Public Health Commons^™

Tracing Sars-Cov-2 Clusters Across Local Scales Using Genomic Data, Leke Lyu, Mandev Gill, Guppy Stott, Sachin Subedi, Cody Dailey, Gabriella Veytsel, Magdy Alabady, Kayo Fujimoto, Ryker Penn, Pamela Brown, Roger Sealy, Justin Bahl

Faculty, Staff and Student Publications

A quantitative understanding of local transmission dynamics is essential for designing effective prevention strategies. In this study, we developed a computational workflow to identify viral introductions and trace locally circulating clusters. We analyzed over 26,000 SARS-CoV-2 genomes and their associated metadata, collected between January and October 2021, to explore introduction and local dispersal patterns in Greater Houston, a major metropolitan area known for its demographic diversity. Our analysis identified more than 1,000 independent introduction events, resulting in clusters of varying sizes. The majority of introductions originated from domestic sources, while international introductions occurred earlier and were associated with larger cluster …

Bridging Evidence With Community: Five Routes To Diabetes Prevention In Latino Adults, Ann M. Maliackal

Doctor of Nursing Practice Final Project Abstract

Bridging Evidence with Community: Five Routes to Diabetes Prevention in Latino Adults

Background: This project used the Eightfold Path policy analysis approach to identify and recommend an evidence-based diabetes prevention program (DPP) for Latino adults in the Rio Grande Valley (RGV). The aim was to reduce diabetes prevalence by selecting an intervention that is culturally appropriate and effective for this population.

Methodology: The Eightfold Path policy analysis approach guided this project. A comprehensive literature review identified diabetes prevention programs (DPPs) tailored for Latino adults, and the Critical Appraisal Skills Programme (CASP) was used to assess study quality. Five DPPs were …

Micbg406a Polymorphism Reduces Risk Of Mechanical Ventilation And Death During Viral Acute Lung Injury, Harry Pickering, Narges Alipanah-Lechner, Ernie Chen, Dylan Duchen, Holden T Maecker, Seunghee Kim-Schulze, Ruth R Montgomery, Chris Cotsapas, Hanno Steen, Florian Krammer, Charles R Langelier, Ofer Levy, Lindsey R Baden, Esther Melamed, Lauren Ir Ehrlich, Grace A Mccomsey, Rafick P Sekaly, Charles B Cairns, Elias K Haddad, Albert C Shaw, David A Hafler, David B Corry, Farrah Kheradmand, Mark A Atkinson, Scott C Brakenridge, Nelson I Agudelo Higuita, Jordan P Metcalf, Catherine L Hough, William B Messer, Bali Pulendran, Kari C Nadeau, Mark M Davis, Ana Fernandez Sesma, Viviana Simon, Monica Kraft, Chris Bime, David J Erle, Joanna Schaenmann, Al Ozonoff, Bjoern Peters, Steven H Kleinstein, Alison D Augustine, Joann Diray-Arce, Patrice M Becker, Nadine Rouphael, Matthew C Altman, Steve Bosinger, Walter Eckalbar, Carolyn S Calfee, Oscar A Aguilar, Elaine F Reed, John R Greenland, Daniel R Calabrese

Faculty, Staff and Students Publications

MHC class I polypeptide-related sequence B (MICB) is a ligand for NKG2D. We have shown NK cells are central to lung transplant acute lung injury (ALI) via NKG2D activation, and increased MICB in bronchoalveolar lavage predicts ALI severity. Separately, we found a MICB polymorphism (MICBG406A) is associated with decreased ALI risk. We hypothesized this polymorphism would protect against severe SARS-CoV-2 respiratory disease. We analyzed 1,036 patients hospitalized with SARS-CoV-2 infection from IMPACC. Associations between MICBG406A and outcomes were determined by linear regression or Cox proportional hazards models. We also measured immune profiles of peripheral blood and the upper and lower …

Effects Of Mode And Transitioning To A Mixed-Mode (Web/Phone) Design On Categorical Survey Estimates: Do Question Characteristics Matter?, Mengyao Hu, Vicki A Freedman, Justin Kamens

