Medical Specialties Commons^™

A Curious Case Of Medium-Vessel Vasculitis, Theodore Rosen

Faculty, Staff and Students Publications

Vasculitis, or the inflammation of vessels due to primary or secondary causes, may arise from numerous etiologies, often leading to diagnostic uncertainty. Delayed treatment due to diagnostic or etiologic uncertainty presents a significant clinical risk, with consequences including organ failure and mortality. We describe a case of a 58-year-old male with a history including ankylosing spondylitis who presented with painful ulcers involving the bilateral lower extremities following a trip to the southern Texas border. Histopathology revealed medium-vessel vasculitis; however, the search for a likely etiology in the setting of a unique combination of potential vasculitis precipitants, including glochid inoculation, a …

“Education Would Be Step Number One”: Community Mental Health Clinicians’ Training And Support Needs To Treat Anxiety In Autistic Youth, Daylin Delgado, Whitney S Shepherd, Lauren Brookman-Frazee, Eric A Storch, Brenna B Maddox

Faculty, Staff and Students Publications

Background: Autistic youth experience high rates of anxiety, which has been treated with modified cognitive-behavioral therapy (CBT), often integrating exposure therapy. Such anxiety treatments are effective for this population; however, there remains a gap between these evidence-based mental health interventions and their implementation in community mental health (CMH) services where autistic youth receive care.

Method: This qualitative study conducted semi-structured interviews with four types of community members in the United States: 15 autistic youth with anxiety, 15 caregivers of autistic youth with anxiety, 11 CMH clinicians, and 8 CMH clinic leaders. Participants identified the training needs of CMH clinicians to …

Trends In Chlorine And Chloramine Gas Exposures Reported To United States Poison Centers, Anthony Atalla, Joshua Shulman, Jason Rose, Michael Lynch

Faculty, Staff and Students Publications

Introduction: Chlorine and chloramine gas inhalation can occur when household cleaners are mixed. The increased emphasis on disinfecting practices during the COVID-19 pandemic may have contributed to an increase in chlorine and chloramine gas exposures in the United States, which has not been studied.

Methods: In a retrospective review, reported data on chlorine and chloramine gas exposures in the National Poison Data System were collected from January 1, 2015, to December 31, 2022. Data included demographics and exposure details, including location, dose, formulation, co-exposures, treatments, and outcomes. Demographic analyses and descriptive statistics were conducted.

Results: During the study period, 85,104 …

Diabetes Technology Meeting 2023, Tiffany Tian, Rachel E Aaron, Ashley Y Dunova, Johan H Jendle, David Kerr, Eda Cengiz, Andjela Drincic, John C Pickup, Kong Y Chen, Naomi Schwartz, Douglas B Muchmore, Halis K Akturk, Carol J Levy, Signe Schmidt, Riccardo Bellazzi, Alan H B Wu, Elias K Spanakis, Bijan Najafi, James Geoffrey Chase, Jane Jeffrie Seley, David C Klonoff

Center on Aging Staff Publications

Diabetes Technology Society hosted its annual Diabetes Technology Meeting from November 1 to November 4, 2023. Meeting topics included digital health; metrics of glycemia; the integration of glucose and insulin data into the electronic health record; technologies for insulin pumps, blood glucose monitors, and continuous glucose monitors; diabetes drugs and analytes; skin physiology; regulation of diabetes devices and drugs; and data science, artificial intelligence, and machine learning. A live demonstration of a personalized carbohydrate dispenser for people with diabetes was presented.

Phase 1 Study Of Nedd8 Activating Enzyme Inhibitor Pevonedistat In Combination With Chemotherapy In Pediatric Patients With Recurrent Or Refractory Solid Tumors (Advl1615), Sarah Woodfield, Kristina Z Denic, Emasenyie Isikwei, Stephan D Voss, Marvin Nelson, Xiaowei Liu, Stacey L Berg, Elizabeth Fox, Brenda J Weigel

Faculty, Staff and Students Publications

Purpose: The objective of this study was to determine the recommended Phase 2 dose (RP2D) of pevonedistat, a first in class inhibitor of NEDD8 activating enzyme, in combination with irinotecan (IRN) and temozolomide (TMZ) in children with cancer.

