Medicine and Health Sciences Commons^™

Atrial Myocyte Nlrp3/Camkii Nexus Forms A Substrate For Postoperative Atrial Fibrillation, Jordi Heijman, Azinwi Phina Muna, Tina Veleva, Cristina E Molina, Henry Sutanto, Marcel Tekook, Qiongling Wang, Issam H Abu-Taha, Marcel Gorka, Stephan Künzel, Ali El-Armouche, Hermann Reichenspurner, Markus Kamler, Viacheslav Nikolaev, Ursula Ravens, Na Li, Stanley Nattel, Xander H T Wehrens, Dobromir Dobrev

Faculty, Staff and Students Publications

RATIONALE: Postoperative atrial fibrillation (POAF) is a common and troublesome complication of cardiac surgery. POAF is generally believed to occur when postoperative triggers act on a preexisting vulnerable substrate, but the underlying cellular and molecular mechanisms are largely unknown.

OBJECTIVE: To identify cellular POAF mechanisms in right atrial samples from patients without a history of atrial fibrillation undergoing open-heart surgery.

METHODS AND RESULTS: Multicellular action potentials, membrane ion-currents (perforated patch-clamp), or simultaneous membrane-current (ruptured patch-clamp) and [Ca

CONCLUSIONS: Preexisting Ca

Loss Of Speg Inhibitory Phosphorylation Of Ryanodine Receptor Type-2 Promotes Atrial Fibrillation, Hannah M Campbell, Ann P Quick, Issam Abu-Taha, David Y Chiang, Carlos F Kramm, Tarah A Word, Sören Brandenburg, Mohit Hulsurkar, Katherina M Alsina, Hui-Bin Liu, Brian Martin, Dennis Uhlenkamp, Oliver M Moore, Satadru K Lahiri, Eleonora Corradini, Markus Kamler, Albert J R Heck, Stephan E Lehnart, Dobromir Dobrev, Xander H T Wehrens

Faculty, Staff and Students Publications

BACKGROUND: Enhanced diastolic calcium (Ca

METHODS: Western blotting was performed with right atrial biopsies from patients with paroxysmal AF. SPEG atrial knockout mice were generated using adeno-associated virus 9. In mice, AF inducibility was determined using intracardiac programmed electric stimulation, and diastolic Ca

RESULTS: Western blotting revealed decreased SPEG protein levels in atrial biopsies from patients with paroxysmal AF in comparison with patients in sinus rhythm. SPEG atrial-specific knockout mice exhibited increased susceptibility to pacing-induced AF by programmed electric stimulation and enhanced Ca

CONCLUSIONS: Unlike other kinases (PKA, CaMKII) that increase RyR2 activity, SPEG phosphorylation reduces RyR2-mediated sarcoplasmic reticulum Ca

Inherited Risk For Autism Through Maternal And Paternal Lineage, Dan Bai, Natasha Marrus, Benjamin Hon Kei Yip, Abraham Reichenberg, John N Constantino, Sven Sandin

2020-Current year OA Pubs

BACKGROUND: Autism spectrum disorder (ASD) is highly familial, with a positively skewed male-to-female ratio that is purported to arise from the so-called female protective effect. A serious implication of a female protective effect is that familial ASD liability would be expected to aggregate asymptomatically in sisters of affected probands, who would incur elevated rates of ASD among their offspring. Currently, there exist no data on second-generation recurrence rates among families affected by ASD.

METHODS: We analyzed data from the Swedish National Patient Register and the Multi-Generation Register for a cohort of children born between 2003 and 2012. ASD was ascertained …

Swell1 Regulates Skeletal Muscle Cell Size, Intracellular Signaling, Adiposity And Glucose Metabolism, Ashutosh Kumar, Litao Xie, Chau My Ta, Antentor O Hinton, Susheel K Gunasekar, Rachel A Minerath, Karen Shen, Joshua M Maurer, Chad E Grueter, E Dale Abel, Gretchen Meyer, Rajan Sah

2020-Current year OA Pubs

Maintenance of skeletal muscle is beneficial in obesity and Type 2 diabetes. Mechanical stimulation can regulate skeletal muscle differentiation, growth and metabolism; however, the molecular mechanosensor remains unknown. Here, we show that SWELL1 (

