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Articles 31 - 60 of 531
Full-Text Articles in Medical Sciences
Preventing Cholesterol-Induced Perk (Protein Kinase Rna-Like Endoplasmic Reticulum Kinase) Signaling In Smooth Muscle Cells Blocks Atherosclerotic Plaque Formation, Abhijnan Chattopadhyay, Pujun Guan, Suravi Majumder, Kaveeta Kaw, Zhen Zhou, Chen Zhang, Siddharth K Prakash, Anita Kaw, L Maximillian Buja, Callie S Kwartler, Dianna M Milewicz
Preventing Cholesterol-Induced Perk (Protein Kinase Rna-Like Endoplasmic Reticulum Kinase) Signaling In Smooth Muscle Cells Blocks Atherosclerotic Plaque Formation, Abhijnan Chattopadhyay, Pujun Guan, Suravi Majumder, Kaveeta Kaw, Zhen Zhou, Chen Zhang, Siddharth K Prakash, Anita Kaw, L Maximillian Buja, Callie S Kwartler, Dianna M Milewicz
Journal Articles
BACKGROUND: Vascular smooth muscle cells (SMCs) undergo complex phenotypic modulation with atherosclerotic plaque formation in hyperlipidemic mice, which is characterized by de-differentiation and heterogeneous increases in the expression of macrophage, fibroblast, osteogenic, and stem cell markers. An increase of cellular cholesterol in SMCs triggers similar phenotypic changes in vitro with exposure to free cholesterol due to cholesterol entering the endoplasmic reticulum, triggering endoplasmic reticulum stress and activating Perk (protein kinase RNA-like endoplasmic reticulum kinase) signaling.
METHODS: We generated an SMC-specific
RESULTS: SMC-specific deletion of Perk reduces atherosclerotic plaque formation in male hyperlipidemic mice by 80%. Single-cell transcriptomic data identify 2 …
Diagnostic Accuracy Of Macular Thickness Map And Texture En Face Images For Detecting Glaucoma In Eyes With Axial High Myopia, Christopher Bowd, Akram Belghith, Jasmin Rezapour, Mark Christopher, Leslie Hyman, Jost B Jonas, Robert N Weinreb, Linda M Zangwill
Diagnostic Accuracy Of Macular Thickness Map And Texture En Face Images For Detecting Glaucoma In Eyes With Axial High Myopia, Christopher Bowd, Akram Belghith, Jasmin Rezapour, Mark Christopher, Leslie Hyman, Jost B Jonas, Robert N Weinreb, Linda M Zangwill
Wills Eye Hospital Papers
Purpose: To evaluate the diagnostic accuracy of a novel optical coherence tomography texture-based en face image analysis (SALSA-Texture) that requires segmentation of only 1 retinal layer for glaucoma detection in eyes with axial high myopia, and to compare SALSA-Texture with standard macular ganglion cell-inner plexiform layer (GCIPL) thickness, macular retinal nerve fiber layer (mRNFL) thickness, and ganglion cell complex (GCC) thickness maps.
Design: Comparison of diagnostic approaches.
Methods: Cross-sectional data were collected from 92 eyes with primary open-angle glaucoma (POAG) and 44 healthy control eyes with axial high myopia (axial length >26 mm). Optical coherence tomography texture en face images, …
A Mouse Model With Widespread Expression Of The C9orf72-Linked Glycine-Arginine Dipeptide Displays Non-Lethal Als/Ftd-Like Phenotypes, Brandie Morris Verdone, Maria Elena Cicardi, Xinmei Wen, Sindhu Sriramoji, Katelyn Russell, Shashirekha S Markandaiah, Brigid K Jensen, Karthik Krishnamurthy, Aaron R. Haeusler, Piera Pasinelli, Davide Trotti
A Mouse Model With Widespread Expression Of The C9orf72-Linked Glycine-Arginine Dipeptide Displays Non-Lethal Als/Ftd-Like Phenotypes, Brandie Morris Verdone, Maria Elena Cicardi, Xinmei Wen, Sindhu Sriramoji, Katelyn Russell, Shashirekha S Markandaiah, Brigid K Jensen, Karthik Krishnamurthy, Aaron R. Haeusler, Piera Pasinelli, Davide Trotti
Department of Neuroscience Faculty Papers
Translation of the hexanucleotide G4C2 expansion associated with C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD) produces five different dipeptide repeat protein (DPR) species that can confer toxicity. There is yet much to learn about the contribution of a single DPR to disease pathogenesis. We show here that a short repeat length is sufficient for the DPR poly-GR to confer neurotoxicity in vitro, a phenomenon previously unobserved. This toxicity is also reported in vivo in our novel knock-in mouse model characterized by widespread central nervous system (CNS) expression of the short-length poly-GR. We observe sex-specific chronic ALS/FTD-like phenotypes in these …
68-Year Old Man With Progressive Weakness And Ventilator Dependent Respiratory Failure: A Case Report Of Sporadic Late Onset Nemaline Myopathy, P. Kirupaharan, Daniel Kramer, Alan Gandler, Lawrence C. Kenyon, Ross Summer
68-Year Old Man With Progressive Weakness And Ventilator Dependent Respiratory Failure: A Case Report Of Sporadic Late Onset Nemaline Myopathy, P. Kirupaharan, Daniel Kramer, Alan Gandler, Lawrence C. Kenyon, Ross Summer
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Background: Neuromuscular pathologies must be considered when caring for patients with persistent or progressive respiratory failure. Pertinent disease states may involve skeletal muscles of respiration or associated neurologic structures including motor neurons, peripheral neurons and the neuromuscular junction. Diagnosis may require pulmonary function testing, neurophysiologic studies, imaging, and/or muscle biopsy.
