Medicine and Health Sciences Commons^™

Perceptions Of Risk For Stress Fractures: A Qualitative Study Of Female Runners With And Without Stress Fracture Histories., Therese E Johnston, Jeremy Close, Phil Jamora, Susan F Wainwright

Department of Physical Therapy Faculty Papers

OBJECTIVES: To gain insight into perceived factors related to bone health and stress fracture (SF) prevention for female runners and to understand their experiences within the medical community.

DESIGN: Cohort qualitative study.

SETTING: University health system.

PARTICIPANTS: Forty female runners, 20 who had SF histories and 20 age-and-running-distance matched women without SF.

MAIN OUTCOME MEASURES: Women participated in audiotaped qualitative semi-structured interviews. For women with a SF history, questions sought their perspectives on factors that they felt contributed to SF, experiences with the medical community, and changes made post SF. For women without a SF history, questions sought perspectives on …

Characterization Of Adnexal Masses Using Contrast-Enhanced Subharmonic Imaging: A Pilot Study., Lauren J. Delaney, Priscilla Machado, Mehnoosh Torkzaban, Andrej Lyshchik, Corinne Wessner, Christine H. Kim, Md, Norman G Rosenblum, Scott D. Richard, Kirk Wallace, Flemming Forsberg

Department of Radiology Faculty Papers

OBJECTIVES: This pilot study evaluated whether contrast-enhanced subharmonic imaging (SHI) could be used to characterize adnexal masses before surgical intervention.

METHODS: Ten women (with 12 lesions) scheduled for surgery of an ovarian mass underwent an SHI examination of their adnexal region using a modified LOGIQ E9 scanner (GE Healthcare, Waukesha, WI) with an endocavitary transducer, in which digital clips were acquired by pulse destruction-replenishment SHI across the lesions. Time-intensity curves were created offline to quantitatively evaluate SHI parameters (fractional tumor perfusion, peak contrast intensity, time to peak contrast enhancement, and area under the time-intensity curve), which were compared to pathologic …

Bispecific Human Il2-Ccr4 Immunotoxin Targets Human Cutaneous T-Cell Lymphoma, Haoyu Wang, Zhaohui Wang, Huiping Zhang, Zeng Qi, Ariel C Johnson, David Mathes, Elizabeth A Pomfret, Erin Rubin, Christene A Huang, Zhirui Wang

Faculty, Staff and Student Publications

The majority of clinically diagnosed cutaneous T‐cell lymphomas (CTCL) highly express the cell‐surface markers CC chemokine receptor 4 (CCR4) and/or CD25. Recently, we have developed diphtheria toxin‐based recombinant Ontak®‐like human IL2 fusion toxin (IL2 fusion toxin) and anti‐human CCR4 immunotoxin (CCR4 IT). In this study, we first compared the efficacy of the CCR4 IT vs IL2 fusion toxin for targeting human CD25+CCR4+ CTCL. We demonstrated that CCR4 IT was more effective than IL2 fusion toxin. We further constructed an IL2‐CCR4 bispecific IT. The bispecific IT was significantly more effective than either IL2 fusion toxin or CCR4 IT alone. The bispecific …

Results Of The Adhere Upper Airway Stimulation Registry And Predictors Of Therapy Efficacy., Erica Thaler, Richard Schwab, Joachim Maurer, Ryan Soose, Christopher Larsen, Suzanne Stevens, Damien Stevens, Maurits Boon, Colin Huntley, Karl Doghramji, Tina Waters, Alan Kominsky, Armin Steffen, Eric Kezirian, Benedikt Hofauer, Ulrich Sommer, Kirk Withrow, Kingman Strohl, Clemens Heiser

Department of Psychiatry and Human Behavior Faculty Papers

OBJECTIVE/HYPOTHESIS: The ADHERE Registry is a multicenter prospective observational study following outcomes of upper airway stimulation (UAS) therapy in patients who have failed continuous positive airway pressure therapy for obstructive sleep apnea (OSA). The aim of this registry and purpose of this article were to examine the outcomes of patients receiving UAS for treatment of OSA.

STUDY DESIGN: Cohort Study.

