Scholarship Program Research Articles

Virtual Cross-Cultural Mentorship: Insights into the Millennium Scholars Program

Virtual Cross-Cultural Mentorship: Insights into the Millennium Scholars Program

Improving Healthcare Professionals' Access to Addiction Medicine Education Through VHA Addiction Scholars Program.

The seemingly inexorable rise of opioid-related overdose deaths despite the reduced number of COVID-19 pandemic deaths demands novel responses and partnerships in our public health system's response. Addiction medicine is practiced in a broad range of siloed clinical environments that need to be included in addiction medicine training beyond the traditional fellowship programs. Our objective in this project was to implement a knowledge-based, live virtual training program that would provide clinicians and other healthcare professionals with an overview of addiction, substance use disorders (SUD), and clinical diagnosis and management of opioid use disorder (OUD). The Veterans Health Administration (VHA) Emergency Department Opioid Safety Initiative (ED OSI) offered a four-day course for healthcare professionals interested in gaining knowledge and practical skills to improve VHA-based SUD care. The course topics centered around the diagnosis and treatment of SUD, with a focus on OUD. Additionally, trainees received six months of support to develop addiction medicine treatment programs. Evaluations of the course were performed immediately after completion of the program and again at the six-month mark to assess its effectiveness. A total of 56 clinicians and other healthcare professionals participated in the Addiction Scholars Program (ASP). The participants represented nine Veteran Integrated Service Networks and 21 different VHA medical facilities. Nearly 70% of participants completed the initial post-survey. Thirty-eight respondents (97.4%) felt the ASP series contained practical examples and useful information that could be applied in their work. Thirty-eight respondents (97.4%) felt the workshop series provided new information or insights into the diagnosis and treatment of SUD. Eleven capstone projects based on the information acquired during the ASP were funded (a total of $407,178). Twenty participants (35.7%) completed the six-month follow-up survey. Notably, 90% of respondents reported increased naloxone prescribing and 50% reported increased prescribing of buprenorphine to treat patients with OUD since completing the course. The ASP provided healthcare professionals with insight into managing SUD and equipped them with practical clinical skills. The students translated the information from the course to develop medication for opioid use disorder (M-OUD) programs at their home institutions.

Merit-based scholarships for university graduates: A generation of Italian economists

We examine the role of financial aid in shaping the formation of human capital. We study the impact of a large merit-based scholarship for graduate studies in affecting individuals’ occupational choices, career trajectories, and labor market outcomes of a generation of Italian economists, with special focus on gender gaps and the role of social mobility. We construct a unique dataset that combines archival sources and includes microdata for the universe of applicants to the scholarship program and follow these individuals over their professional life. We discuss five main results: (i) it is easier to become a high achiever for individuals from households with a lower socio-economic status if they reside in high social mobility provinces; (ii) women are less likely to be shortlisted for a scholarship as they tend to receive lower scores in the most subjective criteria used in the initial screening of candidates; (iii) scholarship winners are much more likely to choose a research career and this effect is larger for women; (iv) women who work in Italian universities tend to have less citations than men who work in Italy. However, the citation gender gap is smaller for candidates who received a scholarship and (iv) women take longer to be promoted to the rank of full professor, even after controlling for academic productivity.

English Access Scholarship Program (DOS)

English Access Scholarship Program (DOS)

Student-to-staff partnership experience in a university-based humanitarian organization

My journey of student-faculty partnership is one that I did not anticipate joining when I signed up for the International Students Overcoming War (ISOW) Scholarship Initiative. ISOW is part student-club, part humanitarian organization that provides students the opportunities to hone their leadership skills as they administer the operations of the scholarship program. The partnerships between students, staff, and Faculty create (experiential) learning for all that enhances personal and professional development in this community. Over the course of four years, with progressive leadership responsibilities ranging from Secretary to a full-time contract position, I have been able to experience partnership from the student and staff perspective. In this essay I share the key lessons I have learned about partnership as I moved through these roles and experienced the challenges of self-reflection, holding multiple identities, and moving on.

