Digital Commons Network^™

Tbx5-Encoded T-Box Transcription Factor 5 Variant T223m Is Associated With Long Qt Syndrome And Pediatric Sudden Cardiac Death, Alexandra M Markunas, Perathu K R Manivannan, Jordan E Ezekian, Agnim Agarwal, William Eisner, Katherina Alsina, Hugh D Allen, Gregory A Wray, Jeffrey J Kim, Xander H T Wehrens, Andrew P Landstrom

Faculty, Staff and Students Publications

Long QT syndrome (LQTS) is a genetic disease resulting in a prolonged QT interval on a resting electrocardiogram, predisposing affected individuals to polymorphic ventricular tachycardia and sudden death. Although a number of genes have been implicated in this disease, nearly one in four individuals exhibiting the LQTS phenotype are genotype-negative. Whole-exome sequencing identified a missense T223M variant in TBX5 that cosegregates with prolonged QT interval in a family with otherwise genotype-negative LQTS and sudden death. The TBX5-T223M variant was absent among large ostensibly healthy populations (gnomAD) and predicted to be pathogenic by in silico modeling based on Panther, PolyPhen-2, Provean, …

Deficiency Of Stat1 In Cd11c+ Cells Alters Adipose Tissue Inflammation And Improves Metabolic Dysfunctions In Mice Fed A High-Fat Diet, Antu Antony, Zeqin Lian, Xiaoyuan Dai Perrard, Jerry Perrard, Hua Liu, Aaron R Cox, Pradip Saha, Lothar Hennighausen, Sean M Hartig, Christie M Ballantyne, Huaizhu Wu

Faculty, Staff and Students Publications

CD11c+ macrophages/dendritic cells (MDCs) are increased and display the classically activated M1-like phenotype in obese adipose tissue (AT) and may contribute to AT inflammation and insulin resistance. Stat1 is a key transcription factor for MDC polarization into the M1-like phenotype. Here, we examined the role of Stat1 in obesity-induced AT MDC polarization and inflammation and insulin resistance using mice with specific knockout of Stat1 in MDCs (cKO). Stat1 was upregulated and phosphorylated, indicating activation, early and persistently in AT and AT MDCs of wild-type mice fed a high-fat diet (HFD). Compared with littermate controls, cKO mice fed an HFD (16 …

Pegylated Arginine Deiminase Depletes Plasma Arginine But Maintains Tissue Arginine Availability In Young Pigs, Mahmoud A Mohammad, Inka C Didelija, Barbara Stoll, Trung C Nguyen, Juan C Marini

Faculty, Staff and Students Publications

Pegylated arginine deiminase (ADI-PEG20) results in the depletion of arginine with the production of isomolar amounts of citrulline. This citrulline has the potential to be utilized by the citrulline recycling pathway regenerating arginine and sustaining tissue arginine availability. The goal of this research was to test the hypothesis that ADI-PEG20 depletes circulating arginine in pigs but maintains tissue arginine concentration and function, and to characterize the kinetics of citrulline and arginine. Two multitracer approaches (bolus dose and primed-continuous infusion) were used to investigate the metabolism of arginine and citrulline in Control (

A Brazilian National Preparedness Survey Of Anesthesiologists During The Coronavirus Pandemic, Vinícius Caldeira Quintão, Claudia Marquez Simões, Gibran Elias Harcha Munoz, Paul Barach, Maria José Carvalho Carmona, Brazilian Network For Research On Complications In Anesthesia Branca

College of Population Health Faculty Papers

No abstract provided.