METHODS: Demographic and sleep study data collection occurred at baseline, implantation visit, post-titration (6 months), and final visit (12 months). Patient and physician reported outcomes were also collected. Post hoc univariate and multivariate analysis was used to identify predictors of …

Unique Case Of Anca-Negative Pauci-Immune Necrotizing Glomerulonephritis With Diffuse Alveolar Hemorrhage, Potentially Associated With Midostaurin, Jonathan D Pankow, Guillaume Richard-Carpentier, Naval G Daver, William F Glass, Jaya Kala

Faculty, Staff and Student Publications

We present a 61-year-old male with FLT3-mutated acute myeloid leukemia treated with midostaurin who developed acute kidney injury requiring hemodialysis and pulmonary renal syndrome. Antibodies to proteinase-3, myeloperoxidase, and glomerular basement membrane were negative. Renal biopsy confirmed acute pauci-immune focal necrotizing glomerulonephritis (GN) with fibrin crescents indicating rapidly progressing glomerulonephritis. He improved with pulse methylprednisolone, intravenous cyclophosphamide, and plasma exchange with resolution of hemoptysis. This case highlights the importance of prompt renal biopsy to guide early initiation of life-saving therapies. To our knowledge, this is the first reported case of ANCA-negative pauci-immune necrotizing GN likely secondary to midostaurin.

Vasopressor Treatment And Mortality Following Nontraumatic Subarachnoid Hemorrhage: A Nationwide Electronic Health Record Analysis, George Williams, Vahed Maroufy, Laila Rasmy, Derek Brown, Duo Yu, Hai Zhu, Yashar Talebi, Xueying Wang, Emy Thomas, Gen Zhu, Ashraf Yaseen, Hongyu Miao, Luis Leon Novelo, Degui Zhi, Stacia M Desantis, Hongjian Zhu, Jose-Miguel Yamal, David Aguilar, Hulin Wu

Faculty, Staff and Student Publications

OBJECTIVE: Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular condition, not only due to the effect of initial hemorrhage, but also due to the complication of delayed cerebral ischemia (DCI). While hypertension facilitated by vasopressors is often initiated to prevent DCI, which vasopressor is most effective in improving outcomes is not known. The objective of this study was to determine associations between initial vasopressor choice and mortality in patients with nontraumatic SAH.

METHODS: The authors conducted a retrospective cohort study using a large, national electronic medical record data set from 2000-2014 to identify patients with a new diagnosis of nontraumatic SAH …

Catabolic Degradation Of Endothelial Vegfa Via Autophagy, Thomas Neill, Carolyn Chen, Simone Buraschi, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Extracellular matrix-evoked angiostasis and autophagy within the tumor microenvironment represent two critical, but unconnected, functions of the small leucine-rich proteoglycan, decorin. Acting as a partial agonist of vascular endothelial growth factor 2 (VEGFR2), soluble decorin signals via the energy sensing protein, AMP-activated protein kinase (AMPK), in the autophagic degradation of intracellular vascular endothelial growth factor A (VEGFA). Here, we discovered that soluble decorin evokes intracellular catabolism of endothelial VEGFA that is mechanistically independent of mTOR, but requires an autophagic regulator, paternally expressed gene 3 (PEG3). We found that administration of autophagic inhibitors such as chloroquine or bafilomycin A1, or depletion …

Dermatologists In The Wild West, 1870-1900: The Early Pioneers From The Mississippi River To The Pacific Coast., Leonard J Hoenig, Lawrence Charles Parish

Department of Dermatology and Cutaneous Biology Faculty Papers

During the Wild West era of American history (approximately 1870-1900), at least 53 dermatologists settled between the Mississippi River and the Pacific Coast. In 1870, two dermatologists began their practice in the city of St Louis, Missouri (William Augustus Hardaway and Solomon Claiborne Martin, Sr) and one dermatologist started his practice in San Francisco, California (George J. Bucknall). By 1900, 50 more dermatologists had settled in 19 cities located in the American West (Tables 1,2). There, they established practices, initiated academic programs, and pioneered dermatology as a medical specialty in the western United States. This contribution provides brief biographic profiles …