Social media marketing and customer purchase intention: Evidence-based bibliometrics and text analysis

The rapid proliferation of social media platforms has sparked heightened interest among businesses seeking to leverage them to enhance customer purchase intentions. Consequently, there has been a surge in research exploring the intersection of social media marketing and consumer behavior. However, gaps persist regarding the primary themes within this research domain. This study analyzes 282 research papers spanning from 2012 to 2022, sourced from the Web of Science Core Collection, focusing on social media and customer purchase intentions. Leveraging Latent Dirichlet Allocation (LDA) commands in STATA and VOSviewer software, the study investigates emerging trends and prevalent themes, visualizing the dataset. The findings indicate a notable increase in research output, particularly from developed countries, with significant collaboration between developed and developing nations. Moreover, the study identifies five principal research topics: 1) the impact of social media marketing on consumer purchase intention, 2) the consequences of online brand communities on purchase behavior, 3) factors influencing consumer purchase intention, 4) influencer effects on purchase intention, and 5) social media advertising and marketing strategies. Future inquiries should delve into various factors shaping customer purchase intentions, including the role of influencers, word-of-mouth dynamics, and advertising strategies while considering the diverse cultural contexts across different regions. This comprehensive analysis provides valuable insights for researchers and practitioners alike, guiding future endeavors in understanding and harnessing the power of social media in consumer decision-making processes. AcknowledgmentsGiang Hai Ha was funded by the Master, PhD Scholarship Programme of Vingroup Innovation Foundation (VINIF), code VINIF.2022.TS030.

Data-Driven Decision Making in Scholarship Programs: Leveraging Decision Trees and Clustering Algorithms

Data-Driven Decision Making in Scholarship Programs: Leveraging Decision Trees and Clustering Algorithms

Effects of higher education subsidies on equity and efficiency across developmental stages

This study investigates the impact of taxes and subsidies for higher education on equity–efficiency trade-offs under various phases of higher education development. A scholarship program emerges as the most effective subsidy for higher education across all developmental stages. During both early and later phases, a universal grant proves more effective than a scholarship grant in reducing inequality. At the later stages of higher education development, the enrollment rate increases for universal grants but decreases for other policies, implying that the recent shift away from universal grant schemes in the UK could lead the enrollment rate to decline.

Modulation of Cardiac Ryanodine Receptors by Chloride Intracellular Ion Channel 2

Pathogenic variants of the Chloride intracellular ion channel 2 (CLIC2) are implicated in hypertrophic cardiomyopathy (HCM), a diverse heart condition leading to arrhythmic sudden cardiac death and heart failure. CLIC2 is a unique class of metamorphic protein, related to the enzymatic glutathione s-transferase family and form functional ion channel. Artificial bilayer studies have shown that CLIC2 negatively modulates the activity of cardiac ryanodine receptor 2 (RyR2), implicating the sarcoplasmic/endoplasmic reticulum (SR/ER) Ca2+ release. However, the subsequent consequences of RyR2 and CLIC2 interaction in cardiac physiology remains unknown. Therefore, we ablated clic2 in human induced pluripotent stem cell (hiPSC) line using the CRISPR-Cas9 system and performed cardiomyocyte differentiation. clic2−/− hiPSC-derived cardiomyocytes (hiPSC-CMs) showed altered electrophysiological properties leading to impaired excitation-contraction coupling. clic2−/− hiPSC-CMs showed an increase in beat rate and field potential duration by 143.49±5.96% and 162.43±5.82%, respectively, whereas conduction velocity and spike amplitude decreased by 43.81±2.22% and 43.32±3.54%, respectively compared to WT hiPSC-CMs. Additionally, action potential duration measurements of clic2−/− hiPSC-CMs showed a decrease in APD30, APD50, and APD90 by 74.42%, 65.19%, and 66.46%, respectively compared to WT hiPSC-CMs. Moreover, clic2−/− hiPSC-CMs showed altered Ca2+ handling, with a decrease in peak amplitude (57.07±2.25%) and duration (38.29±1.30%) compared to the WT hiPSC-CMs. The caffeine induced Ca2+ release in clic2−/− hiPSC-CMs, attributed to the SR/ER Ca2+ overload which decreased by 72.19±3.51% compared to WT hiPSC-CMs. Transcriptomics analysis of clic2−/− hiPSC-CMs revealed 223 transcripts with significant changes in expression levels (89 upregulated and 134 downregulated), implicating CLIC2 in hypertrophy cardiomyopathy, dilated cardiomyopathy, and other heart diseases. Furthermore, the protein expression of CLIC2 increases in end-stage failing human heart samples compared to the non-failing heart. In conclusion, our study sheds light on the novel role of CLIC2 in the regulation of cardiac (patho)physiology. National Institutes of Health (NIH) (HL133050, and HL157453); American Heart Association-Transformational Project Award; National Center for advancing translational sciences (TR004178, understudied proteins and druggable targets) (HS). Presidential Predoctoral Fellowship; Margaret T. Nishikawara Merit Scholarship Endowment in Physiology; Graduate School’s Alumni Grants for Graduate Research and Scholarship Program, The Ohio State University (SS). This is the full abstract presented at the American Physiology Summit 2024 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.

