Digital Commons Network^™

The Contributions Of Motor Skill Proficiency To Cognitive And Social Development In Early Childhood, Catherine M. Capio, Norman B. Mendoza, Rachel A. Jones, Rich S.W. Masters, Kerry Lee

Health Sciences Faculty Publications

With limited evidence from intervention studies, causal relationships between motor competence and cognitive and social development have yet to be clearly established. In this research, we investigated whether a targeted training programme to improve fundamental movement skills (i.e., object control, locomotor) in young children would also lead to improvements in the cognitive (i.e., executive function) and social (i.e., socioemotional competence) domains. Using a two-arm group randomised intervention design, 185 children aged 36 to 60 months (mean 47.51, SD 8.11 months) were allocated to a motor skill intervention group or an active control group. The intervention was implemented over one school …

Point Of Care Ultrasound For Gastric Residual: An Objective Structured Clinical Examination, Brandon Quinn, Kaitlyn Gray

Doctoral Projects

Point of care ultrasound (POCUS) has become an invaluable tool in modern medical practice offering real-time diagnostic and procedural guidance for anesthesia providers. POCUS is a non-invasive assessment tool that gives anesthesia insight into a quantitative assessment of gastric residuals. Furthermore, POCUS assessments are useful in preventing anesthetic complications that can cause major morbidity and mortality such as aspiration pneumonia. Despite the growing relevance, formalized training on POCUS for assessing gastric residuals remains limited in many nurse anesthesia programs. The University of Southern Mississippi currently lacks a standardized curriculum for teaching student registered nurse anesthetists how to utilize gastric ultrasound …

Myosin Xva Isoforms Participate In The Mechanotransduction-Dependent Remodeling Of The Actin Cytoskeleton In Auditory Stereocilia, Ana I. López-Porras, Ava M. Kruse, Mark T. Mcclendon, A. Catalina Vélez-Ortega

Neurology Faculty Publications

Auditory hair cells form precise and sensitive staircase-like actin protrusions known as stereocilia. These specialized microvilli detect deflections induced by sound through the activation of mechano-electrical transduction (MET) channels located at their tips. At rest, a small MET channel current results in a constant calcium influx which regulates the morphology of the actin cytoskeleton in the shorter ‘transducing’ stereocilia. However, the molecular mechanisms involved in this novel type of activity-driven plasticity in the stereocilium cytoskeleton are currently unknown. Here, we tested the contribution of myosin XVA (MYO15A) isoforms, given their known roles in the regulation of stereocilia dimensions during hair …

Kinetics Of Naturally Induced Binding And Neutralising Anti-Sars-Cov-2 Antibody Levels And Potencies Among Sars-Cov-2 Infected Kenyans With Diverse Grades Of Covid-19 Severity: An Observational Study, John Kimotho, Yiakon Sein, Shahin Sayed, Reena Shah, Mansoor Saleh, Ann Karanu, Viviane Oluoch, Jasmit Shah, Julius Mutiso, Zaitun Nneka, Alfred Mburu, Peter Betti, Francis M. Ndungu

Pathology, East Africa

Background: Given the low levels of coronavirus disease 2019 (COVID-19) vaccine coverage in sub-Saharan Africa (sSA), despite high levels of natural severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) exposures, strategies for extending the breadth and longevity of naturally acquired immunity are warranted. Designing such strategies will require a good understanding of naturally acquired immunity.

Methods: We measured whole-spike immunoglobulin G (IgG) and spike-receptor binding domain (RBD) total immunoglobulins (Igs) on 585 plasma samples collected longitudinally over five successive time points within six months of COVID-19 diagnosis in 309 COVID-19 patients. We measured antibody-neutralising potency against the wild-type (Wuhan) SARS-CoV-2 …

Effectiveness Of Clinical Training In Influencing The Outcome Of Visual Inspection With Acetic Acid In Selected Facilities At A County In Kenya, Evah Maina, Abednego Ongeso, Nancy Maingi

School of Nursing & Midwifery, East Africa

Background: Cervical cancer remains a major health concern in developing countries, primarily due to the presence of human papillomavirus (HPV) types 16 and 18. Visual Inspection with Acetic Acid (VIA) is a common and affordable screening method, yet its effectiveness is closely tied to the skills and competency of healthcare providers. This study aimed to assess the impact of clinical training on improving VIA screening outcomes for cervical cancer in a county in Kenya.

