Medicine and Health Sciences Commons^™

Therapeutics Development For Pseudoxanthoma Elasticum And Related Ectopic Mineralization Disorders: Update 2020., Hongbin Luo, Qiaoli Li, Yi Cao, Jouni Uitto

Department of Dermatology and Cutaneous Biology Faculty Papers

Pseudoxanthoma elasticum (PXE), the prototype of heritable ectopic mineralization disorders, manifests with deposition of calcium hydroxyapatite crystals in the skin, eyes and arterial blood vessels. This autosomal recessive disorder, due to mutations in ABCC6, is usually diagnosed around the second decade of life. In the spectrum of heritable ectopic mineralization disorders are also generalized arterial calcification of infancy (GACI), with extremely severe arterial calcification diagnosed by prenatal ultrasound or perinatally, and arterial calcification due to CD73 deficiency (ACDC) manifesting with arterial and juxta-articular mineralization in the elderly; the latter disorders are caused by mutations in ENPP1 and NT5E, respectively. The …

Use Of A Cancer Registry To Evaluate Patient-Reported Outcomes Of Immune Checkpoint Inhibitors., Heather S L Jim, Sarah L Eisel, Aasha I Hoogland, Sandra Shaw, Jennifer C King, Adam P Dicker

Department of Radiation Oncology Faculty Papers

Immune checkpoint inhibitors (ICIs) are increasingly used for advanced lung cancer, butfew studies have reported on patient-reported outcomes (PROs) outside the context of a clinicaltrial. The goal of the current study was to assess PROs in participants of a lung cancer registry whohad been treated with an ICI. Patients participating in the GO2Foundation’s Lung Cancer Registrywho reported receiving atezolizumab, durvalumab, nivolumab, or pembrolizumab were invited toparticipate in a survey about their experiences during treatment. Quality of life was evaluated usingthe Functional Assessment of Cancer Therapy–General (FACT-G). Common symptomatic adverseevents were evaluated using an item bank generated for ICIs. Internationally, 226 …

Epidemiology Of Non-Alcoholic Fatty Liver Disease And Risk Of Hepatocellular Carcinoma Progression, Krishna Chaitanya Thandra, Adam Barsouk, Kalyan Saginala, John Sukumar Aluru, Prashanth Rawla, Alexander Barsouk

Kimmel Cancer Center Faculty Papers

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. Its incidence has grown alongside the increasing global prevalence of type 2 diabetes, obesity, and metabolic syndrome. The risk of progression to hepatocellular carcinoma for nonalcoholic steatohepatitis patients over 5 years is 8%, and despite targeted and immunotherapy treatment advances, HCC maintains a bleak 5-year survival of 19%. NAFLD’s primary risk factors are components of metabolic syndrome as well as possible sleep disturbances. NAFLD is most common among men 50-60 years of age, though incidence in women catches up after menopause. In the US, Hispanics are …

Modulation Of Aub-Tdrd Interactions Elucidates Pirna Amplification And Germplasm Formation., Nicholas Vrettos, Manolis Maragkakis, Panagiotis Alexiou, Paraskevi Sgourdou, Fadia Ibrahim, Daniel Palmieri, Yohei Kirino, Phd, Zissimos Mourelatos

Computational Medicine Center Faculty Papers

Aub guided by piRNAs ensures genome integrity by cleaving retrotransposons, and genome propagation by trapping mRNAs to form the germplasm that instructs germ cell formation. Arginines at the N-terminus of Aub (Aub-NTRs) interact with Tudor and other Tudor domain-containing proteins (TDRDs). Aub-TDRD interactions suppress active retrotransposons via piRNA amplification and form germplasm via generation of Aub-Tudor ribonucleoproteins. Here, we show that Aub-NTRs are dispensable for primary piRNA biogenesis but essential for piRNA amplification and that their symmetric dimethylation is required for germplasm formation and germ cell specification but largely redundant for piRNA amplification.

