Digital Commons Network^™

The De Winter Pattern In A Single Precordial Lead Caused By High-Grade Stenosis Of The Proximal Left Anterior Descending Artery With Plaque Rupture: A Case Report, Zhizhou Song, Yuehong Huo, Qi Wu, Xinjian Yu, Youdong Yang, Zejun Meng, Xia Li

Children’s Nutrition Research Center Staff Publications

The de Winter electrocardiogram (ECG) pattern indicates severe stenosis or occlusion of the left anterior descending artery (LAD). We present a 72-year-old female with 1.5-h chest pain. Angiography and optical coherence tomography (OCT) revealed 90 % LAD stenosis with plaque rupture, but no ST-segment elevation in the precordial leads. The de Winter pattern, characterized by upsloping ST-segment depression in V1-V6, appeared only in lead V2. Following successful percutaneous coronary intervention (PCI), the de Winter pattern disappeared. This case underscores the significance of the de Winter pattern in one precordial lead, necessitating prompt angiography and PCI for improved patient outcomes.

Phototaxis Is A Satiety-Dependent Behavioral Sequence In Hydra Vulgaris, Soonyoung Kim, Krishna N Badhiwala, Guillaume Duret, Jacob T Robinson

Faculty, Staff and Students Publications

Understanding how internal states such as satiety are connected to animal behavior is a fundamental question in neuroscience. Hydra vulgaris, a freshwater cnidarian with only 12 neuronal cell types, serves as a tractable model system for studying state-dependent behaviors. We found that starved hydras consistently move towards light, while fed hydras do not. By modeling this behavior as a set of three sequences of head orientation, jump distance and jump rate, we demonstrate that the satiety state only affects the rate of the animal jumping to a new position, while the orientation and jump distance are unaffected. These findings yield …

Effects Of Synergistic Application Of Viscozyme L–Wet Ball Milling On Structural, Physicochemical And Functional Properties Of Insoluble Dietary Fiber From Ginseng Residue, Guihun Jiang, Kashif Ameer, Karna Ramachandraiah, Xiaoyu Feng, Chaoyi Tan, Nanjie Cai

School of Medicine Faculty Publications

Synergistic effect of Viscozyme L with wet ball milling treatment on structural, physicochemical and functional aspects of insoluble dietary fiber (IDF) from ginseng residue were examined. SEM examination showed that IDF extracted by Viscozyme L in conjunction with wet ball milling (WBE-IDF) exhibited loose microstructural arrangement, and particle size of WBE-IDF was much smaller than that of IDF extracted by Viscozyme L (E-IDF) and along IDF (untreated). The FTIR spectra demonstrated the variations in the peak intensities in three modified ginseng IDFs. Besides, the highest thermal stability and viscosity was displayed by WBE-IDF among examined samples. In addition, WBE-IDF has …

A Qualitative Study Of The Knowledge Of Metabolic Syndrome, Attitudes About Lifestyle Modifications, And Preferences For Lifestyle Interventions Among Patients With Cancer And Metabolic Syndrome, Isabel Martinez Leal, Ashwathy B Pillai, Jessica T Foreman, Kimberly W Siu, Natalia I Heredia, Carmen P Escalante, Ellen F Manzullo, Aimee J Christie, Tamara E Lacourt, Zayd Adnan Razouki, Jessica P Hwang

Faculty, Staff and Student Publications

Metabolic syndrome is a group of disorders-hypertension, dyslipidemia, obesity, and insulin resistance-that together increase the risk of coronary heart disease, stroke, and diabetes. Although ~60% of cancer patients have metabolic syndrome, which increases their risk of mortality, oncology providers lack clear guidance about its management. The development of metabolic syndrome lifestyle interventions requires a better understanding of these patients' knowledge, attitudes, and intervention preferences in order to inform management. During 2022-2023, 19 adult cancer patients with metabolic syndrome engaged in semistructured interviews focused on metabolic syndrome and lifestyle interventions. Interviews were analyzed using hybrid thematic analysis involving deductive and inductive …

Polyp Puzzle, Get To Know Your Family. An Unfortunate Late Diagnosis Of Familial Adenomatous Polyposis: A Case Report., Jorge A. Aboytes, Aura Calderon

Research Colloquium

Introduction: Familial Adenomatous Polyposis (FAP) is a rare genetic condition affecting the APC gene characterized by the development of hundreds to thousands of colorectal polyps increasing the risk of cancer. Diagnosis usually occurs between ages 20 and 40. We present the unfortunate case of a patient with FAP that developed colon cancer and many years of complications. Had her family history been properly obtained at a younger age with early screening and testing, outcome and prognosis could have been different.

