Medicine and Health Sciences Commons^™

Correlational Analysis Of Sarcopenia And Multimorbidity Among Older Inpatients, Wenjing Xia, Kang Luo, Ziwei Gu, Jianping Hu, Xintong Liu, Qian Xiao

Faculty, Staff and Student Publications

BACKGROUND: Sarcopenia and multimorbidity are common in older adults, and most of the available clinical studies have focused on the relationship between specialist disorders and sarcopenia, whereas fewer studies have been conducted on the relationship between sarcopenia and multimorbidity. We therefore wished to explore the relationship between the two.

METHODS: The study subjects were older patients (aged ≥ 65 years) who were hospitalized at the Department of Geriatrics of the First Affiliated Hospital of Chongqing Medical University between March 2016 and September 2021. Their medical records were collected. Based on the diagnostic criteria of the Asian Sarcopenia Working Group in …

An Estrogen Receptor Α-Derived Peptide Improves Glucose Homeostasis During Obesity, Wanbao Yang, Wen Jiang, Wang Liao, Hui Yan, Weiqi Ai, Quan Pan, Wesley A Brashear, Yong Xu, Ling He, Shaodong Guo

Faculty, Staff and Students Publications

Estrogen receptor α (ERα) plays a crucial role in regulating glucose and energy homeostasis during type 2 diabetes mellitus (T2DM). However, the underlying mechanisms remain incompletely understood. Here we find a ligand-independent effect of ERα on the regulation of glucose homeostasis. Deficiency of ERα in the liver impairs glucose homeostasis in male, female, and ovariectomized (OVX) female mice. Mechanistic studies reveal that ERα promotes hepatic insulin sensitivity by suppressing ubiquitination-induced IRS1 degradation. The ERα 1-280 domain mediates the ligand-independent effect of ERα on insulin sensitivity. Furthermore, we identify a peptide based on ERα 1-280 domain and find that ERα-derived peptide …

An Approach To Identify Gene-Environment Interactions And Reveal New Biological Insight In Complex Traits, Xiaofeng Zhu, Yihe Yang, Noah Lorincz-Comi, Gen Li, Amy R Bentley, Paul S De Vries, Michael Brown, Alanna C Morrison, Charles N Rotimi, W James Gauderman, Dabeeru C Rao, Hugues Aschard, Charge Gene-Lifestyle Interactions Working Group

2020-Current year OA Pubs

There is a long-standing debate about the magnitude of the contribution of gene-environment interactions to phenotypic variations of complex traits owing to the low statistical power and few reported interactions to date. To address this issue, the Gene-Lifestyle Interactions Working Group within the Cohorts for Heart and Aging Research in Genetic Epidemiology Consortium has been spearheading efforts to investigate G × E in large and diverse samples through meta-analysis. Here, we present a powerful new approach to screen for interactions across the genome, an approach that shares substantial similarity to the Mendelian randomization framework. We identify and confirm 5 loci …

Glycemia And Gluconeogenesis With Metformin And Liraglutide: A Randomized Trial In Youth-Onset Type 2 Diabetes, Katrina B Dietsche, Sheela N Magge, Sydney A Dixon, Faith S Davis, Andrea Krenek, Aruba Chowdhury, Lilian Mabundo, Michael Stagliano, Amber B Courville, Shanna Yang, Sara Turner, Hongyi Cai, Kannan Kasturi, Arthur S Sherman, Joon Ha, Eileen Shouppe, Mary Walter, Peter J Walter, Kong Y Chen, Robert J Brychta, Cody Peer, Yi Zeng, William Figg, Fran Cogen, D Elizabeth Estrada, Shaji Chacko, Stephanie T Chung

Children’s Nutrition Research Center Staff Publications

OBJECTIVE: Elevated rates of gluconeogenesis are an early pathogenic feature of youth-onset type 2 diabetes (Y-T2D), but targeted first-line therapies are suboptimal, especially in African American (AA) youth. We evaluated glucose-lowering mechanisms of metformin and liraglutide by measuring rates of gluconeogenesis and β-cell function after therapy in AA Y-T2D.