Case presentation: A 68-year-old male was transferred to our intensive care unit (ICU) for management of ventilator dependent respiratory failure. Upon further historical review, he described gradually worsening gait instability and muscle weakness, which was previously attributed to vascular Parkinsonism in the setting of known cerebrovascular disease. Upon arrival to …
Noncoding-Rna-Based Therapeutics With An Emphasis On Prostatic Carcinoma-Progress And Challenges., Victor E. Nava, Pin-Yu Perera, Nirbhay Kumar, Maneesh Jain
Noncoding-Rna-Based Therapeutics With An Emphasis On Prostatic Carcinoma-Progress And Challenges., Victor E. Nava, Pin-Yu Perera, Nirbhay Kumar, Maneesh Jain
Pathology Faculty Publications
Noncoding RNAs (ncRNAs) defy the central dogma by representing a family of RNA molecules that are not translated into protein but can convey information encoded in their DNA. Elucidating the exact function of ncRNA has been a focus of discovery in the last decade and remains challenging. Nevertheless, the importance of understanding ncRNA is apparent since these molecules regulate gene expression at the transcriptional and post-transcriptional level exerting pleiotropic effects critical in development, oncogenesis, and immunity. NcRNAs have been referred to as "the dark matter of the nucleus", and unraveling their role in physiologic and pathologic processes will provide vast …
When Eating Becomes Torturous: Understanding Nutrition-Related Cancer Treatment Side Effects Among Individuals With Cancer And Their Caregivers, Brandy-Joe Milliron, Lora Packel, Dan Dychtwald, Cynthia Klobodu, Laura Pontiggia, Ochi Ogbogu, Byron Barksdale, Jonathan Deutsch
When Eating Becomes Torturous: Understanding Nutrition-Related Cancer Treatment Side Effects Among Individuals With Cancer And Their Caregivers, Brandy-Joe Milliron, Lora Packel, Dan Dychtwald, Cynthia Klobodu, Laura Pontiggia, Ochi Ogbogu, Byron Barksdale, Jonathan Deutsch
Institute of Emerging Health Professions Faculty Papers
Individuals living with cancer often experience multiple nutrition-related side effects from cancer treatment, including changes in taste and smell, nausea, diarrhea, loss of appetite, and pain during eating. These side effects can profoundly impact nutritional status and quality of life. The purpose of this study was to explore experiences with nutrition-related cancer treatment side effects among cancer patients and their family caregivers, the way they manage such side effects, and the resulting changes in food preferences and behaviors. Structured surveys and in-depth interviews were conducted. Interviews focused on the presence and management of treatment side effects, how those changes influenced …
Progranulin Loss Results In Sex-Dependent Dysregulation Of The Peripheral And Central Immune System, Madelyn C Houser, Oihane Uriarte Huarte, Rebecca L Wallings, Cody E Keating, Kathryn P Macpherson, Mary K Herrick, George T Kannarkat, Sean D Kelly, Jianjun Chang, Nicholas H Varvel, Jessica E Rexach, Malú Gámez Tansey
Progranulin Loss Results In Sex-Dependent Dysregulation Of The Peripheral And Central Immune System, Madelyn C Houser, Oihane Uriarte Huarte, Rebecca L Wallings, Cody E Keating, Kathryn P Macpherson, Mary K Herrick, George T Kannarkat, Sean D Kelly, Jianjun Chang, Nicholas H Varvel, Jessica E Rexach, Malú Gámez Tansey
Journal Articles
INTRODUCTION: Progranulin (PGRN) is a secreted glycoprotein, the expression of which is linked to several neurodegenerative diseases. Although its specific function is still unclear, several studies have linked it with lysosomal functions and immune system regulation. Here, we have explored the role of PGRN in peripheral and central immune system homeostasis by investigating the consequences of PGRN deficiency on adaptive and innate immune cell populations.
METHODS: First, we used gene co-expression network analysis of published data to test the hypothesis that
RESULTS: Male PGRN KO mice exhibited a lower abundance of microglial cells with higher MHC-II expression, increased CD44 expression …
Breakthroughs In Hormonal Male Contraception, Alexander Patton, Seth Vann
Breakthroughs In Hormonal Male Contraception, Alexander Patton, Seth Vann
Physician Assistant Capstones, 2020-current
Objective: Assess the efficacy of a nestorone plus testosterone gel at suppressing progestin levels and spermatogenesis.
Design: Systematic literature review.
Methods: Searches were done in PubMed and Dartmouth library using the terms nestorone, randomized control trial, human, and male. Limits used while searching included published in the last 10 years, randomized control trials, and English.
Results: Using the search criteria the following three studies were found that met the inclusion/exclusion criteria of this study: Ilani et al, Zitzmann et al, and Anawalt et al. All three studies were found on PubMed and reference the Ilani et al study.