Methods: Seven government health facilities equipped with cryotherapy machines were selected, with two healthcare providers sampled from each. A six-day VIA training intervention was conducted, combining …

Labrad : Vol 49, Issue 2 - December 2024, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• EDITORIAL
• ARTICLES
• Anti-Glomerular Basement Membrane (GBM) Disease: Pathogenesis, Presentation, and Diagnostic Insights
• Advanced Total Laboratory Automation (TLA) Workflow: A Comprehensive Approach towards High-Throughput Analyzers in Clinical Chemistry
• Precision Under Pressure: Challenges in Therapeutic Drug Monitoring for Immunosuppressants
• Frozen Section: Diagnostic Accuracy, Pitfalls and Use of Digital Pathology
• Working Environment Perspective of a Learner
• AI Training: A Must-Have Skill for Tomorrow’s Radiologists
• Challenges in Blood Supply: Importance of Voluntary Donations
• Leadership Skills and Emotional Intelligence For Professional Capacity Building in Histopathology – A Broad Perspective
• Factor VIII and XI Deficiency; A Finding That Could Have Been Missed-A Case Report
• Accelerated Phase …

Plasma Transfusion In The Intensive Care Unit, Maite M. T. Van Haeren, Senta Jorinde Raasveld, Sanne De Bruin, Merijn C. Reuland, Claudia Van Den Oord, Jimmy Schenk, Cécile Aubron, Jan Bakker, Maurizio Cecconi, Marcus Lance

Anaesthesiology, East Africa

Background: Current guidelines discourage prophylactic plasma use in non-bleeding patients. This study assesses global plasma transfusion practices in the intensive care unit (ICU) and their alignment with current guidelines.

Study Design and Methods: This was a sub-study of an international, prospective, observational cohort. Primary outcomes were in-ICU occurrence rate of plasma transfusion, proportion of plasma events of total blood products events, and number of plasma units per event. Secondary outcomes included transfusion indications, INR/PT, and proportion of events for non-bleeding indications.

Results: Of 3643 patients included, 356 patients (10%) experienced 547 plasma transfusion events, accounting for 18% …

Improving Primary Care Providers Awareness, Knowledge, Attitude, And Intention To Change Practice About Uncontrolled Obstructive Sleep Apnea And Its Effect On Metabolic Dysfunction-Associated Steatotic Liver Disease, Formerly Non-Alcoholic Fatty Liver Disease Prognosis, Olivia Amoakowaa-Senya

Doctoral Scholarly Projects & Capstones

Non-alcoholic fatty liver disease (NAFLD), now known as metabolic dysfunction-associated steatotic liver disease (MASLD), is the leading cause of chronic liver disease in the world. The mechanisms involved in its development and progression continue to be a mystery that scientists are trying to unravel. However, many research studies found a correlation between uncontrolled obstructive sleep apnea (OSA) and worsening of NAFLD. Chronic intermittent hypoxia and sleep fragmentation in OSA increase sympathetic activity and promote oxidative stress, pro-inflammatory cytokine production, and metabolic dysregulation, which increases the risk of various diseases, including NAFLD/MASLD progression. Early assessment and screening for OSA in patients …

Association Of Common And Rare Variants With Alzheimer’S Disease In More Than 13,000 Diverse Individuals With Whole-Genome Sequencing From The Alzheimer’S Disease Sequencing Project, Wan-Ping Lee, Seung Hoan Choi, Margaret G Shea, Po-Liang Cheng, Beth A Dombroski, Achilleas N Pitsillides, Nancy L Heard-Costa, Hui Wang, Katia Bulekova, Amanda B Kuzma, Yuk Yee Leung, John J Farrell, Honghuang Lin, Brian W Kunkle, Adam Naj, Elizabeth E Blue, Frederick Nusetor, Dongyu Wang, Eric Boerwinkle, William S Bush, Xiaoling Zhang, Philip L De Jager, Josée Dupuis, Lindsay A Farrer, Myriam Fornage, Eden Martin, Margaret Pericak-Vance, Sudha Seshadri, Ellen M Wijsman, Li-San Wang, Alzheimer's Disease Sequencing Project, Gerard D Schellenberg, Anita L Destefano, Jonathan L Haines, Gina M Peloso

Center for Medical Ethics and Health Policy Staff Publications

Introduction: Alzheimer's disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous.