A Biallelic Pathogenic Variant In The Ogdh Gene Results In A Neurological Disorder With Features Of A Mitochondrial Disease, Zheng Yie Yap, Klaudia Strucinska, Satoshi Matsuzaki, Sukyeong Lee, Yue Si, Kenneth Humphries, Mark A Tarnopolsky, Wan Hee Yoon

Faculty, Staff and Students Publications

2-Oxoglutarate dehydrogenase (OGDH) is a rate-limiting enzyme in the mitochondrial TCA cycle, encoded by the OGDH gene. α-Ketoglutarate dehydrogenase (OGDH) deficiency was previously reported in association with developmental delay, hypotonia, and movement disorders and metabolic decompensation, with no genetic data provided. Using whole exome sequencing, we identified two individuals carrying a homozygous missense variant c.959A>G (p.N320S) in the OGDH gene. These individuals presented with global developmental delay, elevated lactate, ataxia and seizure. Fibroblast analysis and modeling of the mutation in Drosophila were used to evaluate pathogenicity of the variant. Skin fibroblasts from subject # 2 showed a decrease in …

Covid-19 In Solid Organ Transplantation: Disease Severity And Clinical Update., Akanksha Arya, Michael Li, Nana Aburjania, Pooja Singh, Tricia. Royer, Sean Moss, Katherine A. Belden

Department of Medicine Faculty Papers

BACKGROUND: Solid organ transplant (SOT) recipients are a complex, immunocompromised population in whom greater coronavirus disease 2019 (COVID-19) mortality has been reported compared with the general population.

METHODS: We examined a retrospective cohort of 58 SOT recipients with first-wave COVID-19, comparing patients with severe and nonsevere illness. Additionally, SOT recipients are compared with general patients with first-wave COVID-19.

RESULTS: Organs transplanted included 38 kidneys, 8 livers, 5 hearts, and 3 pancreases. Average SOT recipient age was 57.4 years; 62% were male; 46.6% were African American 36.2% were white. Comorbidities included hypertension (86%), chronic kidney disease (86%), diabetes mellitus (50%), coronary …

Psychological Experience And Coping Strategies Of Patients In The Northeast Us Delaying Care For Infertility During The Covid-19 Pandemic., David B Seifer, William D Petok, Alisha Agrawal, Tanya L Glenn, Arielle H Bayer, Barry R Witt, Blair D Burgin, Harry J Lieman

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: On March 17, 2020 an expert ASRM task force recommended the temporary suspension of new, non-urgent fertility treatments during an ongoing world-wide pandemic of Covid-19. We surveyed at the time of resumption of fertility care the psychological experience and coping strategies of patients pausing their care due to Covid-19 and examined which factors were associated and predictive of resilience, anxiety, stress and hopefulness.

METHODS: Cross sectional cohort patient survey using an anonymous, self-reported, single time, web-based, HIPPA compliant platform (REDCap). Survey sampled two Northeast academic fertility practices (Yale Medicine Fertility Center in CT and Montefiore's Institute for Reproductive Medicine …

Metabolic Flexibility Across The Spectrum Of Glycemic Regulation In Youth, Fida Bacha, Sara Klinepeter Bartz, Maurice Puyau, Anne Adolph, Susan Sharma

Children’s Nutrition Research Center Staff Publications

BACKGROUNDMetabolic flexibility (MF) refers to the relative ability to utilize lipid and carbohydrate substrates and to transition between them. It is not clear whether MF is impaired in obese youth and what the determining factors are.METHODSWe investigated the determinants of MF (increased respiratory exchange ratio [ΔRER] under insulin-stimulated conditions) in pubertal youth (n = 104; 15.6 ± 1.8 years) with obesity across the spectrum of glucose tolerance compared with normal weight (NW) controls, including body composition (fat-free mass [FFM], %body fat), visceral adipose fat (VAT) (MRI), glycemia, and insulin sensitivity (IS) [3-hour hyperinsulinemic-euglycemic clamp with measurement of lipolysis ([2H5] glycerol), …

Allocation Of Anchors During Labral Repair: A Multicenter Cohort Analysis Of Labral Treatment In Hip Arthroscopy., Ryan P Mcgovern, John J Christoforetti, Benjamin R Kivlan, Shane J Nho, Andrew B Wolff, John P Salvo, Dean Matsuda, Thomas J Ellis, Allston J Stubbs, Dominic S Carreira

Rothman Institute Papers

Background: While previous studies have established several techniques for suture anchor repair of the acetabular labrum to bone during arthroscopic surgery, the current literature lacks evidence defining the appropriate number of suture anchors required to effectively restore the function of the labral tissue.