METHODS: In this parallel randomized clinical trial, 22 youth with Y-T2D-age 15.3 ± 2.1 years (mean ± SD), 68% female, body mass index (BMI) 40.1 ± 7.9 kg/m2, duration of diagnosis 1.8 ± 1.3 years-were randomized to metformin alone (Met) or metformin + liraglutide (Lira) (Met + Lira) and evaluated before …

Dismantling Barriers To Hepatitis B And Delta Screening, Prevention, And Linkage To Care Among The Pwud Community In Philadelphia, Beatrice Zovich, Catherine Freeland, Holly Moore, Kara Sapp, Anousha Qureshi, Rachel Holbert, Jason Zambrano, Daljinder Bhangoo, Chari Cohen, Richard W. Hass, Amy Jessop

College of Population Health Faculty Papers

The prevalence of hepatitis B and delta viruses (HBV/HDV) among people who use drugs (PWUD) remains largely unknown. In the context of one Philadelphia-based harm reduction organization (HRO), this study aimed to assess HBV/HDV prevalence and facilitate linkage to care. Participants completed a demographic HBV/HDV risk factor survey and were screened for HBV and reflexively for HDV if positive for HBV surface antigen or isolated core antibody. Fisher's exact tests and regression were used to understand relationships between risks and HBV blood markers. Of the 498 participants, 126 (25.3%) did not have hepatitis B immunity, 52.6% had been vaccinated against …

Somatic Mutations Of Esophageal Adenocarcinoma: A Comparison Between Black And White Patients, Hyeyeun Lim, Marie-Claude Gingras, Jing Zhao, Jinyoung Byun, Patricia D Castro, Spiridon Tsavachidis, Jianhong Hu, Harshavardhan Doddapaneni, Yi Han, Donna M Muzny, Richard A Gibbs, Christopher I Amos, Aaron P Thrift

Faculty, Staff and Students Publications

Esophageal adenocarcinoma is the most common histological subtype of esophageal cancer in Western countries and shows poor prognosis with rapid growth. EAC is characterized by a strong male predominance and racial disparity. EAC is up to fivefold more common among Whites than Blacks, yet Black patients with EAC have poorer survival rates. The racial disparity remains largely unknown, and there is limited knowledge of mutations in EAC regarding racial disparities. We used whole-exome sequencing to show somatic mutation profiles derived from tumor samples from 18 EAC male patients. We identified three molecular subgroups based on the pre-defined esophageal cancer-specific mutational …

The Brain Gene Registry: A Data Snapshot, Dustin Baldridge, Levi Kaster, Catherine Sancimino, Siddharth Srivastava, Sophie Molholm, Aditi Gupta, Inez Oh, Virginia Lanzotti, Daleep Grewal, Erin Rooney Riggs, Juliann M Savatt, Rachel Hauck, Abigail Sveden, Brain Gene Registry Consortium, John N Constantino, Joseph Piven, Christina A Gurnett, Maya Chopra, Heather Hazlett, Philip R O Payne

2020-Current year OA Pubs

Monogenic disorders account for a large proportion of population-attributable risk for neurodevelopmental disabilities. However, the data necessary to infer a causal relationship between a given genetic variant and a particular neurodevelopmental disorder is often lacking. Recognizing this scientific roadblock, 13 Intellectual and Developmental Disabilities Research Centers (IDDRCs) formed a consortium to create the Brain Gene Registry (BGR), a repository pairing clinical genetic data with phenotypic data from participants with variants in putative brain genes. Phenotypic profiles are assembled from the electronic health record (EHR) and a battery of remotely administered standardized assessments collectively referred to as the Rapid Neurobehavioral Assessment …

Relating Preoperative Mcs-12 To Microdiscectomy Outcomes, Jeremy C. Heard, Yunsoo Lee, Teeto Ezeonu, Mark J. Lambrechts, Rajkishen Narayanan, Caleb Yeung, Justin Wright, John Paulik, Caroline Purtill, John J. Mangan, Mark F. Kurd, Ian D. Kaye, Jose A. Canseco, Alan S. Hilibrand, Alex R. Vaccaro, Gregory D. Schroeder, Christopher K. Kepler

Rothman Institute Papers

PURPOSE: To determine the impact of poor mental health on patient-reported and surgical outcomes after microdiscectomy.

