Digital Commons Network^™

Can Alternate-Day Statin Regimen Minimize Its Adverse Effects On Muscle And Tendon?: A Systematic Review, Zehra Abdul Muhammad, Tashfeen Ahmad, Naveed Baloch

Section of Orthopaedic Surgery

Objective: To review evidence-based data with respect to safety and efficacy of alternate-day statin therapy in dyslipidaemia compared to the standard daily dose.
Methods: The literature review was conducted at Aga Khan University Hospital, Karachi from July, 2016 to August, 2017. Electronic database search was carried out to compile available literature using PubMed, Excerpta Medica database and Google Scholar. The most relevant evidence-based research articles published over 10 years were selected. The latest search was dated August 03, 2017.
Results: A total of 2,074 articles were initially located. Alternate day statin regimen was reported in 53% of articles. Adverse effects …

Evaluation Of Kidney Injury Molecule-1 As A Disease Progression Biomarker In Diabetic Nephropathy, Fatima Abid Khan, Syeda Sadia Fatima, Ghulam Mustafa Khan, Sana Shahid

Department of Biological & Biomedical Sciences

Background & Objective: Kidney Injury Molecule-1 (KIM-1) is a peptide whose release into circulation is specific to tubular injury. This study aimed to estimate levels of kidney injury molecule-1 in diabetic patients with and without kidney disease. And evaluate the role of KIM-1 as an early screening marker of progressive kidney injury.
Methods: This follow-up study included n=85 subjects from the diabetic clinic of Jinnah Post Graduate Medical Center (JPMC) in collaboration with Aga Khan University from November 2016 till September 2017. They were divided as: i) Group A1 (n=30) participants with diabetes for <5 years without microalbuminuria ii) Group A2 (n= 30) subjects with diabetes for 6-10 years with microalbuminuria; iii) Group B (n=25) subjects as healthy control group. All study participants were followed for 6 months and their blood glucose, urea, creatinine, electrolytes, albuminuria and serum KIM-1 were assayed.
Results: High KIM-1 at baseline was …

The Current State Of Molecular Testing In The Treatment Of Patients With Solid Tumors, 2019., Wafik S El-Deiry, Richard M Goldberg, Heinz-Josef Lenz, Anthony F Shields, Geoffrey T Gibney, Antoinette R Tan, Jubilee Brown, Burton Eisenberg, Elisabeth I Heath, Surasak Phuphanich, Edward Kim, Andrew J Brenner, John L Marshall

Articles, Abstracts, and Reports

The world of molecular profiling has undergone revolutionary changes over the last few years as knowledge, technology, and even standard clinical practice have evolved. Broad molecular profiling is now nearly essential for all patients with metastatic solid tumors. New agents have been approved based on molecular testing instead of tumor site of origin. Molecular profiling methodologies have likewise changed such that tests that were performed on patients a few years ago are no longer complete and possibly inaccurate today. As with all rapid change, medical providers can quickly fall behind or struggle to find up-to-date sources to ensure he or …

Diagnosis Of Non-Small Cell Lung Cancer For Early Stage Asymptomatic Patients., Cherylle Goebel, Christopher L Louden, Robert Mckenna, Osita Onugha, Andrew Wachtel, Thomas Long

Articles, Abstracts, and Reports

BACKGROUND/AIM: In 2016 in the United States, 7 of 10 patients were estimated to die following lung cancer diagnosis. This is due to a lack of a reliable screening method that detects early-stage lung cancer. Our aim is to accurately detect early stage lung cancer using algorithms and protein biomarkers.

PATIENTS AND METHODS: A total of 1,479 human plasma samples were processed using a multiplex immunoassay platform. 82 biomarkers and 6 algorithms were explored. There were 351 NSCLC samples (90.3% Stage I, 2.3% Stage II, and 7.4% Stage III/IV).

RESULTS: We identified 33 protein biomarkers and developed a classifier using …

Metastatic Breast Cancer In Kenya: Presentation, Pathologic Characteristics, And Patterns-Findings From A Tertiary Cancer Center, Etoroabasi Ekpe, Asim Jamal, Jasmit Shah, Judith S. Jacobson, Shahin Sayed

Internal Medicine, East Africa

Purpose: The purpose of this research was to describe the sociodemographic and clinical characteristics of Kenyan women with metastatic breast cancer diagnosed and treated at Aga Khan University Hospital in Nairobi, Kenya from 2012 to 2018.