Purpose/Hypothesis: To define the location and size of labral tears identified during hip arthroscopy for acetabular labral treatment in a large multicenter cohort. The secondary purpose was to differentiate the number of anchors used during arthroscopic labral repair. The hypothesis was that the location and size of the labral tear as well as the number of anchors …

Targeting Nsd2-Mediated Src-3 Liquid-Liquid Phase Separation Sensitizes Bortezomib Treatment In Multiple Myeloma, Jing Liu, Ying Xie, Jing Guo, Xin Li, Jingjing Wang, Hongmei Jiang, Ziyi Peng, Jingya Wang, Sheng Wang, Qian Li, Linquan Ye, Yuping Zhong, Qiguo Zhang, Xiaozhi Liu, David M Lonard, Jin Wang, Bert W O'Malley, Zhiqiang Liu

Faculty, Staff and Students Publications

Development of chemoresistance is the main reason for failure of clinical management of multiple myeloma (MM), but the genetic and epigenetic aberrations that interact to confer such chemoresistance remains unknown. In the present study, we find that high steroid receptor coactivator-3 (SRC-3) expression is correlated with relapse/refractory and poor outcomes in MM patients treated with bortezomib (BTZ)-based regimens. Furthermore, in immortalized cell lines, high SRC-3 enhances resistance to proteasome inhibitor (PI)-induced apoptosis. Overexpressed histone methyltransferase NSD2 in patients bearing a t(4;14) translocation or in BTZ-resistant MM cells coordinates elevated SRC-3 by enhancing its liquid-liquid phase separation to supranormally modify histone …

Patient Experience With Ner1006 As A Bowel Preparation For Colonoscopy: A Prospective, Multicenter Us Survey, Brooks D Cash, Mary Beth C Moncrief, Michael S Epstein, David M Poppers

Faculty, Staff and Student Publications

BACKGROUND: NER1006 (Plenvu

METHODS: Adults were recruited from 444 US community gastrointestinal practices and provided a kit number for enrollment into an online survey to be completed within 2 weeks. Survey questions evaluated colonoscopy history and prior bowel preparation(s) prescribed, patient experience during NER1006 administration, and patient satisfaction with the bowel preparation process. A 9-point predefined grading scale was used to evaluate ease of NER1006 preparation and consumption (range, 1 "very difficult" to 9 "very easy"); the perceived importance of volume requirement and clear liquid options (range, 1 "not important at all" to 9 "very important"); and patient satisfaction (range, …

The Rac-Gef Tiam1 Promotes Dendrite And Synapse Stabilization Of Dentate Granule Cells And Restricts Hippocampal-Dependent Memory Functions, Jinxuan Cheng, Federico Scala, Francisco A Blanco, Sanyong Niu, Karen Firozi, Laura Keehan, Shalaka Mulherkar, Emmanouil Froudarakis, Lingyong Li, Joseph G Duman, Xiaolong Jiang, Kimberley F Tolias

Faculty, Staff and Students Publications

The dentate gyrus (DG) controls information flow into the hippocampus and is critical for learning, memory, pattern separation, and spatial coding, while DG dysfunction is associated with neuropsychiatric disorders. Despite its importance, the molecular mechanisms regulating DG neural circuit assembly and function remain unclear. Here, we identify the Rac-GEF Tiam1 as an important regulator of DG development and associated memory processes. In the hippocampus, Tiam1 is predominantly expressed in the DG throughout life. Global deletion of Tiam1 in male mice results in DG granule cells with simplified dendritic arbors, reduced dendritic spine density, and diminished excitatory synaptic transmission. Notably, DG …

Phenytoin Inhibits Cell Proliferation Through Microrna-196a-5p In Mouse Lip Mesenchymal Cells, Hiroki Yoshioka, Sai Shankar Ramakrishnan, Akiko Suzuki, Junichi Iwata

