our findings indicate that glucose and mannitol reduce endothelial Kir currents without affecting channel expression, suggesting that functional impairment of the channels is induced by elevated sugars. This is further supported by preliminary studies that indicate that membrane Kir2.1 expression is increased in response to elevated sugars, suggesting that a possible compensatory trafficking mechanism fails to restore Kir2.1 channel function despite an increased membrane presence. As the observed decreases in Kir channel current are not mediated by an increase in osmotic pressure under these conditions, we aim to next test if damage to the glycocalyx, which is established to occur in obesity and renders endothelial Kir channels dysfunctional, occurs in the presence of elevated sugars. This study was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under award number 2P20GM113125 (Ibra Fancher). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

An animal physiology Pressbook (OER) creation process, a synergistic collaboration with undergraduates and faculty

OERs or Open Educational Resources have shown to reduce financial barriers in undergraduates by providing low cost or no cost textbooks. However, the potential OER textbooks available for a three-hundred level Biological Sciences and Natural Sciences majors Animal Physiology course (BIOLA310) at UAA do not align with the foundation of this course’s structure of homeostasis and core concepts in physiology. Thus an OER Pressbook was created by a former BIOLA310 undergraduate student for future students that mapped the course outline, utilizing the essential core concepts of Homeostasis, Systems Integration, and Scientific reasoning. This study explores current attitudes regarding OER usage of undergraduates enrolled in BIOLA310 as compared to undergraduates that were enrolled in Fall 2021 BIOLA310, when there was not an official OER textbook. Anonymous demographic data, including first generation student and pell grant status will be collected for all participants to explore any potential differences in OER impression based on student resources. Data will also be collected regarding the informational component of the OER pressbook that students engage with the most. Hypothesis: Students connected more directly with the material of the undergraduate created Pressbook OER’s, as compared to a previous version of instructor curated OER materials in Fall 2021, due to low cost, the information presented from a near peer, and how the textbook was designed for the course. Data will be collected by an anonymous qualtrics survey to protect the identity of the volunteers. Pressbooks, the web host of the Animal Physiology OER gathers Key Performance Indicators (KPIs) and tracks relevant metrics, to compare student perception of use to actual use of the materials. Data will be analyzed to assess usage evaluated by financial barriers and perceived inclination due to the OER being designed by a fellow student. Supporting student learning from diverse perspectives, OER’s created with content expert faculty and undergraduate student interpretation might increase OER availability. By lowering the barrier of OER creation, then potentially more curated resources are created that resonate with near peer learning that will increase the diversity of learning viewpoints to support undergraduate students. Research reported in this publication was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM103395. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Gating defects in K1126I, a putative hypokalemic periodic paralysis mutation in hNav1.4.

We investigated the impact of mutation K1126I reported to be associated with hypokalemic periodic paralysis, but not yet characterized. The location of this mutation is the extracellular positive charge in domain III S4, and characterization of artificial mutations at this locus suggest it is outside the electric field. We used cut-open oocyte electrophysiology to characterize the steady-state and kinetic gating parameters in wild type hNaV1.4, K1126I in both the native background and with incorporation of the 1303IFM/QQQ mutation to isolate activation from fast inactivation. K1126I produced an 11 mV hyperpolarizing (left-)shift in the midpoint of the steady-state fast inactivation curve, and decreased slope. Activation midpoint was left-shifted by 4 mV by K1126I with decreased slope. Recovery from fast inactivation was slowed and entry from closed states was accelerated by K1126I, with open-state fast inactivation and deactivation not significantly altered. Simulated action potentials for which steady-state fast inactivation and activation parameters were incorporated showed a 10 mV attenuation of the skeletal muscle fiber action potential. We used the IFM/QQQ background to compare slow inactivation in wild type and K1126I channels. The midpoint of the steady-state slow inactivation was hyperpolarized by 8 mV in K1126I/QQQ compared to hNaV1.4 / QQQ, with onset unaffected and recovery accelerated. This work was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under Grant #P20GM103408.