Methods: We investigated the association of AD with both common variants and aggregates of rare coding and non-coding variants in 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data.

Results: Pooled-population analyses of all individuals identified genetic variants at apolipoprotein E (APOE) and BIN1 associated with AD (p < 5 × 10-8). Subgroup-specific analyses identified a haplotype on chromosome 14 including PSEN1 associated with AD in Hispanics, further supported by aggregate testing of rare coding and non-coding variants in the region. Common variants in LINC00320 were observed associated with AD in Black individuals (p = 1.9 × 10-9). Finally, we observed rare non-coding variants in the promoter of TOMM40 distinct of APOE in pooled-population analyses (p = 7.2 × 10-8).

Discussion: We observed that complementary pooled-population and subgroup-specific analyses offered unique insights into the genetic architecture of AD.

Highlights: We determine the association of genetic variants with Alzheimer's disease (AD) using …

“Breaking Barriers: Empowering African Youth Through Implementation Of A Therapeutic Patient Education Program For Juvenile Idiopathic Arthritis”, Wafa Hamdi, Angela Migowa, Hanene Lassoued Ferjani, Alia Fazaa, Saoussen Miladi, Kaouther Maatallah, Kawther Ben Abdelghani, Ayodele Faleye

Paediatrics and Child Health, East Africa

Introduction: Patient education is crucial in managing chronic diseases like Juvenile Idiopathic Arthritis (JIA). Traditional methods such as videos and brochures often fail to maintain long-term knowledge retention. Therapeutic Patient Education (TPE) offers a more effective, patient-centered approach.

Objective: PAFLAR aimed to implement a TPE program with a “train the trainers” masterclass to ensure effective delivery and improve outcomes for children with JIA.

Methods: PAFLAR’s TPE program was designed through a focus group, involving a literature review and strategic planning for the implementation step. The program includes specialized training for healthcare professionals enhancing their abilities to deliver …

Random C-Peptide And Islet Antibodies At Onset Predict Β Cell Function Trajectory And Insulin Dependence In Pediatric Diabetes, Mustafa Tosur, Saima Deen, Xiaofan Huang, Serife Uysal, Marcela Astudillo, Richard A Oram, Maria J Redondo, Farook Jahoor, Ashok Balasubramanyam

Children’s Nutrition Research Center Staff Publications

Objective: Identification of prognostic biomarkers in pediatric diabetes is important for precision medicine. We assessed whether C-peptide and islet autoantibodies are useful to predict the natural history of children with new-onset diabetes.

Methods: We prospectively studied 72 children with new-onset diabetes (median follow-up: 8 months) by applying the Aβ classification system ("A+": islet autoantibody positive, "β+": random serum C-peptide ≥1.3 ng/mL at diagnosis). Beta-cell function was assessed longitudinally with 2 hours postprandial/stimulated urinary C-peptide-to-creatinine ratio (UCPCR) 3-12 weeks (V1) and 6 to 12 months after diagnosis (V2). We obtained a type 1 diabetes genetic risk score for each participant, and …

Comparison Of Two Learning Methodologies: Virtual Reality And Osce Simulation, Connor Blackwell, Tabor Mcgee

Doctoral Projects

Anesthesia education has evolved immensely over the past twenty years, and with the new virtual reality (VR) simulations created by SIMVANA, the exponential growth can continue. The anesthesia program at The University of Southern Mississippi (USM) currently utilizes an educational platform known as the Objective Structured Clinical Examination (OSCE) for their students’ clinical curriculum. With the development of technology and education models, the purpose of the doctoral project is to determine if VR simulation can produce more effective learning than the OSCE modules. To determine the effectiveness, pharmacologic lessons for intraoperative hypotension were administered through both platforms and then tested …

Independent Evolution Of Oleate Hydratase Clades In Bacillales Reflects Molecular Convergence, Robert J. Neff, Priscilla C. Lages, Shannon K. Donworth, James D. Brien, Christopher D. Radka