Faculty, Staff and Student Publications

Cleft lip (CL) is one of the most common birth defects. It is caused by either genetic mutations or environmental factors. Recent studies suggest that environmental factors influence the expression of noncoding RNAs [e.g., microRNA (miRNA)], which can regulate the expression of genes crucial for cellular functions. In this study, we examined which miRNAs are associated with CL. Among 10 candidate miRNAs (miR-98-3p, miR-101a-3p, miR-101b-3p, miR-141-3p, miR-144-3p, miR-181a-5p, miR-196a-5p, miR-196b-5p, miR-200a-3p, and miR-710) identified through our bioinformatic analysis of CL-associated genes, overexpression of miR-181a-5p, miR-196a-5p, miR-196b-5p, and miR-710 inhibited cell proliferation through suppression of genes associated with CL in cultured …

Association Of Nt-Probnp, Blood Pressure, And Cardiovascular Events: The Aric Study, Aliza Hussain, Wensheng Sun, Anita Deswal, James A De Lemos, John W Mcevoy, Ron C Hoogeveen, Kunihiro Matsushita, David Aguilar, Biykem Bozkurt, Salim S Virani, Amil M Shah, Elizabeth Selvin, Chiadi Ndumule, Christie M Ballantyne, Vijay Nambi

Faculty, Staff and Students Publications

BACKGROUND: Although intensive blood pressure reduction has cardiovascular benefits, the absolute benefit is greater in those at higher cardiovascular disease (CVD) risk.

OBJECTIVES: This study examined whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) helps identify subjects at higher risk for CVD events across systolic blood pressure (SBP), diastolic blood pressure (DBP), or pulse pressure (PP) categories.

METHODS: Participants from the ARIC (Atherosclerosis Risk In Communities) study visit 4 (1996 to 98) were grouped according to SBP, DBP, or PP categories and further stratified by NT-proBNP categories. Cox regression models were used to estimate hazard ratios for incident CVD (coronary heart disease, …

Common Questions And Misconceptions About Creatine Supplementation: What Does The Scientific Evidence Really Show?, Jose Antonio, Darren G Candow, Scott C Forbes, Bruno Gualano, Andrew R Jagim, Richard B Kreider, Eric S Rawson, Abbie E Smith-Ryan, Trisha A Vandusseldorp, Darryn S Willoughby, Tim N Ziegenfuss

Faculty, Staff and Students Publications

Supplementing with creatine is very popular amongst athletes and exercising individuals for improving muscle mass, performance and recovery. Accumulating evidence also suggests that creatine supplementation produces a variety of beneficial effects in older and patient populations. Furthermore, evidence-based research shows that creatine supplementation is relatively well tolerated, especially at recommended dosages (i.e. 3-5 g/day or 0.1 g/kg of body mass/day). Although there are over 500 peer-refereed publications involving creatine supplementation, it is somewhat surprising that questions regarding the efficacy and safety of creatine still remain. These include, but are not limited to: 1. Does creatine lead to water retention? 2. …

Efficacy And Safety Of The Mrna-1273 Sars-Cov-2 Vaccine, Lindsey R Baden, Hana M El Sahly, Brandon Essink, Karen Kotloff, Sharon Frey, Rick Novak, David Diemert, Stephen A Spector, Nadine Rouphael, C Buddy Creech, John Mcgettigan, Shishir Khetan, Nathan Segall, Joel Solis, Adam Brosz, Carlos Fierro, Howard Schwartz, Kathleen Neuzil, Larry Corey, Peter Gilbert, Holly Janes, Dean Follmann, Mary Marovich, John Mascola, Laura Polakowski, Julie Ledgerwood, Barney S Graham, Hamilton Bennett, Rolando Pajon, Conor Knightly, Brett Leav, Weiping Deng, Honghong Zhou, Shu Han, Melanie Ivarsson, Jacqueline Miller, Tal Zaks, Cove Study Group

Faculty, Staff and Students Publications

BACKGROUND: Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19.

METHODS: This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. …

Risk Factors For Stress Fractures In Female Runners: Results Of A Survey, Therese Johnston, Allison E Jakavick, Caroline A Mancuso, Kathleen C Mcgee, Lily Wei, Morgan L Wright, Jeremy Close, Md, Ayako Shimada, Benjamin E Leiby

Department of Rehabilitation Medicine Faculty Papers

Background: Few studies compare women with and without stress fractures and most focus on younger, elite runners.