Faculty, Staff and Student Publications

An increasing number of telephone surveys are introducing a web option. Limited experimental research has explored the implications of such design changes and how they vary by question characteristics. Using an experimental design and propensity score matching techniques, this study examines the effects of mode (web vs. telephone) and transitioning to a mixed-mode design (from telephone-only to the choice of web or telephone) on survey estimates and how effects differ by question characteristics. We draw upon an experiment embedded in the National Study of Caregiving (NSOC), in which half of NSOC-eligible caregivers were randomized to a telephone-only design and the …

Dual-Function Polyester Nanoparticles For Amplified Anti-Inflammatory Effects, Ingrid M Heyns, Abiodun T Wahab, Raghu Ganugula, David Sheikh-Hamad, M N V Ravi Kumar, Meenakshi Arora

Faculty, Staff and Students Publications

This study investigates a dual-acting drug delivery system using naringenin (NAR) as a folate receptor ligand to enhance intestinal uptake and encapsulated NAR for combating inflammation. The dual-acting systems were tested in vitro on cisplatin-induced human kidney-2 cells and in vivo in a mouse model of cisplatin-induced acute kidney injury (AKI). NAR-loaded passive nanoparticles [P2Ns(NAR)] and dual-acting systems [P2Ns-NAR(NAR)] showed notable advantages over unformulated NAR, reducing the required dose by up to 57 and 79%, respectively. These nanoparticles modulated immune responses, restored T cell function, and shifted macrophage polarization from proinflammatory M1 to tissue-repairing M2. In addition, P2Ns-NAR(NAR) alleviated AKI …

Proactive Planning For Contextual Fit: The Role Of The Implementation Premortem, Guillermo M Wippold, Kaylyn A Garcia, Ariel Domlyn, Dylan Wong, Maria E Fernandez

Faculty, Staff and Student Publications

Background: Implementation failure is a major barrier to program success. It is widely acknowledged that context matters-individual, community, and organizational norms, values, environment, and priorities influence successful program implementation. A mismatch between how the program was intended to be delivered and the constraints of the context in which it was delivered is a major cause of implementation failure. The barriers to implementation are usually understood after a program has failed. Although there are tools that can help accommodate for, or overcome, contextually-driven sources of implementation failure, there remains a significant gap - a tool and structured approach to analyze data …

Sulfated Dietary Fiber Protects Gut Microbiota From Antibiotics, Fuqing Wu, Xiaoqian Annie Yu, David Angeles-Albores, Susan E Erdman, Eric J Alm

Faculty, Staff and Student Publications

Background: Antibiotics, while essential for combating pathogens, also disrupt commensal bacteria, leading to gut microbiota imbalance and associated diseases. However, strategies to mitigate such collateral damage remain largely underexplored.

Result: In this study, we found that fucoidan, a marine polysaccharide derived from brown seaweed, provides broad-spectrum growth protection against multiple classes of antibiotics for human gut microbial isolates in vitro and for fecal communities ex vivo. This protective effect is dependent on the structural integrity, molecular weight, and sulfur content of the polysaccharide. Transcriptomic analysis showed that while fucoidan had minimal impact on baseline gene expression, it counteracted about 60% …

Development Of A Customizable Web-Based Dashboard For Remote Blood Pressure Monitoring: Feasibility And Usability Implementation Study, Joshua Wollen, Thuy Nguyen, Charles Coton, Gina Dewildt, Gabretta Cooksey, Audrey Cohen, Nicholas Hoang, Munachi Okpala, Michael Gonzalez, Mengxi Wang, Chigozirim Izeogu, Elmer Bernstam, Charles Green, Sean Savitz, Jose-Miguel Yamal, Anjail Sharrief

Faculty, Staff and Student Publications

Background: Effective blood pressure (BP) management is essential for several disease states, including secondary stroke prevention. Remote BP monitoring used in combination with an electronic data capture (EDC) system offers potential for improved BP control for patients. While such systems currently exist, there are many patient-, provider-, and system-specific challenges these systems currently do not address. In addition, such systems are rarely described transparently and comprehensively in the literature with enough detail to be reproduced by other clinicians.