Patients and Methods: We reviewed charts of Kenyan women with metastatic breast cancer and analyzed sociodemographic data, breast cancer risk factors, and tumor characteristics associated with stage at diagnosis, receptor status (ie, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 [HER2]), and site of metastasis using χ2, analysis of variance, two-sample t tests, and logistic regressions.

Results: A total of 125 …

Labrad : Vol 45, Issue 2 - July 2019, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• Novel Molecular Technique for Identifying Respiratory Tract Pathogens
• Role of Serum Galactomannan (GM) Assay in Diagnosing Invasive Aspergillosis (IA)
• Factor VIII Inhibitor – A Diagnostic Approach
• PET/CT Hybrid Imaging Technology at Aga Khan University Hospital
• Diagnostic Tests for Von Willebrand Disease
• Iron Deficiency Anemia
• Sweat Testing for Diagnosis of Cystic Fibrosis
• Flow Cytometric Identification of Abnormal B-Cells
• Direct Immunofluorescence in Bullous Skin Disorders
• Radiology-Pathology Correlation; Orthopedic Pathology
• Fecal Elastase: A Marker For Exocrine Pancreatic Function
• Edward Syndrome: Rare Autosomal Aneuploidy
• Sirolimus in Renal Transplant
• Latest Trends in Clinical Laboratory Science Technology
• Radiology-Neuropathology Correlation
• Nuchal Translucency Scan
• Bio-risk Management System in …

Survivin Is A Prognostic Marker And Therapeutic Target For Extranodal, Nasal-Type Natural Killer/T Cell Lymphoma., Li Zhang, Yi Wei, Xiaowei Yan, Na Li, Haolan Song, Li Yang, Yang Wu, Yu-Feng Xi, Hua-Wei Weng, Jian-Hua Li, Edward H Lin, Li-Qun Zou

Articles, Abstracts, and Reports

Background: The relationship between survivin and extranodal, nasal-type natural killer/T cell lymphoma (ENKTCL) was unclearly established yet. We here studied the potential prognostic roles of survivin and its implication as a target in ENKTCL therapy.

Methods: ENKTCL patients' peripheral blood were collected and tested by ELISA. ENKTCL cell lines were cultured with or without survivin inhibitor and tested by MTT and Flow cytometry. According to the gene expression profiles from the ArrayExpress Archive under E-TABM-702, survivin co-regulated cluster was established by Coupled Two-way Clustering Algorithm.

Results: Seventeen point six percent of total 17 ENKTCL patients were serum survivin-positive. These patients …

Exploring The Connections Between The Presence Of Developmental Trauma And Clinical Reasoning: The Lived Experience Of Pediatric Occupational Therapists, Gwendolyn R. Blake, Briar E. Plantinga, Julie Shafer

Pediatrics

Background: Developmental trauma is a current issue facing the nation. It adversely affects participation in occupations across the lifespan. This paper examines how the clinical reasoning of practicing pediatric occupational therapists changes when treating clients who have experienced developmental trauma.

Methods: A phenomenological approach was applied using multiple cases. Four individuals, who identified as working with clients with developmental trauma, were interviewed using a series of semi-structured and open-ended questions on their experience treating these clients.

Results: Narrative transcripts were reviewed by the authors and organized into themes of performance patterns of the therapist and the context of developmental trauma …

Blunted Evoked Prouroguanylin Endocrine Secretion In Chronic Constipation., Scott A. Waldman, Renata Tenenbaum, Henry C. Foehl, Peter Winkle, Patrick Griffin

Department of Pharmacology and Experimental Therapeutics Faculty Papers

OBJECTIVES: Prouroguanylin (ProUGN) in the intestine is cleaved to form uroguanylin (UGN), which stimulates guanylate cyclase C (GUCY2C), inducing cyclic guanosine monophosphate signaling. Paracrine release regulates fluid secretion, contributing to bowel function, whereas endocrine secretion evoked by eating forms a gut-brain axis, controlling appetite. Whereas hormone insufficiency contributes to hyperphagia in obesity, its contribution to the pathophysiology of constipation syndromes remains unexplored. Here, we compared circulating ProUGN and UGN in healthy subjects and in patients with chronic idiopathic constipation (CIC) and patients with irritable bowel syndrome with constipation (IBS-C).