Hypothesis/purpose: Compare risk factors between female runners with and without a stress fracture history.

Study design: Case control.

Methods: An online survey targeting women age ≥18 years was distributed primarily via social media. Questions included demographics, running details, cross training, nutrition, injury history, medical/menstrual history, and medications. Women with stress fracture histories answered questions about location, number, and changes made. Data were compared between groups using t-tests, chi-square tests, or Fisher's exact tests. Multivariable logistic regression models simultaneously investigated associations of multiple factors …

Levonorgestrel Intrauterine Device Use For Medical Indications In Nulliparous Adolescents And Young Adults., Beth I Schwartz, Morgan Alexander, Lesley L Breech

Department of Obstetrics and Gynecology Faculty Papers

PURPOSE: Intrauterine devices (IUDs) are highly effective at preventing pregnancy. Levonorgestrel (LNG) IUDs also have beneficial effects on menstrual bleeding and abdominal and pelvic pain. Although there are increasing data on use of IUDs for contraception in adolescents and for medical indications in adults, there are extremely limited data on LNG IUD use for medical indications in adolescents. Our objective is to describe the characteristics and experiences of LNG IUD use in nulliparous adolescents and young women using IUDs for medical indications.

METHODS: We conducted a retrospective chart review of all nulliparous patients aged 22 years and younger who underwent …

Association Of Baseline Characteristics With Insulin Sensitivity And Β-Cell Function In The Glycemia Reduction Approaches In Diabetes: A Comparative Effectiveness (Grade) Study Cohort, Neda Rasouli, Naji Younes, Kristina M Utzschneider, Silvio E Inzucchi, Ashok Balasubramanyam, Andrea L Cherrington, Faramarz Ismail-Beigi, Robert M Cohen, Darin E Olson, Ralph A Defronzo, William H Herman, John M Lachin, Steven E Kahn

Faculty, Staff and Students Publications

OBJECTIVE: We investigated sex and racial differences in insulin sensitivity, β-cell function, and glycated hemoglobin (HbA

RESEARCH DESIGN AND METHODS: This is a cross-sectional analysis of baseline data from 3,108 GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) participants. All had type 2 diabetes diagnosedβ-cell function were evaluated using the HOMA of insulin sensitivity and estimates from oral glucose tolerance tests, including the Matsuda Index, insulinogenic index, C-peptide index, and oral disposition index (DI).

RESULTS: The cohort was 56.6 ± 10 years of age (mean ± SD), 63.8% male, with BMI 34.2 ± 6.7 kg/m

CONCLUSIONS: In the …

Relation Of Magnetic Resonance Imaging Based Arterial Signal Enhancement To Markers Of Peripheral Artery Disease, Olga A Gimnich, Jonathan Holbrook, Tatiana Belousova, Christina M Short, Addison A Taylor, Vijay Nambi, Joel D Morrisett, Christie M Ballantyne, Jean Bismuth, Dipan J Shah, Gerd Brunner

Faculty, Staff and Students Publications

Peripheral artery disease (PAD) is associated with impaired lower extremity function. We hypothesized that contrast-enhanced magnetic resonance imaging (CE-MRI) based arterial signal enhancement (SE) measures are associated with markers of PAD. A total of 66 participants were enrolled, 10 were excluded due to incomplete data, resulting in 56 participants for the final analyses (36 PAD, 20 matched controls). MR imaging was performed postreactive hyperemia using bilateral thigh blood-pressure cuffs. First pass-perfusion images were acquired at the mid-calf region with a high-resolution saturation recovery gradient echo pulse sequence, and arterial SE was measured for the lower extremity arteries. As expected, peak …

Association Of Long-Term Trajectories Of Neighborhood Socioeconomic Status With Weight Change In Older Adults, Dong Zhang, Cici Bauer, Tiffany Powell-Wiley, Qian Xiao

Faculty, Staff and Student Publications

IMPORTANCE: Studying long-term changes in neighborhood socioeconomic status (SES) may help to better understand the associations between neighborhood exposure and weight outcomes and provide evidence supporting neighborhood interventions. Little previous research has been done to examine associations between neighborhood SES and weight loss, a risk factor associated with poor health outcomes in the older population.

