Diseases Commons^™

Randomized Phase Iii Bmt Ctn Trial Of Calcineurin Inhibitor-Free Chronic Graft-Versus-Host Disease Interventions In Myeloablative Hematopoietic Cell Transplantation For Hematologic Malignancies, Leo Luznik, Marcelo C Pasquini, Brent Logan, Robert J Soiffer, Juan Wu, Steven M Devine, Nancy Geller, Sergio Giralt, Helen E Heslop, Mary M Horowitz, Richard J Jones, Mark R Litzow, Adam Mendizabal, Lori Muffly, Eneida R Nemecek, Lynn O'Donnell, Richard J O'Reilly, Raquel Palencia, Johannes Schetelig, Leyla Shune, Scott R Solomon, Sumithira Vasu, Vincent T Ho, Miguel-Angel Perales

Faculty, Staff and Students Publications

PURPOSE: Calcineurin inhibitors (CNI) are standard components of graft-versus-host disease (GVHD) prophylaxis after hematopoietic cell transplantation (HCT). Prior data suggested that CNI-free approaches using donor T-cell depletion, either by ex vivo CD34 selection or in vivo post-transplant cyclophosphamide (PTCy) as a single agent, are associated with lower rates of chronic GVHD (cGVHD).

METHODS: This multicenter phase III trial randomly assigned patients with acute leukemia or myelodysplasia and an HLA-matched donor to receive CD34-selected peripheral blood stem cell, PTCy after a bone marrow (BM) graft, or tacrolimus and methotrexate after BM graft (control). The primary end point was cGVHD (moderate or …

Race/Ethnicity And Birthplace As Risk Factors For Gastric Intestinal Metaplasia In A Multiethnic United States Population, Mimi C Tan, Taher Jamali, Theresa H Nguyen, Amy Galvan, Robert J Sealock, Anam Khan, Neda Zarrin-Khameh, Ashley Holloman, Ourania Kampagianni, David Henriquez Ticas, Yan Liu, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

INTRODUCTION: Several US subgroups have increased risk of gastric cancer and gastric intestinal metaplasia (GIM) and may benefit from targeted screening. We evaluated demographic and clinical risk factors for GIM and examined the interaction between race/ethnicity and birthplace on GIM risk.

METHODS: We identified patients who had undergone esophagogastroduodenoscopy with gastric biopsy from 3/2006-11/2016 using the pathology database at a safety net hospital in Houston, Texas. Cases had GIM on ≥1 gastric biopsy histopathology, whereas controls lacked GIM on any biopsy. We estimated odds ratios and 95% confidence intervals (CI) for associations with GIM risk using logistic regression and developed …

Comparative Performance Of Risk Prediction Models For Hepatitis B-Related Hepatocellular Carcinoma In The United States, Hyun-Seok Kim, Xian Yu, Jennifer Kramer, Aaron P Thrift, Pete Richardson, Yao-Chun Hsu, Avegail Flores, Hashem B El-Serag, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Guidelines recommend hepatocellular carcinoma (HCC) surveillance in patients with chronic HBV infection. Several HCC risk prediction models are available to guide surveillance decisions, but their comparative performance remains unclear.

METHODS: Using a retrospective cohort of patients with HBV treated with nucleos(t)ide analogues at 130 Veterans Administration facilities between 9/1/2008 and 12/31/2018, we calculated risk scores from 10 HCC risk prediction models (REACH-B, PAGE-B, m-PAGE-B, CU-HCC, HCC-RESCUE, CAMD, APA-B, REAL-B, AASL-HCC, RWS-HCC). We estimated the models' discrimination and calibration. We calculated HCC incidence in risk categories defined by the reported cut-offs for all models.