Structure And Mechanism Of Human Diacylglycerol O-Acyltransferase 1, Lie Wang, Hongwu Qian, Yin Nian, Yimo Han, Zhenning Ren, Hanzhi Zhang, Liya Hu, B V Venkataram Prasad, Arthur Laganowsky, Nieng Yan, Ming Zhou

Faculty, Staff and Students Publications

Diacylglycerol O-acyltransferase-1 (DGAT1) synthesizes triacylglycerides and is required for dietary fat absorption and fat storage in humans1. DGAT1 belongs to the superfamily of membrane-bound O-acyltransferases (MBOAT) that are found in all kingdoms of life and involved in acylation of lipids and proteins2,3. It remains unclear how human DGAT1 (hDGAT1) or other mammalian members of the MBOAT family recognize their substrates and catalyze their reactions. The absence of three-dimensional structures also hampers rational targeting of hDGAT1 for therapeutic purposes. Here we present the structure of hDGAT1 in complex with a substrate oleoyl Coenzyme A solved …

Ubiquitination Of The Dna-Damage Checkpoint Kinase Chk1 By Traf4 Is Required For Chk1 Activation, Xinfang Yu, Wei Li, Haidan Liu, Qipan Deng, Xu Wang, Hui Hu, Zijun Y Xu-Monette, Wei Xiong, Zhongxin Lu, Ken H Young, Wei Wang, Yong Li

Faculty, Staff and Students Publications

BACKGROUND: Aberrant activation of DNA damage response (DDR) is a major cause of chemoresistance in colorectal cancer (CRC). CHK1 is upregulated in CRC and contributes to therapeutic resistance. We investigated the upstream signaling pathways governing CHK1 activation in CRC.

METHODS: We identified CHK1-binding proteins by mass spectrometry analysis. We analyzed the biologic consequences of knockout or overexpression of TRAF4 using immunoblotting, immunoprecipitation, and immunofluorescence. CHK1 and TRAF4 ubiquitination was studied in vitro and in vivo. We tested the functions of TRAF4 in CHK1 phosphorylation and CRC chemoresistance by measuring cell viability and proliferation, anchorage-dependent and -independent cell growth, and mouse …

Late Effects Of Clubfoot Deformity In Adolescent And Young Adult Patients Whose Initial Treatment Was An Extensive Soft-Tissue Release: Topic Review And Clinical Case Series, Jeffrey E Johnson, Thomas A Fortney, Pamela C Luk, Sandra E Klein, Jeremy J Mccormick, Matthew B Dobbs, J Eric Gordon, Perry L Schoenecker

2020-Current year OA Pubs

Children with congenital clubfoot often have residual deformity, pain, and limited function in adolescence and young adulthood. These patients represent a heterogeneous group that often requires an individualized management strategy. This article reviews the available literature on this topic while proposing a descriptive classification system based on a review of patients at our institution who underwent surgery for problems related to previous clubfoot deformity during the period between January 1999 and January 2012. Seventy-two patients (93 feet) underwent surgical treatment for the late effects of clubfoot deformity at an average age of 13 years (range 9 to 19 years). All …

International Society For Peritoneal Dialysis Practice Recommendations: Prescribing High-Quality Goal-Directed Peritoneal Dialysis., Edwina A. Brown, Peter G. Blake, Neil Boudville, Simon Davies, Javier De Arteaga, Jie Dong, Fred Finkelstein, Marjorie Foo, Helen Hurst, David W. Johnson, Mark Johnson, Adrian Liew, Thyago Moraes, Jeff Perl, Rukshana Shroff, Isaac Teitelbaum, Angela Yee-Moon Wang, Bradley A. Warady

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Prevalence And Risk Factors Of Falls In Adults 1 Year After Total Hip Arthroplasty For Osteoarthritis: A Cross-Sectional Study, Susan W. Hunter, Pavlos Bobos, Lyndsay Somerville, James Howard, Edward M Vasarhelyi, Brent Lanting