Plasma circulating extracellular vesicles indicate dysregulation of synaptic vesicle-associated signaling pathways in SHIV-infected rhesus macaque

Background: Recent studies point out the involvement of circulating extracellular vesicles (crEVs), in regulating neurotransmission via transferring proteins, lipids, and nucleic acids. Recently, we reported that plasma crEV proteins of either simian human immunodeficiency virus (SHIV) infected rhesus macaque or HIV-infected patient indicate a link to neuropathogenesis. Here, we tested the hypothesis that crEV proteins are indicative of dysfunction of synaptic vesicle (SV)-associated signaling pathways of SHIV-infected rhesus macaques. Methods: Plasma crEVs were isolated from SHIV-infected (SHIV-crEVs) and uninfected (CTL-crEVs) rhesus macaque and characterized by the ZetaView analyzer. Proteomic analysis of the isolated crEVs was performed using liquid chromatography/mass spectrometry (LC-MS/MS). Results: Our ZetaView analysis indicated that isolated crEVs were predominantly exosomes (particle size < 150 nm). In the LC-MS/MS study, 5,654 proteins were quantified, with 236 proteins (~ 4%) significantly differentially expressed between SHIV-crEVs and CTL-crEVs. Several SV and SV-signaling pathway associated proteins were quantified by tandem mass tags-based proteomic analysis both in SHIV-crEVs and CTL-crEVs. We observed that synaptogyrin, synaptotagmins, synaptobrevin, synaptosomal-associated proteins, syntaxin, and other SV-associated proteins were abundantly under expressed in SHIV-crEVs than in CTL-crEVs. Ingenuity Pathway Analysis demonstrated that proteins in SHIV-crEVs were involved in the deactivation of synaptogenesis, synaptic long-term protentiation/depression, and glutamate receptor signaling pathways. On the other hand, semaphorin neuronal repulsive signaling pathway and amyloid processing were activated in SHIV-crEVs. Bioinformatic analysis revealed that these proteins in SHIV-crEVs were involved in several CNS-related disorders/diseases such as abnormal morphology of synapses, motor dysfunction and movement disorder, seizure disorder, early/progressive neurological disorder, cognitive impairment, tauopathy, dementia, and Alzheimer’s disease. Conclusions: Our novel findings suggest that plasma crEVs could be an attractive noninvasive technique, which may elucidate the development of neuronal dysfunction and progression of neurological diseases. Funding: AG075988, HL148836, AG063345, AI110158, HL141143, HL168568, and the Louisiana Board of Regents Endowed Chairs for Eminent Scholars program. This is the full abstract presented at the American Physiology Summit 2024 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.

Unexplained infant death in Houston, TX: A 17-year retrospective

SIDS/SUID (henceforth referred to as SIDS) is a leading cause of neonate death, taking the lives of ~10 infants every day in the US alone. SIDS is defined as the death of an infant for which no cause of death can be determined after a complete autopsy, death scene investigation, and medical history review, all of which makes SIDS a very diffcult disease to study. Death scene investigations have identified several contributing environmental factors. However, etiological investigation has been complicated by inconsistencies in classification of death by medical examiners or coroners and unreliable resources for law enforcement to complete death scene investigations, which leads to epidemiological studies often lacking rigor or suffcient data. Using data from Child Fatality Review Team (CFRT) of Harris County, the Medical Examiner’s Offce, and the Texas Department of State Health Services, we performed a retrospective analysis of 17-years of SIDS cases in Harris County, Texas. We applied a novel birth rate correction for SIDS rates over the first year of life. Associations were tested using a Tukey HSD and linear regression models with co-linear factors considered. To focus on biologically unexplained SIDS cases, we subsetted our dataset to only include SIDS and Undetermined causes of death. Our preliminary data includes 1,094 cases comprised of ~43% black, ~32% Hispanic, ~20% white, ~3% Asian, and ~0.4% unknown and 57% male infants. Distribution of death across the first 12 months of life shows a peak of death around 2 months of age. We do not see an association with month or season in the raw SIDS data nor when using our novel correction for birth rates. When we apply the standard per 1,000 live births normalization, we see a significant increase in Spring and Winter. We also report race-dependent significant differences in yearly and monthly case numbers, male-to-female ratios, and age at death and additional significant race-dependent associations between SIDS cases and adults diagnosed with asthma, income level, and overcrowding based on Zip Code. This dataset represents one of the most racially and socio-economically diverse in the United States. Our data suggests that standard trends may be driven by majority white datasets and that response to socioeconomic stress varies by race/ ethnicity, which leads to differences in risk between classically described minority groups. NIH: 1F32HL160073-01A1, R01HL130249 44617-S4. BCM McNair Scholar Program, March of Dimes Basil O'Connor Research Award, Parker B. Francis Fellowship, CJ Foundation for SIDS. This is the full abstract presented at the American Physiology Summit 2024 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.