Case Report: A 34-year-old woman diagnosed with colon cancer in 2016 had total proctocolectomy with chemoradiation. From 2018 to 2024 …

Evaluation Of The Garmin Vivofit 4 For Assessing Sleep In Youth Experiencing Sleep Disturbances., Paul R. Hibbing, Madison Pilla, Lauryn Birmingham, Aniya Byrd, Tumusifu Ndagijimana, Sara Sadeghi, Nedra Seigfreid, Danielle Farr, Baha Al-Shawwa Md, David G. Ingram Md, Jordan A. Carlson

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Wearable monitors are increasingly used to assess sleep. However, validity is unknown for certain monitors and populations. We tested the Garmin Vivofit 4 in a pediatric clinical sample.

METHODS: Participants (n = 25) wore the monitor on their nondominant wrist during an overnight polysomnogram. Garmin and polysomnography were compared using 95% equivalence testing, mean absolute error, and Bland-Altman analysis.

RESULTS: On average (mean ± SD), the Garmin predicted later sleep onset (by 0.84 ± 1.60 hours) and earlier sleep offset (by 0.34 ± 0.70 hours) than polysomnography. The resulting difference for total sleep time was -0.55 ± 1.21 hours. …

Barriers And Opportunities In Pancreatic Cancer Immunotherapy, Yixin Ju, Dongzhi Xu, Miao-Miao Liao, Yutong Sun, Wen-Dai Bao, Fan Yao, Li Ma

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) presents a fatal clinical challenge characterized by a dismal 5-year overall survival rate, primarily due to the lack of early diagnosis and limited therapeutic efficacy. Immunotherapy, a proven success in multiple cancers, has yet to demonstrate significant benefits in PDAC. Recent studies have revealed the immunosuppressive characteristics of the PDAC tumor microenvironment (TME), including immune cells with suppressive properties, desmoplastic stroma, microbiome influences, and PDAC-specific signaling pathways. In this article, we review recent advances in understanding the immunosuppressive TME of PDAC, TME differences among various mouse models of pancreatic cancer, and the mechanisms underlying resistance to …

Understanding Biopsychosocial Influences On Physical Activity And Quality Of Life In Breast Cancer Survivors, Erica A. Schleicher

All ETDs from UAB

Receiving a breast cancer diagnosis and subsequent treatment can be life-altering, presenting numerous challenges. Breast cancer treatments are effective at allowing women to live longer, but often impose long-term side-effects that survivors must manage for years. Exercise is an effective way to address many long-term side-effects of breast cancer treatment, yet 63-83% of breast cancer survivors do not meet recommended physical activity (PA) guidelines. Due to the complexity of cancer and treatment options, cancer-related factors have potential biopsychosocial impacts that can influence exercise habits, attitudes toward PA (i.e., social cognitive theory (SCT) constructs), and potentially quality of life (QoL). It …

Parp-1 Selectively Impairs Kras-Driven Phenotypic And Molecular Features In Intrahepatic Cholangiocarcinoma, Friederike L Keggenhoff, Darko Castven, Diana Becker, Stojan Stojkovic, Jovana Castven, Carolin Zimpel, Beate K Straub, Tiemo Gerber, Harald Langer, Patricia Hähnel, Thomas Kindler, Jörg Fahrer, Colm J O'Rourke, Ursula Ehmer, Anna Saborowski, Lichun Ma, Xin Wei Wang, Timo Gaiser, Matthias S Matter, Christian Sina, Stefanie Derer, Ju-Seog Lee, Stephanie Roessler, Bernd Kaina, Jesper B Andersen, Peter R Galle, Jens U Marquardt

Faculty, Staff and Student Publications

Objective: Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer with limited therapeutic options. KRAS mutations are among the most abundant genetic alterations in iCCA associated with poor clinical outcome and treatment response. Recent findings indicate that Poly(ADP-ribose)polymerase1 (PARP-1) is implicated in KRAS-driven cancers, but its exact role in cholangiocarcinogenesis remains undefined.