Return-To-Play And Competitive Outcomes After Ulnar Collateral Ligament Reconstruction Among Baseball Players: A Systematic Review, Stephen J. Thomas, Ryan W. Paul, Adam B. Rosen, Sam J. Wilkins, Joseph Scheidt, John D. Kelly Iv, Ryan L. Crotin

Department of Exercise Science Faculty Papers

Background: Ulnar collateral ligament (UCL) reconstruction (UCLR) is very common in baseball. However, no review has compared the return-to-play (RTP) and in-game performance statistics of pitchers after primary and revision UCLR as well as of position players after UCLR.

Purpose: To review, synthesize, and evaluate the published literature on outcomes after UCLR in baseball players to determine RTP and competitive outcomes among various populations of baseball players.

Study Design: Systematic review; Level of evidence, 4.

Methods: A literature search including studies between 1980 and November 4, 2019, was conducted for articles that included the following terms: ulnar collateral ligament, elbow, …

Adrenal Ectopy And Lipoma Of An Inguinal Hernia Sac: A Case Report & Literature Review., Jenna R Adalbert, Rafael E Pajaro

Student Papers, Posters & Projects

INTRODUCTION & IMPORTANCE: Ectopic adrenocortical tissue is the presence of accessory adrenal cortex tissue located outside of the adrenal glands. It is a rare, incidental finding during inguinal hernia repair. This case report aims to discuss the anatomy and important patient implications related to this finding.

CASE PRESENTATION: A 61-year-old male presented with a long-standing right direct inguinal hernia increasing in size and pain frequency. During open right anterior inguinal hernia repair, a lipoma was identified inside the hernia sac and removed. Further histopathological examination of the specimen revealed the presence of adrenocortical tissue inside the lipoma. No further interventions …

Electrophysiological Properties Of The Mitochondrial Permeability Transition Pores: Channel Diversity And Disease Implication., M. A. Neginskaya, E. V. Pavlov, S.-S. Sheu

Center for Translational Medicine Faculty Papers

The mitochondrial permeability transition pore (mPTP) is a channel that, when open, is responsible for a dramatic increase in the permeability of the mitochondrial inner membrane, a process known as the mitochondrial permeability transition (mPT). mPTP activation during Ca2+ dyshomeostasis and oxidative stress disrupts normal mitochondrial function and induces cell death. mPTP opening has been implicated as a critical event in many diseases, including hypoxic injuries, neurodegeneration, and diabetes. Discoveries of recent years indicate that mPTP demonstrates very complicated behavior and regulation, and depending on specific induction or stress conditions, it can function as a high-conductance pore, a small channel, …

Short-Term Outcomes Of Lower Trapezius Tendon Transfer With Achilles Allograft For Irreparable Posterosuperior Rotator Cuff Tears., Michael A. Stone, Liam T. Kane, Jason C. Ho, Surena Namdari

Rothman Institute Faculty Papers

Purpose: To evaluate functional outcomes, return to work, and reoperations associated with lower trapezius tendon transfer (LTT) for irreparable rotator cuff tears.

Methods: This is a retrospective study performed by a single surgeon with minimum 1-year follow-up. LTT was performed using an open (n = 9; 60%) or arthroscopically assisted (n = 6, 40%) technique. Outcomes included failure rate, range of motion, satisfaction, return to work, and pre- and postoperative functional scores, as well as American Shoulder and Elbow Surgeons score, Single Assessment Numeric Evaluation, and the Simple Shoulder Test.

Results: Fifteen patients were included. LTT was performed using an …

Gunshot-Related Pediatric Left Ventricular Apical Aneurysm, Achala Donuru, David Saul, Maansi Parekh, Maruti Kumaran, Vinay Kandula, Rami Kharouf

Department of Radiology Faculty Papers

Penetrating injuries of the thorax and abdomen, such as gunshot and stabbing, are rare in children. We present the case of a pediatric patient with a history of remote gunshot injury presenting with a late aneurysm in the left ventricle.