Stressed Out: Identifying Inequities and Underlying Causes Associated With Pre-med Student Stress

Stress is among the top mental health concerns of US college students and hypothesized to be especially high among pre-med students. Yet, the extent to which pre-meds’ stress differs from other college science students’ stress, as well as the underlying factors contributing to pre-meds’ stress are understudied. Given that stress is disproportionately likely to impact students who are already underrepresented and underserved in science and medicine, it is integral to identify what underlies student stress. Study Objective: We conducted a sequential mixed-methods study to identify what factors exacerbate pre-med stress and the severity of pre-med stress compared to students who are not pre-med. Hypothesis: We hypothesized the competitive nature of being pre-med would account for the majority of pre-med stress and that their overall stress levels would be higher than those of their counterparts. Methods: In Study 1, we conducted an exploratory qualitative interview study with 30 undergraduate pre-meds to assess what aspects of being pre-med exacerbate their stress. We built on this work in Study 2, with a survey of 551 science undergraduates to (a) assess how generalizable the findings from Study 1 were among undergraduate pre-meds at scale and to (b) assess whether students with different career tracks express different levels of stress. Our specific research questions were: 1) On average, do students perceive that pre-meds have higher stress than non-pre-med science majors? 2) Do pre-meds report higher levels of academic stress, perfectionism, social comparison, and perceived competitive environment in science college courses? 3) What aspects of being pre-med induce stress? and 4) What recommendations do pre-meds have for instructors and institutions to decrease pre-med stress? We used open coding methods and regressions to analyze our data. Results: We found that most students perceived that pre-med students had higher stress than their peers. However, while pre-meds reported higher levels of social comparison, they did not express higher academic stress, perfectionism, or perceived competition compared to their peers in science. Regardless of career path, being a woman or non-binary, identifying as a person excluded because of their ethnicity or race (PEER), financially unstable and having a lower GPA significantly predicted a higher academic stress score. Aspects of the medical school application underlying pre-med stress include worrying about not being good enough or maintaining a competitive GPA. Conclusion: This study highlights the levels of stress among pre-meds do not differ compared to non-pre-med science undergraduates, but that women or non-binary students, PEERs, students who are financially unstable and those with lower GPAs are more likely to experience stress in the context of undergraduate science. This work provides student-produced recommendations for ways in which instructors and institutions can decrease the stress associated with being a pre-med student. This study was funded by an ASU Online Undergraduate Research Scholars program seed grant. Graduate student Mohammed is funded by an NSF GRFP #026257-001 and PI Cooper is funded by an NSF CAREER #2143671. This is the full abstract presented at the American Physiology Summit 2024 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.

Concurrent, dual perturbations of the 5-HT and NA systems reveal dynamic interplay in regulating the neonate autoresuscitation reflex

Sudden Infant Death Syndrome (SIDS) is a leading cause of infant mortality worldwide. Failure of the neonate auto-resuscitation reflex is hypothesized to be a common endpoint in many SIDS cases. Although SIDS is idiopathic, postmortem studies indicate abnormalities in the serotonergic (5-HT) and noradrenergic (NA) systems of the respiratory network. To better understand the contributions and interactions of these two systems in autoresuscitation, we combined a novel series of Cre- and FLPo- recombinase driver mouse lines and conditional inhibitory and excitatory DREADD lines for singular excitation or inhibition of either the whole 5-HT or whole NA systems. These models were then uniquely combined to further enable 1) concurrent excitation or inhibition of both systems in the same neonate or 2) inhibition of one system while exciting the other system in the same neonate. In total, we developed 8 distinct sets of conditional genetic mouse models for singular and combined 5-HT and NA system perturbation paradigms. The 8 experimental groups and 2 control groups were repeatedly assayed for the autoresuscitation reflex using a robotic neonate cardiorespiratory assessment platform, Looper. Neonates are repeatedly tested until they succumb. Resulting data were analyzed with our recently published waveform analysis software, Breathe Easy, to calculate operant outcomes. In 320 mice total, we found 4 groups with decreased autoresuscitation success: NA activation, NA activation + 5-HT activation, NA activation + 5-HT inhibition, and 5-HT activation. There was no change in survival in any of the other groups including 5-HT inhibition. Preliminary results suggest a potential cardiovascular mechanism of autoresuscitation failure independent of respiratory outcomes. At baseline, all 4 groups with decreased survival showed increased heart rate (HR) whereas the other groups either had the same HR or a decreased HR. During early recovery, defined as beginning at the 10th breath following the primary gasp until recovery, the 4 groups with decreased survival show higher HR than the other groups following the 1st bout of autoresuscitation. As recovery progressed in these groups, HR continued to increase as well until the next autoresuscitation test. Ventilatory frequency, tidal volume, and ventilation all increased in the 3 groups where NA was activated either in isolation or in combination, but there were decreases in all other groups, including 5-HT activation. As the underlying genetic and environmental mechanisms driving SIDS are likely to have pleiotropic effects across multiple neural systems, our first-of-its-kind dual 5-HT and NA system modulations set the stage to more comprehensively model key aspects of SIDS neuropathology that reveal a previously uncharacterized dynamic functional interplay between the NA and 5-HT systems in protective respiratory reflexes. NIH: 1F32HL160073-01A1, R01HL130249 44617-S4. BCM McNair Scholar Program, March of Dimes Basil O'Connor Research Award, Parker B. Francis Fellowship, CJ Foundation for SIDS. This is the full abstract presented at the American Physiology Summit 2024 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.