Design: PARP-1 inhibition was performed in patient-derived and established iCCA cells using RNAi, CRISPR/Cas9 and pharmacological inhibition in KRAS-mutant, non-mutant cells. In addition, Parp-1 knockout mice were combined with iCCA induction by hydrodynamic tail vein injection to evaluate an impact on phenotypic and molecular …

Early Identification Of Hepatocellular Carcinoma Patients At High-Risk Of Recurrence Using The Adv Score: A Multicenter Retrospective Study, Shuya Cao, Zheyu Zhou, Chaobo Chen, Wenwen Li, Jinsong Liu, Jiawei Xu, Chunlong Zhao, Yihang Yuan, Zhenggang Xu, Huaiyu Wu, Guwei Ji, Xiaoliang Xu, Ke Wang

Faculty, Staff and Student Publications

BACKGROUND: Postoperative recurrence is a vital reason for poor 5-year overall survival in hepatocellular carcinoma (HCC) patients. The ADV score is considered a parameter that can quantify HCC aggressiveness. This study aimed to identify HCC patients at high-risk of recurrence early using the ADV score.

METHODS: The medical data of consecutive HCC patients undergoing hepatectomy from The First Affiliated Hospital of Nanjing Medical University (TFAHNJMU) and Nanjing Drum Tower Hospital (NJDTH) were retrospectively reviewed. Based on the status of microvascular invasion and the Edmondson-Steiner grade, HCC patients were divided into three groups: low-risk group (group 1: no risk factor exists), …

The Food Environment Of Female Athletes Attending Historically Black Colleges And Universities: A Qualitative Study On The Dimensions Of Food Access And Nutrition, Na Uriegas, Zk Winkelmann, Dm Emerson

Clinical Practice in Athletic Training

Context: Student-athletes are a subset of college students who face additional stressors related to the demands of their sport and academic workload. The food choices of student-athletes may be influenced by the unique food environment they are in. Further challenges may present for Historically Black Colleges and Universities (HBCUs) student-athletes as their institutions tend to be in low food access areas. We aimed to assess food security and explore the lived experiences of HBCU female student-athletes surrounding their food environment and ability to access food based on the five dimensions of food access: availability, accessibility, affordability, accommodation, and acceptability. Methods: …

Clinical Practice Guideline-Inconsistent Chemotherapy-Induced Vomiting Prophylaxis In Pediatric Cancer Patients In Community Settings: A Children's Oncology Group Study, Aaron J. Sugalski, Allison C. Grimes, Michelle M. Nuño, Subhash Ramakrishnan, Melissa P. Beauchemin, Paula D. Robinson, Nancy Santesso, Alexandra M. Walsh, Andrea R. Wrightson, Lolie C. Yu, Susan K. Parsons, Lillian Sung, L. Lee Dupuis

School of Medicine Faculty Publications

Background: This study aimed to determine the proportion of patients receiving clinical practice guideline (CPG)-inconsistent care related to chemotherapy-induced vomiting (CIV) prophylaxis, and to describe the association between CPG-inconsistent care and site size. The association between delivery of CPG-inconsistent care and patient outcomes (CIV control, admission prolongation, and unplanned healthcare visits) was also described. Methods: This was a retrospective study conducted at Children's Oncology Group (COG) National Cancer Institute Community Oncology Research Program (NCORP) sites. Eligible patients received highly (HEC) or moderately emetogenic chemotherapy (MEC) as inpatients from January 2014 through December 2015, and were previously enrolled in a COG …

Small Gtp-Binding Protein Gdp Dissociation Stimulator Influences Cisplatin-Induced Acute Kidney Injury Via Perk-Dependent Er Stress, Yuxue Yang, Ting Xiong, Ti Wang, Xiwei Chen, Ziwei Ma, Bangyun Zuo, Dong Ning, Ruilong Song, Xuesong Liu, Daxin Wang