Objective: This study aims to describe the development and design of a web-based EDC system tailored for remote BP monitoring and management …

Drug Development Studies Supporting Zileuton As A Parenteral Adjuvant To Attenuate Antibiotic-Associated Nephrotoxicity, Cole S Hudson, James E Smith, Linh T Vuong, Nicholas S Teran, Nazanin Pouya, David Sheikh-Hamad, Xinli Liu, Shama Kajiji, Vincent H Tam

Faculty, Staff and Students Publications

Glycopeptide, polymyxin, and aminoglycoside antibiotics are among the most commonly used agents to treat drug-resistant bacterial infections; however, their clinical use is hindered by nephrotoxicity. We previously reported that zileuton has the potential to attenuate antibiotic-associated nephrotoxicity in an animal model. Here, we further report the development of a parenteral formulation and exploration of dosing strategies for zileuton. The solubility, stability, and multi-dose safety of two zileuton formulations were evaluated. Zileuton serum and renal tissue pharmacokinetics were evaluated after a single dose and compared to steady state after 10 days. Different dosing strategies of zileuton to attenuate vancomycin-, polymyxin B-, …

Three Things We Can Do Now To Reduce The Risk Of Avian Influenza Spillovers, Kenneth B Yeh, William P Bahnfleth, Elaine Bradford, Carol Cardona, Kristen K Coleman, Peter J Hudson, Bernadeta Dadonaite, Rebecca J Hutchins, Anthony Maresso, C Raina Macintyre, Matthew Scotch

Faculty, Staff and Students Publications

No abstract provided.

Real-Time Experiences Of Racism And Stress In Association With Postpartum Weight Retention: A Longitudinal Ecological Momentary Assessment Study, Dara M Méndez, Amanda L Tapia, Sarah A Sanders, Andrea D Casas, Marquita Smalls, Esa M Davis, Stephen L Rathbun, Tiffany L Gary-Webb, Lora E Burke, Serwaa S Omowale, Linda A Adodoadji, John J Gianakas, Y Lai, Maisa Feghali, Meredith L Wallace

Faculty, Staff and Student Publications

Racial inequities in postpartum weight have been documented with limited studies on the influences of racism and other forms of discrimination. In a prospective longitudinal study applying ecological momentary assessment (EMA) and ambulatory assessment of weight, we measured the association between discrimination, stress, and postpartum weight change. The Postpartum Mothers Mobile Study is a cohort of 313 pregnant and birthing individuals who were followed during their second and third trimesters through 1 year postpartum. They were recruited in clinical settings between 2017 and 2020 in a major city center in Pennsylvania. Measures of racism and gender-based discrimination were collected via …

Increased Fungal Burden In The Gastrointestinal Tract Of Brain-Dead Organ Donors, Erika J Nachman, Colleen K Ardis, A Kyle B Ardis, Javier Nieto, Madeline M Bresson, Clare M Robertson, Maggie N Seale, Nora M Villafuerte, Zhe Lyu, Eva C Preisner, Heather A Danhof, Sara C Di Rienzi, Yolanda T Becker, Robert A Britton

Faculty, Staff and Students Publications

Approximately 3% of organ transplant recipients will be diagnosed with an invasive fungal infection (IFI), with 10%-47% being fatal. The source of IFI is typically not known, but Candida spp. cause the majority of IFI cases. We obtained intestines from two types of organ donors, brain-dead (BD) (n = 7) and donation after circulatory death (DCD) (n = 5), to sample microbes from the mucosal surface and the lumen. BD donors were parenterally fed and treated with corticosteroids in the days before procurement, whereas DCD donors were enterally fed and not given corticosteroids. We found fungi present in …

Development And Validation Of Venous Thromboembolism-Bidirectional Encoder Representations From Transformers (Vte-Bert) Natural Language Processing Model, Omid Jafari, Shengling Ma, Barbara D Lam, Jun Y Jiang, Emily Zhou, Mrinal Ranjan, Justine Ryu, Raka Bandyo, Arash Maghsoudi, Bo Peng, Christopher I Amos, Abiodun Oluyomi, Nathanael R Fillmore, Jennifer La, Ang Li

Faculty, Staff and Students Publications

Background: Accurate and rapid phenotyping of venous thromboembolism (VTE) in longitudinal studies is important. A natural language processing (NLP) tool externally validated in representative patients is lacking.