The Er Stress/Upr Axis In Chronic Obstructive Pulmonary Disease And Idiopathic Pulmonary Fibrosis., Mahmoud Aghaei, Sanaz Dastghaib, Sajjad Aftabi, Mohamad-Reza Aghanoori, Javad Alizadeh, Pooneh Mokarram, Parvaneh Mehrbod, Milad Ashrafizadeh, Ali Zarrabi, Kielan Darcy Mcalinden, Mathew Suji Eapen, Sukhwinder Singh Sohal, Pawan Sharma, Amir A Zeki, Saeid Ghavami

Center for Translational Medicine Faculty Papers

Cellular protein homeostasis in the lungs is constantly disrupted by recurrent exposure to various external and internal stressors, which may cause considerable protein secretion pressure on the endoplasmic reticulum (ER), resulting in the survival and differentiation of these cell types to meet the increased functional demands. Cells are able to induce a highly conserved adaptive mechanism, known as the unfolded protein response (UPR), to manage such stresses. UPR dysregulation and ER stress are involved in numerous human illnesses, such as metabolic syndrome, fibrotic diseases, and neurodegeneration, and cancer. Therefore, effective and specific compounds targeting the UPR pathway are being considered …

Upfront Treatment Of Flt3-Mutated Aml: A Look Back At The Ratify Trial And Beyond., Gina Keiffer, Kimberly L Aderhold, Neil D Palmisiano

Department of Medical Oncology Faculty Papers

In April 2017, following the results of the RATIFY trial (1), midostaurin, a multikinase FLT3 inhibitor, became the first FDA approved targeted agent for the treatment of acute myeloid leukemia (AML) (2). The addition of midostaurin to standard induction therapy with anthracycline and cytarabine (7 + 3) rapidly became the new standard of care for treatment-naïve, fit patients with FLT3-mutated (FLTmut+) AML (3). More recently, gilteritinib, a selective FLT3 inhibitor, showed superiority to chemotherapy in the treatment of relapsed or refractory FLTmut+ AML (4). With two FLT3 inhibitors now approved by the FDA—that is, the more selective gilteritinib and the …

Radiology In The Era Of Value-Based Healthcare: A Multi-Society Expert Statement From The Acr, Car, Esr, Is3r, Ranzcr, And Rsna., Adrian P Brady, Jaqueline A Bello, Lorenzo E Derchi, Michael Fuchsjäger, Stacy Goergen, Gabriel P Krestin, Emil J Y Lee, David C Levin, Josephine Pressacco, Vijay M Rao, John Slavotinek, Jacob J Visser, Richard E A Walker, James A Brink

Department of Radiology Faculty Papers

Background: The Value-Based Healthcare (VBH) concept is designed to improve individual healthcare outcomes without increasing expenditure, and is increasingly being used to determine resourcing of and reimbursement for medical services. Radiology is a major contributor to patient and societal healthcare at many levels. Despite this, some VBH models do not acknowledge radiology’s central role; this may have future negative consequences for resource allocation.

Methods, fndings and interpretation: This multi-society paper, representing the views of Radiology Societies in Europe, the USA, Canada, Australia, and New Zealand, describes the place of radiology in VBH models and the healthcare value contributions of radiology. …

Salinomycin Inhibits Proliferative Vitreoretinopathy Formation In A Mouse Model., Alison M. Heffer, Victor Wang, Richard T. Libby, Steven E. Feldon, Collynn F. Woeller, Ajay E. Kuriyan

Wills Eye Hospital Papers

Proliferative vitreoretinopathy (PVR) is a progressive disease that develops in a subset of patients who undergo surgery for retinal detachment repair, and results in significant vision loss. PVR is characterized by the migration of retinal pigment epithelial (RPE) cells into the vitreous cavity, where they undergo epithelial-to-mesenchymal transition and form contractile membranes within the vitreous and along the retina, resulting in recurrent retinal detachments. Currently, surgical intervention is the only treatment for PVR and there are no pharmacological agents that effectively inhibit or prevent PVR formation. Here, we show that a single intravitreal injection of the polyether ionophore salinomycin (SNC) …

A Comparison Of Standardized Letters Of Evaluation For Emergency Medicine Residency Applicants., David Wilson, Chaiya Laoteppitaks, Shruti Chandra

Department of Emergency Medicine Faculty Papers

INTRODUCTION: Medical students pursuing an emergency medicine (EM) residency are advised to obtain at least two Standardized Letters of Evaluation (SLOE). Students often complete one rotation at their home institution and at least one "away" rotation at a program separate from their home institution. The SLOE was introduced as an objective evaluation tool. The aim of this study was to determine whether there was a difference in scores between home rotation and away rotation SLOEs.