METHODS: Circulating ProUGN and UGN levels were measured in 60 healthy …

Commentary: The History Of Neurosurgery At Albany Medical College And Albany Medical Center Hospital, Albany, New York., Pouya Entezami, Michael R. Gooch, Adedamola Adepoju, Julie Pilitsis, Tyler J. Kenning, Alan Boulos, David L. Semenoff

Department of Neurosurgery Faculty Papers

The origins of the Department of Neurosurgery at Albany Medical College closely parallel the development of early America and the establishment of modern health care.The tales of Washington Irving, the works of the Hudson River School of painters, and summers in the Catskill Mountains or Adirondacks are the stories that color the history of Upstate New York (Figure1). As a social, industrial, and political hub of the American colonies, New England’s need for centers providing structured medicine led to the creation of Albany Medical College in1839, one of the earliest such institutions in the young nation.1 Rapid progress in nearly …

Horizontal Rna Transfer Goes Deep: Platelet Consumption And Microrna Utilization By Vascular Smooth Muscle Cells., Lawrence E. Goldfinger, Leonard C. Edelstein

Department of Medicine Faculty Papers

No abstract provided.

Gangliosides: Treatment Avenues In Neurodegenerative Disease., Pierre J. Magistretti, Fred H. Geisler, Jay S. Schneider, P. Andy Li, Hubert Fiumelli, Simonetta Sipione

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Gangliosides are cell membrane components, most abundantly in the central nervous system (CNS) where they exert among others neuro-protective and -restorative functions. Clinical development of ganglioside replacement therapy for several neurodegenerative diseases was impeded by the BSE crisis in Europe during the 1990s. Nowadays, gangliosides are produced bovine-free and new pre-clinical and clinical data justify a reevaluation of their therapeutic potential in neurodegenerative diseases. Clinical experience is greatest with monosialo-tetrahexosyl-ganglioside (GM1) in the treatment of stroke. Fourteen randomized controlled trials (RCTs) in overall >2,000 patients revealed no difference in survival, but consistently superior neurological outcomes vs. placebo. GM1 was shown …

Unique Classification Of Parathyroid Dysfunction In Patients With Transfusion Dependent Thalassemia Major Using Nomogram: A Cross Sectional Study, Hafsa Majid, Lena Jafri, Jamsheer Jehangir Talati, Sibtain Ahmed, Bushra Moiz, Aysha Habib Khan

Department of Pathology and Laboratory Medicine

Introduction: Hypoparathyroidism is a rare complication of iron overload in patients with transfusion dependent β thalassemia major (β-TM). We aim to determine the prevalence of parathyroid dysfunction in patients with β-TM.
Methods:Diagnosed cases of transfusion dependent β-TM between 5 and 17 years of age were recruited from outpatient clinics of a non-profit organization in Karachi, Pakistan. Blood and urine samples were collected in fasting to determine Ca, P, Alb, Mg, Cr 25OHD and iPTH. Patients were grouped on the basis of upper and lower levels of Ca, 25OHD and iPTH for assessing parathyroid dysfunction into primary hypoparathyroidism [low calcium …

Factors Associated With The Discontinuation Of Modern Methods Of Contraception In The Low Income Areas Of Sukh Initiative Karachi: A Community-Based Case Control Study, Rozina Thobani, Saleem Jessani, Iqbal Azam Syed, Sayyeda Reza, Neelofar Sami, Shafquat Rozi, Farina Abrejo, Sarah Saleem

Department of Paediatrics and Child Health

Introduction:
Discontinuation of a contraceptive method soon after its initiation is becoming a public health problem in Low middle income countries and may result in unintended pregnancy and related unwanted consequences. A better understanding of factors behind discontinuation of a modern method would help in designing interventions to continue its use till desired spacing goals are achieved. |
Objective:
To determine factors associated with the discontinuation of modern contraceptive methods within six months of its use compared to continued use of modern method for at least six months in low-income areas of Karachi, Pakistan.
Method:
Community-based case-control study was …