Objectives: To train and validate an efficient NLP model to detect incident VTE event.

Methods: We designed a novel NLP platform, NLPMed, to assist thrombosis researchers with data preprocessing, phenotype annotation, language model finetuning, and NLP application. Using clinical notes, discharge summaries, and radiology reports from patients with cancer at 2 healthcare institutions, we finetuned Bio_Clinical Bidirectional Encoder Representations from Transformers (BERT) to develop VTE-BERT. The new model was trained to detect acute …

Factors Influencing Covid-19 Vaccine Uptake Among Vulnerable Communities In Texas: Perceptions Of 2-1-1 Helpline Callers, Lara S Savas, Paula Cuccaro, Kehe Zhang, Rodrigo Hernandez, Meghan E Haffey, Belinda Reininger, Anais Mendiola, Olivia Dominguez, Maribel Sifuentes, Cici Bauer, Maria E Fernandez

Faculty, Staff and Student Publications

Background: Vaccination effectively and safely prevents serious illness from coronavirus disease 2019 (COVID-19). This study examines the complex factors associated with vaccination uptake among economically disadvantaged adults calling the Texas/United Way 2-1-1 helpline. Results informed the development of strategies to increase COVID-19 vaccine uptake among vulnerable populations disproportionately impacted by COVID-19-related morbidity and mortality.

Material and methods: We conducted a cross-sectional survey among 2-1-1 adult callers (May 2021-September 2022). The survey examined demographic, sociocultural, healthcare access, and psychosocial factors, as well as mistrust in health agencies. We used multivariable logistic regression models to examine factors associated with vaccination uptake, and …

Trauma Resuscitation With Low-Titer Group O Whole Blood Or Products: Study Protocol For A Randomized Clinical Trial (The Troop Trial), Jan O Jansen, Claudia Pedroza, Luis Leon Novelo, Tianyao Hao, Gina R Dewildt, Charles F Coton, Kiran Mansoor, Shannon W Stephens, Marisa B Marques, James R Stubbs, Jillian R Richter, Henry E Wang, John B Holcomb, Stacia M Desantis

Faculty, Staff and Student Publications

Background: Hemorrhage is the most common cause of potentially preventable death after injury. Balanced transfusion with red blood cells, plasma, and platelets (component therapy, CT) has been shown to reduce mortality, and is the standard of care. Low-Titer Group O Whole Blood (LTOWB) is an attractive alternative to CT, but existing evidence comprises observational studies, and a small single center pilot randomized controlled trial, which evaluated a type of whole blood that is no longer in use. The aim of the "Trauma Resuscitation with Low-Titer Group O Whole Blood Or Products" (TROOP) trial is to compare the effectiveness and safety …

Dissecting The Heterogeneous Effects Of Opioid Prescribing Limit Laws On Pediatric Mortality: A Multidimensional And Negative Binomial Modeling Approach, Francine R. Vega

Dissertations and Theses (Open Access)

Opioid prescribing for children and adolescents continues to be a significant health crisis in the United States. Early naïve exposure to opioid prescriptions has been linked to later misuse, opioid use disorder, and death. In response to the crisis, many states have implemented opioid prescribing limit laws (OPLLs) aimed at reducing exposure to opioids. These laws vary widely in their approach, including differences in dosage restrictions, prescription duration limits, informed consent requirements, educational provisions, and whether they offer explicit protections specifically for minors. Despite their widespread adoption, there is limited understanding of how heterogeneity in legal regulations affects outcomes for …

Rethinking Health Systems Responsiveness In Low–And Middle-Income Countries, Meesha Iqbal

Dissertations and Theses (Open Access)

Health systems responsiveness (HSR) refers to a health system’s ability to meet legitimate non-health expectations of the population. Traditionally, HSR has been conceptualized across eight domains: respect for dignity, autonomy, confidentiality, prompt attention to health needs, availability of basic amenities, choice of provider, access to social support networks, and clarity of communication. However, as the expectations of populations in high-income countries (HICs) and low- and middle-income countries (L&MICs) differ significantly due to diverse social and cultural contexts, the conceptualization of HSR also varies. We conducted a systematic review of literature to adapt and contextualize the HSR framework for L&MICs based …