Methods: This Phase 1 study used a rolling 6 design to evaluate escalating doses of pevonedistat in combination with standard doses of IRN and TMZ in pediatric patients with recurrent/refractory solid or CNS tumors. During cycle 1, pevonedistat was administered intravenously on days 1, 8, 10, and 12, with IRN (IV, 50 mg/m2) and TMZ (orally, 100 mg/m2), on days 8-12 of …

Effects Of Intermittent Senolytic Therapy On Bone Metabolism In Postmenopausal Women: A Phase 2 Randomized Controlled Trial, Tammie L Volkman, Amanda J Tweed, Stephanie J Vos, Ming Ruan, Jad Sfeir, Matthew T Drake, Dominik Saul, Madison L Doolittle, Irina Bancos, Kai Yu, Tamara Tchkonia, Nathan K Lebrasseur, James L Kirkland, David G Monroe, Sundeep Khosla

Faculty, Staff and Students Publications

Preclinical evidence demonstrates that senescent cells accumulate with aging and that senolytics delay multiple age-related morbidities, including bone loss. Thus, we conducted a phase 2 randomized controlled trial of intermittent administration of the senolytic combination dasatinib plus quercetin (D + Q) in postmenopausal women (n = 60 participants). The primary endpoint, percentage changes at 20 weeks in the bone resorption marker C-terminal telopeptide of type 1 collagen (CTx), did not differ between groups (median (interquartile range), D + Q -4.1% (-13.2, 2.6), control -7.7% (-20.1, 14.3); P = 0.611). The secondary endpoint, percentage changes in the bone formation marker procollagen …

Treatment Response To Onabotulinumtoxina In Cervical Dystonia Patients With Anterocollis And Retrocollis, Shyamal Mehta, Hubert H Fernandez, Marc Schwartz, Joseph Jankovic

Faculty, Staff and Students Publications

Anterocollis (AC) and retrocollis (RC) are less common cervical dystonia (CD) subtypes that are often under-represented in CD clinical trials. Herein we describe real-world demographics, disease characteristics, and treatment response to onabotulinumtoxinA (onabotA) in AC or RC patients from an observational, multicenter, prospective registry, CD PROBE. After three onabotA treatments, outcomes (CDIP-58, PGIC, CGIC, CD severity, TWSTRS) in patients with predominant AC or RC were compared to torticollis (TC) and all CD subtypes combined. The mean dosages at each treatment ranged from 153.5 to 195.4 U (AC) to 184.0-213.4 U (RC). After treatment, AC and RC patients reported improvements in …

Targeting Nuclear Receptor Coactivator Src-1 Prevents Colorectal Cancer Immune Escape By Reducing Transcription And Protein Stability Of Pd-L1, Yong Zhang, Bei Li, Hanshi Guo, Chuanzhong Huang, Xu Kong, Pingli Mo, Nengming Xiao, Jianming Xu, Yunbin Ye, Chundong Yu

Faculty, Staff and Students Publications

Programmed death-ligand 1 (PD-L1) is overexpressed in multiple cancers and critical for their immune escape. It has previously shown that the nuclear coactivator SRC-1 promoted colorectal cancer (CRC) progression by enhancing CRC cell viability, yet its role in CRC immune escape is unclear. Here, we demonstrate that SRC-1 is positively correlated with PD-L1 in human CRC specimens. SRC-1 deficiency significantly inhibits PD-L1 expression in CRC cells and retards murine CRC growth in subcutaneous grafts by enhancing CRC immune escape via increasing tumor infiltration of CD8

Neuroimaging Of The Effects Of Drug Exposure Or Self-Administration In Rodents: A Systematic Review, Anna Zilverstand

Faculty, Staff and Students Publications

A systematic review of functional neuroimaging studies on drug (self-) administration in rodents is lacking. Here, we summarized effects of acute or chronic drug administration of various classes of drugs on brain function and determined consistency with human literature. We performed a systematic literature search and identified 125 studies on in vivo rodent resting-state functional magnetic resonance imaging (n = 84) or positron emission tomography (n = 41) spanning depressants (n = 27), opioids (n = 23), stimulants (n = 72), and cannabis (n = 3). Results primarily showed alterations in the striatum, consistent with the human literature. The anterior …

