Digital Commons Network^™

Structural Insights Into Light-Gating Of Potassium-Selective Channelrhodopsin, Takefumi Morizumi, Kyumhyuk Kim, Hai Li, Probal Nag, Tal Dogon, Oleg A Sineshchekov, Yumei Wang, Leonid S Brown, Songhwan Hwang, Han Sun, Ana-Nicoleta Bondar, Igor Schapiro, Elena G Govorunova, John L Spudich, Oliver P Ernst

Faculty, Staff and Student Publications

Structural information on channelrhodopsins' mechanism of light-gated ion conductance is scarce, limiting its engineering as optogenetic tools. Here, we use single-particle cryo-electron microscopy of peptidisc-incorporated protein samples to determine the structures of the slow-cycling mutant C110A of kalium channelrhodopsin 1 from Hyphochytrium catenoides (HcKCR1) in the dark and upon laser flash excitation. Upon photoisomerization of the retinal chromophore, the retinylidene Schiff base NH-bond reorients from the extracellular to the cytoplasmic side. This switch triggers a series of side chain reorientations and merges intramolecular cavities into a transmembrane K+ conduction pathway. Molecular dynamics simulations confirm K+ flux through the illuminated state …

Plant-Nanoparticles Enhance Anti-Pd-L1 Efficacy By Shaping Human Commensal Microbiota Metabolites, Yun Teng, Chao Luo, Xiaolan Qiu, Jingyao Mu, Mukesh K Sriwastva, Qingbo Xu, Minmin Liu, Xin Hu, Fangyi Xu, Lifeng Zhang, Juw Won Park, Jae Yeon Hwang, Maiying Kong, Zhanxu Liu, Xiang Zhang, Raobo Xu, Jun Yan, Michael L Merchant, Craig J Mcclain, Huang-Ge Zhang

Faculty, Staff and Student Publications

Diet has emerged as a key impact factor for gut microbiota function. However, the complexity of dietary components makes it difficult to predict specific outcomes. Here we investigate the impact of plant-derived nanoparticles (PNP) on gut microbiota and metabolites in context of cancer immunotherapy with the humanized gnotobiotic mouse model. Specifically, we show that ginger-derived exosome-like nanoparticle (GELN) preferentially taken up by Lachnospiraceae and Lactobacillaceae mediated by digalactosyldiacylglycerol (DGDG) and glycine, respectively. We further demonstrate that GELN aly-miR159a-3p enhances anti-PD-L1 therapy in melanoma by inhibiting the expression of recipient bacterial phospholipase C (PLC) and increases the accumulation of docosahexaenoic acid …

Safety And Tolerability Of Letetresgene Autoleucel (Gsk3377794): Pilot Studies In Patients With Advanced Non-Small Cell Lung Cancer, Mehmet Altan, Gilberto Lopes, T Jeroen N Hiltermann, Ramaswamy Govindan, Liza C Villaruz, Emiliano Calvo, Martin J Edelman, Muhammad Furqan, Joel Neal, Enriqueta Felip, Jennifer W Carlisle, John V Heymach, Róisín Eilish O'Cearbhaill, Marjorie Zauderer, Michael Chisamore, Ellie Corigliano, Ioanna Eleftheriadou, Stefan Zajic, Ben Jenkins, Sophia Goodison, Sunil Suchindran, Natalia Ramos-Hernandez, Nidale Tarek, Adam J Schoenfeld

Faculty, Staff and Student Publications

Purpose: The study aims to evaluate the safety, tolerability, and antitumor response of letetresgene autoleucel (lete-cel), genetically modified autologous T cells expressing a T-cell receptor specific for New York esophageal squamous cell carcinoma 1 (NY-ESO-1)/LAGE-1a shared epitope, alone or in combination with pembrolizumab, in HLA-A*02-positive (HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06) patients with NY-ESO-1- and/or LAGE-1a-positive non-small cell lung cancer.

Patients and methods: Study 208749 was a single-arm study of lete-cel alone. Study 208471 was a multiarm study of lete-cel alone or in combination with pembrolizumab in patients with advanced or recurrent non-small cell lung cancer.