RESULTS: Of 3,101 patients …

Utilization Rates Of Sglt2 Inhibitors And Glp-1 Receptor Agonists And Their Facility-Level Variation Among Patients With Atherosclerotic Cardiovascular Disease And Type 2 Diabetes: Insights From The Department Of Veterans Affairs, Dhruv Mahtta, David J Ramsey, Michelle T Lee, Liang Chen, Mahmoud Al Rifai, Julia M Akeroyd, Elizabeth M Vaughan, Michael E Matheny, Karla Rodrigues Do Espirito Santo, Sankar D Navaneethan, Carl J Lavie, Yochai Birnbaum, Christie M Ballantyne, Laura A Petersen, Salim S Virani

Faculty, Staff and Students Publications

OBJECTIVE: There is mounting evidence regarding the cardiovascular benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA) among patients with atherosclerotic cardiovascular disease (ASCVD) and type 2 diabetes mellitus (T2DM). There is paucity of data assessing real-world practice patterns for these drug classes. We aimed to assess utilization rates of these drug classes and facility-level variation in their use.

RESEARCH DESIGN AND METHODS: We used the nationwide Veterans Affairs (VA) health care system data set from 1 January 2020 to 31 December 2020 and included patients with established ASCVD and T2DM. Among these patients, …

Is Tissue Still The Issue? The Promise Of Liquid Biopsy In Uveal Melanoma, Daniël P. De Bruyn, Aaron B. Beasley, Robert M. Verdijk, Natasha M. Van Poppelen, Dion Paridaens, Ronald O.B. De Keizer, Nicole C. Naus, Elin S. Gray, Annelies De Klein, Erwin Brosens, Emine Kiliç

Research outputs 2022 to 2026

Uveal melanoma (UM) is the second most frequent type of melanoma. Therapeutic options for UM favor minimally invasive techniques such as irradiation for vision preservation. As a consequence, no tumor material is obtained. Without available tissue, molecular analyses for gene expression, mutation or copy number analysis cannot be performed. Thus, proper patient stratification is impossible and patients' uncertainty about their prognosis rises. Minimally invasive techniques have been studied for prognostication in UM. Blood-based biomarker analysis has become more common in recent years; however, no clinically standardized protocol exists. This review summarizes insights in biomarker analysis, addressing new insights in circulating …

Head And Neck Cancer Survivorship Consensus Statement From The American Head And Neck Society, Neerav Goyal, Andrew Day, Joel Epstein, Joseph Goodman, Evan Graboyes, Scharukh Jalisi, Ana P Kiess, Jamie A Ku, Matthew C Miller, Aru Panwar, Vijay A Patel, Assuntina Sacco, Vlad Sandulache, Amy M Williams, Daniel Deschler, D Gregory Farwell, Cherie-Ann Nathan, Carole Fakhry, Nishant Agrawal

Faculty, Staff and Students Publications

OBJECTIVES: To provide a consensus statement describing best practices and evidence regarding head and neck cancer survivorship.

METHODS: Key topics regarding head and neck cancer survivorship were identified by the multidisciplinary membership of the American Head and Neck Society Survivorship, Supportive Care & Rehabilitation Service. Guidelines were generated by combining expert opinion and a review of the literature and categorized by level of evidence.

RESULTS: Several areas regarding survivorship including dysphonia, dysphagia, fatigue, chronic pain, intimacy, the ability to return to work, financial toxicity, lymphedema, psycho-oncology, physical activity, and substance abuse were identified and discussed. Additionally, the group identified and …

Adult Pulmonary Langerhans Cell Histiocytosis With Osseous Involvement: Understanding This Rare Mimic Of Malignancy, Samantha A. Smith Ms Iii, Adam M. Franks Md, William Rollyson Ms Iv, Doreen Griswold, Tammy Bannister Md

Marshall Journal of Medicine

Langerhans cells are dendritic cells that form the antigenic barrier of the human body. They occur in nearly any tissue but are most prevalent in the skin, submucosa of the bronchial tree, and other mucosae. Langerhans Cell Histiocytosis (LCH) develops when these cells damage the tissues in which they reside through a combination of inflammatory and monoclonal stimulation. The pulmonary variant of LCH involves the lung parenchyma and creates a wide variety of disturbances: pulmonary hypertension and both obstructive and restrictive lung disease. Osseous involvement, in addition to the pulmonary variant, presents with pulmonary masses and lytic bone lesions, which …

Zoonotic Pathogens From Illegally Traded Wildlife Justify Adopting The One Health Perspective In Disease Response, Marianne Allison G. Lee, Vinyl Joseph S. Valeza, Jonathan Patrick H. Yan, Ronald Allan L. Cruz