METHODS: Patients ≥ 18 years who underwent a single-level lumbar microdiscectomy from 2014 to 2021 at a single academic institution were retrospectively identified. Patient-reported outcomes (PROMs) were collected at preoperative, three-month, and one-year postoperative time points. PROMs included the Oswestry Disability Index (ODI), Visual Analog Scale Back and Leg (VAS Back and VAS Leg, respectively), and the mental and physical component of the short form-12 survey (MCS and PCS). The minimum clinically important differences (MCID) were employed to compare scores for each PROM. Patients …

Regimen For Accelerated Propranolol Initial Dosing (Rapid), Charles Y. Huang, Marissa J. Perman, Albert C. Yan

Student Papers, Posters & Projects

BACKGROUND: Infantile hemangiomas are common vascular tumors in children. Propranolol has proven effective in treating infantile hemangiomas and while generally safe, has potential risk for more serious side effects of hypoglycemia, hypotension, bradycardia, bronchospasm, and cardiovascular or respiratory compromise. Current prescribing guidelines recommend initiating propranolol doses at 1 mg/kg/day, with up-titration to 2 mg/kg/day. This study aims to compare the incidence of adverse events in infants and children treated with propranolol initiated at 1 mg/kg/day versus being initiated directly at 2 mg/kg/day.

METHODS: A retrospective cohort study was conducted using medical records of patients receiving propranolol therapy for infantile hemangiomas …

Inaccurate Diagnosis Of Diabetes Type In Youth: Prevalence, Characteristics, And Implications, Mustafa Tosur, Xiaofan Huang, Audrey S Inglis, Rebecca Schneider Aguirre, Maria J Redondo

Faculty, Staff and Students Publications

Classifying diabetes at diagnosis is crucial for disease management but increasingly difficult due to overlaps in characteristics between the commonly encountered diabetes types. We evaluated the prevalence and characteristics of youth with diabetes type that was unknown at diagnosis or was revised over time. We studied 2073 youth with new-onset diabetes (median age [IQR] = 11.4 [6.2] years; 50% male; 75% White, 21% Black, 4% other race; overall, 37% Hispanic) and compared youth with unknown versus known diabetes type, per pediatric endocrinologist diagnosis. In a longitudinal subcohort of patients with data for ≥ 3 years post-diabetes diagnosis (n = 1019), …

Encoding Of Visual Objects In The Human Medial Temporal Lobe, Yue Wang, Runnan Cao, Shuo Wang

2020-Current year OA Pubs

The human medial temporal lobe (MTL) plays a crucial role in recognizing visual objects, a key cognitive function that relies on the formation of semantic representations. Nonetheless, it remains unknown how visual information of general objects is translated into semantic representations in the MTL. Furthermore, the debate about whether the human MTL is involved in perception has endured for a long time. To address these questions, we investigated three distinct models of neural object coding-semantic coding, axis-based feature coding, and region-based feature coding-in each subregion of the human MTL, using high-resolution fMRI in two male and six female participants. Our …

Successful Percutaneous Thoracic Duct Embolization For Chylothorax After Total Arch Replacement, Fumihiro Kitashima, Naohiro Shimada, Yojiro Machii, Masashi Tanaka

The Texas Heart Institute Journal

Chylothorax after cardiac surgery is a rare complication associated with severe morbidity and mortality. This report documents successful treatment with percutaneous thoracic duct embolization for chylothorax after total arch replacement. A 69-year-old man underwent replacement of the aortic arch to treat a ruptured aortic aneurysm. After surgery, the left thoracic drain discharged 2,000 to 3,000 mL serosanguineous fluid per day, even though the patient took nothing orally and was administered subcutaneous octreotide therapy. On postoperative day 9, percutaneous thoracic duct embolization was performed, and the drain could be removed. The chylothorax did not recur, and the patient was discharged on …

Proportion Of Cancer Cases And Deaths Attributable To Potentially Modifiable Risk Factors In Peru, Jhony A De La Cruz-Vargas, Willy Ramos, Willer Chanduví, Lucy E Correa-López, Nadia Guerrero, Joan Loayza-Castro, Irene Tami-Maury, Diego Venegas

Faculty, Staff and Student Publications

BACKGROUND: Limited evidence exists on the population attributable fraction (PAF) of cancer cases and deaths in Latin America. In Peru several studies have been published regarding the PAF of various risk factors and their associated diseases. The objective of this study was to estimate the fraction of cancer cases and deaths attributable to potentially modifiable risk factors in Peru in 2018, before the COVID-19 pandemic in the population of 15 years old and older.