Conclusion: Nestorone …
Ifit3 (Interferon Induced Protein With Tetratricopeptide Repeats 3) Modulates Stat1 Expression In Small Extracellular Vesicles., Nicole M Naranjo, Israa Salem, Maisha A Harris, Lucia R Languino
Ifit3 (Interferon Induced Protein With Tetratricopeptide Repeats 3) Modulates Stat1 Expression In Small Extracellular Vesicles., Nicole M Naranjo, Israa Salem, Maisha A Harris, Lucia R Languino
Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers
We have previously shown that the αvβ6 integrin plays a key role in promoting prostate cancer (PrCa) and it can be transferred to recipient cells via small extracellular vesicles (sEVs). Furthermore, we have reported in a proteomic analysis that αvβ6 integrin down-regulation increases the expression of IFIT3 (interferon induced protein with tetratricopeptide repeats 3) in PrCa cells and their derived sEVs. IFIT3 is a protein well known for being an antiviral effector, but recently its role in cancer has also been elucidated. To study the relationship between IFIT3 and STAT1 (signal transducer and activator of transcription 1), an upstream regulator …
Effects Of The Tailored Activity Program (Tap) On Dementia-Related Symptoms, Health Events And Caregiver Wellbeing: A Randomized Controlled Trial, Laura N Gitlin, Katherine Marx, Catherine V. Piersol, Nancy A Hodgson, Jin Huang, David L Roth, Constantine Lyketsos
Effects Of The Tailored Activity Program (Tap) On Dementia-Related Symptoms, Health Events And Caregiver Wellbeing: A Randomized Controlled Trial, Laura N Gitlin, Katherine Marx, Catherine V. Piersol, Nancy A Hodgson, Jin Huang, David L Roth, Constantine Lyketsos
Department of Occupational Therapy Faculty Papers
BACKGROUND: People living with dementia (PLWD) and caregivers are adversely impacted by lack of meaningful activity leading to worse symptoms and impaired quality-of-life. There is a critical need to develop effective and well-tolerated treatments that mitigate clinical symptoms, engage PLWD and support caregiver wellbeing. We tested whether, compared to attention control, the Tailored Activity Program (TAP) reduced clinical symptoms and health-related events, and improved caregiver wellbeing, and if TAP activities were well-tolerated.
METHODS: We conducted a single-blind randomized controlled trial among 250 dyads recruited from Baltimore-Washington DC (2012-2016) with a dementia diagnosis and clinically significant agitation/aggression. Dyads were randomized to …
Long-Term Survival Of Older Patients Hospitalized For Covid-19. Do Clinical Characteristics Upon Admission Matter?, Michał Chojnicki, Agnieszka Neumann-Podczaska, Mikołaj Seostianin, Zofia Tomczak, Hamza Tariq, Jerzy Chudek, Sławomir Tobis, Iwona Mozer-Lisewska, Aleksandra Suwalska, Andrzej Tykarski, Piotr Merks, Sylwia Kropińska, Małgorzata Sobieszczańska, Frank Romanelli, Katarzyna Wieczorowska-Tobis
Long-Term Survival Of Older Patients Hospitalized For Covid-19. Do Clinical Characteristics Upon Admission Matter?, Michał Chojnicki, Agnieszka Neumann-Podczaska, Mikołaj Seostianin, Zofia Tomczak, Hamza Tariq, Jerzy Chudek, Sławomir Tobis, Iwona Mozer-Lisewska, Aleksandra Suwalska, Andrzej Tykarski, Piotr Merks, Sylwia Kropińska, Małgorzata Sobieszczańska, Frank Romanelli, Katarzyna Wieczorowska-Tobis
Pharmacy Practice and Science Faculty Publications
Older adults are particularly susceptible to COVID-19 in terms of both disease severity and risk of death. To compare clinical differences between older COVID-19 hospitalized survivors and non-survivors, we investigated variables influencing mortality in all older adults with COVID-19 hospitalized in Poznań, Poland, through the end of June 2020 (n = 322). In-hospital, post-discharge, and overall 180-day mortality were analyzed. Functional capacity prior to COVID-19 diagnosis was also documented. The mean age of subjects was 77.5 ± 10.0 years; among them, 191 were females. Ninety-five (29.5%) died during their hospitalization and an additional 30 (9.3%) during the post-discharge period …
Chloride Sensing By Wnk1 Regulates Nlrp3 Inflammasome Activation And Pyroptosis., Lindsey Mayes-Hopfinger, Aura Enache, Jian Xie, Chou-Long Huang, Robert Köchl, Victor L.J. Tybulewicz, Teresa Fernandes-Alnemri, Emad S. Alnemri
Chloride Sensing By Wnk1 Regulates Nlrp3 Inflammasome Activation And Pyroptosis., Lindsey Mayes-Hopfinger, Aura Enache, Jian Xie, Chou-Long Huang, Robert Köchl, Victor L.J. Tybulewicz, Teresa Fernandes-Alnemri, Emad S. Alnemri
Department of Biochemistry and Molecular Biology Faculty Papers