The Concentration Of Total Nucleated Cells In Harvested Bone Marrow For Transplantation Has Decreased Over Time., Nicole L. Prokopishyn, Brent R. Logan, Deidre M. Kiefer, Jennifer A. Sees, Pintip Chitphakdithai, Ibrahim A. Ahmed, Paolo N. Anderlini, Amer M. Beitinjaneh, Christopher Bredeson, Jan Cerny, Saurabh Chhabra, Andrew Daly, Miguel Angel Diaz, Nosha Farhadfar, Haydar A. Frangoul, Siddhartha Ganguly, Dennis A. Gastineau, Usama Gergis, Gregory A. Hale, Peiman Hematti, Rammurti T. Kamble, Kimberly A. Kasow, Hillard M. Lazarus, Jane L. Liesveld, Hemant S. Murthy, Maxim Norkin, Richard F. Olsson, Mona Papari, Bipin N. Savani, Jeffrey Szer, Edmund K. Waller, Baldeep Wirk, Jean A. Yared, Michael A. Pulsipher, Nirali N. Shah, Galen E. Switzer, Paul V. O'Donnell, Dennis L. Confer, Bronwen E. Shaw

Manuscripts, Articles, Book Chapters and Other Papers

Bone marrow (BM) is an essential source of hematopoietic stem cell grafts for many allogeneic hematopoietic cell transplant (HCT) recipients, including adult patients (for specific diseases and transplantation strategies) and the majority of pediatric recipient. However, since the advent of granulocyte colony-stimulating factor-mobilized peripheral blood stem cell (PBSC) grafts, there has been a significant decrease in the use of BM in HCT, thought to be due mainly to the increased logistical challenges in harvesting BM compared with PBSCs, as well as generally no significant survival advantage of BM over PBSCs. The decreased frequency of collection has the potential to impact …

Biochemical And Clinical Response After Umbilical Cord Blood Transplant In A Boy With Early Childhood-Onset Beta-Mannosidosis., Troy C. Lund, Weston P. Miller, Julie B. Eisengart, Katrina Simmons, Laura Pollard, Deborah L. Renaud, David A. Wenger, Marc C. Patterson, Paul J. Orchard

Department of Neurology Faculty Papers

BACKGROUND: Deficiency in the enzyme β-mannosidase was described over three decades ago. Although rare in occurrence, the presentation of childhood-onset β-mannosidase deficiency consists of hypotonia in the newborn period followed by global development delay, behavior problems, and intellectual disability. No effective pharmacologic treatments have been available.

METHODS: We report 2-year outcomes following the first umbilical cord blood transplant in a 4-year-old boy with early childhood-onset disease.

RESULTS: We show restoration of leukocyte β-mannosidase activity which remained normal at 2 years posttransplant, and a simultaneous increase in plasma β-mannosidase activity and dramatic decrease in urine-free oligosaccharides were also observed. MRI of …

Trial Of Canakinumab, An Il-1Β Receptor Antagonist, In Patients With Inclusion Body Myositis., Michalis L Kosmidis, Dimitris Pikazis, Panayotis Vlachoyiannopoulos, Athanasios G Tzioufas, Marinos C. Dalakas

Department of Neurology Faculty Papers

Objective: To assess whether canakinumab, a monoclonal antibody against IL-1β approved for autoinflammatory diseases, is effective as target-specific therapy in patients with sporadic inclusion body myositis (sIBM).

Methods: Because in sIBM IL-1β colocalizes with amyloid precursor protein and upregulates amyloid aggregates enhancing degeneration, targeting IL-1β with canakinumab may arrest disease progression. On this basis, 5 ambulatory patients with sIBM participated in an institutional review board--approved open-labeled study with 150 mg canakinumab [4 bimonthly, then monthly subcutaneous injections] for a mean period of 15.8 months. Patients were assessed bimonthly with a manual dynamometer in 12 proximal and distal muscles and with …

Clinical Diagnostic Matrix (Cdm) As A Tool To Diagnose Subtypes Of Epidermolysis Bullosa Cases In Children, Suci Widhiati, Benazier Marcella, Susanti Rosmala Dewi, Anggana Rafika Paramitasari, Endra Yustin Ellistari, Indah Julianto

Journal of General - Procedural Dermatology and Venereology Indonesia

Background: Epidermolysis bullosa (EB) is a rare genetic skin disease characterized by trauma-induced blisters, which appear shortly after birth. Immunofluorescence antigen mapping and mutational analysis are essential for establishing an accurate diagnosis of EB. However, in limited resource settings like in Indonesia, such techniques are not always readily available, forcing many clinicians to diagnose EB based on clinical features alone that is often inaccurate. Recently, a novel clinical diagnostic matrix (CDM) tool has been developed to improve the diagnostic accuracy of EB in such settings.