OBJECTIVE: to determine whether improvements in neighborhood SES are associated with reduced likelihoods of excessive weight gain and excessive weight loss and whether declines are associated with increased likelihoods of these weight outcomes.

DESIGN, STUDY, AND PARTICIPANTS: This cohort study was conducted using data from …

Association Of Baseline Characteristics With Insulin Sensitivity And Β-Cell Function In The Glycemia Reduction Approaches In Diabetes: A Comparative Effectiveness (Grade) Study Cohort, Neda Rasouli, Naji Younes, Kristina M Utzschneider, Silvio E Inzucchi, Ashok Balasubramanyam, Andrea L Cherrington, Faramarz Ismail-Beigi, Robert M Cohen, Darin E Olson, Ralph A Defronzo, William H Herman, John M Lachin, Steven E Kahn, Grade Research Group

Faculty, Staff and Students Publications

OBJECTIVE: We investigated sex and racial differences in insulin sensitivity, β-cell function, and glycated hemoglobin (HbA

RESEARCH DESIGN AND METHODS: This is a cross-sectional analysis of baseline data from 3,108 GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) participants. All had type 2 diabetes diagnosedβ-cell function were evaluated using the HOMA of insulin sensitivity and estimates from oral glucose tolerance tests, including the Matsuda Index, insulinogenic index, C-peptide index, and oral disposition index (DI).

RESULTS: The cohort was 56.6 ± 10 years of age (mean ± SD), 63.8% male, with BMI 34.2 ± 6.7 kg/m

CONCLUSIONS: In the …

Genome-Wide Meta-Analysis Of Muscle Weakness Identifies 15 Susceptibility Loci In Older Men And Women, Garan Jones, Katerina Trajanoska, Adam J Santanasto, Najada Stringa, Chia-Ling Kuo, Janice L Atkins, Joshua R Lewis, Thuyvy Duong, Shengjun Hong, Mary L Biggs, Jian'an Luan, Chloe Sarnowski, Kathryn L Lunetta, Toshiko Tanaka, Mary K Wojczynski, Ryan Cvejkus, Maria Nethander, Sahar Ghasemi, Jingyun Yang, M Carola Zillikens, Stefan Walter, Kamil Sicinski, Erika Kague, Cheryl L Ackert-Bicknell, Dan E Arking, B Gwen Windham, Eric Boerwinkle, Megan L Grove, Misa Graff, Dominik Spira, Ilja Demuth, Nathalie Van Der Velde, Lisette C P G M De Groot, Bruce M Psaty, Michelle C Odden, Alison E Fohner, Claudia Langenberg, Nicholas J Wareham, Stefania Bandinelli, Natasja M Van Schoor, Martijn Huisman, Qihua Tan, Joseph Zmuda, Dan Mellström, Magnus Karlsson, David A Bennett, Aron S Buchman, Philip L De Jager, Andre G Uitterlinden, Uwe Völker, Thomas Kocher, Alexander Teumer, Leocadio Rodriguéz-Mañas, Francisco J García, José A Carnicero, Pamela Herd, Lars Bertram, Claes Ohlsson, Joanne M Murabito, David Melzer, George A Kuchel, Luigi Ferrucci, David Karasik, Fernando Rivadeneira, Douglas P Kiel, Luke C Pilling

Faculty, Staff and Student Publications

Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n = 48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1 p = 4 × 10

Absent B Cells, Agammaglobulinemia, And Hypertrophic Cardiomyopathy In Folliculin-Interacting Protein 1 Deficiency, Francesco Saettini, Cecilia Poli, Jaime Vengoechea, Sonia Bonanomi, Julio C Orellana, Grazia Fazio, Fred H Rodriguez, Loreani P Noguera, Claire Booth, Valentina Jarur-Chamy, Marissa Shams, Maria Iascone, Maja Vukic, Serena Gasperini, Manuel Quadri, Amairelys Barroeta Seijas, Elizabeth Rivers, Mario Mauri, Raffaele Badolato, Gianni Cazzaniga, Cristina Bugarin, Giuseppe Gaipa, Wilma G M Kroes, Daniele Moratto, Monique M Van Oostaijen-Ten Dam, Frank Baas, Silvère Van Der Maarel, Rocco Piazza, Zeynep H Coban-Akdemir, James R Lupski, Bo Yuan, Ivan K Chinn, Lucia Daxinger, Andrea Biondi