Physical Therapy Publications

Total hip arthroplasty is very successful in alleviating the pain from osteoarthritis. However, deficits in lower limb strength, gait, and balance after surgery has identified this group at risk of falls. Considering the high number of people annually receiving a total hip arthroplasty, further elaboration of factors associated with falls is needed to refine fall prevention guidelines. The objective was to examine the prevalence and circumstances of falling and the risk factors associated with falling in older adults in the first year after total hip arthroplasty surgery. This was a cross-sectional study involving 108 individuals (age of 72.4 ± 6.5 …

Efficacy Of Quality Improvement And Patient Safety Workshops For Students: A Pilot Study, Kevin P Shah, Shreya Goyal, Vignesh Ramachandran, Jaden R Kohn, Jonathan A Go, Zachary Wiley, Anoosha Moturu, Meera K Namireddy, Anjali Kumar, Ryan C Jacobs, Matthew Stampfl, Jesal R Shah, Justin Fu, Weijie V Lin, Brandon Ho, Grace Wey, Sophie Y Lin, Andrew C Caruso, Lindsey Jordan Gay, Diana E Stewart, Sara Andrabi

Faculty, Staff and Students Publications

BACKGROUND: While the Association of American Medical Colleges encourages medical schools to incorporate quality improvement and patient safety (QI/PS) into their curriculum, medical students continue to have limited QI/PS exposure. To prepare medical students for careers that involve QI/PS, the Institute for Healthcare Improvement chapter at an allopathic medical school and school of allied health professions initiated self-directed learning by offering student-led workshops to equip learners with skills to improve the quality and safety of healthcare processes.

METHODS: In this prospective cohort study, workshops were hosted for medical students between 2015 and 2018 on five QI/PS topics: Process Mapping, Root-Cause …

Association Of Intensive Lifestyle Intervention, Fitness, And Body Mass Index With Risk Of Heart Failure In Overweight Or Obese Adults With Type 2 Diabetes Mellitus: An Analysis From The Look Ahead Trial, Ambarish Pandey, Kershaw V Patel, Judy L Bahnson, Sarah A Gaussoin, Corby K Martin, Ashok Balasubramanyam, Karen C Johnson, Darren K Mcguire, Alain G Bertoni, Dalane Kitzman, Jarett D Berry, Look Ahead Research Group

Faculty, Staff and Students Publications

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with a higher risk for heart failure (HF). The impact of a lifestyle intervention and changes in cardiorespiratory fitness (CRF) and body mass index on risk for HF is not well established.

METHODS: Participants from the Look AHEAD trial (Action for Health in Diabetes) without prevalent HF were included. Time-to-event analyses were used to compare the risk of incident HF between the intensive lifestyle intervention and diabetes support and education groups. The associations of baseline measures of CRF estimated from a maximal treadmill test, body mass index, and longitudinal changes in these …

Executive Function As A Mediating Factor Between Visual Acuity And Postural Stability In Cognitively Healthy Adults And Adults With Alzheimer's Dementia, Susan W. Hunter, Alison Divine, Edward Madou, Humberto Omana, Keith D Hill, Andrew M Johnson, Jeffrey D Holmes, Walter Wittich

Physical Therapy Publications

BACKGROUND: Falls in older adults, notably those with Alzheimer's dementia (AD), are prevalent. Vision and balance impairments are prominent falls risk factors in older adults. However, recent literature in the cognitively impaired suggests that executive function (EF) is important for falls risk assessments. The study objectives were to: 1) to compare balance among people with AD, healthy older adults (OA), and healthy young adults (YA) and 2) to quantify the interaction of visual acuity and EF on postural stability.

METHODS: We recruited 165 individuals (51 YA, 48 OA, and 66 AD). Trail Making Tests (A and B) quantified EF and …

Rna-Induced Conformational Switching And Clustering Of G3bp Drive Stress Granule Assembly By Condensation, Jordina Guillén-Boixet, Alex S. Holehouse, Rohit V. Pappu, Et Al.