Results: More than 2,500 patients were …

Distinct Roles Of Mtorc2 In Excitatory And Inhibitory Neurons In Inflammatory And Neuropathic Pain, Wei He, Xin Ge, Ru-Rong Ji

Faculty, Staff and Student Publications

No abstract provided.

The Landscape Of Ctdna In Appendiceal Adenocarcinoma, Michael G White, Mohammad A Zeineddine, Eleanor A Fallon, Fadl A Zeineddine, Julia Dansby, Saikat Chowdhury, Nicholas Hornstein, Abdelrahman Yousef, Mahmoud Yousef, Neal Bhutiani, Yue Gu, Bryan Kee, Arvind Dasari, Michael J Overman, Kanwal Raghav, Scott Kopetz, Abhineet Uppal, Melissa Taggart, Timothy Newhook, Keith Fournier, Beth Helmink, Leylah M Drusbosky, John Paul Shen

Faculty, Staff and Student Publications

Purpose: Appendiceal adenocarcinoma is a rare malignancy with distinct histopathologic subtypes and a natural history with metastasis primarily limited to the peritoneum. Little is known about the molecular pathogenesis of appendiceal adenocarcinoma relative to common tumors.

Experimental design: We analyzed molecular data for patients within the Guardant Health database with appendix cancer (n = 718). We then identified patients with appendiceal adenocarcinoma at our institution (from October 2004-September 2022) for whom ctDNA mutation profiling (liquid biopsy) was performed (n = 168) and extracted clinicopathologic and outcomes data. Of these 168 patients, 57 also had tissue-based tumor mutational profiling, allowing for …

Phase I/Ii Study Of The Aurora Kinase A Inhibitor Alisertib And Pembrolizumab In Refractory, Rb-Deficient Head And Neck Squamous Cell Carcinomas, Faye M Johnson, Madison P O'Hara, Lacin Yapindi, Peixin Jiang, Hai T Tran, Alexandre Reuben, Weihong Xiao, Maura L Gillison, Xiaowen Sun, Alexander Khalaf, J Jack Lee, Jagannadha K Sastry, Soma Ghosh

Faculty, Staff and Student Publications

Purpose: Effective therapy for recurrent head and neck squamous cell carcinoma (HNSCC) that is refractory to chemotherapy and immunotherapy is a considerable need. Aurora kinase A inhibition leads to apoptosis and immunogenic cell death in preclinical models of human papilloma virus (HPV)-driven cancers.

Patients and methods: Alisertib was administered orally twice daily on days 1-7 and pembrolizumab on day 1 of a 21-day cycle to adults with advanced solid tumors (phase I) or with immunotherapy- and platinum-resistant, HPV-positive HNSCC (phase II).

Results: The recommended phase II alisertib dose was 40 mg, which had only the expected toxicity including cytopenia that …

Deescalation Perils In Inflammatory Breast Cancer, Wendy A Woodward

Faculty, Staff and Student Publications

No abstract provided.

Antitumor Activity And Biomarker Analysis For Trop2 Antibody-Drug Conjugate Datopotamab Deruxtecan In Patient-Derived Breast Cancer Xenograft Models, Funda Meric-Bernstam, Erkan Yuca, Kurt W Evans, Ming Zhao, Takanori Maejima, Tsuyoshi Karibe, Maria Gabriela Raso, Ximing Tang, Xiaofeng Zheng, Yasmeen Qamar Rizvi, Argun Akcakanat, Stephen M Scott, Bailiang Wang, Lauren A Byers, Debu Tripathy, Daisuke Okajima, Senthil Damodaran

Faculty, Staff and Student Publications

PURPOSE: Datopotamab deruxtecan (Dato-DXd) is a humanized anti-trophoblast cell-surface antigen-2 (TROP2) IgG1 mAb linked to a potent topoisomerase I inhibitor payload (DXd). Dato-DXd has already shown antitumor activity in breast cancer; however, the determinants of response, including the importance of TROP2 expression, remain unclear. We tested the activity of Dato-DXd in a panel of breast cancer patient-derived xenografts (BCX) varying in TROP2 expression.