METHODS: We retrospectively reviewed the SLOEs of all applicants to an urban, academic EM residency program. For each SLOE, we calculated a composite score from …

Outcomes Of Chronic Distal Biceps Reconstruction With Tendon Grafting: A Matched Comparison With Primary Repair., Benjamin A. Hendy, Eric M. Padegimas, Thomas Harper, Mark D Lazarus, Joseph A Abboud, Surena Namdari, John Horneff Iii, Md

Rothman Institute Faculty Papers

Background: The purpose of this analysis was to analyze outcomes of distal biceps reconstruction with soft tissue allograft in the setting of chronic, irreparable distal biceps ruptures. The outcomes of these cases were then compared with a matched cohort of distal biceps ruptures that were able to be repaired primarily.

Methods: Retrospective review of an institutional elbow surgery database was conducted. All cases of distal biceps repairs were identified by Common Procedural Terminology, ICD-9, and ICD-10 codes from January 2009 to March 2018. A direct review of operative reports was then conducted to identify which cases required allograft reconstruction. After …

Infection-Induced 5'-Half Molecules Of Trnahisgug Activate Toll-Like Receptor 7., Kamlesh Pawar, Megumi Shigematsu, Soroush Sharbati, Yohei Kirino

Computational Medicine Center Faculty Papers

Toll-like receptors (TLRs) play a crucial role in the innate immune response. Although endosomal TLR7 recognizes single-stranded RNAs, their endogenous RNA ligands have not been fully explored. Here, we report 5'-tRNA half molecules as abundant activators of TLR7. Mycobacterial infection and accompanying surface TLR activation up-regulate the expression of 5'-tRNA half molecules in human monocyte-derived macrophages (HMDMs). The abundant accumulation of 5'-tRNA halves also occur in HMDM-secreted extracellular vehicles (EVs); the abundance of EV-5'-tRNAHisGUG half molecules is >200-fold higher than that of the most abundant EV-microRNA (miRNA). Sequence identification of the 5'-tRNA halves using cP-RNA-seq revealed abundant and selective packaging …

Local Injections Of Β-Ngf Accelerates Endochondral Fracture Repair By Promoting Cartilage To Bone Conversion., Kevin O. Rivera, Fabrizio Russo, Ryan M. Boileau, Ryan E. Tomlinson, Theodore Miclau, Ralph S. Marcucio, Tejal A. Desai, Chelsea S. Bahney

Department of Orthopaedic Surgery Faculty Papers

There are currently no pharmacological approaches in fracture healing designed to therapeutically stimulate endochondral ossification. In this study, we test nerve growth factor (NGF) as an understudied therapeutic for fracture repair. We first characterized endogenous expression of Ngf and its receptor tropomyosin receptor kinase A (TrkA) during tibial fracture repair, finding that they peak during the cartilaginous phase. We then tested two injection regimens and found that local β-NGF injections during the endochondral/cartilaginous phase promoted osteogenic marker expression. Gene expression data from β-NGF stimulated cartilage callus explants show a promotion in markers associated with endochondral ossification such as Ihh, Alpl, …

Needs Of Individuals Living With Hepatitis Delta Virus And Their Caregivers, 2016-2019., Priyanka Kumar, Catherine Freeland, Sierra Bodor, Sean Farrell, Chari Cohen, Rosemary Frasso Phd, Msc, Cph

Department of Medicine Faculty Papers

INTRODUCTION: Hepatitis delta virus (HDV) is a serious coinfection of the hepatitis B virus (HBV) that is estimated to affect between 48 to 72 million people worldwide. Data are limited on the informational needs of people living with HDV. The Hepatitis B Foundation, a US-based nonprofit organization that provides support to people living with HBV and HDV, receives emails (queries) as part of a helpline, a service to provide information, resources, and support to people affected by HBV and HDV.