The NLRP3 inflammasome mediates the production of proinflammatory cytokines and initiates inflammatory cell death. Although NLRP3 is essential for innate immunity, aberrant NLRP3 inflammasome activation contributes to a wide variety of inflammatory diseases. Understanding the pathways that control NLRP3 activation will help develop strategies to treat these diseases. Here we identify WNK1 as a negative regulator of the NLRP3 inflammasome. Macrophages deficient in WNK1 protein or kinase activity have increased NLRP3 activation and pyroptosis compared with control macrophages. Mice with conditional knockout of WNK1 in macrophages have increased IL-1β production in response to NLRP3 stimulation compared with control mice. Mechanistically, …
Rnase Κ Promotes Robust Pirna Production By Generating 2',3'-Cyclic Phosphate-Containing Precursors, Megumi Shigematsu, Takuya Kawamura, Keisuke Morichika, Natsuko Izumi, Takashi Kiuchi, Shozo Honda, Venetia Pliatsika, Ryuma Matsubara, Isidore Rigoutsos, Susumu Katsuma, Yukihide Tomari, Yohei Kirino
Rnase Κ Promotes Robust Pirna Production By Generating 2',3'-Cyclic Phosphate-Containing Precursors, Megumi Shigematsu, Takuya Kawamura, Keisuke Morichika, Natsuko Izumi, Takashi Kiuchi, Shozo Honda, Venetia Pliatsika, Ryuma Matsubara, Isidore Rigoutsos, Susumu Katsuma, Yukihide Tomari, Yohei Kirino
Computational Medicine Center Faculty Papers
In animal germlines, PIWI proteins and the associated PIWI-interacting RNAs (piRNAs) protect genome integrity by silencing transposons. Here we report the extensive sequence and quantitative correlations between 2′,3′-cyclic phosphate-containing RNAs (cP-RNAs), identified using cP-RNA-seq, and piRNAs in the Bombyx germ cell line and mouse testes. The cP-RNAs containing 5′-phosphate (P-cP-RNAs) identified by P-cP-RNA-seq harbor highly consistent 5′-end positions as the piRNAs and are loaded onto PIWI protein, suggesting their direct utilization as piRNA precursors. We identified Bombyx RNase Kappa (BmRNase κ) as a mitochondria-associated endoribonuclease which produces cP-RNAs during piRNA biogenesis. BmRNase κ-depletion elevated transposon levels and disrupted a piRNA-mediated …
Reduced Mitochondrial Dna And Oxphos Protein Content In Skeletal Muscle Of Children With Cerebral Palsy, Ferdinand Von Walden, Ivan J. Vechetti Jr., Davis A. Englund, Vandré C. Figueiredo, Rodrigo Fernandez-Gonzalo, Kevin A. Murach, Jessica Pingel, John J. Mccarthy, Per Stål, Eva Pontén
Reduced Mitochondrial Dna And Oxphos Protein Content In Skeletal Muscle Of Children With Cerebral Palsy, Ferdinand Von Walden, Ivan J. Vechetti Jr., Davis A. Englund, Vandré C. Figueiredo, Rodrigo Fernandez-Gonzalo, Kevin A. Murach, Jessica Pingel, John J. Mccarthy, Per Stål, Eva Pontén
Physiology Faculty Publications
AIM: To provide a detailed gene and protein expression analysis related to mitochondrial biogenesis and assess mitochondrial content in skeletal muscle of children with cerebral palsy (CP).
METHOD: Biceps brachii muscle samples were collected from 19 children with CP (mean [SD] age 15y 4mo [2y 6mo], range 9-18y, 16 males, three females) and 10 typically developing comparison children (mean [SD] age 15y [4y], range 7-21y, eight males, two females). Gene expression (quantitative reverse transcription polymerase chain reaction [PCR]), mitochondrial DNA (mtDNA) to genomic DNA ratio (quantitative PCR), and protein abundance (western blotting) were analyzed. Microarray data sets (CP/aging/bed rest) were …
Candida Cell-Surface-Specific Monoclonal Antibodies Protect Mice Against Candida Auris Invasive Infection, Jonothan Rosario-Colon, Karen Eberle, Abby Adams, Evan Courville, Hong Xin
Candida Cell-Surface-Specific Monoclonal Antibodies Protect Mice Against Candida Auris Invasive Infection, Jonothan Rosario-Colon, Karen Eberle, Abby Adams, Evan Courville, Hong Xin
School of Graduate Studies Faculty Publications
Candida auris is a multidrug-resistant fungal pathogen that can cause disseminated bloodstream infections with up to 60% mortality in susceptible populations. Of the three major classes of antifungal drugs, most C. auris isolates show high resistance to azoles and polyenes, with some clinical isolates showing resistance to all three drug classes. We reported in this study a novel approach to treating C. auris disseminated infections through passive transfer of monoclonal antibodies (mAbs) targeting cell surface antigens with high homology in medically important Candida species. Using an established A/J mouse model of disseminated infection that mimics human candidiasis, we showed that …