Launching IDeA state early career clinician-scientists with mentored just-in-time grant-writing support.

Institutional Development Award (IDeA) programs build research infrastructure in regions with historically low access to NIH funds. The Mentored Research Development Award (MRDA), a professional development program embedded in our IDeA-funded center, provides junior investigators with mentorship and effort offset to write a grant. We evaluated outcomes from the first eight years (2013-2021; N = 55) using administrative records, publicly available data, and a self-report survey (n = 46, 84% response rate). Fifteen MRDA recipients (27%) went on to receive NIH funding. Providing just-in-time grant-writing support may launch early career clinician-scientists in an IDeA state context.

Social network analysis of biomedical research growth at a primarily undergraduate institution.

The National Institutes of Health Institutional Development Award Programs support the establishment and growth of biomedical research infrastructure in states that receive a low level of federal funding for biomedical research. The purpose of this investigation was to analyze the growth in research productivity over time. This program fostered an environment in which a biomedical research program could be developed and allowed to grow at Boise State University, a primarily undergraduate institution. The growth of the biomedical research community can be visualized through social network analysis.

Alaska Backcountry Expeditionary Hunting Promotes Exceptional Rates Of Muscle Protein Synthesis

Our Alaskan Backcountry Expeditionary Hunting (ABEH) paradigm represents an 8-14 day unscripted, remote expedition in the uninhabited Brooks Range. Despite negative energy balance (i.e., -9.7 ± 3.4 MJ/day) and significant weight loss (Δ-1.5 ± 0.7 kg) largely influenced by high levels of energy expenditure (i.e., 17.4 ± 2.6 MJ/day), participants retained skeletal muscle as determined by magnetic resonance imaging and lean tissue mass as indicated by dual energy x-ray absorptiometry. Preliminary evidence from these investigations demonstrated an increase in skeletal muscle follistatin-like protein 1, potentially enhancing the anabolism of skeletal muscle. PURPOSE: To determine integrated rates of skeletal muscle protein synthesis throughout the ABEH paradigm that may be relevant to skeletal muscle preservation. METHODS: The use of the virtual biopsy method was employed via 2H2O dosing and liquid chromatography/tandem mass spectrometry analysis to evaluate fractional synthetic rates (FSR) of muscle proteins in four participants (2 females [28 and 62 yr; 66.2 and 71.8 kg; 25.5 and 26.7 kg/m2] and 2 males [47 and 56 yr; 87.5 and 91.4 kg; 26.1 and 28.3 kg/m2]). RESULTS: As an indicator of skeletal muscle synthesis, mean FSR of serum carbonic anhydrase and creatine kinase M-type was 2.4% per day (range: 1.3-5.1% per day) and 4.0% per day (range: 1.4-8.2% per day), respectively. CONCLUSION: Our preliminary findings suggest that the ABEH-induced alterations in skeletal muscle FSR in our cohort are ~four-fold higher than reported in young individuals at baseline and ~ two-fold higher than after 3 weeks of exhaustive sprint interval training. Therefore, chronic mechanical overload may promote a sustained increase in the FSR of skeletal muscle despite limited nutritional provisions and negative energy balance. Research was supported by Pristine Ventures, Inc. Funding was also provided by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number 2P20GM103395 and Sloan Foundation Fellowship to Mr. Brandon Kowalski. The content is solely the responsibility of the authors and does not necessarily reflect the official views of the NIH and/or the Sloan Foundation.