Faculty, Staff and Student Publications

Agammaglobulinemia is the most profound primary antibody deficiency that can occur due to an early termination of B-cell development. We here investigated 3 novel patients, including the first known adult, from unrelated families with agammaglobulinemia, recurrent infections, and hypertrophic cardiomyopathy (HCM). Two of them also presented with intermittent or severe chronic neutropenia. We identified homozygous or compound-heterozygous variants in the gene for folliculin interacting protein 1 (FNIP1), leading to loss of the FNIP1 protein. B-cell metabolism, including mitochondrial numbers and activity and phosphatidylinositol 3-kinase/AKT pathway, was impaired. These defects recapitulated the Fnip1-/- animal model. Moreover, we identified either uniparental disomy …

Post-Partum Skin-To-Skin Care And Infant Safety: Results Of A State-Wide Hospital Survey, Eileen Tyrala, Md, Michael H. Goodstein, Md, Erich Batra, Md, Barbara Kelly, Md, Judy Bannon, Mba, Ted Bell, Ms

Department of Medicine Faculty Papers

Objectives: Survey current experience with Skin to Skin care (SSC) in Pennsylvania Maternity Centers.

Study Design: The nursing director of each Maternity Center in PA (n = 95) was sent an on-line confidential survey querying SSC practices. Responses were compared by delivery size, location, and nature of affiliation. Statistics analyzed by chi-square and student t-test.

Results: Of these 64/95 MCs (67%) responded. All allowed SSC after vaginal deliveries, 55% after C-section, 73% mother’s room. Monitoring included delivery room nurse (94%) with support from other providers (61%), family members (37%), and electronic monitoring (5%). If SSC occurred in mother’s …

Spliceosome-Targeted Therapies Trigger An Antiviral Immune Response In Triple-Negative Breast Cancer, Elizabeth A Bowling, Jarey H Wang, Fade Gong, William Wu, Nicholas J Neill, Ik Sun Kim, Siddhartha Tyagi, Mayra Orellana, Sarah J Kurley, Rocio Dominguez-Vidaña, Hsiang-Ching Chung, Tiffany Y-T Hsu, Julien Dubrulle, Alexander B Saltzman, Heyuan Li, Jitendra K Meena, Gino M Canlas, Srinivas Chamakuri, Swarnima Singh, Lukas M Simon, Calla M Olson, Lacey E Dobrolecki, Michael T Lewis, Bing Zhang, Ido Golding, Jeffrey M Rosen, Damian W Young, Anna Malovannaya, Fabio Stossi, George Miles, Matthew J Ellis, Lihua Yu, Silvia Buonamici, Charles Y Lin, Kristen L Karlin, Xiang H-F Zhang, Thomas F Westbrook

Faculty, Staff and Students Publications

Many oncogenic insults deregulate RNA splicing, often leading to hypersensitivity of tumors to spliceosome-targeted therapies (STTs). However, the mechanisms by which STTs selectively kill cancers remain largely unknown. Herein, we discover that mis-spliced RNA itself is a molecular trigger for tumor killing through viral mimicry. In MYC-driven triple-negative breast cancer, STTs cause widespread cytoplasmic accumulation of mis-spliced mRNAs, many of which form double-stranded structures. Double-stranded RNA (dsRNA)-binding proteins recognize these endogenous dsRNAs, triggering antiviral signaling and extrinsic apoptosis. In immune-competent models of breast cancer, STTs cause tumor cell-intrinsic antiviral signaling, downstream adaptive immune signaling, and tumor cell death. Furthermore, RNA …