The Impact Of Margins And Re-Resection In Pediatric Synovial Sarcoma, Hannah Todd, Kelley Harrell, Alfred F Trappey, John Doski, Eumenia C Castro, Nicole I Montgomery, M Fatih Okcu, Rajkumar Venkatramani, Dai H Chung, Sanjeev A Vasudevan

Faculty, Staff and Students Publications

INTRODUCTION: Synovial sarcoma is one of the most common soft tissue sarcomas in children. Guidelines regarding the adequate extent of resection margins and the role of re-resection are lacking. We sought to evaluate the adequate resection margin and the role of re-resection in predicting outcomes in children with synovial sarcomas.

METHODS: A cohort of 36 patients less than 18 years of age at diagnosis who were treated for localized synovial sarcoma at three tertiary pediatric hospitals between January 2004 and December 2020 were included in this study. Patient and tumor demographics, treatment information, and margin status after surgical resection were …

Determining Predictors Of Actual Living Kidney Donation Based On Potential Donor Characteristics, Jonathan Daw, Krista L Lentine, John Devin Peipert, Ahmed Osama Gaber, David A Axelrod, Francis L Weng, Amy D Waterman

Faculty, Staff and Students Publications

Background: Living donor kidney transplantation is the optimal treatment for end-stage kidney disease; however, few living donor candidates (LDCs) who begin evaluation actually donate. While some LDCs are deemed medically ineligible, others discontinue for potentially modifiable reasons.

Methods: At five transplant centers, we conducted a prospective cohort study measuring LDCs' clinical and psychosocial characteristics, educational preparation, readiness to donate, and social determinants of health. We followed LDCs for 12 months after evaluation to determine whether they donated a kidney, opted to discontinue, had modifiable reasons for discontinuing, were medically ineligible, or had other recipient-related reasons for discontinuing.

Results: Among 2184 …

Prolonged Cytopenias After Immune Effector Cell Therapy And Lymphodepletion In Patients With Leukemia, Lymphoma And Solid Tumors, Mengfen Wu, Candise Tat, Thomas Pfeiffer, Shoba Navai, Andras Heczey, Meenakshi Hegde, Nabil Ahmed, Sarah B Whittle, Laquisa Hill, Caridad Martinez, Robert Krance, Carlos A Ramos, Rayne H Rouce, Premal Lulla, Helen E Heslop, Bilal Omer, Meghan Shekar

Faculty, Staff and Students Publications

Background aims: The success of chimeric antigen receptor (CAR) T-cell therapy in treating B-cell malignancies has led to the evaluation of CAR T-cells targeting a variety of other malignancies. Although the efficacy of CAR T-cells is enhanced when administered post-lymphodepleting chemotherapy, this can trigger bone marrow suppression and sustained cytopenia after CD19.CAR T-cell therapy. Additionally, systemic inflammation associated with CAR T-cell activity may contribute to myelosuppression. Cytopenias, such as neutropenia and thrombocytopenia, elevate the risk of severe infections and bleeding, respectively. However, data on the incidence of prolonged cytopenias after immune effector therapy in the solid tumor context remain limited. …

A Novel Deep Learning Model Based On Transformer And Cross Modality Attention For Classification Of Sleep Stages

Faculty, Staff and Students Publications

The classification of sleep stages is crucial for gaining insights into an individual's sleep patterns and identifying potential health issues. Employing several important physiological channels in different views, each providing a distinct perspective on sleep patterns, can have a great impact on the efficiency of the classification models. In the context of neural networks and deep learning models, transformers are very effective, especially when dealing with time series data, and have shown remarkable compatibility with sequential data analysis as physiological channels. On the other hand, cross-modality attention by integrating information from multiple views of the data enables to capture relationships …

Spinal Cord Stimulator Implantation For Complex Regional Pain Syndrome In Patient With Extensive Vertebral Surgical History: A Case Report

Faculty, Staff and Students Publications

Spinal cord stimulation (SCS) has emerged as a novel therapeutic option for refractory complex regional pain syndrome (CRPS). However, SCS placement is often complicated by a prior history of surgical manipulation and hardware implantation along the spinal column. Through this case exploration, we aim to expand the technical approach to SCS implantation in CRPS and encourage further research into innovative approaches for this treatment modality. Our patient is a 61-year-old female with a past medical history of bilateral C7 cervical pedicle fracture status and extensive surgical manipulation, including cervical laminectomy and hardware placement along the cervical spine. The development of …