Abstract 1090: Repurposing an overactive bladder drug to treat chemoresistant lung cancer

Abstract Background: Non-small cell lung cancer (NSCLC) is one of the most common types of cancer diagnosis among men and women leads the most cancer-related deaths in the United States. This is largely due to treatment failure which arises from therapy-resistant tumors. The current study investigates the role of muscarinic acetylcholine receptor 3 (CHRM3) in the development and treatment of NSCLC chemotherapy-resistance and the potential of the overactive bladder CHRM3 antagonist darifenacin to treat this lethal form of cancer. Methods: Human NSCLC cell cultures were used to harvest protein for Western blot analyses of protein expression and activity of intracellular pathways. The chemotherapy drug docetaxel’s (DTX) ability to induce apoptosis was measured with crystal violet survival assay and colony formation assay. Results: CHRM3 expression was measured in chemonaive NSCLC cells (A549) and chemoresistant cells (A549R), which showed increased expression in A549R cells. Chemoresistant A549R were pretreated with the CHRM3 antagonist darifenacin (Dari, 10 μM, 24 hrs) before treatment with DTX (48 hrs). Crystal violet survival assay and colony formation assays showed a significant reduction in cell survival in the Dari + DTX combination treatment group suggesting that CHRM3 signaling is necessary in a chemoresistant state. Chemonaive A549 cells and CHRM3 overexpressing A549 cells (A549 M3OE) were pretreated with carbachol (10 µM, 24 hrs) to activate CHRM3 before treatment with a set of serial dilutions of DTX (48 hrs). Crystal violet survival assay results showed that carbachol was not able to protect either cell line from DTX-induced cell death, suggesting that CHRM3 signaling alone is not sufficient to induce a chemoresistant state. Conclusion: CHRM3 overexpression is observed in chemoresistant forms of NSCLC. While activation of CHRM3 does not instill a resistant state in chemonaive cells, its signaling is essential for maintenance of the chemoresistant state. The repurposing of the CHRM3 antagonist darifenacin shows strong potential as a therapeutic to treat lethal chemoresistant forms of NSCLC.The project described was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under Grant #P20GM103408 Citation Format: Joslyn Bassett, Tyler Bland. Repurposing an overactive bladder drug to treat chemoresistant lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1090.

Added Sugars Intake Explained by Amino Acid Carbon Isotope Ratio Profiles in a Controlled Feeding Study of U.S. Adults

ObjectivesTo evaluate an amino acid carbon stable isotope ratio (CIRAA) biomarker of added sugars (AS) intake in a controlled feeding study of men and women across age and BMI groups.MethodsWe conducted a 15-d feeding study in Phoenix, AZ, of men and women (N = 100, aged 18–70 y, BMI 17.9–35.0) who were recruited across sex, age, and BMI groups. Participants were provided personalized diets that resembled their habitual intakes, based on 2 consecutive 7-d food records. We measured CIRAAs in serum samples (N = 99) collected at the end of the feeding period and determined correlations with dietary intakes. We used forward selection to construct a model to explain AS intake using participant characteristics and 14 measured CIRAAs. This model was internally validated using a bootstrap optimism correction.ResultsMedian (25th, 75th percentile) AS intake was 65.2 g/d (44.7, 81.4) and 9.5% (7.2%, 12.4%) of energy. The CIR of alanine had the highest, though still modest, correlation with AS intake (Pearson r = 0.32, P = 0.001). Serum CIRAAs were more highly correlated with animal food intakes, especially the ratio of animal to total protein intake (APR). The highest correlations were between the APR and the CIRs of phenylalanine (Pearson r = 0.85, P < 0.001) and leucine (Pearson r = 0.84, P < 0.001). The model of AS intake included participant sex and body weight and the CIRs of 6 AAs: alanine, valine, lysine, glutamic acid, serine, and glycine. This model had modest explanatory power (multiple R2 = 0.38), and the optimism-corrected R2 for the model was lower (R2 = 0.15).ConclusionsThe observed association between serum CIRAAs and AS intake in the U.S. diet is encouraging; however, further investigation in populations with wider ranges of AS intake is warranted.Funding SourcesNational Cancer Institute; Institutional Development Award (IDeA) from the National Institutes of General Medical Sciences.