Long-Term Impacts Of Acute Stressor Exposure On Locus Coeruleus Function And Anxiety-Like Behavior In Rats, Olga Borodovitsyna
Long-Term Impacts Of Acute Stressor Exposure On Locus Coeruleus Function And Anxiety-Like Behavior In Rats, Olga Borodovitsyna
Graduate School of Biomedical Sciences Theses and Dissertations
Stress is a physiological state characterized by behavioral arousal that occurs during exposure to harmful or threatening stimuli, and usually facilitates an adaptive behavioral response. The persistence of stress sometimes causes it to become maladaptive, potentially contributing to disease development, including physiological complications with altered neuroendocrine signaling and impaired function of organ systems, and psychological conditions including depression and anxiety. Anxiety disorders in particular are associated with a history of stress and are the most common class of mental disorders, with a lifetime prevalence of 33.7% in the general population. The locus coeruleus (LC) is a major node in the …
Severe Acute Respiratory Syndrome Coronavirus 2-Induced Acute Aortic Occlusion: A Case Report, Artem Minalyan, Franklin L. Thelmo, Vincent Chan, Stephanie Tzarnas, Faizan Ahmed
Severe Acute Respiratory Syndrome Coronavirus 2-Induced Acute Aortic Occlusion: A Case Report, Artem Minalyan, Franklin L. Thelmo, Vincent Chan, Stephanie Tzarnas, Faizan Ahmed
Department of Medicine Faculty Papers
Background: Severe acute respiratory syndrome coronavirus 2 infection can lead to a constellation of viral and immune symptoms called coronavirus disease 2019. Emerging literature increasingly supports the premise that severe acute respiratory syndrome coronavirus 2 promotes a prothrombotic milieu. However, to date there have been no reports of acute aortic occlusion, itself a rare phenomenon. We report a case of fatal acute aortic occlusion in a patient with coronavirus disease 2019.
Case report: A 59-year-old Caucasian male with past medical history of peripheral vascular disease presented to the emergency department for evaluation of shortness of breath, fevers, and dry cough. …
Point-Of-Care Lung Ultrasound For Covid-19: Findings And Prognostic Implications From 105 Consecutive Patients, Kosuke Yasukawa, Taro Minami, David R Boulware, Ayako Shimada, Ernest A Fischer
Point-Of-Care Lung Ultrasound For Covid-19: Findings And Prognostic Implications From 105 Consecutive Patients, Kosuke Yasukawa, Taro Minami, David R Boulware, Ayako Shimada, Ernest A Fischer
Department of Pharmacology and Experimental Therapeutics Faculty Papers
Background: The prognostic value of point-of-care lung ultrasound has not been evaluated in a large cohort of patients with COVID-19 admitted to general medicine ward in the United States. The aim of this study was to describe lung ultrasound findings and their prognostic value in patients with COVID-19 admitted to internal medicine ward.
Method: This prospective observational study consecutively enrolled 105 hospitalized participants with COVID-19 at 2 tertiary care centers. Ultrasound was performed in 12 lung zones within 24 hours of admission. Findings were assessed relative to 4 outcomes: intensive care unit (ICU) need, need for intensive respiratory support, length …
Impaired Eif5a Function Causes A Mendelian Disorder That Is Partially Rescued In Model Systems By Spermidine., Víctor Faundes, Martin D. Jennings, Siobhan Crilly, Sarah Legraie, Sarah E. Withers, Sara Cuvertino, Sally J. Davies, Andrew G L Douglas, Andrew E. Fry, Victoria Harrison, Jeanne Amiel, Daphné Lehalle, William G. Newman, Patricia Newkirk, Judith Ranells, Miranda Splitt, Laura A. Cross, Carol J. Saunders, Bonnie Sullivan, Jorge L. Granadillo, Christopher T. Gordon, Paul R. Kasher, Graham D. Pavitt, Siddharth Banka
Impaired Eif5a Function Causes A Mendelian Disorder That Is Partially Rescued In Model Systems By Spermidine., Víctor Faundes, Martin D. Jennings, Siobhan Crilly, Sarah Legraie, Sarah E. Withers, Sara Cuvertino, Sally J. Davies, Andrew G L Douglas, Andrew E. Fry, Victoria Harrison, Jeanne Amiel, Daphné Lehalle, William G. Newman, Patricia Newkirk, Judith Ranells, Miranda Splitt, Laura A. Cross, Carol J. Saunders, Bonnie Sullivan, Jorge L. Granadillo, Christopher T. Gordon, Paul R. Kasher, Graham D. Pavitt, Siddharth Banka
Manuscripts, Articles, Book Chapters and Other Papers