METHODS: An ecological study was conducted using the prevalence of exposure of the Peruvian population to modifiable risk factors for cancer, the relative risk associated with …

Longitudinal Regression Of Covariance Matrix Outcomes, Yi Zhao, Brian S Caffo, Xi Luo

Faculty, Staff and Student Publications

In this study, a longitudinal regression model for covariance matrix outcomes is introduced. The proposal considers a multilevel generalized linear model for regressing covariance matrices on (time-varying) predictors. This model simultaneously identifies covariate-associated components from covariance matrices, estimates regression coefficients, and captures the within-subject variation in the covariance matrices. Optimal estimators are proposed for both low-dimensional and high-dimensional cases by maximizing the (approximated) hierarchical-likelihood function. These estimators are proved to be asymptotically consistent, where the proposed covariance matrix estimator is the most efficient under the low-dimensional case and achieves the uniformly minimum quadratic loss among all linear combinations of the …

Vitamin A Status Modulates Epithelial Mesenchymal Transition In The Lung: The Role Of Furin, M Teresa Cabezuelo, Luis Torres, Elena Ortiz-Zapater, Gerardo López-Rodas, M Pilar Marín, Joaquín Timoneda, Juan R Viña, Rosa Zaragozá, Teresa Barber

Faculty, Staff and Student Publications

Vitamin A deficiency (VAD) induced TGF-β hyperactivation and reduced expression of cell adhesion proteins in the lung, suggesting that the disruption of retinoic acid (RA) signaling leads to epithelial-mesenchymal transition (EMT). To elucidate the role of lung vitamin A status in EMT, several EMT markers and the expression of the proprotein convertase furin, which activates TGF-β, were analyzed in two experimental models. Our in vivo model included control rats, VAD rats, and both control rats and VAD rats, treated with RA. For the in vitro studies, human bronchoalveolar epithelial cells treated with RA were used. Our data show that EMT …

Refractory Chronic Spontaneous Urticaria After Heterologous Covid-19 Booster Vaccination, Miranda Crista Tomaras, Leah Michelle Douglas, Rosa Michelle Schmidt, Maria Suzanne Bloomquist, Abdul Hafeez Diwan, Soo Jung Kim

Faculty, Staff and Students Publications

Chronic spontaneous urticaria (CSU) involves recurrent, pruritic wheals lasting more than 6 weeks in response to various etiologies, including unknown causality. Though most cutaneous reactions to the COVID-19 vaccine series are self-limited and of short duration, more complex presentations including chronic spontaneous urticaria have been described. To the best of our knowledge, this is the first report of chronic spontaneous urticaria following heterologous mRNA COVID-19 booster vaccination that includes vaccination with both forms of the mRNA vaccine. Our patient received Pfizer-BioNTech for the primary series and Moderna for the booster. After failing several therapies, our patient's urticaria was refractory even …

Treating Sex And Gender Differences As A Continuous Variable Can Improve Precision Cancer Treatments, Wei Yang, Joshua B Rubin

2020-Current year OA Pubs

BACKGROUND: The significant sex and gender differences that exist in cancer mechanisms, incidence, and survival, have yet to impact clinical practice. One barrier to translation is that cancer phenotypes cannot be segregated into distinct male versus female categories. Instead, within this convenient but contrived dichotomy, male and female cancer phenotypes are highly overlapping and vary between female- and male- skewed extremes. Thus, sex and gender-specific treatments are unrealistic, and our translational goal should be adaptation of treatment to the variable effects of sex and gender on targetable pathways.