2020-Current year OA Pubs

Stressed cells shut down translation, release mRNA molecules from polysomes, and form stress granules (SGs) via a network of interactions that involve G3BP. Here we focus on the mechanistic underpinnings of SG assembly. We show that, under non-stress conditions, G3BP adopts a compact auto-inhibited state stabilized by electrostatic intramolecular interactions between the intrinsically disordered acidic tracts and the positively charged arginine-rich region. Upon release from polysomes, unfolded mRNAs outcompete G3BP auto-inhibitory interactions, engendering a conformational transition that facilitates clustering of G3BP through protein-RNA interactions. Subsequent physical crosslinking of G3BP clusters drives RNA molecules into networked RNA/protein condensates. We show that …

Insights From Immuno-Oncology: The Society For Immunotherapy Of Cancer Statement On Access To Il-6-Targeting Therapies For Covid-19., Paolo Antonio Ascierto, Bernard Fox, Walter Urba, Ana Carrizosa Anderson, Michael B Atkins, Ernest C Borden, Julie Brahmer, Lisa H Butterfield, Alessandra Cesano, Daniel Chen, Tanja De Gruijl, Robert O Dillman, Charles G Drake, Leisha A Emens, Thomas F Gajewski, James L Gulley, F Stephen Hodi, Patrick Hwu, David Kaufman, Howard Kaufman, Michael Lotze, Douglas G Mcneel, Kim Margolin, Francesco Marincola, Michael J Mastrangelo, Marcela V Maus, David R Parkinson, Pedro J Romero, Paul M Sondel, Stefani Spranger, Mario Sznol, George J Weiner, Jon M Wiggington, Jeffrey S Weber

Department of Microbiology and Immunology Faculty Papers

No abstract provided.

A Validated Composite Organ And Hematologic Response Model For Early Assessment Of Treatment Outcomes In Light Chain Amyloidosis, Surbhi Sidana, Paolo Milani, Moritz Binder, Marco Basset, Nidhi Tandon, Andrea Foli, Angela Dispenzieri, Morie A Gertz, Suzanne R Hayman, Francis K Buadi, Martha Q Lacy, Prashant Kapoor, Nelson Leung, S Vincent Rajkumar, Giampaolo Merlini, Giovanni Palladini, Shaji K Kumar

Faculty, Staff and Student Publications

Newly diagnosed AL amyloidosis patients were evaluated to develop a model for early assessment of treatment benefit at 6 months, integrating both hematologic (HR) and organ response (OR) assessment (testing cohort, Mayo: n = 473; validation cohort, Pavia: n = 575). Multiple OR were assessed as follows: All OR (AOR): response in all organs, mixed OR (MOR): response in some organs, no OR (NOR)]. AOR rates at 6 months improved with deepening HR; complete response (CR; 38%, 35%), very good partial response (VGPR; 30%, 26%), and partial response (PR; 16%, 21%), respectively. A composite HR/OR (CHOR) model was developed using …

Mechanical Thrombectomy For Acute Ischemic Stroke In The Cardiac Catheterization Laboratory., Steven A Guidera, Sudhir Aggarwal, J Doyle Walton, David Boland, Roy Jackel, Jeffrey D Gould, Brooke Kearins, Joseph Mcgarvey, Yan Qi, Brian Furlong

Department of Radiology & Diagnostic Medical Imaging

OBJECTIVES: The aim of this study was to determine the feasibility of establishing a mechanical thrombectomy (MT) program for acute ischemic stroke in a community hospital using interventional cardiologists working closely with neurologists.

BACKGROUND: American Heart Association/American Stroke Association 2018 guidelines give a Class I (Level of Evidence: A) recommendation for MT in eligible patients with large vessel occlusion stroke. Improvement in neurological outcomes with MT is highly time sensitive. Most hospitals do not have trained neurointerventionalists to perform MT, leading to treatment delays that reduce the benefit of reperfusion therapy.