METHODS: Query content was analyzed to assess the impact of HDV at the individual level. A total of 65 HDV-related …

Us-Triggered Microbubble Destruction For Augmenting Hepatocellular Carcinoma Response To Transarterial Radioembolization: A Randomized Pilot Clinical Trial., John R Eisenbrey, Flemming Forsberg, Corinne E Wessner, Lauren J Delaney, Kristen Bradigan, Sriharsha Gummadi, Mohamed Tantawi, Andrej Lyshchik, Patrick O'Kane, Ji-Bin Liu, Charles Intenzo, Jesse Civan, Warren Maley, Scott W Keith, Kevin Anton, Allison Tan, Amanda Smolock, Susan Shamimi-Noori, Colette M Shaw

Department of Radiology Faculty Papers

Combined US-triggered microbubble destruction and hepatocellular carcinoma radioembolization showed improved treatment response compared with radioembolization alone and no changes in vital signs or liver function.

Background US contrast agents are gas-filled microbubbles (MBs) that can be locally destroyed by using external US. Among other bioeffects, US-triggered MB destruction, also known as UTMD, has been shown to sensitize solid tumors to radiation in preclinical models through localized insult to the vascular endothelial cells.

Purpose: To evaluate the safety and preliminary efficacy of combining US-triggered MB destruction and transarterial radioembolization (TARE) in participants with hepatocellular carcinoma (HCC).

Materials and Methods: In this …

Return-To-Play Guidelines After Patellar Instability Surgery Requiring Bony Realignment: A Systematic Review., Rishi Chatterji, Alex E. White, Christopher J. Hadley, Steven B. Cohen, Kevin B. Freedman, Christopher C. Dodson

Rothman Institute Faculty Papers

Background: Recurrent patellar instability can be treated nonoperatively or surgically, and surgical management may vary based on the causative pathology in the structures surrounding the patella. Although isolated soft tissue reconstruction is among the most common operative treatments, certain patient populations require bony realignment for adequate stabilization.

Purpose: To evaluate postoperative guidelines, including return to play and rehabilitation, after bony procedures involving the tibial tubercle for patellar instability.

Study Design: Systematic review; Level of evidence, 4.

Methods: A systematic review on return-to-play guidelines was conducted with studies published from 1997 to 2019 that detailed procedures involving bony realignment by tibial …

Uncalibrated Chronotypes: Circadian Clocks In The Wake Of Covid-19, Nicolas Nelson, Zachary Highley-Gergel, Nicole Simone, Nikolaos Mouchtouris, Adam Dicker

Phase 1

Background: All life is attuned to Earth’s light–dark cycle. In humans, the hypothalamus calibrates the body to circadian cycles of homeostatic activity. The mechanism responsible may run shorter or longer than 24 hours, which is thought to be the basis of chronotype—an intrinsic preference for mornings or evenings. Circadian rhythms can be recalibrated by environmental cues (lighting, temperature, mealtimes) to keep the body aligned with societal time; however, chronic disruptions produce a range of adverse cognitive effects. Early COVID-19 stay-at-home conditions were unique for students because their cues no longer adhered to strict scheduling. Our objective was to determine how …

Mir15a/Mir16-1 Cluster And Its Novel Targeting Molecules Negatively Regulate Cardiac Hypertrophy., Hongchang Guo, Ke Ma, Wenjing Hao, Yao Jiao, Ping Li, Jing Chen, Chen Xu, Fu-Jian Xu, Wayne Bond Lau, Jie Du, Xin-Liang Ma, Yulin Li

Department of Emergency Medicine Faculty Papers

In response to pathological stimuli, the heart develops ventricular hypertrophy that progressively decompensates and leads to heart failure. miRNAs are increasingly recognized as pathogenic factors, clinically relevant biomarkers, and potential therapeutic targets. We identified that mir15a/mir16-1 cluster was negatively correlated with hypertrophic severity in patients with hypertrophic cardiomyopathy. The mir15a/mir16-1 expression was enriched in cardiomyocytes (CMs), decreased in hypertrophic human hearts, and decreased in mouse hearts after transverse aortic constriction (TAC). CM-specific mir15a/mir16-1 knockout promoted cardiac hypertrophy and dysfunction after TAC. CCAAT/enhancer binding protein (C/EBP)β was responsible for the downregulation of mir15a/mir16-1 cluster transcription. Mechanistically, mir15a/mir16-1 cluster attenuated the insulin/IGF1 …