METHODS: To overcome this obstacle, we profiled the similarities in 8370 transcriptomes …

Akap12 Upregulation Associates With Pde8a To Accelerate Cardiac Dysfunction, Hanan Qasim, Mehrdad Rajaei, Ying Xu, Arfaxad Reyes-Alcaraz, Hala Y Abdelnasser, M David Stewart, Satadru K Lahiri, Xander H T Wehrens, Bradley K Mcconnell

Faculty, Staff and Students Publications

BACKGROUND: In heart failure, signaling downstream the β2-adrenergic receptor is critical. Sympathetic stimulation of β2-adrenergic receptor alters cAMP (cyclic adenosine 3',5'-monophosphate) and triggers PKA (protein kinase A)-dependent phosphorylation of proteins that regulate cardiac function. cAMP levels are regulated in part by PDEs (phosphodiesterases). Several AKAPs (A kinase anchoring proteins) regulate cardiac function and are proposed as targets for precise pharmacology. AKAP12 is expressed in the heart and has been reported to directly bind β2-adrenergic receptor, PKA, and PDE4D. However, its roles in cardiac function are unclear.

METHODS: cAMP accumulation in real time downstream of the β2-adrenergic receptor was detected for …

The Stress Of Measuring Plantar Tissue Stress In People With Diabetes-Related Foot Ulcers: Biomechanical And Feasibility Findings From Two Prospective Cohort Studies, Chantal M Hulshof, Madelyn Page, Sjef G Van Baal, Sicco A Bus, Malindu E Fernando, Lisette Van Gemert-Pijnen, Kilian D R Kappert, Scott Lucadou-Wells, Bijan Najafi, Jaap J Van Netten, Peter A Lazzarini

Center on Aging Staff Publications

Reducing high mechanical stress is imperative to heal diabetes-related foot ulcers. We explored the association of cumulative plantar tissue stress (CPTS) and plantar foot ulcer healing, and the feasibility of measuring CPTS, in two prospective cohort studies (Australia (AU) and The Netherlands (NL)). Both studies used multiple sensors to measure factors to determine CPTS: plantar pressures, weight-bearing activities, and adherence to offloading treatments, with thermal stress response also measured to estimate shear stress in the AU-study. The primary outcome was ulcer healing at 12 weeks. Twenty-five participants were recruited: 13 in the AU-study and 12 in the NL-study. CPTS data …

More Than Just A Number: Perspectives From Black Male Participants On Community-Based Interventions And Clinical Trials To Address Cardiovascular Health Disparities., Faith E Metlock, Sarah Addison, Alicia Mckoy, Yesol Yang, Aarhea Hope, Joshua J Joseph, Jing Zhang, Amaris Williams, Darrell M Gray, John Gregory, Timiya S Nolan

Ambulatory and Primary Care Articles

BACKGROUND: Black Americans remain significantly underrepresented and understudied in research. Community-based interventions have been increasingly recognized as an effective model for reckoning with clinical trial participation challenges amongst underrepresented groups, yet a paucity of studies implement this approach. The present study sought to gain insight into Black male participants' perception of clinical trials before and after participating in a community-based team lifestyle intervention in the United States.

METHODS: Black Impact, a 24-week community-based lifestyle intervention, applied the American Heart Association's Life's Simple 7 (LS7) framework to assess changes in the cardiovascular health of seventy-four Black male participants partaking in weekly …

Pparα Is One Of The Key Targets For Dendrobine To Improve Hepatic Steatosis In Nafld., Yanzhe Xu, Miao Wang, Yi Luo, Hao Liu, Hua Ling, Yuqi He, Yanliu Lu

PCOM Scholarly Works

ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium nobile Lindl. (DNL) is a traditional Chinese ethnobotanical herb. Dendrobine (DNE) has been designated as a quality indicator for DNL in the Chinese Pharmacopoeia. DNE exhibits various pharmacological activities, including the reduction of blood lipids, regulation of blood sugar levels, as well as anti-inflammatory and antioxidant properties.

AIM OF THE STUDY: The objective of this study is to explore the impact of DNE on lipid degeneration in nonalcoholic fatty liver disease (NAFLD) liver cells and elucidate its specific mechanism. The findings aim to offer theoretical support for the development of drugs related to DNL.