Evaluating What Works: A Comparison Of Five Diabetes Prevention Programs For Latino Children, Ruchi Patel

Doctor of Nursing Practice Final Project Abstract

Background: Children in the Rio Grande Valley (RGV) are at increased risk of diabetes due to limited access to effective, culturally appropriate prevention programs. Existing programs are often time-intensive, require transportation, and lack cultural relevance, reducing participation and impacting outcomes. This project aimed to evaluate diabetes prevention programs (DPPs) in the literature and identify five that may benefit children in the RGV by reducing diabetes risk.

Methodology: The Eightfold Path policy analysis approach guided this project. A literature review identified DPPs for children, and the Critical Appraisal Skills Programme (CASP) was used to assess study quality. Limitations included difficulty finding …

Measuring The Impact Of A Delay In Care On Pediatric Otolaryngologic Surgery Completion, Geethanjeli N Mahendran, Ching Siong Tey, Mary Frances Musso, Grace Shebha Anand, Jeffrey Larson, Mitesh Mehta, Lara Reichert, Kara Prickett, Nikhila Pinnapureddy Raol

Faculty, Staff and Students Publications

Objective: To determine if postponement of elective pediatric otorhinolaryngology surgeries results in a change in overall healthcare utilization and if there is any commensurate impact on disease progression.

Methods: We identified patients ≤18 years of age whose surgeries were postponed at the onset of the COVID-19 pandemic-related shutdown. We then tracked patients' rate of and patterns of rescheduling surgery. Surveys were also sent to caregivers to better characterize his/her decision regarding moving forward with his/her child's surgery during COVID-19.

Results: A total of 1915 pediatric patients had elective surgeries canceled, of which 992 (51.8%) were rescheduled within 4 months. No …

Molecular Maestro In The Lung: The Sphingolipid Rheostat, Joselyn Rojas-Quintero, Francesca Polverino

Faculty, Staff and Students Publications

No abstract provided.

A Simple, Interpretable Machine Learning Model Based On Clinical Factors Accurately Predicts Incident Dysplasia Or Malignancy In Barrett's Esophagus, Ashwin Rao, Jasmine Haydel, Samuel Ma, Aaron P Thrift, Theresa Nguyen-Wenker, Hashem B El-Serag

Faculty, Staff and Students Publications

Purpose: Identifying patients likely to develop dysplasia or malignancy is critical for effective surveillance in patients with Barrett's Esophagus (BE). However, current predictive models are limited. We evaluated the performance of machine learning (ML) models in predicting incident dysplasia or malignancy in a cohort of veteran patients with BE.

Methods: We analyzed data from 598 patients newly diagnosed with non-dysplastic BE (NDBE), BE indefinite for dysplasia (BE-IND), and BE with non-persistent low-grade dysplasia (LGD) at the Michael DeBakey Veterans Affairs Medical Center from November 1990 to January 2019 with follow-up through January 2024. Progressors were patients who developed persistent LGD, …

Developing Culturally Centered Outreach Materials For Rural Native Veterans, Alexandra B Caloudas, Kelley Arredondo, Gail Beauchamp, Sharon Anastas, Kathy Marchant-Miros, Kristen Frosio, Giselle Day, Katherine Bay, Stephanie Day, Jan Lindsay, Jay Shore

Faculty, Staff and Students Publications

Native Americans serve in the U.S. military at the highest rate per capita of any ethnoracial group and have elevated rates of mental health (MH) difficulties compared to other ethnoracial groups, including posttraumatic stress disorder, alcohol use disorders, and suicide. Almost half of Native Veterans live in rural areas; rurality is associated with significant barriers to MH services. Engaging in outreach with Native Veterans is an important pathway for connecting them with MH care, but the outreach process and educational materials must be culturally aligned to be more effective. We collaborated with partners at a rural Department of Veterans Affairs …

Hemorrhagic Gastropathy From Paclitaxel-Carboplatin Combination Chemotherapy, Kristeen Onyirioha, Maya Balakrishnan