Markey Cancer Center Faculty Publications

Oleate hydratase (OhyA), a flavoenzyme that catalyzes the hydration of unsaturated fatty acids, has been identified in various Bacillales organisms, including those in the Listeria, Lysinibacillus, Paenibacillus, and Staphylococcus genera. In this study, we combine structural biology with molecular and phylogenetic analyses to investigate the evolutionary dynamics of the OhyA protein family within the Bacillales order. Our evolutionary analysis reveals two distinct OhyA clades (clade I and clade II) within Bacillales that, while sharing catalytic function, exhibit significant genomic and structural differences. Our findings suggest that these OhyA clades originated from independent evolutionary processes through convergent evolution rather than gene …

Evaluation Of Stress Ulcer Prophylaxis In Pediatric General Medicine Patients After Transfer From The Intensive Care Unit And At Discharge, Rathi Asaithambi, Surin Lee

Faculty, Staff and Students Publications

OBJECTIVES: The primary aim of this study was to determine continuation rates of stress ulcer prophylaxis (SUP) upon transfer from a pediatric intensive care unit (PICU) to a general medicine unit and upon hospital discharge. The secondary aim was to identify patient characteristics or concomitant medications that were associated with continuation of SUP at transfer from the PICU.

METHODS: This retrospective chart review included patients who were initiated on acid suppression for SUP in the PICU between June 2021 and May 2022 and subsequently transferred to a general medicine unit prior to discharge. Patients were excluded if they were receiving …

Cadasil: A Notch3-Associated Cerebral Small Vessel Disease, Hao Deng

Faculty, Staff and Students Publications

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary cerebral small vessel disease (CSVD), pathologically characterized by a non-atherosclerotic and non-amyloid diffuse angiopathy primarily involving small to medium-sized penetrating arteries and leptomeningeal arteries. In 1996, mutation in the notch receptor 3 gene (NOTCH3) was identified as the cause of CADASIL. However, since that time other genetic CSVDs have been described, including the HtrA serine peptidase 1 gene-associated CSVD and the cathepsin A gene-associated CSVD, that clinically mimic the original phenotype. Though NOTCH3-associated CSVD is now a well-recognized hereditary disorder and the number of …

Hands-On Training About Data Clustering With Orange Data Mining Toolbox

Faculty, Staff and Students Publications

Data clustering is a core data science approach widely used and referenced in the scientific literature. Its algorithms are often intuitive and can lead to exciting, insightful results that are easy to interpret. For these reasons, data clustering techniques could be the first method encountered in data science training. This paper proposes a hands-on approach to data clustering training suitable for introductory courses. The education approach features problem-based training that starts with the data and gradually introduces various data processing and analysis methods, illustrating them through visual representations of data and models. The proposed training is suitable for a general …

Steering Research On Mrna Splicing In Cancer Towards Clinical Translation, Douglas L Black, Angela N Brooks, Chonghui Cheng, Ana Conesa, Edie I Crosse, Eduardo Eyras, Ernesto Guccione, Sydney X Lu, Karla M Neugebauer, Priyanka Sehgal, Xiao Song, Zuzana Tothova, Juan Valcárcel, Kevin M Weeks, Gene W Yeo, Andrei Thomas-Tikhonenko

Faculty, Staff and Students Publications

Splicing factors are affected by recurrent somatic mutations and copy number variations in several types of haematologic and solid malignancies, which is often seen as prima facie evidence that splicing aberrations can drive cancer initiation and progression. However, numerous spliceosome components also 'moonlight' in DNA repair and other cellular processes, making their precise role in cancer difficult to pinpoint. Still, few would deny that dysregulated mRNA splicing is a pervasive feature of most cancers. Correctly interpreting these molecular fingerprints can reveal novel tumour vulnerabilities and untapped therapeutic opportunities. Yet multiple technological challenges, lingering misconceptions, and outstanding questions hinder clinical translation. …

Rfc2 May Contribute To The Pathogenicity Of Williams Syndrome Revealed In A Zebrafish Model, Yu-Ri Lee, Dilan Wellalage Don, Jaya K George-Abraham, Laurie A Robak, Cristina C Trandafir, Pengfei Liu, Jill A Rosenfeld, Tae Hyeong Kim, Florence Petit, Yoo-Mi Kim, Chong Kun Cheon, Yoonsung Lee, Cheol-Hee Kim