METHODS: An MT program based in the cardiac catheterization …

Predicting Hemolytic Uremic Syndrome And Renal Replacement Therapy In Shiga Toxin-Producing Escherichia Coli-Infected Children., Ryan S Mckee, David Schnadower, Phillip I Tarr, Jianling Xie, Yaron Finkelstein, Neil Desai, Roni D Lane, Kelly R Bergmann, Ron L Kaplan, Selena Hariharan, Andrea T Cruz, Daniel M Cohen, Andrew Dixon, Sriram Ramgopal, Annie Rominger, Elizabeth C Powell, Jennifer Kilgar, Kenneth A Michelson, Darcy Beer, Martin Bitzan, Christopher M Pruitt, Kenneth Yen, Garth D Meckler, Amy C Plint, Stuart Bradin, Thomas J Abramo, Serge Gouin, April J Kam, Abigail Schuh, Fran Balamuth, Tracy E Hunley, John T Kanegaye, Nicholas E Jones, Usha Avva, Robert Porter, Daniel M Fein, Jeffrey P Louie, Stephen B Freedman

Paediatrics Publications

BACKGROUND: Shiga toxin-producing Escherichia coli (STEC) infections are leading causes of pediatric acute renal failure. Identifying hemolytic uremic syndrome (HUS) risk factors is needed to guide care.

METHODS: We conducted a multicenter, historical cohort study to identify features associated with development of HUS (primary outcome) and need for renal replacement therapy (RRT) (secondary outcome) in STEC-infected children without HUS at initial presentation. Children agedeligible.

RESULTS: Of 927 STEC-infected children, 41 (4.4%) had HUS at presentation; of the remaining 886, 126 (14.2%) developed HUS. Predictors (all shown as odds ratio [OR] with 95% confidence interval [CI]) of HUS included younger age …

Prevalence Of Clinically Actionable Disease Variants In Exceptionally Long-Lived Families, Paige Carlson, Mary K Wojczynski, Todd Druley, Joseph H Lee, Joseph M Zmuda, Bharat Thyagarajan

2020-Current year OA Pubs

BACKGROUND: Phenotypic expression of pathogenic variants in individuals with no family history of inherited disorders remains unclear.

METHODS: We evaluated the prevalence of pathogenic variants in 25 genes associated with Mendelian-inherited disorders in 3015 participants from 485 families in the Long Life Family Study (LLFS). Boot-strapping and Fisher's exact test were used to determine whether allele frequencies in LLFS were significantly different from the allele frequencies reported in publicly available genomic databases.

RESULTS: The proportions of pathogenic autosomal dominant mutation carriers in BRCA1 and SDHC in LLFS study participants were similar to those reported in publicly available genomic databases (0.03% …

Acetylation Of Histone H3k27 Signals The Transcriptional Elongation For Estrogen Receptor Alpha, Yujing Gao, Lijia Chen, Yali Han, Fangrui Wu, Wen-Si Yang, Zheng Zhang, Tong Huo, Yingmin Zhu, Chengtai Yu, Hong Kim, Mark Lee, Zhen Tang, Kevin Phillips, Bin He, Sung Yun Jung, Yongcheng Song, Bokai Zhu, Rui-Ming Xu, Qin Feng

Faculty, Staff and Students Publications

As approximately 70% of human breast tumors are estrogen receptor α (ERα)-positive, estrogen and ERα play essential roles in breast cancer development. By interrupting the ERα signaling pathway, endocrine therapy has been proven to be an effective therapeutic strategy. In this study, we identified a mechanism by which Transcription Start Site (TSS)-associated histone H3K27 acetylation signals the Super Elongation Complex (SEC) to regulate transcriptional elongation of the ESR1 (ERα) gene. SEC interacts with H3K27ac on ESR1 TSS through its scaffold protein AFF4. Depletion of AFF4 by siRNA or CRISPR/Cas9 dramatically reduces expression of ESR1 and its target genes, consequently inhibiting …

Integrating Mouse And Human Genetic Data To Move Beyond Gwas And Identify Causal Genes In Cholesterol Metabolism, Zhonggang Li, James A Votava, Gregory J M Zajac, Jenny N Nguyen, Fernanda B Leyva Jaimes, Sophia M Ly, Jacqueline A Brinkman, Marco De Giorgi, Sushma Kaul, Cara L Green, Samantha L St Clair, Sabrina L Belisle, Julia M Rios, David W Nelson, Mary G Sorci-Thomas, William R Lagor, Dudley W Lamming, Chi-Liang Eric Yen, Brian W Parks