Psychosocial Outcomes Of Pain And Pain Management In Adults With Osteogenesis Imperfecta: A Qualitative Study, W Conor Rork, M Usman Baig, Kristin M Kostick, Dianne Nguyen, Erin M Carter, Members Of The Bbdc, Chaya N Murali, Marie-Eve Robinson, Sophie C Schneider, Brendan Lee, V Reid Sutton, Eric A Storch

Faculty, Staff and Students Publications

Objectives

Osteogenesis imperfecta (OI) is a genetic disorder characterized by bone fragility and fractures, short stature, dental abnormalities, hearing loss, scoliosis, and chronic pain. Despite a growing literature on the functional outcomes of OI, limited research has explicitly examined the psychosocial outcomes of pain within OI.

Methods

Adults with OI (N=15) were interviewed to understand pain-related experiences through a thematic analysis of semi-structured interview data. Research team members, genetic research experts, and OI clinicians developed an interview guide focused on topics related to pain and mental health challenges. Participants’ transcripts were coded by two independent coders; codes were then merged …

The Cerebellum Modulates Thirst, Ila Mishra, Bing Feng, Bijoya Basu, Amanda M Brown, Linda H Kim, Tao Lin, Mir Abbas Raza, Amelia Moore, Abigayle Hahn, Samantha Bailey, Alaina Sharp, Juan C Bournat, Claire Poulton, Brian Kim, Amos Langsner, Aaron Sathyanesan, Roy V Sillitoe, Yanlin He, Atul R Chopra

Duncan NRI Faculty and Staff Publications

The cerebellum, a phylogenetically ancient brain region, has long been considered strictly a motor control structure. Recent studies have implicated the cerebellum in cognition, sensation, emotion and autonomic function, making it an important target for further investigation. Here, we show that cerebellar Purkinje neurons in mice are activated by the hormone asprosin, leading to enhanced thirst, and that optogenetic or chemogenetic activation of Purkinje neurons induces rapid manifestation of water drinking. Purkinje neuron-specific asprosin receptor (Ptprd) deletion results in reduced water intake without affecting food intake and abolishes asprosin's dipsogenic effect. Purkinje neuron-mediated motor learning and coordination were unaffected by …

Phase Ii Study Of Samotolisib In Children And Young Adults With Tumors Harboring Phosphoinositide 3-Kinase/Mammalian Target Of Rapamycin Pathway Alterations: Pediatric Match Apec1621d, Sinchita Roy-Chowdhuri, David R Patton, Brent Coffey, Joel M Reid, Jin Piao, Lauren Saguilig, Todd A Alonzo, Stacey L Berg, Joyce Mhlanga, Elizabeth Fox, Brenda J Weigel, Douglas S Hawkins, Margaret M Mooney, Naoko Takebe, James V Tricoli, Katherine A Janeway, Nita L Seibel, Donald Williams Parsons

Faculty, Staff and Students Publications

Purpose: Patients age 1-21 years with relapsed or refractory solid and CNS tumors were assigned to phase II studies of molecularly targeted therapies on the National Cancer Institute-Children's Oncology Group (NCI-COG) Pediatric Molecular Analysis for Therapy Choice (MATCH) trial. Patients whose tumors harbored predefined genetic alterations in the phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway and lacked mitogen-activated protein kinase pathway activating alterations were treated with the PI3K/mTOR inhibitor samotolisib.