EXPERIMENTAL DESIGN: The antitumor activity of Dato-DXd and isotype-control-DXd (IgG-DXd) was assessed against 11 BCXs varying in TROP2 expression, 10 representing tumors postneoadjuvant chemotherapy. Pharmacodynamic effects were assessed at 24 and 72 hours. The effects of TROP2 …

Early Tolerance And Late Persistence As Alternative Drug Responses In Cancer, Simona Punzi, Davide Cittaro, Guido Gatti, Gemma Crupi, Oronza A Botrugno, Antonino Alex Cartalemi, Alon Gutfreund, Caterina Oneto, Valentina Giansanti, Chiara Battistini, Giovanni Santacatterina, Lucrezia Patruno, Ilaria Villanti, Martina Palumbo, Daniel J Laverty, Francesca Giannese, Alex Graudenzi, Giulio Caravagna, Marco Antoniotti, Zachary Nagel, Ugo Cavallaro, Luisa Lanfrancone, Timothy A Yap, Giulio Draetta, Nathalie Balaban, Giovanni Tonon

Faculty, Staff and Student Publications

Bacteria withstand antibiotic treatment through three alternative mechanisms: resistance, persistence or tolerance. While resistance and persistence have been described, whether drug-induced tolerance exists in cancer cells remains largely unknown. Here, we show that human cancer cells elicit a tolerant response when exposed to commonly used chemotherapy regimens, propelled by the pervasive activation of autophagy, leading to the comprehensive activation of DNA damage repair pathways. After prolonged drug exposure, such tolerant responses morph into persistence, whereby the increased DNA damage repair is entirely reversed. The central regulator of mitophagy PINK1 drives this reduction in DNA repair via the cytoplasmic relocalization of …

Consistency Of Hfref Treatment Effect In Underrepresented Groups In Randomized Clinical Trials, Guillaume Baudry, Luca Monzo, Mark C. Petrie, Nicolas Girerd, Iliana L Piña, Alexandre Mebazaa, Javed Butler, Leila Abid, Faiez Zannad, Harriette G.C. Van Spall

Division of Cardiology Faculty Papers

Despite the established efficacy of heart failure (HF) guideline-directed medical therapies, implementation varies across demographic groups, including Black, Indigenous, and people of color, older adults, females, and those who are socioeconomically deprived. This review synthesizes the representativeness of trial participants and describes subgroup analyses from pivotal trials in HF with reduced ejection fraction (HFrEF). It reviews the largely consistent treatment effect of medical therapies across the demographic groups represented in trials. It makes arguments for broad implementation of therapies based on these data, while calling for more representative trials to improve research and health equity in HF.

From Bench To Bedside: Murine Models Of Inherited And Sporadic Brain Arteriovenous Malformations, Ashely R Ricciardelli, Gael Genet, Nafiisha Genet, Samuel T Mcclugage, Peter T Kan, Karen K Hirschi, Jason E Fish, Joshua D Wythe

Faculty, Staff and Students Publications

Brain arteriovenous malformations are abnormal vascular structures in which an artery shunts high pressure blood directly to a vein without an intervening capillary bed. These lesions become highly remodeled over time and are prone to rupture. Historically, brain arteriovenous malformations have been challenging to treat, using primarily surgical approaches. Over the past few decades, the genetic causes of these malformations have been uncovered. These can be divided into (1) familial forms, such as loss of function mutations in TGF-β (BMP9/10) components in hereditary hemorrhagic telangiectasia, or (2) sporadic forms, resulting from somatic gain of function mutations in genes involved in …

Combined Clinical, Structural And Cellular Studies Discriminate Pathogenic And Benign Trpv4 Variants, Sarah H Berth, Linh Vo, Do Hoon Kwon, Tiffany Grider, Yasmine S Damayanti, Gage Kosmanopoulos, Andrew Fox, Alexander R Lau, Patrice Carr, Jack K Donohue, Maya Hoke, Simone Thomas, Chafic Karam, Alex J Fay, Ethan Meltzer, Thomas O Crawford, Rachelle Gaudet, Michael E Shy, Ute A Hellmich, Seok-Yong Lee, Charlotte J Sumner, Brett A Mccray