Human Botfly Infestation: Furuncular Myiasis, Rachel Rhee, Christina E. Borchers, Samia Borchers, Gregory Maupin, Jeffery Weinstein

Dermatology Faculty Publications

Dermatobia hominis is one of many species of botflies whose larvae is parasitic to humans and is uniquely indigenous to Central and South America. The larvae of the human botfly gain nutrients to survive by feeding underneath mammal skin. As a consequence, within 24 hours, small 2- 3mm painful, erythematous, draining, and purulent papules with a classical air-pore develop as the initial cutaneous sign. At first, the lesions resemble that of an insect bite, but over time they enlarge to 10-35mm in diameter with a surrounding area of induration. The most common areas where the larvae are cutaneously deposited include …

Aluminum Reproductive Toxicity: A Summary And Interpretation Of Scientific Reports, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Publications addressing aluminum (Al)-induced reproductive toxicity were reviewed. Key details were compiled in summary tables. Approximate systemic Al exposure, a measure of bioavailability, was calculated for each exposure, based on the Al percentage in the dosed Al species, Al bioavailability, and absorption time course reports for the exposure route. This was limited to laboratory animal studies because no controlled-exposure human studies were found. Intended Al exposure was compared to unintended dietary Al exposure. The considerable and variable Al content of laboratory animal diets creates uncertainty about reproductive function in the absence of Al. Aluminum-induced reproductive toxicity in female mice and …

Empirical Fluoroquinolones Versus Broad-Spectrum Beta-Lactams For Gram-Negative Bloodstream Infections In The Absence Of Antimicrobial Resistance Risk Factors, Majdi N. Al-Hasan, Alyssa P. Gould, Chelsea Drennan, Olivia Hill, Julie Ann Justo, Joseph Kohn, P Brandon Bookstaver

Faculty Publications

OBJECTIVES: Increasing antimicrobial resistance rates limit empirical antimicrobial treatment options for Gram-negative bloodstream infections (GN-BSI). However, antimicrobial resistance may be predicted based on patient-specific risk factors using precision medicine concepts. This retrospective, 1:2 matched cohort examined clinical outcomes in hospitalized adults without major risk factors for antimicrobial resistance receiving empirical fluoroquinolones or broad-spectrum beta-lactams (BSBL) for GN-BSI at Prisma Health-Midlands hospitals in Columbia, SC, USA from January 2010 through June 2015. METHODS: Multivariable logistic regression was used to examine early treatment failure at 72-96 h from GN-BSI. Cox proportional hazards regression was used to examine 28-day mortality and hospital length …

Fat And Fat-Free Mass Index References In Children And Young Adults: Assessments Along Racial And Ethnic Lines, Roman J Shypailo, William W Wong

Children’s Nutrition Research Center Staff Publications

Background: Fat-free mass index (FFMI) and fat mass index (FMI) are superior to BMI and fat percentage in evaluating nutritional status. However, existing references fail to account for racial/ethnic differences in body composition among children.

Objectives: Our goal was to produce age-based normative references for FFMI and FMI in children for specific racial/ethnic groups.

Methods: Body composition, weight, and height were measured in 1122 normal healthy children aged 2-21 y. Bone mineral content measured by DXA, total body water by deuterium dilution, and total body potassium by whole-body γ counting were combined to calculate fat-free mass (FFM) and fat mass …

Nine-Year Prospective Efficacy And Safety Of Brain-Responsive Neurostimulation For Focal Epilepsy., Dileep R Nair, Kenneth D Laxer, Peter B Weber, Anthony M Murro, Yong D Park, Gregory L Barkley, Brien J Smith, Ryder P Gwinn, Michael J Doherty, Katherine H Noe, Richard S Zimmerman, Gregory K Bergey, William S Anderson, Christianne Heck, Charles Y Liu, Ricky W Lee, Toni Sadler, Robert B Duckrow, Lawrence J Hirsch, Robert E Wharen, William Tatum, Shraddha Srinivasan, Guy M Mckhann, Mark A Agostini, Andreas V Alexopoulos, Barbara C Jobst, David W Roberts, Vicenta Salanova, Thomas C Witt, Sydney S Cash, Andrew J Cole, Gregory A Worrell, Brian N Lundstrom, Jonathan C Edwards, Jonathan J Halford, David C Spencer, Lia Ernst, Christopher T Skidmore, Michael R Sperling, Ian Miller, Eric B Geller, Michel J Berg, A James Fessler, Paul Rutecki, Alica M Goldman, Eli M Mizrahi, Robert E Gross, Donald C Shields, Theodore H Schwartz, Douglas R Labar, Nathan B Fountain, W Jeff Elias, Piotr W Olejniczak, Nicole R Villemarette-Pittman, Stephan Eisenschenk, Steven N Roper, Jane G Boggs, Tracy A Courtney, Felice T Sun, Cairn G Seale, Kathy L Miller, Tara L Skarpaas, Martha J Morrell, Rns System Ltt Study