MATERIALS AND METHODS: …

Primary Anastomosis With Diverting Loop Ileostomy Vs. Hartmann's Procedure For Acute Diverticulitis: What Happens After Discharge? Results Of A Nationwide Analysis, Arturo J. Rios Diaz, Lisa A. Bevilacqua, Theodore E. Habarth-Morales, Alicja Zalewski, David Metcalfe, Caitlyn Costanzo, Charles J. Yeo, Francesco Palazzo

Department of Surgery Faculty Papers

BACKGROUND: Current guidelines recommend resection with primary anastomosis with diverting loop ileostomy over Hartmann's procedure if deemed safe for acute diverticulitis. The primary objective of the current study was to compare the utilization of these strategies and describe nationwide ostomy closure patterns and readmission outcomes within 1 year of discharge.

METHODS: This was a retrospective, population-based, cohort study of United States Hospitals reporting to the Nationwide Readmissions Database from January 2011 to December 2019. There were 35,774 patients identified undergoing non-elective primary anastomosis with diverting loop ileostomy or Hartmann's procedure for acute diverticulitis. Rates of ostomy closure, unplanned readmissions, and …

First-In-Human Phase I Study Of Tinengotinib (Tt-00420), A Multiple Kinase Inhibitor, As A Single Agent In Patients With Advanced Solid Tumors, Sarina A Piha-Paul, Binghe Xu, Ecaterina E Dumbrava, Siqing Fu, Daniel D Karp, Funda Meric-Bernstam, David S Hong, Jordi A Rodon, Apostolia M Tsimberidou, Kanwal Raghav, Jaffer A Ajani, Anthony P Conley, Frank Mott, Ying Fan, Jean Fan, Peng Peng, Hui Wang, Shumao Ni, Caixia Sun, Xiaoyan Qiang, Wendy J Levin, Brenda Ngo, Qinhua Cindy Ru, Frank Wu, Milind M Javle

Faculty, Staff and Student Publications

PURPOSE: This first-in-human phase I dose-escalation study evaluated the safety, pharmacokinetics, and efficacy of tinengotinib (TT-00420), a multi-kinase inhibitor targeting fibroblast growth factor receptors 1-3 (FGFRs 1-3), Janus kinase 1/2, vascular endothelial growth factor receptors, and Aurora A/B, in patients with advanced solid tumors.

PATIENTS AND METHODS: Patients received tinengotinib orally daily in 28-day cycles. Dose escalation was guided by Bayesian modeling using escalation with overdose control. The primary objective was to assess dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and dose recommended for dose expansion (DRDE). Secondary objectives included pharmacokinetics and efficacy.

RESULTS: Forty-eight patients were enrolled (dose escalation, …

Bi-Allelic Acbd6 Variants Lead To A Neurodevelopmental Syndrome With Progressive And Complex Movement Disorders, Rauan Kaiyrzhanov, Aboulfazl Rad, Sheng-Jia Lin, Aida Bertoli-Avella, Wouter W Kallemeijn, Annie Godwin, Maha S Zaki, Kevin Huang, Tracy Lau, Cassidy Petree, Stephanie Efthymiou, Ehsan Ghayoor Karimiani, Maja Hempel, Elizabeth A Normand, Sabine Rudnik-Schöneborn, Ulrich A Schatz, Marc P Baggelaar, Muhammad Ilyas, Tipu Sultan, Javeria Raza Alvi, Manizha Ganieva, Ben Fowler, Ruxandra Aanicai, Gulsen Akay Tayfun, Abdulaziz Al Saman, Abdulrahman Alswaid, Nafise Amiri, Nilufar Asilova, Vorasuk Shotelersuk, Patra Yeetong, Matloob Azam, Meisam Babaei, Gholamreza Bahrami Monajemi, Pouria Mohammadi, Saeed Samie, Selina Husna Banu, Jorge Pinto Basto, Fanny Kortüm, Mislen Bauer, Peter Bauer, Christian Beetz, Masoud Garshasbi, Awatif Hameed Issa, Wafaa Eyaid, Hind Ahmed, Narges Hashemi, Kazem Hassanpour, Isabella Herman, Sherozjon Ibrohimov, Ban A Abdul-Majeed, Maria Imdad, Maksudjon Isrofilov, Qassem Kaiyal, Suliman Khan, Brian Kirmse, Janet Koster, Charles Marques Lourenço, Tadahiro Mitani, Oana Moldovan, David Murphy, Maryam Najafi, Davut Pehlivan, Maria Eugenia Rocha, Vincenzo Salpietro, Miriam Schmidts, Adel Shalata, Mohammad Mahroum, Jawabreh Kassem Talbeya, Robert W Taylor, Dayana Vazquez, Annalisa Vetro, Hans R Waterham, Mashaya Zaman, Tina A Schrader, Wendy K Chung, Renzo Guerrini, James R Lupski, Joseph Gleeson, Mohnish Suri, Yalda Jamshidi, Kailash P Bhatia, Barbara Vona, Michael Schrader, Mariasavina Severino, Matthew Guille, Edward W Tate, Gaurav K Varshney, Henry Houlden, Reza Maroofian