A Ketogenic Diet Prevents Methylglyoxal-Evoked Nociception by Scavenging Methylglyoxal

Methylglyoxal is a reactive dicarbonyl byproduct of glycolysis that has been implicated in a growing number of chronic pain conditions, including diabetic peripheral neuropathy (DPN). We previously demonstrated the efficacy of a ketogenic diet in reversing sensory symptoms in a rodent model of DPN. The purpose of this study was to determine whether a ketogenic diet modified methylglyoxal-evoked nociception as a potential mechanism of improving sensory symptoms of DPN. We delivered methylglyoxal to C57Bl/6 mice by intraperitoneal or intraplantar injections. Sensory behaviors were quantified for mechanical thresholds as assessed by von Frey filament testing and spontaneous nonreflexive nociceptive behaviors (shaking, biting, lifting, etc. of the injected paw). Intraperitoneal methylglyoxal injection induced lasting mechanical allodynia in standard chow-fed mice, while ketogenic diet-fed mice were protected. Importantly, ketogenic diet-fed mice exhibited significantly decreased methylglyoxylated-protein concentrations following injection relative to standard, chow-fed mice, and methylglyoxylated-protein concentration correlated negatively with blood ketones. A reaction between the ketone body acetoacetate and methylglyoxal was recently demonstrated in vivo as a potential mechanism of methylglyoxal detoxification, consistent with this observation. To assess whether ketone bodies modified methylglyoxal-evoked nociception by direct methylglyoxal detoxification, we incubated methylglyoxal with either β-hydroxybutyrate or acetoacetate overnight prior to intraplantar injection. Mice receiving an injection of methylglyoxal alone exhibited an increase in spontaneous nociceptive behaviors, whereas coincubation of either acetoacetate or β-hydroxybutyrate reduced these behaviors. In summary, a ketogenic diet prevented the onset of methylglyoxal-evoked mechanical allodynia and increased scavenging of circulating methylglyoxal. Ketone bodies were individually capable of detoxifying methylglyoxal to prevent nociception. These findings provide insight to a potential mechanism by which a ketogenic diet improves DPN in mice and provide a rationale for exploring a ketogenic diet as a therapeutic intervention in other chronic pain conditions associated with elevated methylglyoxal. This work was supported by NIH grants RO1 NS043314 (DEW), the Kansas Institutional Development Award (IDeA) P20 GM103418, Kansas University Training Program in Neurological and Rehabilitation Sciences (NIH T32 award) supported by NIH Award Number T32HD057850, and core support from the Kansas IDDRC P30 HD00228. Methylglyoxal is a reactive dicarbonyl byproduct of glycolysis that has been implicated in a growing number of chronic pain conditions, including diabetic peripheral neuropathy (DPN). We previously demonstrated the efficacy of a ketogenic diet in reversing sensory symptoms in a rodent model of DPN. The purpose of this study was to determine whether a ketogenic diet modified methylglyoxal-evoked nociception as a potential mechanism of improving sensory symptoms of DPN. We delivered methylglyoxal to C57Bl/6 mice by intraperitoneal or intraplantar injections. Sensory behaviors were quantified for mechanical thresholds as assessed by von Frey filament testing and spontaneous nonreflexive nociceptive behaviors (shaking, biting, lifting, etc. of the injected paw). Intraperitoneal methylglyoxal injection induced lasting mechanical allodynia in standard chow-fed mice, while ketogenic diet-fed mice were protected. Importantly, ketogenic diet-fed mice exhibited significantly decreased methylglyoxylated-protein concentrations following injection relative to standard, chow-fed mice, and methylglyoxylated-protein concentration correlated negatively with blood ketones. A reaction between the ketone body acetoacetate and methylglyoxal was recently demonstrated in vivo as a potential mechanism of methylglyoxal detoxification, consistent with this observation. To assess whether ketone bodies modified methylglyoxal-evoked nociception by direct methylglyoxal detoxification, we incubated methylglyoxal with either β-hydroxybutyrate or acetoacetate overnight prior to intraplantar injection. Mice receiving an injection of methylglyoxal alone exhibited an increase in spontaneous nociceptive behaviors, whereas coincubation of either acetoacetate or β-hydroxybutyrate reduced these behaviors. In summary, a ketogenic diet prevented the onset of methylglyoxal-evoked mechanical allodynia and increased scavenging of circulating methylglyoxal. Ketone bodies were individually capable of detoxifying methylglyoxal to prevent nociception. These findings provide insight to a potential mechanism by which a ketogenic diet improves DPN in mice and provide a rationale for exploring a ketogenic diet as a therapeutic intervention in other chronic pain conditions associated with elevated methylglyoxal. This work was supported by NIH grants RO1 NS043314 (DEW), the Kansas Institutional Development Award (IDeA) P20 GM103418, Kansas University Training Program in Neurological and Rehabilitation Sciences (NIH T32 award) supported by NIH Award Number T32HD057850, and core support from the Kansas IDDRC P30 HD00228.