Methods: Patients received samotolisib twice daily in 28-day cycles until disease progression or unacceptable toxicity. A rolling 6 limited dose escalation was performed as, to our knowledge, this was …

Phylogenetically Diverse Bacterial Species Produce Histamine, Kathleen M Hoch, Sigmund J Haidacher, Anthony M Haag, Jennifer K Spinler, James Versalovic, Melinda A Engevik, Thomas D Horvath

Faculty, Staff and Students Publications

Histamine is an important biogenic amine known to impact a variety of patho-physiological processes ranging from allergic reactions, gut-mediated anti-inflammatory responses, and neurotransmitter activity. Histamine is found both endogenously within specialized host cells and exogenously in microbes. Exogenous histamine is produced through the decarboxylation of the amino acid L-histidine by bacterial-derived histidine decarboxylase enzymes. To investigate how widespread histamine production is across bacterial species, we examined 102,018 annotated genomes in the Integrated Microbial Genomes Database and identified 3,679 bacterial genomes (3.6 %) which possess the enzymatic machinery to generate histamine. These bacteria belonged to 10 phyla: Bacillota, Bacteroidota, Actinomycetota, Pseudomonadota, …

Fluid Overload In Pediatric Acute Respiratory Distress Syndrome After Allogeneic Hematopoietic Cell Transplantation, Joseph R Angelo, Megan C Daniel, Shira J Gertz, Deyin D Hsing, Kris M Mahadeo, Jennifer A Mcarthur, Courtney M Rowan, Pediatric Acute Lung Injury Sepsis Investigators (Palisi) Network

Faculty, Staff and Students Publications

The aim of the study is to examine the relationship between fluid overload (FO) and severity of respiratory dysfunction in children posthematopoietic cell transplantation (HCT) with pediatric acute respiratory distress syndrome (PARDS). This investigation was a secondary analysis of a multicenter retrospective cohort of children (1month to 21 years) postallogeneic HCT with PARDS receiving invasive mechanical ventilation (IMV) from 2009 to 2014. Daily FO % (FO%) and daily oxygenation index (OI) were calculated for each patient up to the first week of IMV (day 0 = intubation). Linear mixed-effect regression was employed to examine whether FO% and OI were associated …

Satisfaction With Mode Of Delivery Of Genomic Sequencing Results In A Diverse National Sample Of Research Participants Through The Clinical Sequencing Evidence-Generating Research Consortium, Sabrina A Suckiel, Laura M Amendola, Ann Katherine M Foreman, Gail P Jarvik, Christine Rini, Tao Wang, Anne Slavotinek

Faculty, Staff and Students Publications

Purpose: Research that includes diverse patient populations is necessary to optimize implementation of telehealth.

Methods: As part of a Clinical Sequencing Evidence-Generating Research Consortium cross-site study, we assessed satisfaction with mode of return of results (RoR) delivery across a diverse sample of participants receiving genetic testing results in person vs telemedicine (TM).

Results: Ninety-eight percent of participants were satisfied with their mode of results delivery. Participants receiving results by TM were more likely to report a preference for receiving results in a different way and challenges with providers noticing difficulties with understanding. More than 90% reported satisfaction across all items …

Mortality In Recipients Of Durable Left Ventricular Assist Devices Undergoing Ventricular Tachycardia Ablation, Payam Safavi-Naeini, Matthew W Segar, Jitae A Kim, Qussay Marashly, Joanna E Molina-Razavi, Leo Simpson, Selby B Oberton, Lola X Xie, Andrew Civitello, Nilesh Mathuria, Jie Cheng, Abdi Rasekh, Mohammad Saeed, Mehdi Razavi, Ajith Nair, Mihail G Chelu

Faculty, Staff and Students Publications

Background: Left ventricular assist device (LVAD) recipients have a higher incidence of ventricular tachycardia (VT). However, the role of VT ablation in this population is not well-established.

Objectives: This single-center retrospective cohort study sought to examine the impact of post-LVAD implant VT ablation on survival.

Methods: This retrospective study examined a cohort of patients that underwent LVAD implantation at Baylor St. Luke's Medical Center and Texas Heart Institute between January 2011 and January 2021. All-cause estimated mortality was compared across LVAD recipients based on the incidence of VT, timing of VT onset, and the occurrence and timing of VT ablation …

High-Sensitivity Troponin T, Nt-Probnp, And Cognitive Outcomes In Sprint, Nicholas M Pajewski, Ihab Hajjar, James A De Lemos, Wenxin Zhang, Elsayed Z Soliman, Christie M Ballantyne, Vijay Nambi, Naveed Sattar, Anthony A Killeen, Joachim H Ix, Michael G Shlipak, Jarett D Berry, Simon B Ascher

Faculty, Staff and Students Publications

Background: Hs-cTnT (cardiac troponin T measured with a highly sensitive assay) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) may identify adults with hypertension who derive greater cognitive benefits from lower systolic blood pressure targets.