Faculty, Staff and Students Publications

Dominant mutations in the calcium-permeable ion channel TRPV4 (transient receptor potential vanilloid 4) cause diverse and largely distinct channelopathies, including inherited forms of neuromuscular disease, skeletal dysplasias and arthropathy. Pathogenic TRPV4 mutations cause gain of ion channel function and toxicity that can be rescued by small molecule TRPV4 antagonists in cellular and animal models, suggesting that TRPV4 antagonism could be therapeutic for patients. Numerous variants in TRPV4 have been detected with targeted and whole exome/genome sequencing, but for the vast majority, their pathogenicity remains unclear. Here, we used a combination of clinical information and experimental structure-function analyses to evaluate 30 …

Elevated Micro- And Nanoplastics Detected In Preterm Human Placentae, Michael Jochum, Marcus Garcia, Alexandra Hammerquist, Jacquelyne Howell, Myla Stanford, Rui Liu, Marian Olewine, Eliane El Hayek, Emily Phan, Lori Showalter, Cynthia Shope, Melissa Suter, Matthew Campen, Kjersti Aagaard, Enrico Barrozo

Faculty, Staff and Students Publications

Recent analytical advancements have uncovered increasing micro- and nanoplastics (MNPs) in environmental, dietary, and biological domains, raising concerns about their health impacts. Preterm birth (PTB), a leading cause of maternal and neonatal morbidity and mortality, may be influenced by MNP exposure, yet this relationship remains unexplored. This study quantified 12 MNP polymers in placentae from term (n=87) and preterm (n=71) deliveries using pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS). Cumulative MNP concentrations were 28% higher in PTB placentae (mean ±SD: 224.7 ± 180.7 μg/g vs. 175.5 ± 137.9 μg/g; p=0.038). Polyvinyl chloride (PVC), polyethylene terephthalate (PET), polyurethane (PU), and polycarbonate (PC) were significantly …

Update On Cancer Screening In Children With Syndromes Of Bone Lesions, Hereditary Leiomyomatosis And Renal Cell Carcinoma Syndrome, And Other Rare Syndromes, Orli Michaeli, Sun Young Kim, Sarah G Mitchell, Marjolijn C J Jongmans, Jonathan D Wasserman, Melissa R Perrino, Anirban Das, Suzanne P Macfarland, Sarah R Scollon, Mary-Louise C Greer, Nara Sobreira, Bailey Gallinger, Philip J Lupo, David Malkin, Kami Wolfe Schneider, Kris Ann P Schultz, William D Foulkes, Emma R Woodward, Douglas R Stewart

Faculty, Staff and Students Publications

The management of children with syndromes associated with an increased risk of benign and malignant neoplasms is a complex challenge for health care professionals. The 2023 American Association for Cancer Research Childhood Cancer Predisposition Workshop provided updated consensus guidelines on cancer surveillance in these syndromes, aiming to improve early detection and intervention and reduce morbidity associated with such neoplasms. In this article, we review several of the rare conditions discussed in this workshop. Ollier disease and Maffucci syndrome are enchondromatoses (disorders featuring benign bone lesions) with up to 50% risk of malignancy, including chondrosarcoma. These patients require surveillance with baseline …

Cardiovascular Disease In Adults With Osteogenesis Imperfecta: Clinical Characteristics, Care Recommendations, And Research Priorities Identified Using A Modified Delphi Technique, Lars Folkestad, Siddharth K Prakash, Sandesh C S Nagamani, Niels Holmark Andersen, Erin Carter, Jannie Dahl Hald, Riley J Johnson, Bente Langdahl, Eleanor M Perfetto, Cathleen Raggio, Stuart H Ralston, Robert A Sandhaus, Oliver Semler, Laura Tosi, Eric Orwoll

Faculty, Staff and Student Publications

Osteogenesis imperfecta (OI) is a multisystem disorder most often caused by pathogenic variants in genes that encode type I collagen. Type I collagen is abundant not only in bone but also in multiple tissues including skin, tendons, cornea, blood vessels, and heart. Thus, OI can be expected to affect cardiovascular system, and there are numerous reports of cardiovascular disease (CVD) in people with OI. However, there is no consensus on how CVD in OI should be assessed or managed. To fill this gap, a multidisciplinary group was convened to develop clinical guidance. The work included a systematic review of the …