Augmented muscle mass blunts aging-induced cerebrovascular oxidant stress and inflammation

Cerebrovascular dysfunction is a key driver in the cognitive and sensorimotor decline that accompanies aging, contributing to the overall progression of vascular dementia. Exercise is an effective intervention to improve brain health and cognitive function, demonstrating positive effects on cerebral vasculature via a reduction in oxidant stress, thus delaying or partially reversing dementia symptoms. Age-related muscle loss (sarcopenia), however, is prevalent in adults over 50 and sarcopenic older individuals are frequently unable to take advantage of regular exercise, the most effective therapy to reduce risk of cognitive impairment, at a level that confers benefit. Interventions that can effectively replicate the effect of exercise are thus urgently needed to address the medical needs of a large population at exceedingly elevated risk for age-related cognitive impairment. The objective of the work is to determine if augmented muscle mass, a by-product of exercise, can ameliorate both skeletal and cerebrovascular dysfunction in an aging mouse model. Myokine myostatin is a potent negative regulator of skeletal muscle growth that contributes to reduced muscle mass in many muscle-wasting diseases, including aging. To date, research has focused on the protective effect of augmented muscle mass, using genetic or pharmaceutical inhibition of myostatin, in young and obese animals. Our hypothesis is that augmented muscle mass, via myostatin deletion, will improve muscle function and further, blunt the increase in oxidant stress and inflammation that drive cerebrovascular dysfunction in the aging brain. Young adult (3 mo.) and aged (24 mo.) male C57Bl/6J mice were used as controls, in combination with aged mice (24 mo.) with myostatin constitutively deleted. Augmented muscle mass and function were assessed using in vivo plantarflexion. Oxidant stress and inflammatory makers were assessed in micro vessels isolated from the whole brain, using commercially available ELISA’s and mRNA expression. Vascular function is being assessed using pressure myography and immunohistochemistry using the middle cerebral artery. Results show that augmented muscle mass, via myostatin deletion, was successful at increasing muscle mass in the aging mouse, blunting sarcopenia, and improving skeletal muscle function. Further, the aging cerebrovasculature had significantly increased expression of two of the NADPH oxidase isoforms (NOX1, NOX4), along with pivotal cytokines/chemokines associated with vascular inflammation, activation of microglia and astrocytes, and neuroinflammation (IL-1β and CCL5/RANTES). Biomarkers of oxidant stress (3-nitrotyrosine and 8-isoprostane) were also significantly elevated with aging. Taken together, augmented muscle mass may be an effective therapeutic target to prevent and rescue cerebrovascular function and inhibit cognitive decline in an aging population. This research gratefully acknowledges support from the NIA (K01 AG064121), OCAST (HR21-045-1) and the Niblack Research Scholars Program. This is the full abstract presented at the American Physiology Summit 2024 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.