Neuroscience Articles

OBJECTIVE: To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years.

METHODS: Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory.

RESULTS: Of 256 patients treated in the initial trials, 230 participated in …

Efficacy Of Hydroxychloroquine And Tocilizumab In Patients With Covid-19: Single-Center Retrospective Chart Review., Sohaib Roomi, Waqas Ullah, Faizan Ahmed, Soban Farooq, Usama Sadiq, Asad Chohan, Munnam Jafar, Maryum Saddique, Shristi Khanal, Robert Watson, Margot Boigon

Abington Jefferson Health Papers

BACKGROUND: During the initial phases of the COVID-19 pandemic, there was an unfounded fervor surrounding the use of hydroxychloroquine (HCQ) and tocilizumab (TCZ); however, evidence on their efficacy and safety have been controversial.

OBJECTIVE: The purpose of this study is to evaluate the overall clinical effectiveness of HCQ and TCZ in patients with COVID-19. We hypothesize that HCQ and TCZ use in these patients will be associated with a reduction in in-hospital mortality, upgrade to intensive medical care, invasive mechanical ventilation, or acute renal failure needing dialysis.

METHODS: A retrospective cohort study was performed to determine the impact of HCQ …

Loss Of Uncoupling Protein 3 Attenuates Western Diet-Induced Obesity, Systemic Inflammation, And Insulin Resistance In Rats, Tyler M Lomax, Sadia Ashraf, Gizem Yilmaz, Romain Harmancey

Faculty, Staff and Student Publications

OBJECTIVE: Uncoupling protein 3 (UCP3) is a mitochondrial carrier related to fatty acid metabolism. Although gene variants of UCP3 are associated with human obesity, their contribution to increased adiposity remains unclear. This study investigated the impact that loss of UCP3 has on diet-induced obesity in rats.

METHODS: Male UCP3 knockout rats (ucp3

RESULTS: Loss of UCP3 decreased fat mass gain, white adipocytes size, and systemic inflammation. The ucp3

CONCLUSIONS: Loss of UCP3 partially protects rats from diet-induced obesity. This phenotype is related to induction of a compensatory antioxidant mechanism and prevention of iBAT whitening.

Combinatorial Pharmacogenomic Testing Improves Outcomes For Older Adults With Depression, Brent P Forester, Charles R Conway, Et Al

2020-Current year OA Pubs

OBJECTIVE: Evaluate the clinical utility of combinatorial pharmacogenomic testing for informing medication selection among older adults who have experienced antidepressant medication failure for major depressive disorder (MDD).

DESIGN: Post hoc analysis of data from a blinded, randomized controlled trial comparing two active treatment arms.

SETTING: Psychiatry specialty and primary care clinics across 60 U.S. community and academic sites.

PARTICIPANTS: Adults age 65 years or older at baseline (n = 206), diagnosed with MDD and inadequate response to at least one medication on the combinatorial pharmacogenomic test report during the current depressive episode.

INTERVENTION: Combinatorial pharmacogenomic testing to inform medication selection …

Reliability And Validity Of The English Version Of The Aospine Prost (Patient Reported Outcome Spine Trauma), Said Sadiqi, Marcel F Dvorak, Alex R. Vaccaro, Gregory D. Schroeder, Marcel W Post, Lorin M Benneker, Frank Kandziora, S Rajasekaran, Klaus J Schnake, Emiliano N Vialle, F Cumhur Oner

Department of Orthopaedic Surgery Faculty Papers

STUDY DESIGN: Multicenter validation study.

OBJECTIVE: The aim of this study was to translate and adapt the AOSpine PROST (Patient Reported Outcome Spine Trauma) into English, and test its psychometric properties among North-American spine trauma patients.