Case Illustration: We examined clinical photographs and medical records of patients registered at …

Phospholipases D: Making Sense Of Redundancy And Duplication, Andrew J. Morris

Internal Medicine Faculty Publications

Why have two genes when one would suffice? Evolutionary pressure means that biology, unlike government, is generally intolerant of wasted effort. Therefore, when multiple genes exist presumably they are there to provide some benefit to the organism even if that benefit is not immediately obvious to us scientists. A recent report from Raghu and colleagues (Biosci. Rep. (2018) 38, pii: BSR20181690) [1] sheds some light on one possible reason for the existence of two Phospholipases D genes in chordates when only one is present in invertebrates.

Evaluation Of Clinical Outcomes In An Interdisciplinary Abdominal Pain Clinic: A Retrospective, Exploratory Review., Amanda D. Deacy, Craig A. Friesen, Vincent S. Staggs, Jennifer Verrill Schurman

Manuscripts, Articles, Book Chapters and Other Papers

Background: Pediatric functional gastrointestinal disorders (FGIDs) are common and well-accepted to be etiologically complex in terms of the contribution of biological, psychological, and social factors to symptom presentations. Nonetheless, despite its documented benefits, interdisciplinary treatment, designed to address all of these factors, for pediatric FGIDs remains rare. The current study hypothesized that the majority of pediatric patients seen in an interdisciplinary abdominal pain clinic (APC) would demonstrate clinical resolution of symptoms during the study period and that specific psychosocial variables would be significantly predictive of GI symptom improvement.

Aim: To evaluate outcomes with interdisciplinary treatment in pediatric patients with pain-related …

Galcanezumab In Episodic Migraine: Subgroup Analyses Of Efficacy By High Versus Low Frequency Of Migraine Headaches In Phase 3 Studies (Evolve-1 & Evolve-2)., Stephen D. Silberstein, Virginia L. Stauffer, Katie A. Day, Sarah Lipsius, Maria-Carmen Wilson

Department of Neurology Faculty Papers

BACKGROUND: Patients with high-frequency episodic migraine (HFEM) have a greater disease burden than those with low-frequency episodic migraine (LFEM). Acute treatment overuse increases the risk of migraine chronification in patients with HFEM. Galcanezumab, a humanized monoclonal antibody binding calcitonin gene-related peptide (CGRP), is effective for migraine prevention with a favorable safety profile. Here, we investigate whether there are differences in galcanezumab efficacy in patients with LFEM or with HFEM.

METHODS: Data were pooled from two double-blind, placebo-controlled phase 3 trials; EVOLVE-1 and EVOLVE-2. Patients were 18-65 years old, experienced 4-14 monthly migraine headache days (MHDs) for ≥1 year prior, with …

Microrna Regulation Of Epigenetic Modifiers In Breast Cancer, Brock Humphries, Zhishan Wang, Chengfeng Yang

Toxicology and Cancer Biology Faculty Publications

Epigenetics refers to the heritable changes in gene expression without a change in the DNA sequence itself. Two of these major changes include aberrant DNA methylation as well as changes to histone modification patterns. Alterations to the epigenome can drive expression of oncogenes and suppression of tumor suppressors, resulting in tumorigenesis and cancer progression. In addition to modifications of the epigenome, microRNA (miRNA) dysregulation is also a hallmark for cancer initiation and metastasis. Advances in our understanding of cancer biology demonstrate that alterations in the epigenome are not only a major cause of miRNA dysregulation in cancer, but that miRNAs …