Faculty, Staff and Students Publications

The acyl-CoA-binding domain-containing protein 6 (ACBD6) is ubiquitously expressed, plays a role in the acylation of lipids and proteins and regulates the N-myristoylation of proteins via N-myristoyltransferase enzymes (NMTs). However, its precise function in cells is still unclear, as is the consequence of ACBD6 defects on human pathophysiology. Using exome sequencing and extensive international data sharing efforts, we identified 45 affected individuals from 28 unrelated families (consanguinity 93%) with bi-allelic pathogenic, predominantly loss-of-function (18/20) variants in ACBD6. We generated zebrafish and Xenopus tropicalis acbd6 knockouts by CRISPR/Cas9 and characterized the role of ACBD6 on protein N-myristoylation with myristic acid alkyne …

Effect Of Aspirin Versus Low-Molecular-Weight Heparin Thromboprophylaxis On Medication Satisfaction And Out-Of-Pocket Costs: A Secondary Analysis Of A Randomized Clinical Trial, Nathan N O'Hara, Katherine P Frey, Deborah M Stein, Joseph F Levy, Gerard P Slobogean, Renan Castillo, Reza Firoozabadi, Madhav A Karunakar, Joshua L Gary, William T Obremskey, Rachel B Seymour, Joseph Cuschieri, C Daniel Mullins, Robert V O'Toole, Metrc

Faculty, Staff and Student Publications

BACKGROUND: Current guidelines recommend low-molecular-weight heparin for thromboprophylaxis after orthopaedic trauma. However, recent evidence suggests that aspirin is similar in efficacy and safety. To understand patients' experiences with these medications, we compared patients' satisfaction and out-of-pocket costs after thromboprophylaxis with aspirin versus low-molecular-weight heparin.

METHODS: This study was a secondary analysis of the PREVENTion of CLots in Orthopaedic Trauma (PREVENT CLOT) trial, conducted at 21 trauma centers in the U.S. and Canada. We included adult patients with an operatively treated extremity fracture or a pelvic or acetabular fracture. Patients were randomly assigned to receive 30 mg of low-molecular-weight heparin (enoxaparin) …

Oncogenic Oral Human Papillomavirus Clearance Patterns Over 10 Years, Gypsyamber D'Souza, Sakshi R Tewari, Tanya Troy, Jennifer Webster-Cyriaque, Dorothy J Wiley, Cecile Delille Lahiri, Frank Joseph Palella, Maura L Gillison, Howard D Strickler, Linda Struijk, Tim Waterboer, Ken Ho, Jennafer Kwait, Jason Lazar, Kathleen M Weber, Carole Fakhry

Faculty, Staff and Student Publications

Background: Effective screening for oropharyngeal cancer is lacking. Four oncogenic HPV clearance definitions were explored to understand long-term natural history for persistent oncogenic oral HPV (oncHPV), the precursor of oropharyngeal cancer.

Methods: Prospective multicenter cohort of participants living with/at-risk for HIV, with oral rinse and gargle samples collected every 6 to 12 months for up to 10 years and tested for oncHPV. HPV clearance definitions included 1 (clear1), 2 (clear2), 3 (clear3) consecutive negatives, or being negative at last two visits (clearlast).