Faculty, Staff and Students Publications

Williams syndrome (WS) is a rare multisystemic disorder caused by recurrent microdeletions on 7q11.23, characterized by intellectual disability, distinctive craniofacial and dental features, and cardiovascular problems. Previous studies have explored the roles of individual genes within these microdeletions in contributing to WS phenotypes. Here, we report five patients with WS with 1.4 Mb-1.5 Mb microdeletions that include RFC2, as well as one patient with a 167-kb microdeletion involving RFC2 and six patients with intragenic variants within RFC2. To investigate the potential involvement of RFC2 in WS pathogenicity, we generate a rfc2 knockout (KO) zebrafish using CRISPR-Cas9 technology. Additionally, we generate …

Bst2 Facilitates Activation Of Hematopoietic Stem Cells Through Erk Signaling, Holly A Hill, Youngjae Jeong, Brian M Ho, Pawel Kus, Trisha K Wathan, Bailee N Kain, Shixia Huang, Dongsu Park, Katherine Y King

Faculty, Staff and Students Publications

The proinflammatory cytokine interferon-gamma (IFNγ) is upregulated in a variety of infections and contributes to bone marrow failure through hematopoietic stem cell (HSC) activation and subsequent exhaustion. The cell surface protein, bone marrow stromal antigen 2 (BST2), is a key mediator of this process, as it is induced upon interferon stimulation and required for interferon-dependent HSC activation. To identify the mechanism by which BST2 promotes interferon-dependent HSC activation, we evaluated its role in niche localization, immune cell function, lipid raft formation, and intracellular signaling. Our studies indicated that knock out (KO) of BST2 in a murine model does not disrupt …

Proteomic Analysis Uncovers Multiprotein Signatures Associated With Early Diabetic Kidney Disease In Youth With Type 2 Diabetes Mellitus, Kumar Sharma, Sushrut Waikar, Anita Layton, Kalie L Tommerdahl, Ian De Boer, Timothy Vigers, Robert G Nelson, Jane Lynch, Frank Brosius, Pierre J Saulnier, Jesse A Goodrich, Jeanie B Tryggestad, Elvira Isganaitis, Fida Bacha, Kristen J Nadeau, Daniel Van Raalte, Matthias Kretzler, Hiddo Heerspink, Petter Bjornstad

Faculty, Staff and Students Publications

Background: The onset of diabetic kidney disease (DKD) in youth with type 2 diabetes (T2D) mellitus often occurs early, leading to complications in young adulthood. Risk biomarkers associated with the early onset of DKD are urgently needed in youth with T2D.

Methods: We conducted an in-depth analysis of 6596 proteins (SomaScan 7K) in 374 baseline plasma samples from the Treatment Options for Type 2 Diabetes in Adolescents and Youth study to identify multiprotein signatures associated with the onset of albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g), a rapid decline in eGFR (annual eGFR decline >3 ml/min per 1.73 m2 and/or ≥3.3% …

Understanding Health-Related Quality Of Life After Hypospadias Repair: A Qualitative Study With Pre-Adolescent Males And Parents, Heidi W Brown, Walid A Farhat, Marisa E Hilliard

Faculty, Staff and Students Publications

Introduction: Hypospadias is a common disease that affects approximately 1 in every 200 live male births in the United States, and long-term studies of individuals who have undergone repair demonstrate complication rates of 15%-70%. The Hypospadias-Specific Health-related Quality of Life (HRQOL) Conceptual Framework for youth and adults suggests that additional morbidity may be incurred from poor psychological, social, and sexual health. The current study sought to clarify hypospadias-specific HRQOL and care priorities in a pre-pubertal population.

Material and methods: This IRB-approved, semi-structured interview study used rigorous qualitative research methods. Eligible patients were English-speaking 8-12-year-old males with hypospadias and their parents. …

Maternal Glycemic Status And Longitudinal Fetal Body Composition And Organ Volumes Based On Three-Dimensional Ultrasonography, Cuilin Zhang, Stefanie N Hinkle, Dian He, Wesley Lee, Roger B Newman, John Owen, Daniel W Skupski, William A Grobman, Seth Sherman, Fasil Tekola-Ayele, Jagteshwar Grewal, Katherine L Grantz

Faculty, Staff and Students Publications

Objective: Gestational diabetes mellitus (GDM) increases the risk of fetal overgrowth as measured by two-dimensional ultrasonography. Whether fetal three-dimensional (3D) soft tissue and organ volumes provide additional insight into fetal overgrowth is unknown.