The structure of proline prevents it from adopting an optimal position for rapid protein synthesis. Poly-proline-tract (PPT) associated ribosomal stalling is resolved by highly conserved eIF5A, the only protein to contain the amino acid hypusine. We show that de novo heterozygous EIF5A variants cause a disorder characterized by variable combinations of developmental delay, microcephaly, micrognathia and dysmorphism. Yeast growth assays, polysome profiling, total/hypusinated eIF5A levels and PPT-reporters studies reveal that the variants impair eIF5A function, reduce eIF5A-ribosome interactions and impair the synthesis of PPT-containing proteins. Supplementation with 1 mM spermidine partially corrects the yeast growth defects, improves the polysome profiles …
Medicine And Surgery Residents' Perspectives On The Impact Of Covid-19 On Graduate Medical Education., Tanvi Rana, Christopher Hackett, Timothy Quezada, Abhishek Chaturvedi, Veli Bakalov, Jody Leonardo, Sandeep Rana
Medicine And Surgery Residents' Perspectives On The Impact Of Covid-19 On Graduate Medical Education., Tanvi Rana, Christopher Hackett, Timothy Quezada, Abhishek Chaturvedi, Veli Bakalov, Jody Leonardo, Sandeep Rana
COVID-19 Papers, Posters, and Presentations
The COVID-19 crisis has had an unprecedented impact on resident education and well-being: social distancing guidelines have limited patient volumes and forced virtual learning, while personal protective equipment (PPE) shortages, school/daycare closures, and visa restrictions have served as additional stressors. Our study aimed to analyze the effects of COVID-19 crisis-related stressors on residents' professional and personal lives. In April 2020, we administered a survey to residents at a large academic hospital system in order to assess the impact of the pandemic on residency training after >6 weeks of a modified schedule. The primary outcome was to determine which factors or …
Vascular Risk Reduction In Obesity Through Reduced Granulocyte Burden And Improved Angiogenic Monocyte Content Following Bariatric Surgery., David A Hess, Justin Z Trac, Stephen A Glazer, Daniella C Terenzi, Adrian Quan, Hwee Teoh, Mohammed Al-Omran, Deepak L Bhatt, C David Mazer, Ori D Rotstein, Subodh Verma
Vascular Risk Reduction In Obesity Through Reduced Granulocyte Burden And Improved Angiogenic Monocyte Content Following Bariatric Surgery., David A Hess, Justin Z Trac, Stephen A Glazer, Daniella C Terenzi, Adrian Quan, Hwee Teoh, Mohammed Al-Omran, Deepak L Bhatt, C David Mazer, Ori D Rotstein, Subodh Verma
Physiology and Pharmacology Publications
Bariatric surgery, in addition to the benefit of sustained weight loss, can also reduce cardiometabolic risk and mortality. Lifelong vessel maintenance is integral to the prevention of cardiovascular disease. Using aldehyde dehydrogenase activity, an intracellular detoxifying enzyme present at high levels within pro-vascular progenitor cells, we observed an association between chronic obesity and "regenerative cell exhaustion" (RCE), a pathology whereby chronic assault on circulating regenerative cell types can result in adverse inflammation and diminished vessel repair. We also describe that, at 3 months following bariatric surgery, systemic inflammatory burden was reduced and pro-angiogenic macrophage precursor content was improved in subjects …
Precision Medicine And Actionable Alterations In Lung Cancer: A Single Institution Experience, Isa Mambetsariev, Yingyu Wang, Chen Chen, Sorena Nadaf, Rebecca Pharaon, Jeremy Fricke, Idoroenyi Amanam, Arya Amini, Andrea Bild, Peiguo Chu, Loretta Erhunmwunsee, Jae Kim, Janet Munu, Raju Pillai, Dan Raz, Sagus Sampath, Lalit Vora, Fang Qiu, Lynette M. Smith, Surinder K. Batra, Erminia Massarelli, Marianna Koczywas, Karen Reckamp, Ravi Salgia
Precision Medicine And Actionable Alterations In Lung Cancer: A Single Institution Experience, Isa Mambetsariev, Yingyu Wang, Chen Chen, Sorena Nadaf, Rebecca Pharaon, Jeremy Fricke, Idoroenyi Amanam, Arya Amini, Andrea Bild, Peiguo Chu, Loretta Erhunmwunsee, Jae Kim, Janet Munu, Raju Pillai, Dan Raz, Sagus Sampath, Lalit Vora, Fang Qiu, Lynette M. Smith, Surinder K. Batra, Erminia Massarelli, Marianna Koczywas, Karen Reckamp, Ravi Salgia
Journal Articles: Biochemistry & Molecular Biology
OBJECTIVES: Oncology has become more reliant on new testing methods and a greater use of electronic medical records, which provide a plethora of information available to physicians and researchers. However, to take advantage of vital clinical and research data for precision medicine, we must initially make an effort to create an infrastructure for the collection, storage, and utilization of this information with uniquely designed disease-specific registries that could support the collection of a large number of patients.