SUMMARY OF BACKGROUND DATA: In the absence of an outcome instrument specifically designed and validated for traumatic spinal column injury patients, it is difficult to measure the effect size of various treatment options. The AOSpine Knowledge Forum Trauma initiated a project and developed the AOSpine PROST consisting of 19 items.

METHODS: Patients were recruited from two level-1 North-American trauma centers. For concurrent validity, next …

The De Winter Ecg Pattern: Distribution And Morphology Of St Depression, Zhong-Qun Zhan, Yang Li, Li-Hong Han, Kjell C Nikus, Yochai Birnbaum, Adrian Baranchuk

Faculty, Staff and Students Publications

BACKGROUND: The reported positive predictive value (PPV) for the "de Winter ECG pattern" to predict an acute left anterior descending artery (LAD) lesion is inconsistent. Besides, the morphology of upsloping or nonupsloping ST depression (STD) may have different significance of severity and prognostication.

METHODS: We searched the MEDLINE database using "de Winter" or "junctional ST-depression with tall symmetrical T-waves" or "tall T wave" or "STEMI equivalent" as the item up to March 2020. We compared the ECG differences between the different culprit arteries and various morphological STD.

RESULTS: A total of 70 patients with analyzable ECGs were included. In 60 …

Nine-Year Prospective Efficacy And Safety Of Brain-Responsive Neurostimulation For Focal Epilepsy, Dileep R Nair, Kenneth D Laxer, Peter B Weber, Anthony M Murro, Yong D Park, Gregory L Barkley, Brien J Smith, Ryder P Gwinn, Michael J Doherty, Katherine H Noe, Richard S Zimmerman, Gregory K Bergey, William S Anderson, Christianne Heck, Charles Y Liu, Ricky W Lee, Toni Sadler, Robert B Duckrow, Lawrence J Hirsch, Robert E Wharen, William Tatum, Shraddha Srinivasan, Guy M Mckhann, Mark A Agostini, Andreas V Alexopoulos, Barbara C Jobst, David W Roberts, Vicenta Salanova, Thomas C Witt, Sydney S Cash, Andrew J Cole, Gregory A Worrell, Brian N Lundstrom, Jonathan C Edwards, Jonathan J Halford, David C Spencer, Lia Ernst, Christopher T Skidmore, Michael R Sperling, Ian Miller, Eric B Geller, Michel J Berg, A James Fessler, Paul Rutecki, Alica M Goldman, Eli M Mizrahi, Robert E Gross, Donald C Shields, Theodore H Schwartz, Douglas R Labar, Nathan B Fountain, W Jeff Elias, Piotr W Olejniczak, Nicole R Villemarette-Pittman, Stephan Eisenschenk, Steven N Roper, Jane G Boggs, Tracy A Courtney, Felice T Sun, Cairn G Seale, Kathy L Miller, Tara L Skarpaas, Martha J Morrell, Rns System Ltt Study

Faculty, Staff and Students Publications

OBJECTIVE: To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years.

METHODS: Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory.

RESULTS: Of 256 patients treated in the initial trials, 230 participated in …

A Germline Variant At 8q24 Contributes To Familial Clustering Of Prostate Cancer In Men Of African Ancestry, Burcu F Darst, Adam S Kibel, Bettina F Drake, Et Al.

2020-Current year OA Pubs

Although men of African ancestry have a high risk of prostate cancer (PCa), no genes or mutations have been identified that contribute to familial clustering of PCa in this population. We investigated whether the African ancestry-specific PCa risk variant at 8q24, rs72725854, is enriched in men with a PCa family history in 9052 cases, 143 cases from high-risk families, and 8595 controls of African ancestry. We found the risk allele to be significantly associated with earlier age at diagnosis, more aggressive disease, and enriched in men with a PCa family history (32% of high-risk familial cases carried the variant vs …

Aadc Deficiency From Infancy To Adulthood: Symptoms And Developmental Outcome In An International Cohort Of 63 Patients, Toni S Pearson, Laura Gilbert, Kathleen D Meeks, Et Al.