Research design and methods: We prospectively evaluated longitudinal 3D fetal body composition and organ volumes in a diverse U.S. singleton pregnancy cohort (2015-2019). Women were diagnosed with GDM, impaired glucose tolerance (IGT), or normal glucose tolerance (NGT). Up to five 3D ultrasound scans measured fetal body composition and organ volumes; trajectories were modeled using linear mixed models. Overall and weekly mean differences in fetal 3D trajectories were …

Shared Genetic Architecture Of Non-Viral Cirrhosis With Several Pleiotropic Traits: A Nested Case-Control Study In The Uk Biobank, Aaron P Thrift, Sabrina M Lin, Xiangjun Xiao, Hyeyeun Lim, Goo Jun, Stacia M Desantis, Hashem B El-Serag, Fasiha Kanwal, Christopher I Amos

Faculty, Staff and Students Publications

Background & aims: Cirrhosis is a leading cause of liver-related mortality and a multifactorial disease. To date, the complex genetic architecture of non-viral cirrhosis has not been fully explored. Cross-trait genetic correlations can elucidate the common genetic etiology of genetically correlated phenotypes. This study aims to identify polygenic and pleiotropic traits associated with cirrhosis using the linkage disequilibrium score regression analysis.

Methods: We conducted genome-wide association analysis of 9,622,842 imputed SNPs on 3,368 non-viral cirrhosis cases and 258,258 controls, and cross-trait analysis between non-viral cirrhosis and various polygenic and pleiotropic traits using the UK Biobank cohort study. We further performed …

Experiences In Providing A Community Educational Resource For The All Of Us Researcher Workbench, Stephen Richards, Pamela N Luna, Laterrica Williams, Julie R Coleman, Jasmine N Baker, Shamika Ketkar, Ashley M Butler, Latanya Hammonds-Odie, Elizabeth G Atkinson, Kim C Worley, Debra D Murray, Brendan Lee, Steven E Scherer

Faculty, Staff and Students Publications

OBJECTIVE: Educational offerings to fill the bioinformatics knowledge gap are a key component to enhancing access and use of health data from the All of Us Research Program. We developed a Train the Trainer-based, innovative training series including project-based learning, modular on-demand demonstrations, and unstructured tutorial time as a model for educational engagement in the All of Us community.

MATERIALS AND METHODS: We highlight our training modules and content, with training survey data informing cycles of development in the creation of a 6-module training series with modular demonstrations.

RESULTS: We have conducted 2 public iterations of the Train the Trainer …

Performance Of Formulas Included In The Escrs Intraocular Lens Power Calculator

Faculty, Staff and Students Publications

Purpose: To compare the refractive prediction errors (PEs) of formulas included in the ESCRS intraocular lens (IOL) power calculator to aid in informed decisions on IOL power selection based on the output of this tool.

Setting: Cullen Eye Institute, Baylor College of Medicine, Houston, Texas.

Design: Retrospective case-series.

Methods: 748 eyes of 748 patients after implantation of 1 of 3 lenses were included, single-piece: the SN60WF, PCB00/ZCB00 and 3-piece: MA60MA. IOL constants recommended by the calculator were used for the study. We performed analysis for the whole dataset, short (< 22 mm) and long eyes (>25 mm) as well as in subgroups based on the …

Chemogenetic Neuronal Silencing Decouples C-Jun Activation From Cell Death In The Temporal Cortex, Melissa A Rudy, Trent A Watkins, Joanna L Jankowsky

Faculty, Staff and Students Publications

Initial symptoms of neurodegenerative diseases are often defined by the loss of the most vulnerable neural populations specific to each disorder. In the early stages of Alzheimer's disease, vulnerable circuits in the temporal lobe exhibit diminished activity prior to overt degeneration. It remains unclear whether these functional changes contribute to regional vulnerability or are simply a consequence of pathology. We previously found that entorhinal neurons in the temporal cortex undergo cell death following transient suppression of electrical activity, suggesting a causal role for activity disruption in neurodegeneration. Here we demonstrate that electrical arrest of this circuit stimulates the injury-response transcription …