MATERIALS AND METHODS: In this study, we perform an in-depth analysis of a series of lung adenocarcinoma patients (n = 415) with genomic …
Interleukin 1 Alpha Administration Is Neuroprotective And Neuro-Restorative Following Experimental Ischemic Stroke, Kathleen E. Salmeron, Michael E. Maniskas, Danielle N. Edwards, Raymond Wong, Ivana Rajkovic, Amanda L. Trout, Abir A. Rahman, Samantha Hamilton, Justin F. Fraser, Emmanuel Pinteaux, Gregory J. Bix
Interleukin 1 Alpha Administration Is Neuroprotective And Neuro-Restorative Following Experimental Ischemic Stroke, Kathleen E. Salmeron, Michael E. Maniskas, Danielle N. Edwards, Raymond Wong, Ivana Rajkovic, Amanda L. Trout, Abir A. Rahman, Samantha Hamilton, Justin F. Fraser, Emmanuel Pinteaux, Gregory J. Bix
Sanders-Brown Center on Aging Faculty Publications
BACKGROUND: Stroke remains a leading cause of death and disability worldwide despite recent treatment breakthroughs. A primary event in stroke pathogenesis is the development of a potent and deleterious local and peripheral inflammatory response regulated by the pro-inflammatory cytokine interleukin-1 (IL-1). While the role of IL-1β (main released isoform) has been well studied in stroke, the role of the IL-1α isoform remains largely unknown. With increasing utilization of intravenous tissue plasminogen activator (t-PA) or thrombectomy to pharmacologically or mechanically remove ischemic stroke causing blood clots, respectively, there is interest in pairing successful cerebrovascular recanalization with neurotherapeutic pharmacological interventions (Fraser et …
Chronic Obstructive Pulmonary Disease: Thoracic Ct Texture Analysis And Machine Learning To Predict Pulmonary Ventilation, Andrew Westcott, Dante P I Capaldi, David G Mccormack, Aaron D Ward, Aaron Fenster, Grace Parraga
Chronic Obstructive Pulmonary Disease: Thoracic Ct Texture Analysis And Machine Learning To Predict Pulmonary Ventilation, Andrew Westcott, Dante P I Capaldi, David G Mccormack, Aaron D Ward, Aaron Fenster, Grace Parraga
Medical Biophysics Publications
Background Fixed airflow limitation and ventilation heterogeneity are common in chronic obstructive pulmonary disease (COPD). Conventional noncontrast CT provides airway and parenchymal measurements but cannot be used to directly determine lung function. Purpose To develop, train, and test a CT texture analysis and machine-learning algorithm to predict lung ventilation heterogeneity in participants with COPD. Materials and Methods In this prospective study (
Hyperpolarized Helium 3 Mri In Mild-To-Moderate Asthma: Prediction Of Postbronchodilator Reversibility, Rachel L Eddy, Sarah Svenningsen, Christopher Licskai, David G Mccormack, Grace Parraga
Hyperpolarized Helium 3 Mri In Mild-To-Moderate Asthma: Prediction Of Postbronchodilator Reversibility, Rachel L Eddy, Sarah Svenningsen, Christopher Licskai, David G Mccormack, Grace Parraga
Medical Biophysics Publications
Background: Longitudinal progression to irreversible airflow limitation occurs in approximately 10% of patients with asthma, but it is difficult to identify patients who are at risk for this transition.
Purpose: To investigate 6-year longitudinal changes in hyperpolarized helium 3 (3He) MRI ventilation defects in study participants with mild-to-moderate asthma and identify predictors of longitudinal changes in postbronchodilator forced expiratory volume in 1 second (FEV1) reversibility
Materials and Methods: Spirometry and hyperpolarized 3He MRI were evaluated in participants with mild-to-moderate asthma in two prospectively planned visits approximately 6 years apart. Participants underwent methacholine challenge at baseline (January 2010 to April 2011) …
Rheumatoid Arthritis-Relevant Dna Methylation Changes Identified In Acpa-Positive Asymptomatic Individuals Using Methylome Capture Sequencing., Xiaojian Shao, Marie Hudson, Ines Colmegna, Celia M T Greenwood, Marvin J. Fritzler, Philip Awadalla, T Pastinen, Sasha Bernatsky
Rheumatoid Arthritis-Relevant Dna Methylation Changes Identified In Acpa-Positive Asymptomatic Individuals Using Methylome Capture Sequencing., Xiaojian Shao, Marie Hudson, Ines Colmegna, Celia M T Greenwood, Marvin J. Fritzler, Philip Awadalla, T Pastinen, Sasha Bernatsky
Manuscripts, Articles, Book Chapters and Other Papers
OBJECTIVE: To compare DNA methylation in subjects positive vs negative for anti-citrullinated protein antibodies (ACPA), a key serological marker of rheumatoid arthritis (RA) risk.
METHODS: With banked serum from a random subset (N = 3600) of a large general population cohort, we identified ACPA-positive samples and compared them to age- and sex-matched ACPA-negative controls. We used a custom-designed methylome panel to conduct targeted bisulfite sequencing of 5 million CpGs located in regulatory or hypomethylated regions of DNA from whole blood (red blood cell lysed). Using binomial regression models, we investigated the differentially methylated regions (DMRs) between ACPA-positive vs ACPA-negative subjects. …
New Insights Into Dna Methylation Signatures: Smarca2 Variants In Nicolaides-Baraitser Syndrome., Eric Chater-Diehl, Resham Ejaz, Cheryl Cytrynbaum, Michelle T. Siu, Andrei Turinsky, Sanaa Choufani, Sarah J. Goodman, Omar Abdul-Rahman, Melanie Bedford, Naghmeh Dorrani, Kendra Engleman, Josue Flores-Daboub, David Genevieve, Roberto Mendoza-Londono, Wendy Meschino, Laurence Perrin, Nicole Safina, Sharron Townshend, Stephen W. Scherer, Evdokia Anagnostou, Amelie Piton, Matthew Deardorff, Michael Brudno, David Chitayat, Rosanna Weksberg
New Insights Into Dna Methylation Signatures: Smarca2 Variants In Nicolaides-Baraitser Syndrome., Eric Chater-Diehl, Resham Ejaz, Cheryl Cytrynbaum, Michelle T. Siu, Andrei Turinsky, Sanaa Choufani, Sarah J. Goodman, Omar Abdul-Rahman, Melanie Bedford, Naghmeh Dorrani, Kendra Engleman, Josue Flores-Daboub, David Genevieve, Roberto Mendoza-Londono, Wendy Meschino, Laurence Perrin, Nicole Safina, Sharron Townshend, Stephen W. Scherer, Evdokia Anagnostou, Amelie Piton, Matthew Deardorff, Michael Brudno, David Chitayat, Rosanna Weksberg
Manuscripts, Articles, Book Chapters and Other Papers
BACKGROUND: Nicolaides-Baraitser syndrome (NCBRS) is a neurodevelopmental disorder caused by pathogenic sequence variants in SMARCA2 which encodes the catalytic component of the chromatin remodeling BAF complex. Pathogenic variants in genes that encode epigenetic regulators have been associated with genome-wide changes in DNA methylation (DNAm) in affected individuals termed DNAm signatures.