Children’s Nutrition Research Center Staff Publications

Cisplatin is a common anticancer drug, but its frequent nephrotoxicity limits its clinical use. Small GTP-binding protein GDP dissociation stimulator (smgGDS), a small GTPase chaperone protein, was considerably downregulated during cisplatin-induced acute kidney injury (CDDP-AKI), especially in renal tubular epithelial cells. SmgGDS-knockdown mice was established and found that smgGDS knockdown promoted CDDP-AKI, as demonstrated by an increase in serum creatine, blood urea nitrogen levels and the appearance of tubular patterns. RNA sequencing suggested that protein kinase RNA-like ER kinase (PERK), which bridges mitochondria-associated ER membranes, was involved in smgGDS knockdown following CDDP-AKI, and then identified that smgGDS knockdown increased phosphorylated-PERK …

A Clinician’S Perspective On The New Organ Mesentery And Non-Vascular Mesenteropathies, Monjur Ahmed

Division of Gastroenterology and Hepatology Faculty Papers

Mesentery was discovered as a new organ in 2017. It is a continuous membranous tissue from the duodenojejunal flexure to the anorectal junction. It has distinct anatomy, physiology, and disease states. Primary mesenteropathies include vascular and non-vascular diseases. Some of them are common, and some of them are rarely seen in clinical practice. Secondary mesenteropathies occur when infection or malignancy in another organ spreads to the mesentery. Each entity has specific diagnostic and treatment protocols. Increased awareness of different mesenteropathies and an understanding of their various presentations at different stages of life can help in early diagnosis and improved clinical …

Chylopericardium And Superior Vena Cava Syndrome Caused By Central Venous Occlusion From Indwelling Hemodialysis Catheters, Daniel Underberg, Nicholas Demario, Sebastian Rodriguez, Khulkar Mirzozoda, Mark Decaro, Gregary Marhefka

Division of Cardiology Faculty Papers

Chylopericardium is a rare condition. Causes include superior vena cava syndrome resulting from indwelling catheters. We present a case of this condition in a 42-year-old man with end-stage renal disease treated with hemodialysis through a right subclavian vein catheter. He underwent successful endovascular stenting with resolution of his symptoms and chylopericardium.

Cystic Fibrosis-Related Diabetes Screening At A Large Pediatric Center, Anil K Chokkalla, Pamela Tuley, Miray Kurtca, Herda Ona, Fadel E Ruiz, Sridevi Devaraj

Faculty, Staff and Students Publications

Objective: Cystic Fibrosis Foundation guidelines recommend annual diabetes screening by oral glucose tolerance test (OGTT) in pediatric patients with cystic fibrosis (CF) starting at the age of 10 years. Adherence to these guidelines proves to be challenging, and the nationwide screening rates are still considered suboptimal. The aim of this study was to assess and improve the screening rates at our large pediatric center.

Methods: A 4-year retrospective audit of OGTT completion among pediatric patients with CF of age ≥10 years who are not yet diagnosed with diabetes was conducted. A collaborative working group was formed to identify the barriers …

Prospects And Challenges Of Tissue-Derived Extracellular Vesicles, Justin C Lee, Roslyn M Ray, Tristan A Scott

Faculty, Staff and Students Publications

Extracellular vesicles (EVs) are considered a vital component of cell-to-cell communication and represent a new frontier in diagnostics and a means to identify pathways for therapeutic intervention. Recently, studies have revealed the importance of tissue-derived EVs (Ti-EVs), which are EVs present in the interstitial spaces between cells, as they better represent the underlying physiology of complex, multicellular tissue microenvironments in biology and disease. EVs are native, lipid bilayer membraned nano-sized particles produced by all cells that are packaged with varied functional biomolecules including proteins, lipids, and nucleic acids. They are implicated in short- and long-range cellular communication and may elicit …

Parasitic Contamination Of Soil In The Southern United States, Christine Crudo Blackburn, Sally Mingshuang Yan, David Mccormick, Lauren Nicholas Herrera, Roumen Borilov Iordanov, Mark Daniel Bailey, Maria Elena Bottazzi, Peter J Hotez, Rojelio Mejia