M6a Mrna Demethylase Fto Regulates Melanoma Tumorigenicity And Response To Anti-Pd-1 Blockade, Seungwon Yang, Jiangbo Wei, Yan-Hong Cui, Gayoung Park, Palak Shah, Yu Deng, Andrew E. Aplin, Zhike Lu, Seungmin Hwang, Chuan He, Yu-Ying He

Department of Cancer Biology Faculty Papers

Melanoma is one of the most deadly and therapy-resistant cancers. Here we show that N⁶-methyladenosine (m⁶A) mRNA demethylation by fat mass and obesity-associated protein (FTO) increases melanoma growth and decreases response to anti-PD-1 blockade immunotherapy. FTO level is increased in human melanoma and enhances melanoma tumorigenesis in mice. FTO is induced by metabolic starvation stress through the autophagy and NF-κB pathway. Knockdown of FTO increases m⁶A methylation in the critical protumorigenic melanoma cell-intrinsic genes including PD-1 (PDCD1), CXCR4, and SOX10, leading to increased RNA decay through the m⁶A reader YTHDF2. Knockdown of …

Prognostic Role Of Elevated Myeloperoxidase In Patients With Acute Coronary Syndrome: A Systemic Review And Meta-Analysis, Andrew R. Kolodziej, Mohamed Abo-Aly, Eman Elsawalhy, Charles Campbell, Khaled M. Ziada, Ahmed K. Abdel-Latif

Gill Heart & Vascular Institute Faculty Publications

Background. Myocardial inflammation following acute ischemic injury has been linked to poor cardiac remodeling and heart failure. Many studies have linked myeloperoxidase (MPO), a neutrophil and inflammatory marker, to cardiac inflammation in the setting of acute coronary syndrome (ACS). However, the prognostic role of MPO for adverse clinical outcomes in ACS patients has not been well established. Methods. MEDLINE and Cochrane databases were searched for studies from 1975 to March 2018 that investigated the prognostic value of serum MPO in ACS patients. Studies which have dichotomized patients into a high MPO group and a low MPO group reported clinical outcomes …

Pathologic Gene Network Rewiring Implicates Ppp1r3a As A Central Regulator In Pressure Overload Heart Failure., Pablo Cordero, Victoria N Parikh, Elizabeth T Chin, Ayca Erbilgin, Michael J Gloudemans, Ching Shang, Yong Huang, Alex C Chang, Kevin S Smith, Frederick Dewey, Kathia Zaleta, Michael Morley, Jeff Brandimarto, Nicole Glazer, Daryl Waggott, Aleksandra Pavlovic, Mingming Zhao, Christine S Moravec, W H Wilson Tang, Jamie Skreen, Christine Malloy, Sridhar Hannenhalli, Hongzhe Li, Scott Ritter, Mingyao Li, Daniel Bernstein, Andrew Connolly, Hakon Hakonarson, Aldons J Lusis, Kenneth B Margulies, Anna A Depaoli-Roach, Stephen B Montgomery, Matthew T Wheeler, Thomas Cappola, Euan A Ashley

Articles, Abstracts, and Reports

Heart failure is a leading cause of mortality, yet our understanding of the genetic interactions underlying this disease remains incomplete. Here, we harvest 1352 healthy and failing human hearts directly from transplant center operating rooms, and obtain genome-wide genotyping and gene expression measurements for a subset of 313. We build failing and non-failing cardiac regulatory gene networks, revealing important regulators and cardiac expression quantitative trait loci (eQTLs). PPP1R3A emerges as a regulator whose network connectivity changes significantly between health and disease. RNA sequencing after PPP1R3A knockdown validates network-based predictions, and highlights metabolic pathway regulation associated with increased cardiomyocyte size and …

Topological Dna Damage, Telomere Attrition And T Cell Senescence During Chronic Viral Infections, Yingjie Ji, Xindi Dang, Lam Ngoc Thao Nguyen, Lam Nhat Nguyen, Jaun Zhao, Dechao Cao, Sushant Khanal, Madison Schank, Xiao Y. Wu, Zheng D. Morrison, Yue Zou, Mohamed El Gazzar, Shunbin Ning, Ling Wang, Jonathan P. Moorman, Zhi Q. Yao

ETSU Faculty Works

Background: T cells play a key role in controlling viral infections; however, the underlying mechanisms regulating their functions during human viral infections remain incompletely understood. Here, we used CD4 T cells derived from individuals with chronic viral infections or healthy T cells treated with camptothecin (CPT) - a topoisomerase I (Top 1) inhibitor - as a model to investigate the role of DNA topology in reprogramming telomeric DNA damage responses (DDR) and remodeling T cell functions.