Pd1 Inhibitor Induced Inverse Lichenoid Eruption: A Case Series, Mansha Sethi, Vaibhav Garg, Jason Lee, Sherry Yang

Department of Dermatology and Cutaneous Biology Faculty Papers

The increased use of monoclonal antibodies that target the immune checkpoint T cell receptor programmed death-1 (PD1) to treat numerous solid tumors has led to several reports describing associated cutaneous adverse events. Although lichenoid reactions have been well described, we propose that PD1 inhibitor-induced inverse lichenoid eruption (PILE) is a distinct variant. We describe two patients who presented with nearly identical deeply erythematous, malodorous, eroded anogenital plaques with focal crusting. Diagnosis of PILE was established given the biopsy findings and temporal association with PD1 inhibitor therapy. Treatment with clobetasol ointment was successful without necessitating discontinuation of immunotherapy. The findings were …

Ensuring Racial Equity In Midwifery Education Programs: Beginning Steps For Midwifery Education., Ronnie Lichtman, Jennifer Woo, Pamela Reis, Carrie S. Klima, Dana Perlman

College of Health Professions Faculty Papers

No abstract provided.

Association Between Vitamin D Supplementation And Mortality In Critically Ill Patients: A Systematic Review And Meta-Analysis Of Randomized Clinical Trials., Liyuan Peng, Linjie Li, Peng Wang, Weelic Chong, Yin Li, Xi Zha, Haidong Deng, Huaqian Fan, Yu Zhang

Student Papers, Posters & Projects

BACKGROUND: Observational studies suggest that low 25-hydroxyvitamin D status is common and has been associated with higher mortality in critically ill patients. This study aim to investigate whether vitamin D supplementation is associated with lower mortality in critically ill patients.

METHOD: We searched Medline, Embase, and Cochrane databases from inception to January 12, 2020, without language restrictions, for randomized controlled trials comparing the effect of vitamin D supplementation with placebo in critically ill patients. Two authors independently performed data extraction and assessed study quality. The primary outcome was all-cause mortality at the longest follow-up.

RESULT: We identified nine trials with …

Contrast-Enhanced Ultrasound In Association With Serum Biomarkers For Differentiating Combined Hepatocellular-Cholangiocarcinoma From Hepatocellular Carcinoma And Intrahepatic Cholangiocarcinoma., Jie Yang, Ya-Han Zhang, Jia-Wu Li, Ying-Yu Shi, Jia-Yan Huang, Yan Luo, Ji-Bin Liu, Qiang Lu

Department of Radiology Faculty Papers

BACKGROUND: Combined hepatocellular-cholangiocarcinoma (CHC) is a rare type of primary liver cancer. Due to its complex histopathological characteristics, the imaging features of CHC can overlap with those of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).

AIM: To investigate the possibility and efficacy of differentiating CHC from HCC and ICC by using contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) and tumor biomarkers.

METHODS: Between January 2016 and December 2019, patients with histologically confirmed CHC, ICC and HCC with chronic liver disease were enrolled. The diagnostic formula for CHC was as follows: (1) LR-5 or LR-M with elevated alpha-fetoprotein …

Arrhythmogenic Right Ventricular Cardiomyopathy In Patients With Biallelic Jup-Associated Skin Fragility., Hassan Vahidnezhad, Leila Youssefian, Masoomeh Faghankhani, Nikoo Mozafari, Amir Hossein Saeidian, Fatemeh Niaziorimi, Fahimeh Abdollahimajd, Soheila Sotoudeh, Fateme Rajabi, Liaosadat Mirsafaei, Zahra Alizadeh Sani, Lu Liu, Alyson Guy, Sirous Zeinali, Ariana Kariminejad, Reginald T. Ho, John A Mcgrath, Jouni Uitto