Gut microbiome is dispensable for normal respiratory function and respiratory chemoreflex

Increasing evidence indicates that gut microbiota can influence changes in respiratory homeostasis. Alterations to the gut microbiome have been hypothesized to play roles in autoimmune diseases, social behavioral deficits, and metabolic diseases such as diabetes and cardiovascular disease. We therefore aimed to determine if a model of gut dysbiosis, the absence of a gut microbiome, would result in alterations to respiratory homeostasis. After 5 days of habituation inside the Gnotobiotic animal facility, we assayed 8-week-old C57Bl/6J germ-free (GF, n=24) and specific-pathogen-free (SPF, n=24) control mice under normoxic (21% O2,79% N2) conditions, followed by a hypercapnic challenge (5% CO2, 21% O2, 74% N2) and hypoxic challenge (10% O2, 90% N2). Importantly, this germfree model does not involve treatment with high-dose antibiotics, which have been implicated in neurotoxic sequela. Whole-body flow through plethysmography was used to monitor respiratory function and metabolic demand in conscious and unrestrained animals. Recordings were interrogated using our newly published open-source software, Breathe Easy, for breath cycle duration, respiratory rate (Vf), tidal volume (VT), minute ventilation (VE), oxygen consumption (VO2), and minute ventilation normalized by oxygen consumption (VE/VO2) during room air, initial hypoxic and hypercapnic exposures, and steady-state hypoxic and hypercapnic respiratory responses. A linear mixed effects model with a Tukey post-hoc test was performed to test for significant differences wherein respiratory outcomes were dependent variables, and strain and sex were independent variables. In male mice, there was a significant decrease in breath cycle duration during room air in GF compared to SPF controls. We also saw a significant decrease in ventilatory equivalents of oxygen in the initial hypoxic response in GF mice compared to SPF controls in males, but not in the steady-state of hypoxic exposure. Finally, we note a significant increase in oxygen consumption in females during room air measurements. Of note, female mice showed significant irregularity in all respiratory parameters except oxygen consumption whereas males only showed significant irregularity in breath cycle duration during hypoxic steady-state and the hypercapnic steady-state, and tidal volume in the initial hypoxic response. While there are significant changes, it remains to be determined what the underlying mechanisms are and how they may play a contributory role in pathophysiologies co-morbid with gut microbiome dysregulation. Taken together, these results suggest that the gut microbiome is largely dispensable for normal respiratory function and respiratory chemoreflexes in adult mice and that the lack of a gut microbiome, a model of gut dysbiosis, does not result in broad significant changes in respiratory homeostasis. NIH: 1F32HL160073-01A1, R01HL130249 44617-S4. BCM McNair Scholar Program, March of Dimes Basil O'Connor Research Award, Parker B. Francis Fellowship, CJ Foundation for SIDS. This is the full abstract presented at the American Physiology Summit 2024 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 Effective Academic Medical Center-Based Strategy to Enhance Diversity Among Nurse Researchers.

The Connell-Jones Endowed Chair Diversity Nursing Research Scholars Program was created to promote engagement in nursing research and scholarship among nurses of color. Preliminary evaluation suggests that the program was widely beneficial, resulting in enrollment in doctoral education for some. Establishing opportunities that promote exposure and participation in nursing research and scholarship among nurses of color helps cultivate cohorts of diverse nurses armed to address health disparities through the advancement of nursing knowledge.

Breathe Easy, an automated respiratory data pipeline for waveform characteristic analysis

Whole body barometric flow through plethysmography is used to study respiratory output in rodent genetic and disease models. Turn-key commercial and custom systems are both used to gather multiple data streams for respiratory and metabolic parameters. Comprehensive and accurate data analysis is crucial to modelling congenital, pathogenic, and degenerative diseases. However, such studies produce large amounts of data that are time-consuming and diffcult to analyze. The investigator may use cumbersome hand annotation subject to observer bias or a series of software products to manage raw data, calculated data, statistical analysis, and graphing. Commercial software, however, is prohibitively expensive or bundled with turn-key systems limiting options for bespoke respiratory measurement systems. A lack of tools for high-throughput analysis of respiratory datasets remains a major challenge. Here, we present Breathe Easy, a novel open-source pipeline for processing raw recordings and associated metadata into operative outcomes, publication-worthy graphs, and robust statistical analyses including QQ and residual plots for assumption queries and data transformations. This pipeline uses a facile graphical user interface (GUI) for uploading data files, setting waveform feature thresholds, and defining experimental variables. After loading the GUI a, python-based program, Signal Analysis Selection and Segmentation Integration (SASSI) takes the user-settings and selects all quantitatively defined, quality breaths from each period of interest in the signal files. After SASSI, the STatistics and Graph Generator (STAGG) takes those breaths and performs linear mixed effects modeling based on user selections for each dependent variable of interest. Furthermore, our software can integrate non-respiratory experimental outcomes including quantified behavioral or gene expression data to test for breathing related associations. To validate breath selection and generate optimized default values, results from Breathe Easy were compared to manual selection by experts, which represents the current standard in the field. We show high quality breath selection and a significant reduction in quality of breaths that were rejected by the software. We also demonstrate Breathe Easy’s utility and capacity by examining a 2-year longitudinal study of an Alzheimer’s Disease mouse model to assess contributions of forebrain pathology in disordered breathing (600+ files; 1TB data). We show that, at least with this model of AD, there does not seem to be an association between forebrain pathology and respiratory outcomes. Breathe Easy offers a facile and highly customizable platform for automated handling and analysis of animal respiratory and metabolic data that sets the stage for high-throughput studies and machine learning approaches on large data sets. NIH: 1F32HL160073-01A1, R01HL130249 44617-S4. BCM McNair Scholar Program, March of Dimes Basil O'Connor Research Award, Parker B. Francis Fellowship, CJ Foundation for SIDS. This is the full abstract presented at the American Physiology Summit 2024 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.