Faculty, Staff and Students Publications

Parasites are generally associated with lower income countries in tropical and subtropical areas. Still, they are also prevalent in low-income communities in the southern United States. Studies characterizing the epidemiology of parasites in the United States are limited, resulting in little comprehensive understanding of the problem. This study investigated the environmental contamination of parasites in the southern United States by determining each parasite's contamination rate and burden in five low-income communities. A total of 499 soil samples of approximately 50 g were collected from public parks and private residences in Alabama, Louisiana, Mississippi, South Carolina, and Texas. A technique using …

Glycemic Control In Diabetic Patients Improved Overall Lung Cancer Survival Across Diverse Populations, Wayne Y Wu, Brian Luke, Xiao-Cheng Wu, J Jack Lee, Yong Yi, Samuel C Okpechi, Barry Gause, Paras Mehta, Steven I Sherman, Augusto Ochoa, Ethan Dmitrovsky, Xi Liu

Faculty, Staff and Student Publications

Background: The consequence of diabetes on lung cancer overall survival (OS) is debated. This retrospective study used 2 large lung cancer databases to assess comprehensively diabetes effects on lung cancer OS in diverse demographic populations, including health disparity.

Methods: The University of Texas MD Anderson Cancer Center database (32 643 lung cancer patients with 11 973 patients with diabetes) was extracted from electronic health records (EHRs) using natural language processing (NLP). Associations were between diabetes and lung cancer prognostic features (age, sex, race, body mass index [BMI], insurance status, smoking, stage, and histopathology). Hemoglobin A1C (HgbA1c) and glucose levels assessed …

Peritoneal Baclofen Pump Migration: A Rare Complication Of Subfascial Placement Illustrative Cases, Ashley Ricciardelli, Jordan Guntin, Joshua Korb, Daniel J Curry, Nisha Gadgil

Faculty, Staff and Students Publications

BACKGROUND: The intrathecal baclofen pump is an effective treatment option for patients with severe spasticity. In children, subfascial pump placement is often preferred given concerns for infection and wound healing. However, this approach is not without risk, and rare complications, such as peritoneal pump migration, can occur.

OBSERVATIONS: The authors describe three pediatric cases of peritoneal pump migration at their institution over the past 14 years (3/545, 0.5%). All three patients had low body weight (below the 39th percentile), and two had scoliosis requiring surgery. All pumps had been placed using the subfascial technique. The first case occurred 6 months …

Setrusumab For The Treatment Of Osteogenesis Imperfecta: 12-Month Results From The Phase 2b Asteroid Study, Francis H Glorieux, Bente Langdahl, Roland Chapurlat, Suzanne Jan De Beur, Vernon Reid Sutton, Kenneth E S Poole, Kathryn M Dahir, Eric S Orwoll, Bettina M Willie, Nicholas Mikolajewicz, Elizabeth Zimmermann, Seyedmahdi Hosseinitabatabaei, Michael S Ominsky, Chris Saville, James Clancy, Alastair Mackinnon, Arun Mistry, Muhammad K Javaid

Faculty, Staff and Students Publications

Osteogenesis imperfecta (OI) is a rare genetic disorder commonly caused by variants of the type I collagen genes COL1A1 and COL1A2. OI is associated with increased bone fragility, bone deformities, bone pain, and reduced growth. Setrusumab, a neutralizing antibody to sclerostin, increased areal bone mineral density (aBMD) in a 21-week phase 2a dose escalation study. The phase 2b Asteroid (NCT03118570) study evaluated the efficacy and safety of setrusumab in adults. Adults with a clinical diagnosis of OI type I, III, or IV, a pathogenic variant in COL1A1/A2, and a recent fragility fracture were randomized 1:1:1:1 to receive 2, 8, or …

World Allergy Organization (Wao) Diagnosis And Rationale For Action Against Cow's Milk Allergy (Dracma) Guideline Update – Xi – Milk Supplement/Replacement Formulas For Infants And Toddlers With Cma – Systematic Review, Antonio Bognanni, Ramon Firmino, Stefania Arasi, Derek Chu, Alexandro Chu, Siw Waffenschmidt, Arnav Agarwal, Piotr Dziechciarz, Andrea Horvath, Rose Kamenwa