Department of Dermatology and Cutaneous Biology Faculty Papers

Arrhythmogenic right ventricular cardiomyopathy (ARVC), with skin manifestations, has been associated with mutations in JUP encoding plakoglobin. Genotype-phenotype correlations regarding the penetrance of cardiac involvement, and age of onset have not been well established. We examined a cohort of 362 families with skin fragility to screen for genetic mutations with next-generation sequencing-based methods. In two unrelated families, a previously unreported biallelic mutation, JUP: c.201delC; p.Ser68Alafs*92, was disclosed. The consequences of this mutation were determined by expression profiling both at tissue and ultrastructural levels, and the patients were evaluated by cardiac and cutaneous work-up. Whole-transcriptome sequencing by RNA-Seq revealed JUP as …

Plasma Inorganic Pyrophosphate Deficiency Links Multiparity To Cardiovascular Disease Risk., Almudena Veiga-Lopez, Visalakshi Sethuraman, Nastassia Navasiolava, Barbara Makela, Isoken Olomu, Robert Long, Koen Van De Wetering, Ludovic Martin, Tamas Aranyi, Flóra Szeri

Department of Dermatology and Cutaneous Biology Faculty Papers

Epidemiological studies indicate that elevated alkaline phosphatase activity is associated with increased cardiovascular disease risk. Other epidemiological data demonstrate that mothers giving multiple childbirths (multipara) are also at increased risk of developing late-onset cardiovascular disease. We hypothesized that these two associations stem from a common cause, the insufficient plasma level of the ectopic mineralization inhibitor inorganic pyrophosphate, which is a substrate of alkaline phosphatase. As alkaline phosphatase activity is elevated in pregnancy, we hypothesized that pyrophosphate concentrations decrease gestationally, potentially leading to increased maternal vascular calcification and cardiovascular disease risk in multipara. We investigated plasma pyrophosphate kinetics pre- and postpartum …

Purification And Use Of Trna For Enzymatic Post-Translational Addition Of Amino Acids To Proteins., Irem Avcilar-Kucukgoze, Howard Gamper, Ya-Ming Hou, Anna Kashina

Department of Biochemistry and Molecular Biology Faculty Papers

Post-translational addition of amino acids to proteins by enzymes using aminoacyl-tRNA is an emerging regulatory mechanism. Examples include Arg transfer in eukaryotes, Leu/Phe transfer in bacteria, and tRNA-synthetase-mediated addition of amino acids to Lys side chains. Here, we present a method of purification and use of tRNA for such reactions, focusing on tRNA^Arg and its use for arginylation. This method can also be used for other tRNA-mediated reactions. For complete details on the use and execution of this protocol, please refer to Avcilar-Kucukgoze et al. (2020).

International Evidence-Based Consensus Diagnostic And Treatment Guidelines For Unicentric Castleman Disease., Frits Van Rhee, Eric Oksenhendler, Gordan Srkalovic, Peter Voorhees, Megan Lim, Angela Dispenzieri, Makoto Ide, Sophia Parente, Stephen Schey, Matthew Streetly, Raymond Wong, David Wu, Ivan Maillard, Joshua Brandstadter, Nikhil Munshi, Wilbur Bowne, Kojo S Elenitoba-Johnson, Alexander Fössa, Mary Jo Lechowicz, Shanmuganathan Chandrakasan, Sheila K Pierson, Amy Greenway, Sunita Nasta, Kazuyuki Yoshizaki, Razelle Kurzrock, Thomas S Uldrick, Corey Casper, Amy Chadburn, David C Fajgenbaum

Department of Surgery Faculty Papers

Castleman disease (CD) includes a group of rare and heterogeneous disorders with characteristic lymph node histopathological abnormalities. CD can occur in a single lymph node station, which is referred to as unicentric CD (UCD). CD can also involve multicentric lymphadenopathy and inflammatory symptoms (multicentric CD [MCD]). MCD includes human herpesvirus-8 (HHV-8)-associated MCD, POEMS-associated MCD, and HHV-8-/idiopathic MCD (iMCD). The first-ever diagnostic and treatment guidelines were recently developed for iMCD by an international expert consortium convened by the Castleman Disease Collaborative Network (CDCN). The focus of this report is to establish similar guidelines for the management of UCD. To this purpose, …