Methods: In the SPRINT (Systolic Blood Pressure Intervention Trial) MIND study, participants were categorized as having both hs-cTnT and NT-proBNP in the lower 2 tertiles (n=4226), one in the highest tertile (n=2379), and both in the highest tertile (n=1506). We assessed the effect of intensive versus standard treatment on the composite of mild cognitive impairment (MCI) or probable dementia (PD) across biomarker categories.

Results: Over a median …

Clinical Outcomes Of Patients With Newly Diagnosed Large B-Cell Lymphoma In A Safety-Net Hospital System, Rockbum Kim, Abiodun O Oluyomi, Omar Rosales, Raka Bandyo, Courtney N Miller-Chism, Mark M Udden, Martha P Mims, Hilary Ma, Gustavo A Rivero, Akiva Diamond, Purnima S Teegavarapu, Ang Li, Christopher R Flowers

Faculty, Staff and Students Publications

Real-world outcome data for patients with large B-cell lymphomas (LBCLs) who are uninsured or have socioeconomic barriers to care are limited. We performed a retrospective cohort study of patients with newly diagnosed LBCL treated in a large safety-net hospital system. Between January 2011 and June 2022, 496 patients aged >18 years were diagnosed with LBCL at Harris Health System, Houston, Texas. The median age was 53 years, 75% were uninsured, and 81% were in the most disadvantaged Area Deprivation Index national quartiles. Most (69%) had stage III/IV disease, 44% had poor-risk disease by the Revised International Prognostic Index (R-IPI), and …

Bempedoic Acid In Secondary Prevention, Sadeer G Al-Kindi, Michael D Shapiro, Laurence Sperling, Salim S Virani, Abdul Mannan Khan Minhas

Faculty, Staff and Students Publications

•Bempedoic acid has been shown to reduce major adverse cardiovascular outcomes in patients unable to take statins due to statin-associated side effects.•Analysis of CLEAR Outcomes trial data reveals possible differences in baseline characteristics between the primary and secondary prevention subgroups.•Further research is needed to optimize use of bempedoic acid and clarify its impact on cardiovascular outcomes in diverse patient populations.

Leveraging Preclinical Models Of Metastatic Breast Cancer, Jeffrey M Rosen

Faculty, Staff and Students Publications

Women that present to the clinic with established breast cancer metastases have limited treatment options. Yet, the majority of preclinical studies are actually not directed at developing treatment regimens for established metastatic disease. In this review we will discuss the current state of preclinical macro-metastatic breast cancer models, including, but not limited to syngeneic GEMM, PDX and xenografts. Challenges within these models which are often overlooked include fluorophore-immunogenic neoantigens, differences in experimental vs spontaneous metastasis and tumor heterogeneity. Furthermore, due to cell plasticity in the tumor immune microenvironment (TIME) of the metastatic landscape, the treatment efficacy of newly approved immune …

Characteristics Of Patients With Spontaneous Coronary Artery Dissection Presenting With Sudden Cardiac Arrest In The United States And The Potential Role Of Implantable Cardioverter Defibrillator Therapy, Zhen Wang, Mahboob Alam, Samin Sharma, Hani Jneid

Faculty, Staff and Students Publications

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a disease entity that often occurs in young, healthy women and can cause life-threatening ventricular arrhythmias and sudden cardiac arrest. However, the characteristics and outcomes of SCAD with cardiac arrest are not well characterized.

METHODS: This study investigated the baseline characteristics of SCAD patients with cardiac arrest using the National Inpatient Sample (NIS) database between 2016 and 2020. In addition, we also sought to determine the potential impact that implantable cardioverter defibrillator (ICD) therapy had on morbidity and mortality in SCAD patients presenting with cardiac arrest.