MP36-19 PROSTACYCLIN (TREPROSTINIL) THERAPY IMPROVES RENAL HEMODYNAMICS DURING RAT RENAL ISCHEMIA-REPERFUSION INJURY

You have accessJournal of UrologyCME1 May 2022MP36-19 PROSTACYCLIN (TREPROSTINIL) THERAPY IMPROVES RENAL HEMODYNAMICS DURING RAT RENAL ISCHEMIA-REPERFUSION INJURY Frances Kazal, Meiwen Ding, Dicken Ko, Reginald Gohh, and Nisanne Ghonem Frances KazalFrances Kazal More articles by this author , Meiwen DingMeiwen Ding More articles by this author , Dicken KoDicken Ko More articles by this author , Reginald GohhReginald Gohh More articles by this author , and Nisanne GhonemNisanne Ghonem More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002590.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Renal ischemia-reperfusion injury (IRI) is a crucial factor causing acute kidney injury (AKI). To date, no pharmacological treatments are available for the prevention of I/R-induced renal injury. Here, we investigate the renal hemodynamics and reno-protective effects of the prostacyclin analog, treprostinil, against renal IRI in vivo. METHODS: Male Sprague Dawley rats were subjected to bilateral renal ischemia (45 minutes) followed by reperfusion (1–48 hour). Treprostinil (100 ng/kg/min) was administered subcutaneously either (A) at the time of ischemia (IRI-immT) or (B) approximately 18-24 hours before renal IRI (IRI-preT). RESULTS: Serum and urine creatinine were elevated at 24 hours post-reperfusion in the IRI group vs. sham (P <0.001), which both the IRI-immT and IRI-preT reduced the peak of serum creatinine at 24 hours after renal IRI (P <0.001). Also, medullary and cortical renal blood flow (RBF) were significantly reduced in the IRI group vs. sham (P <0.001), whereas the IRI-immT (P <0.01) and IRI-preT (P <0.05) groups improved RBF at 90 minutes post-reperfusion and maintained throughout 120 minutes. In parallel, animals in the IRI injury group experienced a decreased eGFR, increased urinary sodium (UNa 2+) excretion and proteinuria during the first 24 hours post-reperfusion vs. sham (P <0.01). Meanwhile, treprostinil reduced the UNa 2+ and proteinuria and completely restored the eGRF to baseline by 48 hours post-reperfusion and, compared to the IRI group (P <0.01). CONCLUSIONS: This study demonstrates the efficacy of treprostinil in improving renal hemodynamics and kidney function early post-IRI in a clinically relevant rat model of AKI. Specifically, our data show that treprostinil remarkably increased renal blood flow and GFR, and reduced sodium excretion and proteinuria post-reperfusion. Importantly, these data suggest that treprostinil has the potential to serve as a therapeutic agent to protect the kidney against renal IRI. Source of Funding: Funding support for this project was provided in part by the Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health, which funds the University of Rhode Island Core Lab (P20GM103430). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e605 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Frances Kazal More articles by this author Meiwen Ding More articles by this author Dicken Ko More articles by this author Reginald Gohh More articles by this author Nisanne Ghonem More articles by this author Expand All Advertisement PDF DownloadLoading ...