2020-Current year OA Pubs

Aromatic l-amino acid decarboxylase deficiency (AADCD) is a rare, autosomal recessive neurodevelopmental disorder characterized by impaired synthesis of dopamine, noradrenaline, adrenaline and serotonin, leading to a complex syndrome of motor, behavioral, and autonomic symptoms. This retrospective study assessed the symptoms and developmental outcome of a large international cohort of patients with AADCD via physician and/or caregiver responses to a detailed, standardized questionnaire. Sixty-three patients (60% female; ages 6 months-36 years, median 7 years; 58 living) from 23 individual countries participated. Common symptoms at onset (median age 3 months, range 0-12 months) were hypotonia, developmental delay, and/or oculogyric crises. Oculogyric crises …

Impact Of Investigational Microbiota Therapeutic Rbx2660 On The Gut Microbiome And Resistome Revealed By A Placebo-Controlled Clinical Trial, Suryang Kwak, Joohee Choi, Tiffany Hink, Kimberly A Reske, Kenneth Blount, Courtney Jones, Margaret H Bost, Xiaoqing Sun, Carey-Ann D Burnham, Erik R Dubberke, Gautam Dantas, Cdc Prevention Epicenter Program

2020-Current year OA Pubs

BACKGROUND: Intestinal microbiota restoration can be achieved by complementing a subject's perturbed microbiota with that of a healthy donor. Recurrent Clostridioides difficile infection (rCDI) is one key application of such treatment. Another emerging application of interest is reducing antibiotic-resistant genes (ARGs) and organisms (AROs). In this study, we investigated fecal specimens from a multicenter, randomized, double-blind, placebo-controlled phase 2b study of microbiota-based investigational drug RBX2660. Patients were administered either placebo, 1 dose of RBX2660 and 1 placebo, or 2 doses of RBX2660 via enema and longitudinally tracked for changes in their microbiome and antibiotic resistome.

RESULTS: All patients exhibited significant …

Regional Correlation Of Biochemical Measures Of Amyloid And Tau Phosphorylation In The Brain, Kanta Horie, Nicolas R Barthélemy, Nipun Mallipeddi, Yan Li, Erin E Franklin, Richard J Perrin, Randall J Bateman, Chihiro Sato

2020-Current year OA Pubs

Alzheimer's disease (AD) neuropathologic change is characterized by amyloid plaques and neurofibrillary tangles (NFTs) that consist of aggregated amyloid beta (Abeta) and hyperphosphorylated tau proteins (p-tau), respectively. Although the global relationship between Abeta and p-tau has been studied for decades, it is still unclear whether a regional correlation exists between Abeta and p-tau in the human brain. Recent studies in cerebrospinal fluid (CSF) have suggested that tau phosphorylation at specific sites such as T217 is modified at an early stage of AD when amyloid plaques become detectable. We applied biochemical and mass spectrometry methods in human brain samples with and …

Removal Of High Frequency Contamination From Motion Estimates In Single-Band Fmri Saves Data Without Biasing Functional Connectivity, Caterina Gratton, Ally Dworetsky, Rebecca S Coalson, Babatunde Adeyemo, Timothy O Laumann, Deanna M Barch, Nico U F Dosenbach, Abraham Z Snyder, Joel S Perlmutter, Steven E Petersen, Meghan C Campbell, Et Al.

2020-Current year OA Pubs

Denoising fMRI data requires assessment of frame-to-frame head motion and removal of the biases motion introduces. This is usually done through analysis of the parameters calculated during retrospective head motion correction (i.e., 'motion' parameters). However, it is increasingly recognized that respiration introduces factitious head motion via perturbations of the main (B0) field. This effect appears as higher-frequency fluctuations in the motion parameters (>0.1 ​Hz, here referred to as 'HF-motion'), primarily in the phase-encoding direction. This periodicity can sometimes be obscured in standard single-band fMRI (TR 2.0-2.5 ​s) due to aliasing. Here we examined (1) how prevalent HF-motion effects are …

The Effect Of Neighborhood Social Environment On Prostate Cancer Development In Black And White Men At High Risk For Prostate Cancer, Shannon M Lynch, Elizabeth Handorf, Kristen A Sorice, Elizabeth Blackman, Lisa Bealin, Veda N. Giri, Elias Obeid, Camille Ragin, Mary Daly

Department of Medical Oncology Faculty Papers

INTRODUCTION: Neighborhood socioeconomic (nSES) factors have been implicated in prostate cancer (PCa) disparities. In line with the Precision Medicine Initiative that suggests clinical and socioenvironmental factors can impact PCa outcomes, we determined whether nSES variables are associated with time to PCa diagnosis and could inform PCa clinical risk assessment.