Biology Faculty Publications

Recent studies have described a direct relationship between the illegal wildlife trade (IWT) and the prevalence of zoonotic pathogens in human populations. In the Philippines, the Philippine Integrated Disease Surveillance and Response (PIDSR) framework outlines the monitoring, response, and management of disease outbreaks, but needs to be updated in the wake of zoonoses from IWT. Here, we identified zoonotic pathogens that may be introduced to human populations through the IWT, pinpointed potential outbreak hotspots, and provided recommendations on how to improve the Philippines’ public health response while considering One Health. Using seizure data from the Biodiversity Management Bureau (DENR-BMB) covering …

A Predictive Model For Geographical Location Using Microbiome Composition And Covid-19 Based Analysis, Ahmed Adel Aboushanab

Theses and Dissertations

The human microbiome is a main contributor for the health and welfare of the human body. It is affected by many factors like diet and hygiene. These factors differ between different populations. Testing the population-microbiome differences using healthy samples from different countries is the first objective of this study. This data was then used in training and testing machine learning models (Random Forest and L2-logistic Regression Classifiers) for the prediction of the geographical location based on the microbiome data. Random Forest Classifier had the highest accuracy. Feature importance analysis showed that the data for Proteobacteria, Actinobacteria, and Bacteroidetes improved the …

Selective Gsk3Β Inhibition Mediates An Nrf2-Independent Anti-Inflammatory Microglial Response, Mohamed H. Yousef

Theses and Dissertations

Glycogen Synthase Kinase 3 (GSK3) is associated with the proinflammatory phenotype of microglia and has been shown to act in concert with Nuclear factor kappa B (NF-κB). . GSK3 is also a suppressor of Nuclear factor erythroid 2-related factor 2 (Nrf2), the principal regulator of redox homeostasis. Agreeing with the oxidative paradigm of aging, Nrf2 is often deregulated in parainflammatory and neurodegenerative diseases. In this study, we aimed to explore a multimodal disease-modifying utility of GSK3 inhibition, beyond neuronal proteopathologies, Furthermore, we aimed to underscore the difference in therapeutic value between the two GSK3 paralogs by isoform-selective chemical inhibition.

The …

Repurposing Metformin And Antifolates For The Treatment Of Hepatocellular Carcinoma, Sherouk Mohamed Tawfik

Theses and Dissertations

Hepatocellular carcinoma (HCC), one of the most prevalent types of cancers worldwide, continues to maintain high levels of resistance to standard therapy. As clinical data revealed poor response rates, the need for developing new methods has increased to improve the overall wellbeing of patients with HCC. Due to its safety, wide availability and previously reported anti-cancer effects, metformin (MET) serves to be a possible therapeutic agent when combined with other well-known anti-cancer agents. The aim of this study was to investigate the potential anti-cancer effects of MET, an anti-diabetic agent, when combined with two antifolate drugs: trimethoprim (TMP) or methotrexate …

It’S About Lyme: Why Congress Must Enact Medical Insurance Coverage Laws For Lyme Disease Patients Now, Jennifer Barrett

Seattle University Law Review Online

The Centers for Disease Control and Prevention (CDC) estimates approximately 476,000 people are diagnosed with Lyme disease in the United States each year. While many will recover with a short course of antibiotics, up to 35% will suffer from persistent symptoms after initial treatment. Despite scientific evidence showing the infection can persist long after initial treatment, most insurance companies restrict access to treatment beyond twenty-eight days, leaving patients to bear much of the financial burden. To limit crippling out-of-pocket expenses, Congress must enact legislation mandating coverage for the treatment of clinically diagnosed Lyme disease and co-infections based on the International …