Faculty, Staff and Students Publications

Identifying the causal gene(s) that connects genetic variation to a phenotype is a challenging problem in genome-wide association studies (GWASs). Here, we develop a systematic approach that integrates mouse liver co-expression networks with human lipid GWAS data to identify regulators of cholesterol and lipid metabolism. Through our approach, we identified 48 genes showing replication in mice and associated with plasma lipid traits in humans and six genes on the X chromosome. Among these 54 genes, 25 have no previously identified role in lipid metabolism. Based on functional studies and integration with additional human lipid GWAS datasets, we pinpoint Sestrin1 as …

Associations Between Food Insecurity And Psychotropic Medication Use Among Women Living With Hiv In The United States, Henry J. Whittle, William R. Wolfe, Lila A. Sheira, Edward A. Frongillo Jr., Kartika Palar, Daniel Merenstein, Tracey E. Wilson, Adebola Adedimeji, Mardge H. Cohen, Eryka L. Wentz, Phyllis C. Tien, Sheri D. Weiser

Faculty Publications

AIMS: Psychotropic prescription rates continue to increase in the United States (USA). Few studies have investigated whether social-structural factors may play a role in psychotropic medication use independent of mental illness. Food insecurity is prevalent among people living with HIV in the USA and has been associated with poor mental health. We investigated whether food insecurity was associated with psychotropic medication use independent of the symptoms of depression and anxiety among women living with HIV in the USA. METHODS: We used cross-sectional data from the Women's Interagency HIV Study (WIHS), a nationwide cohort study. Food security (FS) was the primary …

Principles Of Rna Processing From Analysis Of Enhanced Clip Maps For 150 Rna Binding Proteins, Eric L Van Nostrand, Gabriel A Pratt, Brian A Yee, Emily C Wheeler, Steven M Blue, Jasmine Mueller, Samuel S Park, Keri E Garcia, Chelsea Gelboin-Burkhart, Thai B Nguyen, Ines Rabano, Rebecca Stanton, Balaji Sundararaman, Ruth Wang, Xiang-Dong Fu, Brenton R Graveley, Gene W Yeo

Faculty, Staff and Students Publications

BACKGROUND: A critical step in uncovering rules of RNA processing is to study the in vivo regulatory networks of RNA binding proteins (RBPs). Crosslinking and immunoprecipitation (CLIP) methods enable mapping RBP targets transcriptome-wide, but methodological differences present challenges to large-scale analysis across datasets. The development of enhanced CLIP (eCLIP) enabled the mapping of targets for 150 RBPs in K562 and HepG2, creating a unique resource of RBP interactomes profiled with a standardized methodology in the same cell types.

RESULTS: Our analysis of 223 eCLIP datasets reveals a range of binding modalities, including highly resolved positioning around splicing signals and mRNA …

Phosphoinositides In Retinal Function And Disease, Theodore G Wensel

Faculty, Staff and Students Publications

Phosphatidylinositol and its phosphorylated derivatives, the phosphoinositides, play many important roles in all eukaryotic cells. These include modulation of physical properties of membranes, activation or inhibition of membrane-associated proteins, recruitment of peripheral membrane proteins that act as effectors, and control of membrane trafficking. They also serve as precursors for important second messengers, inositol (1,4,5) trisphosphate and diacylglycerol. Animal models and human diseases involving defects in phosphoinositide regulatory pathways have revealed their importance for function in the mammalian retina and retinal pigmented epithelium. New technologies for localizing, measuring and genetically manipulating them are revealing new information about their importance for the …

De Novo Frameshift Variants In The Neuronal Splicing Factor Nova2 Result In A Common C-Terminal Extension And Cause A Severe Form Of Neurodevelopmental Disorder, Francesca Mattioli, Gaelle Hayot, Nathalie Drouot, Bertrand Isidor, Jérémie Courraud, Maria-Victoria Hinckelmann, Frederic Tran Mau-Them, Chantal Sellier, Alica Goldman, Aida Telegrafi, Alicia Boughton, Candace Gamble, Sebastien Moutton, Angélique Quartier, Nolwenn Jean, Paul Van Ness, Sarah Grotto, Sophie Nambot, Ganka Douglas, Yue Cindy Si, Jamel Chelly, Zohra Shad, Elisabeth Kaplan, Richard Dineen, Christelle Golzio, Nicolas Charlet-Berguerand, Jean-Louis Mandel, Amélie Piton