An Economic And Disease Transmission Model Of Human Papillomavirus And Oropharyngeal Cancer In Texas, Chengxue Zhong, Li Xu, Ho-Lan Peng, Samantha Tam, Li Xu, Kristina R Dahlstrom, Chi-Fang Wu, Shuangshuang Fu, Wenyaw Chan, Erich M Sturgis, Lois M Ramondetta, Libin Rong, David R Lairson, Hongyu Miao

Faculty, Staff and Student Publications

In 2017, 46,157 and 3,127 new oropharyngeal cancer (OPC) cases were reported in the U.S. and Texas, respectively. About 70% of OPC were attributed to human papillomavirus (HPV). However, only 51% of U.S. and 43.5% of Texas adolescents have completed the HPV vaccine series. Therefore, modeling the demographic dynamics and transmission of HPV and OPC progression is needed for accurate estimation of the economic and epidemiological impacts of HPV vaccine in a geographic area. An age-structured population dynamic model was developed for the U.S. state of Texas. With Texas-specific model parameters calibrated, this model described the dynamics of HPV-associated OPC …

Houston Hurricane Harvey Health (Houston-3h) Study: Assessment Of Allergic Symptoms And Stress After Hurricane Harvey Flooding, Abiodun O Oluyomi, Kristen Panthagani, Jesus Sotelo, Xiangjun Gu, Georgina Armstrong, Dan Na Luo, Kristi L Hoffman, Diana Rohlman, Lane Tidwell, Winifred J Hamilton, Elaine Symanski, Kimberly Anderson, Joseph F Petrosino, Cheryl Lyn Walker, Melissa Bondy

Faculty, Staff and Students Publications

BACKGROUND: In August 2017, Hurricane Harvey caused unprecedented flooding across the greater Houston area. Given the potential for widespread flood-related exposures, including mold and sewage, and the emotional and mental toll caused by the flooding, we sought to evaluate the short- and long-term impact of flood-related exposures on the health of Houstonians. Our objectives were to assess the association of flood-related exposures with allergic symptoms and stress among Houston-area residents at two time points: within approximately 30 days (T1) and 12 months (T2) after Hurricane Harvey's landfall.

METHODS: The Houston Hurricane Harvey Health (Houston-3H) Study enrolled a total of 347 …

A Randomized Control Trial To Test A Peer Support Group Approach For Reducing Social Isolation And Depression Among Female Mexican Immigrants, Janet Page-Reeves, Cristina Murray-Krezan, Lidia Regino, Jackie Perez, Molly Bleecker, Daniel Perez, Bill Wagner, Susan Tigert, Elaine L. Bearer, Cathleen E. Willging

Pathology Research and Scholarship

BACKGROUND: Female Mexican Immigrants (FMIs) experience high rates of depression compared with other populations. For this population, depression is often exacerbated by social isolation associated with the experience of immigration. Aim 1. To measure whether a culturally situated peer group intervention will reduce depression and stress associated with the experience of immigration. Aim 2. To test whether an intervention using a "women's funds of knowledge" approach results in improved resilience, knowledge and empowerment. Aim 3. To investigate whether a culturally situated peer group intervention using a women's funds of knowledge approach can give participants a sense and experience of social …

Disparities In Cardiovascular Disease Outcomes Among Pregnant And Post-Partum Women, Mohamed M Gad, Islam Y Elgendy, Ahmed N Mahmoud, Anas M Saad, Toshiaki Isogai, Isadora Sande Mathias, Rabel Misbah Rameez, Johnny Chahine, Hani Jneid, Samir R Kapadia

Faculty, Staff and Students Publications

Background

The incidence of cardiovascular disease among pregnant women is rising in the United States. Data on racial disparities for the major cardiovascular events during pregnancy are limited.

Methods and Results

Pregnant and post‐partum women hospitalized from January 2007 to December 2017 were identified from the Nationwide Inpatient Sample. The outcomes of interest included: in‐hospital mortality, myocardial infarction, stroke, pulmonary embolism, and peripartum cardiomyopathy. Multivariate regression analysis was used to assess the independent association between race and in‐hospital outcomes. Among 46 700 637 pregnancy‐related hospitalizations, 21 663 575 (46.4%) were White, 6 302 089 (13.5%) were Black, and 8 914 …