Conformational Flexibility And Local Frustration In The Functional States Of The Sars-Cov-2 Spike B.1.1.7 And B.1.351 Variants: Mutation-Induced Allosteric Modulation Mechanism Of Functional Dynamics And Protein Stability, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Structural and functional studies of the SARS-CoV-2 spike proteins have recently determined distinct functional states of the B.1.1.7 and B.1.351 spike variants, providing a molecular framework for understanding the mechanisms that link the effect of mutations with the enhanced virus infectivity and transmissibility. A detailed dynamic and energetic analysis of these variants was undertaken in the present work to quantify the effects of different mutations on functional conformational changes and stability of the SARS-CoV-2 spike protein. We employed the efficient and accurate coarse-grained (CG) simulations of multiple functional states of the D614G mutant, B.1.1.7 and B.1.351 spike variants to characterize …

Evaluation Of Step-Down Oral Antibiotic Therapy For Uncomplicated Streptococcal Bloodstream Infections On Clinical Outcomes, Amy Y. Kang, Richard Beuttler, Emi Minejima

Pharmacy Faculty Articles and Research

Background: Despite the severity and frequency of streptococcal bloodstream infections (BSIs), the effectiveness of oral definitive therapy remains unknown. The objective of this study was to evaluate the clinical outcomes of step-down oral antibiotics for the treatment of uncomplicated streptococcal BSIs.

Methods: In this retrospective cohort study, adult patients admitted with uncomplicated streptococcal BSI between June 2015 and June 2017 were included. Patients were excluded if they received <48 h of antibiotic therapy; therapy was started >48 h after first positive culture; had complicated infections of endocarditis, bone and joint infections, or central nervous system infections; Pitt bacteremia score (PBS) ⩾ 4; or failed to respond …

(#Womeninddw) Persistent Speaker Gender Gap At The Premier Digestive Disease Event, Zubair Khan, Rabia Rukhshan, Asmeen Bhatt, Sushovan Guha, Srinivas Ramireddy, Prithvi Patil, Ricardo Badillo, Roy Tomas Davee, Nirav Thosani

Faculty, Staff and Student Publications

BACKGROUND: Over the last few decades, advances have been made regarding gender equality starting from medical students to trainees, to leadership in academics. The female representation in specialty academic conferences not only reflects the existing gender disparities in that specialty but also can influence young female trainees to join that field. Digestive Disease Week (DDW) is the premier digestive disease event. We aimed to calculate the proportion of female representation among speakers and moderators at the DDW meetings held from 2018 to 2020.

METHODS: The data for DDW 2018-2020 were collected via the online web-based planner. The gender of speakers …

Coronavirus Update 1-27-22, The Coronavirus Planning Team

University Briefings & Virtual Events

Today’s dashboard shows 57 positive cases. We are lifting the additional restrictions that we announced at the beginning of the semester. To help with the severe shortage of blood on-campus blood drives are planned.

The Covid-19 Pandemic: The New Way Of Living, Anonymous

Community Reflections

The coronavirus came to America in the beginning of the year, 2021. My contribution is based on the virus's peak and how it affected my family. My essay ranges from what life was like as a high school student in New York witnessing the pandemic to my family being exposed. It touches on the important features of being in lockdown and the adjustment society had to make that still exists today. A common theme throughout my assessment is the development of fear from the coronavirus. It discusses how fear has driven many of the restrictions that my community has had …

Clinical Outcomes Of Immunomodulatory Therapies In The Management Of Covid-19: A Tertiary-Care Experience From Pakistan, Noreen Nasir, Salma Tajuddin, Sarah Khaskheli, Naveera Khan, Hammad Niamatullah, Nosheen Nasir

Section of Internal Medicine

The pharmacological management of COVID-19 has evolved significantly and various immunomodulatory agents have been repurposed. However, the clinical efficacy has been variable and a search for cure for COVID-19 continues. A retrospective cohort study was conducted on 916 patients hospitalized with polymerase chain reaction (PCR)-confirmed COVID-19 between February 2020 and October 2020 at a tertiary care academic medical center in Karachi, Pakistan. The median age was 57 years (interquartile range (IQR) 46–66 years). The most common medications administered were Methylprednisolone (65.83%), Azithromycin (50.66%), and Dexamethasone (46.6%). Majority of the patients (70%) had at least two or more medications used in …

Comprehensive Evaluation Of Left Ventricular Deformation Using Speckle Tracking Echocardiography In Normal Children: Comparison Of Three-Dimensional And Two-Dimensional Approaches, Doaa Aly, Nitin Madan, Laura Kuzava, Alison Samrany, Anitha Parthiban

Faculty, Staff and Students Publications

BACKGROUND: Three-dimensional (3D) speckle tracking echocardiography (STE) can overcome some of the inherent limitations of two-dimensional (2D) STE; however, clinical experience is lacking. We aimed to assess and compare the feasibility, agreement, and reproducibility of left ventricular (LV) global longitudinal (GLS), and regional strain by 3D vs 2D STE in normal children.