Ischemic Conditioning Improves the Microvascular Hyperemic Response to Passive Limb Movement in Young Adults

Background: Passive limb movement (PLM) of the lower extremity is a simple and clinically relevant approach to measure peripheral microvascular health. PLM causes an acute increase in hyperemic leg blood flow (LBF) without an increase in skeletal muscle metabolism, and the hyperemic response is ~80% nitric oxide-mediated. A known therapeutic stimulus to increase large conduit artery vascular health is ischemic conditioning (IC). Whether a single session of IC can improve the hyperemic response to PLM remains unknown. Objective: To quantify the microvascular response to PLM after a single session of IC in young adults. Hypothesis: The hyperemic response to PLM, measured as a change in peak femoral artery blood flow, will be greater following IC vs. sham-IC. Methods: This was a prospective, cross-over, blinded clinical trial (NCT05935670). Young adults aged 18-30 years who were free of cardiovascular disease were recruited, and study participants completed two study visits. Participants were seated in a Biodex dynamometer and superficial femoral artery resting blood flow and diameter were measured in the dominant leg using ultrasonography. The dynamometer then passively moved the knee 90 degrees at a frequency of 1 Hz for a single PLM while blood flow was continuously measured. The ΔLBF was calculated as the absolute (ml/min) and relative (% change) difference in LBF from rest to peak. Participants were then randomized to receive either IC or sham-IC, and the vascular assessor was blinded to the condition. For IC, the cuff was placed around the proximal dominant thigh and repetitively inflated to 225 mmHg for 5 min then deflated for 5 min, for a total of 5 cycles. For sham-IC, the thigh cuff was inflated to only 25 mmHg. Fifteen minutes after IC or sham-IC the hyperemic response to PLM was re-assessed. The pre-/post- change in the PLM hyperemic response was calculated as the difference from pre- vs. post-IC or sham-IC. Statistical analysis included one-sided paired t-tests. Results: Seven individuals (3 female, age 26 ± 4 years old) completed the study. Compared to pre-IC, the relative peak hyperemic response to PLM was augmented post-IC (%ΔLBF = 89 ± 42% pre- vs. 136 ± 49% post-IC, p=0.001). Conversely, there was no change in the relative peak hyperemic response in the sham-IC condition (%ΔLBF = 108 ± 61% pre- vs. 108 ± 77% post-sham-IC, p=0.50). The pre-/post- change score of absolute peak hyperemic response to PLM was also higher after IC vs. sham-IC (change in ΔLBF = 50 ± 78 IC ml/min vs. -44 ± 127 ml/min sham-IC, p = 0.03). Conclusion: These results show an improvement in the peripheral microvascular response to PLM following IC. Future studies should examine the mechanistic pathways responsible for an improved PLM response as well as the potential benefits of IC on microvascular health in clinical populations with underlying peripheral microvascular dysfunction. AAW was supported by the National Heart, Lung and Blood Institute (T32HL13464) and Cardiovascular Center’s A.O. Smith Fellowship Scholars Program. Research was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development R01-HD099340 (ASH and MJD) and R01-HD112258 (MJD and ASH). This is the full abstract presented at the American Physiology Summit 2024 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.