Paediatrics and Child Health, East Africa

Background: Cow's milk allergy (CMA) is the most complex and common food allergy in infants. Elimination of cow's milk from the diet and replacement with a specialized formula for infants with cow's milk allergy who cannot be breastfed is an established approach to minimize the risk of severe allergic reactions while avoiding nutritional deficiencies. Given the availability of multiple options, such as extensively hydrolyzed cow's milk-based formula (eHF-CM), aminoacid formula (AAF), hydrolyzed rice formula (HRF), and soy formula (SF), there is some uncertainty regarding which formula might represent the most suitable choice with respect to health outcomes. The addition of …

Evaluating Efficacy Of Vedolizumab, Ustekinumab, And Golimumab In The Management Of Inflammatory Bowel Disease And The Combined Role Of Nutritional Therapy With Biologics: A Review, Shahed Kamal, Karan Varshney, Danielle Josefa F. Uayan, Fides Myles C. Caliwag

Ateneo School of Medicine and Public Health Publications

Inflammatory bowel disease (IBD), which encompasses both ulcerative colitis (UC) and Crohn’s disease (CD), is a major health burden worldwide. There are increasing concerns surrounding the impacts of this disease due to significant rises in the prevalence rates of IBD across the world. In consideration of the complexities of managing IBD along with this marked rise in prevalence and incidence, developing new forms of treatment for this condition has become a major priority. In recent years, a potential new form of treatment for IBD has emerged in the form of biologic therapies. While there is a high level of optimism …

Neurological Symptoms And Cause Of Death Among Young Children In Low- And Middle-Income Countries, Sara Ajanovic, Zachary Madewell, Shams El Arifeen, Emily Gurley, Mohammad Zahid Hossain, Kazi Munisul Islam, Afruna Rahman, Nega Assefa, Lola Madrid, R Gunturu

Pathology, East Africa

Importance: The emergence of acute neurological symptoms in children necessitates immediate intervention. Although low- and middle-income countries (LMICs) bear the highest burden of neurological diseases, there is a scarcity of diagnostic and therapeutic resources. Therefore, current understanding of the etiology of neurological emergencies in LMICs relies mainly on clinical diagnoses and verbal autopsies.

Objective: To characterize the association of premortem neurological symptoms and their management with postmortem-confirmed cause of death among children aged younger than 5 years in LMICs and to identify current gaps and improve strategies to enhance child survival.

Design, Setting, and Participants: This cross-sectional …

The Seattle Amyotrophic Lateral Sclerosis (Als) Patient Project Database: Observational, Longitudinal, Dyadic Characterization Of People With Als And Their Partners, Suzanne C. Segerstrom, Edward J. Kasarskis

Neurology Faculty Publications

Introduction: The median survival time in ALS is approximately 3 years, but survival times range from less than a year to more than 10 years and much variance in disease course remains to be explained. As is true for physical outcomes, there is considerable variance in QOL, which is influenced by psychological health, coping, and social support, among other psychosocial factors. The Seattle ALS Patient Project Database (SALSPPD) provides a unique opportunity for researchers to address established and novel hypotheses about disease progression and QOL in ALS.

Methods: The SALSPPD is a longitudinal dataset of people with ALS (n = …

Special Considerations For The Child With Obesity: An Obesity Medicine Association (Oma) Clinical Practice Statement (Cps) 2024., Suzanne Cuda, Marisa Censani, Valerie O'Hara, Jennifer Paisley, Roohi Kharofa, Rushika Conroy, Brooke Sweeney, Cristina Fernandez Md, Meredith Dreyer, Nancy T. Browne

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) details assessment and management of the child with overweight or obesity. The term "child" is defined as the child between 2 and 12 years of age. Because children are in a continual state of development during this age range, we will specify when our discussion applies to subsets within this age range. For the purposes of this CPS, we will use the following definitions: overweight in the child is a body mass index (BMI) ≥ 85th andpercentile, obesity in the child is a BMI ≥95th percentile, and severe obesity is …

Hereditary Spherocytosis Due To A Novel Variant, P.Q1034x, In The Beta Subunit Of The Spectrin Gene: A Case Report, Emmalee M. Kugler, Akash Patel, Faraz Afridi, Maria I. Scarano, Rafat Ahmed