METHODS: Healthy pediatric subjects (n = 105, age mean = 11.2 ± 5.5 years) were prospectively enrolled. Three-dimensional and 2D LV GLS, as well as regional strain in 16 myocardial segments were quantified. Bland Altman analysis, intra- class correlation coefficients (ICC), percent error and linear regression were used …

Covid-19 Newsletter (Vol. 104), Center For Disaster Medicine, New York Medical College

COVID-19 Newsletter

No abstract provided.

The Emergence Of Covid-19 Associated Mucormycosis: A Review Of Cases From 18 Countries, Martin Hoenigl, Danila Seidel, Agostinho Carvalho, Shivaprakash M. Rudramurthy, Amir Arastehfar, Jean-Pierre Gangneux, Nosheen Nasir, Alexandro Bonifaz, Javier Araiza, Nikolai Klimko

Department of Medicine

Reports of COVID-19-associated mucormycosis have been increasing in frequency since early 2021, particularly among patients with uncontrolled diabetes. Patients with diabetes and hyperglycaemia often have an inflammatory state that could be potentiated by the activation of antiviral immunity to SARS-CoV2, which might favour secondary infections. In this Review, we analysed 80 published and unpublished cases of COVID-19-associated mucormycosis. Uncontrolled diabetes, as well as systemic corticosteroid treatment, were present in most patients with COVID-19-associated mucormycosis, and rhino-orbital cerebral mucormycosis was the most frequent disease. Mortality was high at 49%, which was particularly due to patients with pulmonary or disseminated mucormycosis or …

Allogeneic Transplant And Car-T Therapy After Autologous Transplant Failure In Dlbcl: A Noncomparative Cohort Analysis, Mehdi Hamadani, Ajay K Gopal, Marcelo Pasquini, Soyoung Kim, Xianmiao Qiu, Sairah Ahmed, Aleksandr Lazaryan, Vijaya Raj Bhatt, Andrew Daly, Premal Lulla, Stefan Ciurea, Jordan Gauthier, Vaibhav Agrawal, Natalie S Grover, Lazaros Lekakis, Dipenkumar Modi, Parastoo B Dahi, Megan M Herr, P Connor Johnson, Hamza Hashmi, Peiman Hematti, Frederick L Locke

Faculty, Staff and Students Publications

Allogeneic transplant (alloHCT) and chimeric antigen receptor modified (CAR)-T cell therapy are potentially cuarative options of diffuse large B-cell lymphoma (DLBCL) relapsing after an autologous (auto)HCT. Although the Center for International Blood and Marrow Transplant Research (CIBMTR) prognostic model can predict outcomes of alloHCT in DLBCL after autoHCT failure, corresponding models of CAR-T treatment in similar patient populations are not available. In this noncomparative registry analysis, we report outcomes of patients with DLBCL (≥18 years) undergoing a reduced intensity alloHCT or CAR-T therapy with axicabtagene ciloleucel during 2012 to 2019 after a prior auto-HCT failure and apply the CIBMTR prognostic …

Potential Effectiveness Of Registered Dietitian Nutritionists In Healthy Behavior Interventions For Managing Type 2 Diabetes In Older Adults: A Systematic Review, Laurel Dobrow, Isabella Estrada, Nasira Burkholder-Cooley, John Miklavcic

Food Science Faculty Articles and Research

Purpose: A systematic review was conducted to assess how the involvement of a registered dietitian nutritionist (RDN) in healthy behavior interventions (HBIs) potentially affects outcomes in older adults with type 2 diabetes (T2D).