Issues for recruitment and retention of clinical research professionals at academic medical centers: Part 1 - collaborative conversations Un-Meeting findings.

Identification of evidence-based factors related to status of the clinical research professional (CRP) workforce at academic medical centers (AMCs) will provide context for National Center for Advancing Translational Science (NCATS) policy considerations and guidance. The objective of this study is to explore barriers and opportunities related to the recruitment and retention of the CRP workforce. Qualitative data from a series of Un-Meeting breakout sessions and open-text survey questions were analyzed to explore barriers and recommendations for improving AMC CRP recruitment, retention and diversity. While certain institutions have established competency-based frameworks for job descriptions, standardization remains generally lacking across CTSAs. AMCs report substantial increases in unfilled CRP positions leading to operational instability. Data confirmed an urgent need for closing gaps in CRP workforce at AMCs, especially for attracting, training, retaining, and diversifying qualified personnel. Improved collaboration with human resource departments, engagement with principal investigators, and overcoming both organizational and resource challenges were suggested strategies, as well as development of outreach to universities, community colleges, and high schools raising awareness of CRP career pathways. Based on input from 130 CRP leaders at 35 CTSAs, four National Institute of General Medical Sciences' Institutional Development Award (IDeA) program sites, along with industry and government representatives, we identified several barriers to successful recruitment and retention of a highly trained and diverse CRP workforce. Results, including securing institutional support, champions, standardizing and adopting proven national models, improving local institutional policies to facilitate CRP hiring and job progression point to potential solutions.

Evidence-based practice strategies for faculty professional development in clinical translational research at Institutional Development Award (IDeA) state institutions in the Mountain West.

The Mountain West Clinical Translational Research - Infrastructure Network (MW CTR-IN), established in 2013, is a research network of 13 university partners located among seven Institutional Development Award (IDeA) states targeting health disparities. This is an enormous undertaking because of the size of the infrastructure network (encompassing a third of the US landmass and spanning four time zones in predominantly rural and underserved areas, with populations that have major health disparities issues). In this paper, we apply the barriers, strategies, and metrics to an adapted educational conceptual model by Fink (2013). Applying this model, we used four tailored approaches across this regional infrastructure network to: (1) assess individual faculty specific needs, (2) reach out and engage with faculty, (3) provide customized services to meet the situational needs of faculty, and (4) utilize a "closed communication feedback loop" between Professional Development (PD) core and MW CTR-IN faculty within the context of their home institutional environment. Summary statement results from participating faculty show that these approaches were positive. Grounded in best educational practice approaches, we have an opportunity to refine and build from this sound foundation with implications for future use in other CTR-IN networks and institutions in the IDeA states.

Application of a diazepam milligram equivalency algorithm to assess benzodiazepine dose intensity in Rhode Island in 2018.