Department of Emergency Medicine Faculty Papers

Background: Heterozygous pathogenic variants of SPTB cause hereditary spherocytosis (HS) in a quarter of cases. Case report: A 14-day-old male presenting with persistent anemia and hyperbilirubinemia was diagnosed with HS by increased red blood cell osmotic fragility and decreased fluorescence on the eosin-5′-maleimide binding test. For his failure to thrive and hypotonia, genetic sequencing revealed a de novo variant of the SPTB gene (p.Q1034X) on exon 15. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. A variant of uncertain significance (p.R438W) in the chondroitin sulfate synthase 1 (CHSY1) gene …

Target Engagement And Immunogenicity Of An Active Immunotherapeutic Targeting Pathological Α-Synuclein: A Phase 1 Placebo-Controlled Trial, Pepijn Eijsvogel, Pinaki Misra, Luis Concha-Marambio, Justin D Boyd, Shuang Ding, Lauren Fedor, Yueh-Ting Hsieh, Yu Shuang Sun, Madeline M Vroom, Carly M Farris, Yihua Ma, Marieke L De Kam, Igor Radanovic, Maurits F J M Vissers, Dario Mirski, Ghazal Shareghi, Mohammad Shahnawaz, Wolfgang Singer, Philip Kremer, Geert Jan Groeneveld, Hui Jing Yu, Jean-Cosme Dodart

Faculty, Staff and Student Publications

Investigational therapeutics that target toxic species of α-synuclein (αSyn) aim to slow down or halt disease progression in patients with Parkinson's disease (PD). Here this 44-week, randomized, placebo-controlled, double-blind, single-center phase 1 study investigated safety, tolerability and immunogenicity of UB-312, an active immunotherapeutic targeting pathological αSyn, in patients with PD. The primary outcome measures were adverse event frequency and change in anti-αSyn antibody titers in blood and cerebrospinal fluid (CSF). Exploratory outcomes were changes in clinical scales and biomarker-based target engagement as measured by seed amplification assays. Twenty patients were randomized 7:3 (UB-312:placebo) into 300/100/100 μg or 300/300/300 μg (weeks …

Mechanistic Insights Into Metabolic Function Of Dynamin-Related Protein 1, Xin Li, Katherine Pham, Jazmin Ysaguirre, Iqbal Mahmud, Lin Tan, Bo Wei, Long J Shao, Maryam Elizondo, Rabie Habib, Fathima Elizondo, Hiromi Sesaki, Philip L Lorenzi, Kai Sun

Faculty, Staff and Student Publications

Dynamin-related protein 1 (DRP1) plays crucial roles in mitochondrial and peroxisome fission. However, the mechanisms underlying the functional regulation of DRP1 in adipose tissue during obesity remain unclear. To elucidate the metabolic and pathological significance of diminished DRP1 in obese adipose tissue, we utilized adipose tissue-specific DRP1 KO mice challenged with a high-fat diet. We observed significant metabolic dysregulations in the KO mice. Mechanistically, DRP1 exerts multifaceted functions in mitochondrial dynamics and endoplasmic reticulum (ER)-lipid droplet crosstalk in normal mice. Loss of function of DRP1 resulted in abnormally giant mitochondrial shapes, distorted mitochondrial membrane structure, and disrupted cristae architecture. Meanwhile, …

An Analysis Of Suspected Microplastics In The Muscle And Gastrointestinal Tissues Of Fish From Sarasota Bay, Fl: Exposure And Implications For Apex Predators And Seafood Consumers, Eric Conger, Miranda Dziobak, Elizabeth J Berens Mccabe, Tita Curtin, Ayushi Gaur, Randall S Wells, John E Weinstein, Leslie B Hart

Faculty, Staff and Student Publications

Microplastics have been found in the gastrointestinal (GI) fluid of bottlenose dolphins (Tursiops truncatus), inhabiting Sarasota Bay, FL, suggesting exposure by ingestion, possibly via contaminated fish. To better understand the potential for trophic transfer, muscle and GI tissues from 11 species of dolphin prey fish collected from Sarasota Bay were screened for microplastics (particles <5 mm diameter). Suspected microplastics were found in 82% of muscle samples (n=89), and 97% of GI samples (n=86). Particle abundance and shapes varied by species (p<0.05) and foraging habit (omnivore vs. carnivore, p<0.05). Pinfish (Lagodon rhomboides) had the highest particle abundance for both tissue types (muscle: 0.38 …