Most Infants With Prenatal Osteogenesis Imperfecta Diagnosis And Poor Prognosis Survive: Experience Of A Quaternary Care Osteogenesis Imperfecta Center, Ricki S. Carroll, Sarah Little, Tina Mcgreal, Shannon Bonner, Daria Willis, Jeanne M. Franzone, Jeffery Campbell, Margaret Chou, Megan B. Raymond, Andrea Schelhaas, Joanna Costa, Mahim Jain

Department of Obstetrics and Gynecology Faculty Papers

Osteogenesis imperfecta is a genetic condition with improperly or inadequately produced Type I collagen. Manifestations include bowing deformities, fractures, hydrocephalus, respiratory insufficiency, and feeding difficulty. Moderate or severe OI is often diagnosed prenatally based on ultrasound findings and genetic testing may be labeled as lethal. Here, we present 18 infants with moderate to severely presenting OI who received neonatal care at a single center over a 5 yr period, 10 of which were delivered at our institution. All 18 infants survived to neonatal discharge, with 7 infants requiring respiratory support and 9 infants requiring feeding support at discharge. Through Fisher …

Investigating The In Vivo Effects Of Anti-Prion Protein Nanobodies On Prion Disease With Aav Vector, Jingjing Zhang, Mengfei Wang, Dan Wang, Xiangyi Zhang, Yue Ma, Els Pardon, Jan Steyaert, Romany Abskharon, Fei Wang, Jiyan Ma

Faculty, Staff and Student Publications

Prion diseases are fatal neurodegenerative disorders affecting humans and animals, and the central pathogenic event is the conversion of normal prion protein (PrPC) into the pathogenic PrPSc isoform. Previous studies have identified nanobodies that specifically recognize PrPC and inhibit the PrPC to PrPSc conversion in vitro. In this study, we investigated the potential for in vivo expression of anti-PrPC nanobodies and evaluated their impact on prion disease. The coding sequences of three nanobodies were packaged into recombinant adeno-associated virus (rAAV) and were administered via intracerebroventricular (ICV) injection in newborn mice. We found that the expression of these nanobodies remained robust …

Defining The Role Of Adjuvant Radiotherapy For Biliary Tract Cancers: A Site-Specific Propensity-Matched Analysis, Yongwoo David Seo, Belkacem Acidi, Andrew Newton, Antony Haddad, Yi-Ju Chiang, Rainna Coelho, Timothy E Newhook, Ching-Wei D Tzeng, Yun Shin Chun, Ethan B Ludmir, Eugene J Koay, Milind Javle, Jean Nicolas Vauthey, Hop S Tran Cao

Faculty, Staff and Student Publications

Background: Biliary tract cancers (BTCs) have distinct tumor biology but share a poor prognosis, with a 5-year-survival-rate of 5-19%. Surgical resection is the only potential cure, but recurrences are common. The role of adjuvant radiotherapy (XRT) remains unclear.

Methods: Using the National Cancer Database (2006-2018), we analyzed resected non-metastatic BTCs. Patients who survived beyond 90 days post-surgery were included, while those with R2 resections or neoadjuvant therapy were excluded. Propensity matching was performed based on predictors of adjuvant radiation, age, and sex. Survival outcomes were compared between no adjuvant therapy, chemotherapy alone, and XRT ± chemotherapy.

Results: …

Dairy Consumption And The Colonic Mucosa-Associated Gut Microbiota In Humans-A Preliminary Investigation, Ellie Chen, Nadim J Ajami, Donna L White, Yanhong Liu, Shawn Gurwara, Kristi Hoffman, David Y Graham, Hashem B El-Serag, Joseph F Petrosino, Li Jiao

Faculty, Staff and Students Publications

Background: Dairy consumption has been associated with various health outcomes that may be mediated by changes in gut microbiota.