MATERIALS AND METHODS: The study sample included 358 high risk men (PCa family history and/or Black race), aged 35-69 years, enrolled in an early detection program. Patient variables were linked to 78 nSES variables (employment, income, etc.) from previous literature via geocoding. Patient-level models, including baseline age, prostate specific antigen (PSA), …

Atypical Reactivation Of Varicella Zoster Virus Associated With Pancreatitis In A Heart Transplant Patient., Christine Shieh, Ashley Barnes, Drew Johnson, Ilya Danelich, Pharmd, Bcps, Bccp, Preethi Pirlamarla, Rene Alvarez, H. Todd Massey, Md, Mahek Shah

Division of Internal Medicine Faculty Papers & Presentations

BACKGROUND Acute pancreatitis is rare following solid organ transplantation but is associated with high mortality. It has been most commonly reported following renal transplant but can occur with other solid organ transplantations. CASE REPORT A 46-year-old male who had an orthotopic heart transplant 6 months ago presented with a 3-week history of abdominal pain. The patient described it as intermittent, sharp, and stabbing, originating in the periumbilical area and radiating to the back. His lipase was elevated at 232 U/L. Given that the patient's symptoms and lipase were elevated to greater than three times the upper limit of normal, he …

Oral Cancer: Clinicopathological Features And Associated Risk Factors In A High Risk Population Presenting To A Major Tertiary Care Center In Pakistan, Namrah Anwar, Shahid Pervez, Qurratulain Chundriger, Mohammad Sohail Awan, Tariq Moatter, Tazeen Saeed Ali

Department of Pathology and Laboratory Medicine

Oral squamous cell carcinoma (OSCC) has the highest prevalence in head and neck cancers and is the first and second most common cancer in males and females of Pakistan respectively. Major risk factors include peculiar chewing habits like areca nut, betel quid, and tobacco. The majority of OSCC presents at an advanced stage with poor prognosis. On the face of such a high burden of this preventable cancer, there is a relative lack of recent robust data and its association with known risk factors from Pakistan. The aim of this study was to identify the socioeconomic factors and clinicopathological features …

De Novo And Bi-Allelic Pathogenic Variants In Nars1 Cause Neurodevelopmental Delay Due To Toxic Gain-Of-Function And Partial Loss-Of-Function Effects, Andreea Manole, Marwan Shinawi, Marisa V. Andrews, Dustin Baldridge, John F. Mantovani, Et Al.

2020-Current year OA Pubs

Aminoacyl-tRNA synthetases (ARSs) are ubiquitous, ancient enzymes that charge amino acids to cognate tRNA molecules, the essential first step of protein translation. Here, we describe 32 individuals from 21 families, presenting with microcephaly, neurodevelopmental delay, seizures, peripheral neuropathy, and ataxia, with de novo heterozygous and bi-allelic mutations in asparaginyl-tRNA synthetase (NARS1). We demonstrate a reduction in NARS1 mRNA expression as well as in NARS1 enzyme levels and activity in both individual fibroblasts and induced neural progenitor cells (iNPCs). Molecular modeling of the recessive c.1633C>T (p.Arg545Cys) variant shows weaker spatial positioning and tRNA selectivity. We conclude that de novo and …

Medium-Term Complications Associated With Coronary Artery Aneurysms After Kawasaki Disease: A Study From The International Kawasaki Disease Registry., Brian W Mccrindle, Cedric Manlhiot, Jane W Newburger, Ashraf S Harahsheh, Therese M Giglia, Frederic Dallaire, Kevin Friedman, Tisiana Low, Kyle Runeckles, Mathew Mathew, Andrew S Mackie, Nadine F Choueiter, Pei-Ni Jone, Shelby Kutty, Anji T Yetman, Geetha Raghuveer, Elfriede Pahl, Kambiz Norozi, Kimberly E Mchugh, Jennifer S Li, Sarah D De Ferranti, Nagib Dahdah