Methods: Literature was searched for primary research published between 2016 and 2020 on HBI involving a RDN affecting outcomes in older adults with T2D. Evaluations of hemoglobin A1c (HbA1c), blood glucose, blood pressure, cholesterol, anthropometry, body composition, medication usage, healthcare cost, and self-efficacy and/or adherence to healthy behaviors outcomes were selected for inclusion. All the literature included were summarized, evaluated for certainty of evidence criteria, and assessed …

Coronavirus Update 1-21-22, The Coronavirus Planning Team

University Briefings & Virtual Events

Students who are unvaccinated and those who have been randomly selected will need to register for testing next week.

A Pdk-1 Allosteric Agonist Neutralizes Insulin Signaling Derangements And Beta-Amyloid Toxicity In Neuronal Cells And In Vitro, Henry Querfurth, John Marshall, Keykavous Parang, Mengia S. Rioult-Pedotti, Rakesh Tiwari, Bumsup Kwon, Steve Reisinger, Han-Kyu Lee

Pharmacy Faculty Articles and Research

The Alzheimer’s brain is affected by multiple pathophysiological processes, which include a unique, organ-specific form of insulin resistance that begins early in its course. An additional complexity arises from the four-fold risk of Alzheimer’s Disease (AD) in type 2 diabetics, however there is no definitive proof of causation. Several strategies to improve brain insulin signaling have been proposed and some have been clinically tested. We report findings on a small allosteric molecule that reverses several indices of insulin insensitivity in both cell culture and in vitro models of AD that emphasize the intracellular accumulation of β-amyloid (Aβi). PS48, a chlorophenyl …

Serotype-Specific Effectiveness Against Pneumococcal Carriage And Serotype Replacement After Ten-Valent Pneumococcal Conjugate Vaccine (Pcv10) Introduction In Pakistan, Muhammad Imran Nisar, Fyezah Jehan, Shahira Shahid, Sheraz Ahmed, Sadia Shakoor, Furqan Kabir, Aneeta Hotwani, Sahrish Muneer, Farah Khalid, Sajid Muhammad, Asad Ali, Najeeha Talat Iqbal

Department of Paediatrics and Child Health

Objective: Pakistan was one of the first South-Asian countries to introduce the ten-valent pneumococcal conjugate vaccine (PCV10) at the national level, using a 3+0 schedule without catchup, in 2013.
Methods: From 2014-18, fifteen children Matiari, Sindh, and nasopharyngeal swabs were collected. The samples were cultured, and pneumococcus was further serotyped through multiplex PCR at the Aga Khan University Hospital as per the method described by the Centers for Disease Control and Prevention, USA.
Results: Pneumococcus was detected in 2370/3140 (75%) children. Vaccine type (VT) and non-vaccine type (NVT) serotypes were carried by 379 and 1990 children. There was a significant …

Common Genetic Variants Contribute To Risk Of Transposition Of The Great Arteries, Doris Škorić-Milosavljević, Rafik Tadros, Fernanda M Bosada, Federico Tessadori, Jan Hendrik Van Weerd, Odilia I Woudstra, Fleur V Y Tjong, Najim Lahrouchi, Fanny Bajolle, Heather J Cordell, A J Agopian, Gillian M Blue, Daniela Q C M Barge-Schaapveld, Marc Gewillig, Christoph Preuss, Elisabeth M Lodder, Phil Barnett, Aho Ilgun, Leander Beekman, Karel Van Duijvenboden, Regina Bokenkamp, Martina Müller-Nurasyid, Hubert W Vliegen, Thelma C Konings, Joost P Van Melle, Arie P J Van Dijk, Roland R J Van Kimmenade, Jolien W Roos-Hesselink, Gertjan T Sieswerda, Folkert Meijboom, Hashim Abdul-Khaliq, Felix Berger, Sven Dittrich, Marc-Phillip Hitz, Julia Moosmann, Frank-Thomas Riede, Stephan Schubert, Pilar Galan, Mark Lathrop, Hans M Munter, Ammar Al-Chalabi, Christopher E Shaw, Pamela J Shaw, Karen E Morrison, Jan H Veldink, Leonard H Van Den Berg, Sylvia Evans, Marcelo A Nobrega, Ivy Aneas, Milena Radivojkov-Blagojević, Thomas Meitinger, Erwin Oechslin, Tapas Mondal, Lynn Bergin, John F Smythe, Luis Altamirano-Diaz, Jane Lougheed, Berto J Bouma, Marie-A Chaix, Jennie Kline, Anne S Bassett, Gregor Andelfinger, Roel L F Van Der Palen, Patrice Bouvagnet, Sally-Ann B Clur, Jeroen Breckpot, Wilhelmina S Kerstjens-Frederikse, David S Winlaw, Ulrike M M Bauer, Seema Mital, Elizabeth Goldmuntz, Bernard Keavney, Damien Bonnet, Barbara J Mulder, Michael W T Tanck, Jeroen Bakkers, Vincent M Christoffels, Cornelis J Boogerd, Alex V Postma, Connie R Bezzina