Methods: This cross-sectional study investigated the association between the colonic mucosa-associated gut microbiota and the self-reported intake of total dairy, milk, cheese, and yogurt. A total of 97 colonic mucosal biopsies collected from 34 polyp-free individuals were analyzed. Dairy consumption in the past year was assessed using a food frequency questionnaire. The 16S rRNA gene V4 region was amplified and sequenced. Operational taxonomic unit (OTU) classification was performed using the UPARSE and SILVA databases. OTU diversity and relative abundance were compared …

Evaluation Of Hyponatremia Management Pathway, Mahmoud Ammar Pharmd, Jonathan M. Siner, Mary Judson, Christopher Winterbottom

Abstracts

Society of Critical Care Medicine's (SCCM) 2025 Critical Care Congress:

Evaluation of Hyponatremia Management Pathway Implementation in a Large Academic Health System

Submission Number: 1894079

Patients with severe hyponatremia managed using the Care Signature pathway were more likely to receive hypertonic saline and had lower mortality rates compared to those not managed with the pathway. These results suggest that the pathway can improve clinical outcomes and reduce resource use. Further studies are needed to evaluate its impact on other patients’ outcomes and long-term effectiveness.

Aortoduodenal Syndrome: A Rare Case Of Duodenal Obstruction Due To Endovascular Aneurysm Endoleak., Raksha Adhikari, Parth Patel, Christopher Tait

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Aortoduodenal syndrome results from expansion of an abdominal aortic aneurysm, leading to symptoms of upper gastrointestinal obstruction. Endovascular aneurysm repair of large or symptomatic aortic aneurysms has become an important treatment modality for patients with abdominal aortic aneurysm. However, a large proportion of these grafts are complicated by endoleaks that can lead to a spectrum of significant symptoms. We present a case of rapidly worsening gastrointestinal obstructive symptoms in a patient with an already repaired aortic stent graft and a solitary kidney, found to be due to a type III endoleak that improved after emergent repeat endovascular aneurysm repair.

Ultralow-Field Mri Feasibility In Pediatric Ecmo Patients, Jessica S. Wallisch, Asdis Finnsdottir Wagner, Maura Sien, John M. Daniel Iv, Allison Taber, Nathan S. Artz, Sherwin S. Chan

Presentations

INTRODUCTION Extracorporeal membrane oxygenation (ECMO) is used to treat refractory cardiopulmonary failure. Survival has significantly improved, yet high rates of acute brain injury (ABI) in this population results in significant morbidity and mortality. Currently available imaging modalities [ultrasound (US), computed tomography (CT)] have low detection of early hypoxic-ischemic and cerebrovascular-type injuries, which delays the diagnosis of ABI while on ECMO. CT sensitivity increases only when it is too late to effectively intervene. High-field (>=1.5 Tesla) magnetic resonance imaging (MRI) is the gold standard to diagnose pediatric ischemic brain injury but is not compatible with ECMO. An ultralow-field (0.064 T) …

Reperfused Myocardial Infarction: The Road To Ccs Classification Of Acute Mi And Beyond., Rohan Dharmakumar, Robert A Kloner, Michael Fishbein, Gerd Heusch, Keyur P Vora, Robert Gropler, Timothy Henry, Fai Shing-Chan, Dhirendra Singh, Nithya Jambunathan, Ramesh Subramanian, Rolf P Kreutz, Grant W Reed, Richard J Kovacs, Edward Fry, Ankur Kalra, Andreas Kumar, Subha V Raman

Heart and Vascular Articles

The Canadian Cardiovascular Society recently put forth a new classification of acute reperfused myocardial infarction (MI) based on stages of myocardial injury. Backed by more than 5 decades of intense investigation in the field, the key message of this new classification is that not all MIs are the same and that the type and extent of myocardial injury should be considered in diagnosing and treating MI. We review the literature with the goal of highlighting the progressive advances that enabled the synthesis of the Canadian Cardiovascular Society classification into 4 distinct stages of tissue injury. We emphasize the major breakthroughs …

Beyond The Diagnosis: Health-Related Social Needs Screening In Oncology Practice, Rebecca Cammy, Lcsw, Munjireen Sifat, Phd, Celeste Vaughan-Briggs, Lcsw, Michael Dimino, Phd, Valerie Csik, Mph

Department of Medical Oncology Posters

Background

Disparities in cancer care are deeply rooted in social determinants of health, resulting in poorer outcomes for marginalized populations. Health-related social needs (HRSN) screening has emerged as a critical strategy to address these inequities. By identifying and addressing unmet social needs – such as housing instability, food insecurity, and transportation access – we can mitigate barriers to care and improve overall well-being among cancer patients.