RESULTS: Our findings showed that the SCAD …

Targeting Calpain-2-Mediated Junctophilin-2 Cleavage Delays Heart Failure Progression Following Myocardial Infarction, Hui Li, Lucia M Moreira, Mohit M Hulsurkar, Arielys Mendoza, Mara R Turkieltaub Paredes, Jose Alberto Navarro-Garcia, Elda Munivez, Brooke Horist, Oliver M Moore, Gunnar Weninger, Sören Brandenburg, Christof Lenz, Stephan E Lehnart, Rana Sayeed, George Krasopoulos, Vivek Srivastava, Lilei Zhang, Jason M Karch, Svetlana Reilly, Xander H T Wehrens

Faculty, Staff and Students Publications

Coronary heart disease (CHD) is a prevalent cardiac disease that causes over 370,000 deaths annually in the USA. In CHD, occlusion of a coronary artery causes ischemia of the cardiac muscle, which results in myocardial infarction (MI). Junctophilin-2 (JPH2) is a membrane protein that ensures efficient calcium handling and proper excitation-contraction coupling. Studies have identified loss of JPH2 due to calpain-mediated proteolysis as a key pathogenic event in ischemia-induced heart failure (HF). Our findings show that calpain-2-mediated JPH2 cleavage yields increased levels of a C-terminal cleaved peptide (JPH2-CTP) in patients with ischemic cardiomyopathy and mice with experimental MI. We created …

A Genome-Wide Association Meta-Analysis Of All-Cause And Vascular Dementia

Faculty, Staff and Students Publications

INTRODUCTION: Dementia is a multifactorial disease with Alzheimer's disease (AD) and vascular dementia (VaD) pathologies making the largest contributions. Yet, most genome-wide association studies (GWAS) focus on AD.

METHODS: We conducted a GWAS of all-cause dementia (ACD) and examined the genetic overlap with VaD. Our dataset includes 800,597 individuals, with 46,902 and 8702 cases of ACD and VaD, respectively. Known AD loci for ACD and VaD were replicated. Bioinformatic analyses prioritized genes that are likely functionally relevant and shared with closely related traits and risk factors.

RESULTS: For ACD, novel loci identified were associated with energy transport (SEMA4D), neuronal excitability …

Distinct Basal Forebrain-Originated Neural Circuits Promote Homoeostatic Feeding And Suppress Hedonic Feeding In Male Mice, Meng Yu, Olivia Z Ginnard, Kristine M Conde, Mengjie Wang, Xing Fang, Hesong Liu, Longlong Tu, Na Yin, Junying Han, Yongjie Yang, Qingchun Tong, Benjamin R Arenkiel, Chunmei Wang, Yang He, Yong Xu

Faculty, Staff and Students Publications

Feeding behaviour is influenced by two primary factors: homoeostatic needs driven by hunger and hedonic desires for pleasure even in the absence of hunger. While efficient homoeostatic feeding is vital for survival, excessive hedonic feeding can lead to adverse consequences such as obesity and metabolic dysregulations. However, the neurobiological mechanisms that orchestrate homoeostatic versus hedonic food consumption remain largely unknown. Here we show that GABAergic proenkephalin (Penk) neurons in the diagonal band of Broca (DBB) of male mice respond to food presentation. We further demonstrate that a subset of DBBPenk neurons that project to the paraventricular nucleus of the hypothalamus …

An Interdisciplinary Consensus Approach To Pulmonary Hypertension In Developmental Lung Disease, Mary P Mullen, Delphine Yung, R Paul Guillerman, Sara O Vargas, Catherine M Avitabile, Corey A Chartan, Nahir Cortes-Santiago, Michaela Ibach, Emma O Jackson, Jill Ann Jarrell, Roberta L Keller, Usha S Krishnan, Kalyani R Patel, Jennifer Pogoriler, Elise C Whalen, Kathryn A Wikenheiser-Brokamp, Natalie M Villafranco, Rachel K Hopper, J Usha Raj, Steven H Abman

Faculty, Staff and Students Publications

It is increasingly recognised that diverse genetic respiratory disorders present as severe pulmonary hypertension (PH) in the neonate and young infant, but many controversies and uncertainties persist regarding optimal strategies for diagnosis and management to maximise long-term outcomes. To better define the nature of PH in the setting of developmental lung disease (DEVLD), in addition to the common diagnoses of bronchopulmonary dysplasia and congenital diaphragmatic hernia, we established a multidisciplinary group of expert clinicians from stakeholder paediatric specialties to highlight current challenges and recommendations for clinical approaches, as well as counselling and support of families. In this review, we characterise …