Pediatric High Blood Pressure Recognition Associated With Electronic Decision Support: A Cohort Analysis, Justin Rahman, Alisa A Acosta, Jessica F Campbell, Mary Hoang, Katharine E Sigler, Elizabeth A Onugha, Shweta S Shah, S Kristen Sexson-Tejtel, Mark Farrior, Scott Watson

Faculty, Staff and Students Publications

Background: Pediatric high blood pressure (BP) predicts future cardiovascular disease events. High BP is improperly measured, underrecognized, and undermanaged especially in disadvantaged populations. In a large, diverse, academic pediatric practice, we detail the associations of a comprehensive initiative with high BP provider recognition.

Methods: A comprehensive BP initiative was promulgated including (1) retraining providers and staff on BP management; (2) deploying equipment at 55+ sites; and (3) electronic decision support tool alerting staff and clinicians and suggesting management. During the 14-month preintervention and 14-month postintervention periods, data on BP and patient characteristics were collected. The outcome was incident BP recognition …

Chronic Β3-Ar Stimulation Activates Distinct Thermogenic Mechanisms In Brown And White Adipose Tissue And Improves Systemic Metabolism In Aged Mice, Shoba Ekambaram, Weidong Wang, Michael Rudolph, Mahmoud A Mohammad, Shaji K Chacko, Madhan Subramanian, Stefano Tarantini, Andriy Yabluchanskiy, Zoltan Ungvari, Anna Csiszar, Priya Balasubramanian

Faculty, Staff and Students Publications

Adipose thermogenesis has been actively investigated as a therapeutic target for improving metabolic dysfunction in obesity. However, its applicability to middle-aged and older populations, which bear the highest obesity prevalence in the United States (approximately 40%), remains uncertain due to age-related decline in thermogenic responses. In this study, we investigated the effects of chronic thermogenic stimulation using the β3-adrenergic (AR) agonist CL316,243 (CL) on systemic metabolism and adipose function in aged (18-month-old) C57BL/6JN mice. Sustained β3-AR treatment resulted in reduced fat mass, increased energy expenditure, increased fatty acid oxidation and mitochondrial activity in adipose depots, improved glucose homeostasis, and a …

Association Of Left Atrial Function With Frailty: The Atherosclerosis Risk In Communities (Aric) Study, Anne Eaton, Pamela L Lutsey, B Gwen Windham, Riccardo M Inciardi, Scott D Solomon, Christie M Ballantyne, Amil M Shah, Lin Yee Chen

Faculty, Staff and Students Publications

Background: Frailty is common in people with cardiovascular disease. Worse left atrial (LA) function is an independent risk factor for cardiovascular disease. However, whether worse LA function is associated with frailty is unclear.

Methods: We included 3292 older adults from the Atherosclerosis Risk in Communities study who were non-frail at baseline (visit 5, 2011-2013) and had LA function (reservoir, conduit, and contractile strain) measured from two-dimensional speckle-tracking echocardiography. LA stiffness index was calculated as a ratio of E/e' to LA reservoir strain. Frailty was defined using the validated Fried frailty phenotype. Incident frailty was assessed between 2016 and 2019 during …

Pathophysiology And Treatment Of Prediabetes And Type 2 Diabetes In Youth, Julie M Pike, Ashley Butler, Kalie L Tommerdahl, Philip S Zeitler

Faculty, Staff and Students Publications

Youth-onset type 2 diabetes is a heterogeneous disease with increasing prevalence in relation to increased rates of obesity in children. It has genetic, epigenetic, social, and environmental determinants. Youth-onset type 2 diabetes is alarming given a rapidly progressive course compared with the course of adult-onset disease, early-onset vascular complications, and long-term exposure to hyperglycemia and associated complications. It is often preceded by prediabetes, a disease phase where defects in β-cell function relative to insulin sensitivity emerge. Herein, we review the current understanding of the pathophysiology of prediabetes and type 2 diabetes in youth. We describe the mechanisms underlying insulin resistance, …