Paediatrics Publications

Background Coronary artery aneurysms (CAAs) may occur after Kawasaki disease (KD) and lead to important morbidity and mortality. As CAA in patients with KD are rare and heterogeneous lesions, prognostication and risk stratification are difficult. We sought to derive the cumulative risk and associated factors for cardiovascular complications in patients with CAAs after KD. Methods and Results A 34-institution international registry of 1651 patients with KD who had CAAs (maximum CAA

The Landscape Of Rna Polymerase Ii-Associated Chromatin Interactions In Prostate Cancer, Susmita G Ramanand, Yong Chen, Jiapei Yuan, Kelly Daescu, Maryou Bk Lambros, Kathleen E Houlahan, Suzanne Carreira, Wei Yuan, Guemhee Baek, Adam Sharp, Alec Paschalis, Mohammed Kanchwala, Yunpeng Gao, Adam Aslam, Nida Safdar, Xiaowei Zhan, Ganesh V Raj, Chao Xing, Paul C Boutros, Johann De Bono, Michael Q Zhang, Ram S Mani

College of Science & Mathematics Departmental Research

Transcriptional dysregulation is a hallmark of prostate cancer (PCa). We mapped the RNA polymerase II-associated (RNA Pol II-associated) chromatin interactions in normal prostate cells and PCa cells. We discovered thousands of enhancer-promoter, enhancer-enhancer, as well as promoter-promoter chromatin interactions. These transcriptional hubs operate within the framework set by structural proteins - CTCF and cohesins - and are regulated by the cooperative action of master transcription factors, such as the androgen receptor (AR) and FOXA1. By combining analyses from metastatic castration-resistant PCa (mCRPC) specimens, we show that AR locus amplification contributes to the transcriptional upregulation of the AR gene by increasing …

Risk Of New Bloodstream Infections And Mortality Among People Who Inject Drugs With Infective Endocarditis., Charlie Tan, Esfandiar Shojaei, Joshua C. Wiener, Meera Shah, Sharon Koivu, Michael Silverman

Epidemiology and Biostatistics Publications

IMPORTANCE: People who inject drugs (PWID) who are being treated for infective endocarditis remain at risk of new bloodstream infections (BSIs) due to ongoing intravenous drug use (IVDU).

OBJECTIVES: To characterize new BSIs in PWID receiving treatment for infective endocarditis, to determine the clinical factors associated with their development, and to determine whether new BSIs and treatment setting are associated with mortality.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was performed at 3 tertiary care hospitals in London, Ontario, Canada, from April 1, 2007, to March 31, 2018. Participants included a consecutive sample of all PWID 18 years or …

Maternal Obesity Reduces Placental Autophagy Marker Expression In Uncomplicated Pregnancies, Matthew Cohen, Emily Guo, Aidan Pucchio, Barbra De Vrijer, Trevor G Shepherd, Genevieve Eastabrook

Obstetrics & Gynaecology Publications

AIM: Obesity has been associated with changes in autophagy and its increasing prevalence among pregnant women is implicated in higher rates of placental-mediated complications of pregnancy such as pre-eclampsia and intrauterine growth restriction. Autophagy is involved in normal placentation, thus changes in autophagy may lead to impaired placental function and development. The aim of this study was to investigate the connection between obesity and autophagy in the placenta in otherwise uncomplicated pregnancies.

METHODS: Immunohistochemistry and western blot analysis were done on placental and omental samples from obese (body mass index [BMI] ≥30 kg/m

RESULTS: As pre-pregnancy BMI increased, there was …

Atrial Pacing In Wide-Complex Rhythm, Yang Yang, John Allison, Mark Pollet, Yochai Birnbaum

The Texas Heart Institute Journal

No abstract provided.

Profound And Redundant Functions Of Arcuate Neurons In Obesity Development, Canjun Zhu, Zhiying Jiang, Yuanzhong Xu, Zhao-Lin Cai, Qingyan Jiang, Yong Xu, Mingshan Xue, Benjamin R Arenkiel, Qi Wu, Gang Shu, Qingchun Tong

Children’s Nutrition Research Center Staff Publications

The current obesity epidemic faces a lack of mechanistic insights. It is known that the acute activity changes of a growing number of brain neurons rapidly alter feeding behaviour; however, how these changes translate to obesity development and the fundamental mechanism underlying brain neurons in controlling body weight remain elusive. Here, we show that chronic activation of hypothalamic arcuate GABAergic (GABA