Amyloid-Β Predominant Alzheimer’S Disease Neuropathologic Change, Gabor G. Kovacs, Yuriko Katsumata, Xian Wu, Khine Zin Aung, David Fardo, Shelley L. Forrest, Peter T. Nelson

Neurology Faculty Publications

Different subsets of Alzheimer’s disease neuropathologic change (ADNC), including the intriguing set of individuals with severe/widespread amyloid-β (Aβ) plaques but no/mild tau tangles [Aβ-predominant (AP)-ADNC], may have distinct genetic and clinical features. Analysing National Alzheimer’s Coordinating Center data, we stratified 1187 participants into AP-ADNC (n = 95), low Braak primary age-related tauopathy (PART; n = 185), typical-ADNC (n = 832) and high-Braak PART (n = 75). AP-ADNC differed in some clinical features and genetic polymorphisms in the APOE, SNX1, WNT3/MAPT and IGH genes. We conclude that AP-ADNC differs from classical ADNC with implications for in vivo studies.

A Case Of Heterotaxy And Common Atrioventricular Canal With Bradycardia, Mohamed Aashiq Abdul Ghayum, Jenna Schermerhorn, Hayley S. Hancock, Kelsey Brattrud, Melanie Kathol, Maria Kiaffas

Posters

Background: Heterotaxy-polysplenia syndrome (otherwise known as left atrial isomerism) should be suspected in the presence of complete atrioventricular canal defect (CAVC) with interruption of the inferior vena cava (IVC), atrioventricular block (AVB), and viscero-cardiac heterotaxy. The prognosis remains dismal for the fetus with such entity, especially in the presence of major structural heart disease and high-grade atrioventricular block. Early diagnosis, close follow up, and appropriate delivery planning, allows for effective stabilization of the baby after birth and might improve survival. Methods: A 26-year-old mother at 26 weeks gestational age was referred for cardiac evaluation of cardiomegaly, suspected CAVC and bradycardia. …

Prediction Of Lacosamide Concentrations To Support Dose Optimization During Pregnancy, Jessica M. Barry, Sílvia M. Illamola, Page B. Pennell, Catherine M.T. Sherwin, Kimford J. Meador, Angela K. Birnbaum

Pediatrics Faculty Publications

Objective: We aimed to quantify and predict lacosamide exposure during pregnancy by developing a pregnancy physiologically-based pharmacokinetic model, allowing the prediction of potential dose increases to support maintaining a patient's preconception lacosamide concentrations. Methods: Models for nonpregnant adults and pregnant female patients were constructed using physiochemical and pharmacological parameters identified from literature review. Evaluation of plasma concentration data from human males was digitized froM.T.he literature. Concentration data in nonpregnant and pregnant human females were available froM.T.he Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study, a longitudinal observational study which followed 11 nonpregnant and 16 pregnant women receiving lacosamide. …

Pharmacokinetic Effect Of Disease Severity And Use Of Extracorporeal Membrane Oxygenation In Critically Ill Asian Patients Receiving Vancomycin, Charul Avachat, Pi Lien Hung, Angela K. Birnbaum, Daniel P. Healy, Catherine M.T. Sherwin, Alex C. Lin

Pediatrics Faculty Publications

Purpose: Vancomycin is an essential antibiotic for the treatment of severe gram-positive bacterial infections, including methicillin-resistant Staphylococcus aureus (MRSA). In critically ill patients, particularly children, attaining the appropriate dosage is crucial to avert drug resistance and ensure therapeutic efficacy. This study sought to investigate the pharmacokinetics of vancomycin in critically ill Asian pediatric patients and evaluate the influence of extracorporeal membrane oxygenation (ECMO) and disease severity on vancomycin clearance. Methods: This retrospective analysis examined data from 90 critically ill Asian patients residing in Kaohsiung, Taiwan, encompassing 263 data points gathered over 2 years. A one-compartment pharmacokinetic model with first-order elimination …

Acceptability Of Self-Collected Pap Smears Among Karen-Speaking Patients In The Midwest, Neha Khalid, Melanie Menning

Posters and Presentations: Family Medicine

No abstract provided.

Acceptability Of Self-Swab Hpv Cervical Cancer Screenings Among Arabic-Speaking Individuals, Nour Elrokhsi, Melanie Menning

Posters and Presentations: Family Medicine

No abstract provided.