Results: Median time to clearance of oncHPV exceeded 2 years for conservative definitions (clear3: 2.38, clearlast: 2.43), but …

Gabaergic/Glycinergic And Glutamatergic Neurons Mediate Distinct Neurodevelopmental Phenotypes Of Stxbp1 Encephalopathy, Joo Hyun Kim, Wu Chen, Eugene S Chao, Armando Rivera, Heet Naresh Kaku, Kevin Jiang, Dongwon Lee, Hongmei Chen, Jaimie M Vega, Teresa V Chin, Kevin Jin, Kelly T Nguyen, Sheldon S Zou, Zain Moin, Shawn Nguyen, Mingshan Xue 薛名杉

Faculty, Staff and Students Publications

An increasing number of pathogenic variants in presynaptic proteins involved in the synaptic vesicle cycle are being discovered in neurodevelopmental disorders. The clinical features of these synaptic vesicle cycle disorders are diverse, but the most prevalent phenotypes include intellectual disability, epilepsy, movement disorders, cerebral visual impairment, and psychiatric symptoms ( Verhage and Sørensen, 2020; Bonnycastle et al., 2021; John et al., 2021; Melland et al., 2021). Among this growing list of synaptic vesicle cycle disorders, the most frequent is STXBP1 encephalopathy caused by de novo heterozygous pathogenic variants in syntaxin-binding protein 1 (STXBP1, also known as …

A Physiological Approach To Renal Clearance: From Premature Neonates To Adults, Nick Holford, Conor J. O'Hanlon, Karel Allegaert, Brian Anderson, Amilcar Falcão, Nicolas Simon, Yoke Lin Lo, Alison H. Thomson, Catherine M.T. Sherwin, Evelyne Jacqz-Aigrain, Carolina Llanos-Paez, Stefanie Hennig, Linas Mockus, Carl Kirkpatrick

Pediatrics Faculty Publications

Aims: We propose using glomerular filtration rate (GFR) as the physiological basis for distinguishing components of renal clearance. Methods: Gentamicin, amikacin and vancomycin are thought to be predominantly excreted by the kidneys. A mixed-effects joint model of the pharmacokinetics of these drugs was developed, with a wide dispersion of weight, age and serum creatinine. A dataset created from 18 sources resulted in 27,338 drug concentrations from 9,901 patients. Body size and composition, maturation and renal function were used to describe differences in drug clearance and volume of distribution. Results: This study demonstrates that GFR is a predictor of two distinct …

Severity Of Respiratory Syncytial Virus Vs Covid-19 And Influenza Among Hospitalized Us Adults, Diya Surie, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

IMPORTANCE: On June 21, 2023, the Centers for Disease Control and Prevention recommended the first respiratory syncytial virus (RSV) vaccines for adults aged 60 years and older using shared clinical decision-making. Understanding the severity of RSV disease in adults can help guide this clinical decision-making.

OBJECTIVE: To describe disease severity among adults hospitalized with RSV and compare it with the severity of COVID-19 and influenza disease by vaccination status.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, adults aged 18 years and older admitted to the hospital with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively …

Barriers To Opioid Use Disorder Treatment Among People Who Use Drugs In The Rural United States: A Qualitative, Multi-Site Study., T. J. Stopka, A. T. Estadt, G. Leichtling, J. C. Schleicher, L. S. Mixson, J. Bresett, E. Romo, P. Dowd, S. M. Walters, A. M. Young, W. Zule, P. D. Friedmann, V. F. Go, R. Baker, R. J. Fredericksen

Epidemiology and Environmental Health Faculty Publications

BACKGROUND: In 2020, 2.8 million people required substance use disorder (SUD) treatment in nonmetropolitan or 'rural' areas in the U.S. Among this population, only 10% received SUD treatment from a specialty facility, and 1 in 500 received medication for opioid use disorder (MOUD). We explored the context surrounding barriers to SUD treatment in the rural United States.

METHODS: We conducted semi-structured, in-depth interviews from 2018 to 2019 to assess barriers to SUD treatment among people who use drugs (PWUD) across seven rural U.S. study sites. Using the social-ecological model (SEM), we examined individual, interpersonal, organizational, community, and policy factors contributing …