Deletion of Myostatin Significantly and Preferentially Improves Muscle Function in a Sex-Dependent Manner in Both an Obese and Aging Mouse Model

Skeletal muscle mass and function are essential components of health and homeostasis. In addition to its role in balance and locomotion, skeletal muscle is the body’s largest metabolic reservoir, absorbing significant amounts of glucose and amino acids from the blood stream. The loss of muscle mass is associated with impaired glucose tolerance, threatens vascular health and contributes to cardiovascular disease in obese and aging (sarcopenic) populations, along with driving overall mortality. The myokine myostatin (GDF-8) is a potent negative regulator of skeletal muscle growth that is upregulated in humans and animal models of obesity and aging. Loss of myostatin is known to increase the number of glycolytic muscle fibers and has been shown to correct indices that govern cardiometabolic health in obesity and aging, improving endothelial function and glucose homeostasis, and protecting against renal injury and hypertension. However, these studies have largely been conducted using male mice, leaving the question regarding the effectiveness of myostatin deletion on skeletal muscle function, independent of sex, largely unexplored. As such, our hypothesis is that the deletion of myostatin will improve skeletal muscle function in both male and female mice, regardless of the disease phenotype being obesity or aging. Young (3-5 mo.) lean and obese mice were used, along with aged (18-24 mo.) mice. The obese db/db model was utilized as it is a well characterized model of hyperphagia that results in obesity and subsequent metabolic disease, including significant whole-body adiposity and reduced muscle mass. On this background we have crossed mice harboring constitutive genetic deletion of myostatin to reverse muscle loss. Thus, myostatin deletion was crossed onto the relevant backgrounds in combination with aging or obesity and included both sexes. Muscle function was assessed in all groups using in vivo plantarflexion. Young male mice demonstrated an ~20% increase in force production compared to the females. Results show that aging and obesity inhibited skeletal muscle function in both sexes, with female mice showing a lessened impact of obesity or aging. Myostatin deletion improved muscle function in male mice, returning both obesity-derived weakness and aging-induced sarcopenia back to levels of young control. However, female mice without myostatin experienced a relative gain-of-function, with force production significantly exceeding that of the young control. The implication of these results is that weight loss may be more effective in protecting muscle function in diseases in the male population whereas myostatin inhibition, either pharmaceutically or with prescription exercise, may result in greater improvements in the female sex comparatively. This research gratefully acknowledges support from the NIA (K01 AG064121), OCAST (HR21-045-1) and the Niblack Research Scholars Program. This is the full abstract presented at the American Physiology Summit 2024 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.

Actin cytoskeletal proteins in mice cortical microvessels decreased with aging

Background: The actin cytoskeleton regulates many important cellular processes in the brain, including cell division and proliferation, migration, and differentiation. The interactions of actin microfilaments with plaque proteins zonula occludens (ZO)-1, -2, -3 are required ensuring the formation of a polarized brain endothelium which ultimately drives development of blood-brain barrier (BBB). In this study, we carried out an extensive evaluation of proteins involved in the structure and function of mouse brain cortical microvessels (MVs) using a discovery-based quantitative proteomic approach. Methods: Cortical MVs were isolated from equal number of age-matched, male and female, young (4–6 months), middle-aged (12–14 months), and old (20–21 months) mice obtained from Jackson Laboratory [Tg(Thy1-EGFP)MJrs/J] and bred in a C57B16J background (n = 6/group). The presence of end-arterioles, capillaries, and venules in MVs was confirmed by light microscopy and by alkaline phosphate staining. Proteomics analysis was performed using liquid chromatography/mass spectrometry. Results: We quantified 4746, 4216, and 4579 differentially expressed proteins by proteomics in brain cortical MVs of young, middle-aged, and old mice, respectively. We found that several actin cytoskeletal-related alpha actinin-1, -2, -3 (ACTN1/2/4), actin-related protein -2, -3, -3B (ACTR2/3/3B), actin-related protein 2/3 complex subunit -1A, -2, -4, -5 (ARPC1A/2/4/5), and [F-actin]-monooxygenase MICAL3 proteins were significantly downregulated in mice cortical MVs with aging. Under physiological conditions, cerebral endothelial cells are connected by tight junctions (TJs) and adherens junctions (AJs). The TJ and AJ proteins are anchored to the actin cytoskeleton by multiple accessory proteins, ZO-1, ZO-2 and ZO-3. Interestingly, we observed that several TJ, AJ, and their signaling (PKC-α/γ/ε, RHOA, RAB3 and YES1) proteins were significantly downregulated in mice cortical MVs with aging. Moreover, we previously documented that oxidative stress during aging leads to adverse protein profile changes of brain cortical MVs that affect mRNA/protein stability and ATP synthesis capacity in mice. Conclusions: We suggest that increased oxidative stress during aging leads to protein expression profile changes of brain cortical MVs that affect ATP synthesis capacity, which leads to actin cytoskeletal dysregulation, and accelerating to endothelial and BBB dysfunction in the brain microvasculature with aging. Funding: AG075988, HL148836, AG063345, AG074489, NS114286, AG047296, HL141143, HL168568, and the Louisiana Board of Regents Endowed Chairs for Eminent Scholars program. This is the full abstract presented at the American Physiology Summit 2024 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.