Faculty, Staff and Students Publications

The neuro-oncological ventral antigen 2 (NOVA2) protein is a major factor regulating neuron-specific alternative splicing (AS), previously associated with an acquired neurologic condition, the paraneoplastic opsoclonus-myoclonus ataxia (POMA). We report here six individuals with de novo frameshift variants in NOVA2 affected with a severe neurodevelopmental disorder characterized by intellectual disability (ID), motor and speech delay, autistic features, hypotonia, feeding difficulties, spasticity or ataxic gait, and abnormal brain MRI. The six variants lead to the same reading frame, adding a common proline rich C-terminal part instead of the last KH RNA binding domain. We detected 41 genes differentially spliced after NOVA2 …

Organizational Guidance For The Care Of Patients With Head-And-Neck Cancer In Ontario., J Irish, J Kim, J Waldron, A C Wei, E Winquist, J Yoo, A Boasie, M Brouwers, E Meertens, S Mcnair, C Walker-Dilks

Paediatrics Publications

Background: At the request of the Head and Neck Cancers Advisory Committee of Ontario Health (Cancer Care Ontario), a working group and expert panel of clinicians with expertise in the management of head-and-neck cancer developed the present guideline. The purpose of the guideline is to provide advice about the organization and delivery of health care services for adult patients with head-and-neck cancer.

Methods: This document updates the recommendations published in the Ontario Health (Cancer Care Ontario) 2009 organizational guideline

Results: To ensure that all patients have access to the highest standard of care available in Ontario, the guideline establishes the …

Sjs/Ten 2019: From Science To Translation., Wan-Chun Chang, Riichiro Abe, Paul Anderson, Wanpen Anderson, Michael R Ardern-Jones, Thomas M Beachkofsky, Teresa Bellón, Agnieszka K Biala, Charles Bouchard, Gianpiero L Cavalleri, Nicole Chapman, James Chodosh, Hyon K Choi, Ricardo R Cibotti, Sherrie J Divito, Karen Dewar, Ulrike Dehaeck, Mahyar Etminan, Diane Forbes, Esther Fuchs, Jennifer L Goldman, James H Holmes, Elyse A Hope, Shuen-Iu Hung, Chia-Ling Hsieh, Alfonso Iovieno, Julienne Jagdeo, Mee Kum Kim, David M Koelle, Mario E Lacouture, Sophie Le Pallec, Rannakoe J Lehloenya, Robyn Lim, Angie Lowe, Jean Mccawley, Julie Mccawley, Robert G Micheletti, Maja Mockenhaupt, Katie Niemeyer, Michael A Norcross, Douglas Oboh, Cristina Olteanu, Helena B Pasieka, Jonathan Peter, Munir Pirmohamed, Michael Rieder, Hajirah N Saeed, Neil H Shear, Christine Shieh, Sabine Straus, Chonlaphat Sukasem, Cynthia Sung, Jason A Trubiano, Sheng-Ying Tsou, Mayumi Ueta, Simona Volpi, Chen Wan, Hongsheng Wang, Zhao-Qing Wang, Jessica Weintraub, Cindy Whale, Lisa M Wheatley, Sonia Whyte-Croasdaile, Kristina B Williams, Galen Wright, Sonia N Yeung, Li Zhou, Wen-Hung Chung, Elizabeth J Phillips, Bruce C Carleton

Paediatrics Publications

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially life-threatening, immune-mediated adverse reactions characterized by widespread erythema, epidermal necrosis, and detachment of skin and mucosa. Efforts to grow and develop functional international collaborations and a multidisciplinary interactive network focusing on SJS/TEN as an uncommon but high burden disease will be necessary to improve efforts in prevention, early diagnosis and improved acute and long-term management. SJS/TEN 2019: From Science to Translation was a 1.5-day scientific program held April 26-27, 2019, in Vancouver, Canada. The meeting successfully engaged clinicians, researchers, and patients and conducted many productive discussions on research and patient care …