Faculty, Staff and Student Publications

RATIONALE: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored.

OBJECTIVE: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA.

METHODS AND RESULTS: We conducted a genome-wide association study in an international set of 1,237 patients …

An Estrogen-Sensitive Hypothalamus-Midbrain Neural Circuit Controls Thermogenesis And Physical Activity, Hui Ye, Bing Feng, Chunmei Wang, Kenji Saito, Yongjie Yang, Lucas Ibrahimi, Sarah Schaul, Nirali Patel, Leslie Saenz, Pei Luo, Penghua Lai, Valeria Torres, Maya Kota, Devin Dixit, Xing Cai, Na Qu, Ilirjana Hyseni, Kaifan Yu, Yuwei Jiang, Qingchun Tong, Zheng Sun, Benjamin R Arenkiel, Yanlin He, Pingwen Xu, Yong Xu

Faculty, Staff and Students Publications

Estrogen receptor–α (ERα) expressed by neurons in the ventrolateral subdivision of the ventromedial hypothalamic nucleus (ERαvlVMH) regulates body weight in females, but the downstream neural circuits mediating this biology remain largely unknown. Here we identified a neural circuit mediating the metabolic effects of ERαvlVMH neurons. We found that selective activation of ERαvlVMH neurons stimulated brown adipose tissue (BAT) thermogenesis, physical activity, and core temperature and that ERαvlVMH neurons provide monosynaptic glutamatergic inputs to 5-hydroxytryptamine (5-HT) neurons in the dorsal raphe nucleus (DRN). Notably, the ERαvlVMH → DRN circuit responds to changes in ambient temperature and nutritional states. We further showed …

Pparα And Pparγ Activation Is Associated With Pleural Mesothelioma Invasion But Therapeutic Inhibition Is Ineffective, M. Lizeth Orozco Morales, Catherine A. Rinaldi, Emma De Jong, Sally M. Lansley, Joel P. A. Gummer, Bence Olasz, Shabarinath Nambiar, Danika E. Hope, Thomas H. Casey, Y. C. Gary Lee, Connull Leslie, Gareth Nealon, David M. Shackleford, Andrew K. Powell, Marina Grimaldi, Patrick Balaguer, Rachael M. Zemek, Anthony Bosco, Matthew J. Piggott, Alice Vrielink, Richard A. Lake, W. Joost Lesterhuis

Research outputs 2022 to 2026

Mesothelioma is a cancer that typically originates in the pleura of the lungs. It rapidly invades the surrounding tissues, causing pain and shortness of breath. We compared cell lines injected either subcutaneously or intrapleurally and found that only the latter resulted in invasive and rapid growth. Pleural tumors displayed a transcriptional signature consistent with increased activity of nuclear receptors PPARα and PPARγ and with an increased abundance of endogenous PPAR-activating ligands. We found that chemical probe GW6471 is a potent, dual PPARα/γ antagonist with anti-invasive and anti-proliferative activity in vitro. However, administration of GW6471 at doses that provided sustained plasma …

Coronavirus Update 1-20-22, The Coronavirus Planning Team

University Briefings & Virtual Events

There has been some confusion about the process if you test positive through a test not administered by the University. The graphic below explains the process.

We have partnered with our public health program to facilitate COVID-related communications.

Sacred Heart University is becoming a JED Campus.