Faculty, Staff and Students Publications

A 58-year-old woman with endometrial cancer started on paclitaxel in combination with carboplatin chemotherapy, presented to the hospital with severe anemia and melena. An esophagogastroduodenoscopy with biopsies revealed diffuse gastric antrum hemorrhagic gastropathy without inflammatory changes. She had recurrent admissions with similar presentations during her chemotherapy. Her management included frequent blood transfusions, endoscopic Argon plasma coagulation to hemorrhagic lesions, and a prolonged course of proton pump inhibition to facilitate post-Argon plasma coagulation mucosal healing. Weeks after completing chemotherapy, her hemoglobin improved and recurrent upper gastrointestinal bleeding resolved. In this case, we identify a rare paclitaxel, in combination with carboplatin, associated …

Racial And Ethnic Disparity For Cancer Mortality In General And Single-Payer Healthcare Systems In The United States, Rock Bum Kim, Emily Zhou, Kaitlin N Swinnerton, Jennifer La, Shengling Ma, Mrinal Ranjan, Nhan V Do, Mary T Brophy, Nathanael R Fillmore, Ang Li

Faculty, Staff and Students Publications

Background: It remains unclear what factors significantly drive racial disparity in cancer survival in the United States (US). We compared adjusted mortality outcomes in cancer patients from different racial and ethnic groups on a population level in the US and a single-payer healthcare system.

Patients and methods: We selected adult patients with incident solid and hematologic malignancies from the Surveillance, Epidemiology, and End Results (SEER) 2011-2020 and Veteran Affairs national healthcare system (VA) 2011-2021. We classified the self-reported NIH race and ethnicity into non-Hispanic White (NHW), non-Hispanic Black (NHB), non-Hispanic Asian Pacific Islander (API), and Hispanic. Cox regression models for …

Incidence Of And Risk Factors For Hospital-Acquired Bleeding In People With Cancer: A Systematic Review, Mansour Gergi, Jinah Kim, Amalia Dolan, Laura Haines, Ang Li, Neil A Zakai

Faculty, Staff and Students Publications

Background: Hospital-acquired (HA) bleeding (bleeding occurring during hospitalization) in cancer patients is poorly characterized, potentially increasing morbidity and mortality due to under- or overprescription of low-dose anticoagulation for venous thromboembolism prevention.

Objectives: To perform a systematic review and meta-analysis (as appropriate) to identify the incidence of and risk factors for HA bleeding in people with cancer.

Methods: A systematic English-language search was conducted using Ovid MEDLINE, Ovid EMBASE, Google Scholar, and Cochrane Library. Keywords and controlled vocabulary related to bleeding risk in hospitalized cancer patients were iteratively refined. Studies assessing HA bleeding as a primary or coprimary endpoint were included, …

The Resilience Of The Human Lungs: Evolution, Smoke, And Disease, Joan B Soriano, Francesca Polverino

Faculty, Staff and Students Publications

No abstract provided.

Genetic Study Of Von Willebrand Factor Antigen Levels ≤ 50 Iu/Dl Identifies Variants Associated With Increased Risk Of Von Willebrand Disease And Bleeding, Rachel K Friedman, Adam S Heath, Jennifer E Huffman, James T Baker, Natalie R Hasbani, Sarah A Gagliano Taliun, Ming-Huei Chen, Tom E Howard, Joshua P Lewis, Nathan Pankratz, Snehal Patil, Alex P Reiner, Florian Thibord, Lisa R Yanek, Jie Yao, Hung-Hsin Chen, Joanne E Curran, Nauder Faraday, Xiuqing Guo, Marsha M Wheeler, Kathleen A Ryan, Xiang Zhou, Kelly Cho, Laura Almasy, Paul L Auer, Lewis C Becker, Peter W F Wilson, Eric Boerwinkle, Jeffrey R O'Connell, Stephen S Rich, David C Samuels, National Heart, Lung And Blood Institute (Nhlbi) Trans-Omics For Precision Medicine (Topmed) Consortium, Topmed Hematology & Hemostasis Working Group, Va Million Veteran Program, John Blangero, Myriam Fornage, Charles Kooperberg, Rasika A Mathias, Braxton D Mitchell, Jerome I Rotter, Andrew D Johnson, Nicholas L Smith, Zeynep H Coban-Akdemir, Jennifer E Below, Alanna C Morrison, Jill M Johnsen, Paul S De Vries

Faculty, Staff and Student Publications

Background: von Willebrand disease (VWD) is a common inherited bleeding disorder caused by low levels or activity of circulating von Willebrand factor (VWF). Genetic susceptibility to VWF antigen (VWF:Ag) below normal (≤ 50 IU/dL) in the general population is underexplored.