BACKGROUND: Benzodiazepines are indicated for the treatment of many conditions, such as anxiety disorders, muscle spasms, alcohol withdrawal, agitation, movement disorders, and epilepsy, and are one of the most frequently prescribed medication classes. This class of medication has important safety considerations, including an increased risk of dependence and addiction, falls, and death from opioid overdose. Although benzodiazepine safety and prescribing encompasses a rich and important research area, there is a lack of pharmacoepidemiologic literature addressing benzodiazepine dosing intensity in real-world settings. OBJECTIVE: To develop and apply a standardized benzodiazepine milligram equivalency conversion algorithm and assess the dose intensity of benzodiazepine use in Rhode Island (RI) in 2018. METHODS: A systematic literature review was conducted to identify the most commonly used benzodiazepine equivalency values. We then conducted a cross-sectional analysis of 2018 data from the RI Prescription Drug Monitoring Program (PDMP) to calculate the mean daily diazepam milligram equivalency (DME) based on a patient's most recent dispensing. A multivariable logistic regression analysis was conducted to determine the association between higher benzodiazepine doses (≥ 15 DME/day) and recipient characteristics, including concurrent use of opioids or stimulants. RESULTS: We identified 143,026 patients who received at least 1 prescription for a benzodiazepine in RI in 2018. The mean (SD) daily DME was 10.60 (9.05), and 26.2% of individuals had a mean DME per day of at least 15. Approximately 14% (n = 20,168) of patients prescribed a benzodiazepine had concurrent use with a prescription opioid, and 6.7% (n = 9,547) had concurrent use with a prescription stimulant. Females had a 28% lower adjusted odds of receiving a benzodiazepine dose of at least 15 DME per day compared with males (adjusted odds ratio [aOR] = 0.72, 95% CI = 0.70-0.73). The adjusted odds of receiving a benzodiazepine prescription of at least 15 DME per day was lower among the younger (aged 18-34 years) and older age groups (aged 65 years and older) compared with patients aged 35-64 years. Compared with commercial insurance, all other forms of payment had significantly higher adjusted odds of a daily benzodiazepine dose of at least 15 DME per day. The adjusted odds receiving a daily DME of at least 15 was 67% higher among those who also received a concurrent pharmacy dispensing for an opioid and 84% higher among those who also received a concurrent dispensing for a stimulant drug (aOR = 1.67, 95% CI = 1.61-1.72; aOR = 1.84, 95% CI = 1.76-1.93, respectively). CONCLUSIONS: Individuals aged 35-64 years with Medicaid insurance and those aged under 65 years with Medicare were more likely to be prescribed a benzodiazepine of at least 15 DME per day. Higher benzodiazepine DMEs were also dispensed to patients who concurrently used prescription opioids or stimulants who may be at increased risk of medication-related harm. We advocate for routine measurement of benzodiazepine dose intensity as a risk reduction strategy. DISCLOSURES: No funding supported this study. The authors have no conflicts of interest to disclose. The content and results of this study are solely the responsibility of the authors and do not necessarily represent the official views of the Rhode Island Department of Health. Kogut is partially supported by Institutional Development Award Numbers U54GM115677 and P20GM125507 from the National Institute of General Medical Sciences of the National Institutes of Health, which funds Advance Clinical and Translational Research (Advance-CTR) and the RI Lifespan Center of Biomedical Research Excellence (COBRE) on Opioids and Overdose, respectively. The content of this study is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Contents of this study were presented as a poster presentation at AMCP 2019 Nexus; October 29-November 1, 2019; National Harbor, MD.

Building a biomedical pipeline: the impact of the Idaho IDeA INBRE summer research experience at a primarily undergraduate institution.

Idaho Institutional Development Award (IDeA) Network for Biomedical Research Excellence (INBRE) aims to build biomedical research capacity and enhance the scientific and technology knowledge of the Idaho workforce. A key INBRE Program at The College of Idaho, a primarily undergraduate institution of 1,100 students, is a 10-wk summer fellows research experience. This report documents outcomes from 2005 to present, including demographic trends, faculty and student research productivity, self-reported gains, educational attainment, and career outcomes. Of 103 participants, 83.7% were from Idaho, 26.7% from rural areas, and 23.9% first-generation college students. Faculty and student research productivity (conference presentations and peer-reviewed publications) increased threefold. We found that 91.4% of fellows entered a scientific- or healthcare-related career and that 70.7% completed or are currently enrolled in postgraduate training (51.7% doctoral and 19.0% master's level). Anonymous surveys were uniformly positive, with gains in self-confidence and independent laboratory work. Open-ended responses indicated students valued mentoring efforts and improved awareness of scientific opportunities and competitive preparation for postgraduate training. Lastly, we observed that student research involvement increased college-wide during the award period. These data suggest that the summer fellows program is successfully meeting National Institutes of Health IDeA goals and serving as a pipeline to future health research careers and a scientifically trained Idaho workforce.