METHODS: Genome-wide DNAm was assessed in whole-blood samples from the individuals with pathogenic SMARCA2 variants and NCBRS diagnosis (n = 8) compared to neurotypical controls (n = 23) using the Illumina MethylationEPIC array. Differential methylated CpGs between groups (DNAm signature) were identified and used to generate a model enabling classification …
Assessment Of Physical Fitness After Bariatric Surgery And Its Association With Protein Intake And Type Of Cholecalciferol Supplementation, Hendrika J M Smelt, Sjaak Pouwels, Alper Celik, Adarsh Gupta, Johannes F Smulders
Assessment Of Physical Fitness After Bariatric Surgery And Its Association With Protein Intake And Type Of Cholecalciferol Supplementation, Hendrika J M Smelt, Sjaak Pouwels, Alper Celik, Adarsh Gupta, Johannes F Smulders
Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship
Background: Several studies showed that there is a relationship between vitamin and mineral status and muscle strength. In particular this is the case for handgrip strength (HS) and vitamin D deficiency. In bariatric surgery there is a risk of decrease in muscle strength after surgery and also vitamin and mineral deficiencies are not uncommon. The aim of this study is to assess the effect of low vitamin 25 (OH) cholecalciferol levels, high dose cholecalciferol supplementation regime and protein intake on physical fitness, measured using handgrip strength (HS) and the shuttle walk run test (SWRT). Methods: For this retrospective …
Ucp1 Expression-Associated Gene Signatures Of Human Epicardial Adipose Tissue., Kanta Chechi, Jinchu Vijay, Pierre Voisine, Patrick Mathieu, Yohan Bossé, Andre Tchernof, Elin Grundberg, Denis Richard
Ucp1 Expression-Associated Gene Signatures Of Human Epicardial Adipose Tissue., Kanta Chechi, Jinchu Vijay, Pierre Voisine, Patrick Mathieu, Yohan Bossé, Andre Tchernof, Elin Grundberg, Denis Richard
Manuscripts, Articles, Book Chapters and Other Papers
Multiple reports of uncoupling protein 1 (UCP1) expression have established its presence in human epicardial adipose tissue (eAT). Its functional relevance to eAT, however, remains largely unknown. In a recent study, we reported that adrenergic stimulation of eAT was associated with downregulation of secreted proteins involved in oxidative stress-related and immune-related pathways. Here, we explored the UCP1-associated features of human eAT using next-generation deep sequencing. Paired biopsies of eAT, mediastinal adipose tissue (mAT), and subcutaneous adipose tissue (sAT) obtained from cardiac surgery patients, with specific criteria of high and low expression of UCP1 in eAT, were subjected to RNA sequencing. …
Splice-Altering Variant In Col11a1 As A Cause Of Nonsyndromic Hearing Loss Dfna37., Kevin T. Booth, James W. Askew, Zohreh Talebizadeh, Patrick L M Huygen, James Eudy, Judith Kenyon, Denise Hoover, Michael S. Hildebrand, Katherine R. Smith, Melanie Bahlo, William J. Kimberling, Richard J H Smith, Hela Azaiez, Shelley D. Smith
Splice-Altering Variant In Col11a1 As A Cause Of Nonsyndromic Hearing Loss Dfna37., Kevin T. Booth, James W. Askew, Zohreh Talebizadeh, Patrick L M Huygen, James Eudy, Judith Kenyon, Denise Hoover, Michael S. Hildebrand, Katherine R. Smith, Melanie Bahlo, William J. Kimberling, Richard J H Smith, Hela Azaiez, Shelley D. Smith
Manuscripts, Articles, Book Chapters and Other Papers
PURPOSE: The aim of this study was to determine the genetic cause of autosomal dominant nonsyndromic hearing loss segregating in a multigenerational family.
METHODS: Clinical examination, genome-wide linkage analysis, and exome sequencing were carried out on the family.
RESULTS: Affected individuals presented with early-onset progressive mild hearing impairment with a fairly flat, gently downsloping or U-shaped audiogram configuration. Detailed clinical examination excluded any additional symptoms. Linkage analysis detected an interval on chromosome 1p21 with a logarithm of the odds (LOD) score of 8.29: designated locus DFNA37. Exome sequencing identified a novel canonical acceptor splice-site variant c.652-2A>C in the COL11A1 …