Objectives: To identify genetic variants influencing VWF:Ag levels ≤ 50 IU/dL.

Methods: We performed a genome-wide association study in 926 cases with VWF:Ag levels ≤ 50 IU/dL and 12 846 controls from 7 studies from the Trans-Omics for Precision Medicine program. We then examined whether significant genome-wide findings were also associated with clinical diagnosis of VWD in 5 biobanks with …

Low-Dose Metformin Requires Brain Rap1 For Its Antidiabetic Action, Hsiao-Yun Lin, Weisheng Lu, Yanlin He, Yukiko Fu, Kentaro Kaneko, Peimeng Huang, Ana B De La Puente-Gomez, Chunmei Wang, Yongjie Yang, Feng Li, Yong Xu, Makoto Fukuda

Faculty, Staff and Students Publications

Metformin is the most commonly prescribed antidiabetes drug, yet its precise mechanism of action remains controversial. Previous studies have suggested that metformin acts peripherally by reducing hepatic glucose output and altering gut functions. Here, we report a neural mechanism via the small guanosine triphosphatase Ras-related protein 1 (Rap1). Mice with forebrain-specific Rap1 knockout exhibited resistance to the antidiabetic effects of low-dose metformin while remaining sensitive to other antidiabetic agents. Centrally administered metformin inhibited brain Rap1 and reduced hyperglycemia. Conversely, forced activation of brain Rap1 increased glycemia and abolished the glycemic effect of metformin. Metformin activated a specific subset of neurons …

Impaired Rest-Activity Rhythm Characteristics Predict Higher Risk Of Incident Type 2 Diabetes In Uk Biobank Participants, Chris Ho Ching Yeung, Alison K Wright, Daniel P Windred, Angus C Burns, Andrew J K Phillips, Sean W Cain, Martin K Rutter, Qian Xiao

Faculty, Staff and Student Publications

Objective: Circadian rhythms play a key role in metabolic health. Rest-activity rhythms, which are in part driven by circadian rhythms, may be associated with diabetes risk. There is a need for large prospective studies to comprehensively examine different rest-activity metrics to determine their relative strength in predicting risk of incident type 2 diabetes.

Research design and methods: In actigraphy data from 83,887 UK Biobank participants, we applied both parametric and nonparametric algorithms to derive 13 different metrics characterizing different aspects of rest-activity rhythm. Diabetes cases were identified using both self-reported data and health records. We used Cox proportional hazards models …

Linking Chronic Kidney Disease To Incident Heart Failure And Adverse Cardiac Remodeling Through The Plasma Proteome: The Aric Study, Leo F Buckley, Pranav Dorbala, Victoria Lamberson, Brian L Claggett, Yue Ren, Morgan E Grams, Josef Coresh, Kunihiro Matsushita, Ryan T Demmer, Ruth F Dubin, Rajat Deo, Peter Ganz, Christie M Ballantyne, Ron C Hoogeveen, Bing Yu, Amil M Shah

Faculty, Staff and Student Publications

Background: Investigation of circulating plasma proteins may reveal insights into molecular pathways that contribute to the development of heart failure (HF) among people with chronic kidney disease.

Objectives: The authors aimed to identify circulating kidney function-related plasma proteins that are associated with the risk of incident HF.

Methods: The authors studied participants of the ongoing longitudinal ARIC (Atherosclerosis Risk In Communities) study. Relative plasma concentrations of 4,697 unique proteins were measured with the use of an aptamer assay (Somalogic). Each protein was tested for associations with estimated glomerular filtration rate (eGFR), log-transformed urine albumin-to-creatinine ratio (UACR), and incident HF by …