Best Practices for Conducting Clinical Trials With Indigenous Children in the United States.

We provide guidance for conducting clinical trials with Indigenous children in the United States. We drew on extant literature and our experience to describe 3 best practices for the ethical and effective conduct of clinical trials with Indigenous children. Case examples of pediatric research conducted with American Indian, Alaska Native, and Native Hawaiian communities are provided to illustrate these practices. Ethical and effective clinical trials with Indigenous children require early and sustained community engagement, building capacity for Indigenous research, and supporting community oversight and ownership of research. Effective engagement requires equity, trust, shared interests, and mutual benefit among partners over time. Capacity building should prioritize developing Indigenous researchers. Supporting community oversight and ownership of research means that investigators should plan for data-sharing agreements, return or destruction of data, and multiple regulatory approvals. Indigenous children must be included in clinical trials to reduce health disparities and improve health outcomes in these pediatric populations. Establishment of the Environmental Influences on Child Health Outcomes Institutional Development Award States Pediatric Clinical Trials Network (ECHO ISPCTN) in 2016 creates a unique and timely opportunity to increase Indigenous children's participation in state-of-the-art clinical trials.

An assessment tool for evaluating the National Institute of General Medical Sciences COBRE and INBRE mentoring programs

The National Institute of General Medical Sciences (NIGMS) mandates that its Centers of Biomedical Research Excellence (COBRE) and Institutional Development Award Networks of Biomedical Research Excellence (INBRE) institute formal mentoring programs to promote the core program objective of junior investigator development. Despite this NIGMS requirement, and the many career-related benefits associated with mentoring, few tools exist for purposes of rigorously evaluating COBRE and INBRE mentoring programs. The purpose of this project was to develop a mentoring assessment tool to aid in the evaluation of COBRE and INBRE mentoring programs. In study 1, a list of items comprising the tool was created via a multiphase item generation process based on input received from subject matter experts within the Cognitive and Neurobiological Approaches to Plasticity Center. In study 2, feedback about this tool was solicited from 78 grant directors, mentees, and mentors representing 21 unique COBRE programs and 8 unique INBRE programs from across the United States. The results provide initial evidence that this tool possesses suitable psychometric properties, is a flexible instrument with many potential uses, and represents a valuable resource for helping evaluate COBRE and INBRE mentoring programs. Having a tool for evaluating mentoring can help promote the grant success and career development of junior investigators in COBRE and INBRE programs and help program directors develop more sustainable research centers.

Insight into Francisella tularensis-erythrocyte interactions

Francisella tularensis, the causative agent of tularemia, is a pathogenic gram-negative bacterium that enters human red blood cells (RBCs). Previous investigations suggest that invasion of RBCs helps F. tularensis survive in the gut of arthropods – a transmission vector of this bacterium leading to colonization. Since tularemia is a zoonotic infection, humans are not the primary host of F. tularensis. Therefore, we sought to investigate whether F. tularensis was capable of invading RBCs of other animals. Using the gentamicin protection assay, we discovered that while F. tularensis could enter sheep and chicken erythrocytes, bovine RBCs did not support invasion. Because of previous studies published by our lab, and due to intrinsic differences between human and bovine erythrocyte surface protein Band 3, we hypothesized that RBC membrane protein Band 3 is required for invasion. We used anti-band 3 Fab fragments to physically block the Band 3 RBC surface protein and investigated how that impacted F. tularensis invasion. Here, we provide preliminary evidence suggesting that F. tularensis uses Band 3 to enter human RBCs. This study was funded by the National Institute of Allergy and Infectious Diseases (1R15HL147135) and an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health (P20GM103434), which funds WV-INBRE program.