Results: We demonstrated that Top 1 protein expression and enzyme activity were significantly inhibited, while the Top 1 cleavage complex (TOP1cc) was …

A 24-Week Double-Blind Placebo-Controlled Study Of The Efficacy And Safety Of The Ampa Modulator S47445 In Patients With Mild To Moderate Alzheimer's Disease And Depressive Symptoms, Eileen M. Bulger, Sylvie Gouttefangeas, Sylvie Bretin, Stéphanie Galtier, Philippe Robert, Vjera Holthoff-Detto, Jeffrey Cummings, Maria Pueyo

School of Medicine Faculty Research

Introduction S47445 is a novel positive allosteric modulator of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors that may emerge as a favorable candidate for the symptomatic treatment of cognitive and depressive disorders in patients suffering from Alzheimer's disease (AD) of mild to moderate severity and with depressive symptoms. Methods For this double-blind, placebo-controlled 24-week phase II trial, 520 outpatients aged between 55 and 85 years, with probable AD at mild to moderate stages (a Mini-Mental State Examination score of 24-15 inclusive) and exhibiting depressive symptoms (Cornell Scale for Depression in Dementia [CSDD] ≥ 8) were recruited in twelve countries and randomized to 3 doses …

A Transfer Learning Approach For Malignant Prostate Lesion Detection On Multiparametric Mri, Quan Chen, Shiliang Hu, Peiran Long, Fang Lu, Yujie Shi, Yunpeng Li

Radiation Medicine Faculty Publications

Purpose: In prostate focal therapy, it is important to accurately localize malignant lesions in order to increase biological effect of the tumor region while achieving a reduction in dose to noncancerous tissue. In this work, we proposed a transfer learning–based deep learning approach, for classification of prostate lesions in multiparametric magnetic resonance imaging images. Methods: Magnetic resonance imaging images were preprocessed to remove bias artifact and normalize the data. Two state-of-the-art deep convolutional neural network models, InceptionV3 and VGG-16, were pretrained on ImageNet data set and retuned on the multiparametric magnetic resonance imaging data set. As lesion appearances differ by …

Stat3 Genotypic Variant Rs744166 And Increased Tyrosine Phosphorylation Of Stat3 In Il-23 Responsive Innate Lymphoid Cells During Pathogenesis Of Crohn's Disease, Ying Tang, Sanda A. Tan, Atif Iqbal, Jian Li, Sarah C. Glover

Department of Neurology Faculty Papers

Crohn's disease (CD) results from dysregulated immune responses to gut microbiota in genetically susceptible individuals, affecting multiple areas of the gastrointestinal tract. Innate lymphoid cells (ILCs) are tissue-resident innate effector lymphocytes which play crucial roles in mucosal immune defense, tissue repair, and maintenance of homeostasis. The accumulation of IFN-γ-producing ILC1s and increased level of proinflammatory cytokines produced by ILCs has been observed in the inflamed terminal ileum of CD patients. To date, the precise mechanisms of ILC plasticity and gene regulatory pathways in ILCs remain unclear. Signal transducer and activator of transcription 3 (STAT3) regulates gene expression in …

Postoperative Pain: Factors And Tools To Improve Pain Management In Children, Mai M. Makhlouf, Eric Robles Garibay, Brooke N. Jenkins, Zeev N. Kain, Michelle Fortier

Psychology Faculty Articles and Research

Outpatient surgery has made it increasingly common for parents to manage pain in the home setting. Studies have shown that parents often under treat pain, leaving children vulnerable to the negative side effects of suboptimal pain management. Multiple factors affect pain management like child’s age and developmental stage, language, cultural values like stoicism, parental beliefs about medication, biological differences among groups, etc. Understanding all the factors involved can help healthcare providers and parents better understand pain and contribute to optimal pain management. Multiple tools and technological interventions have been created to help create a better understanding of pain and a …