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Ampa Receptor Glua2 Subunit Defects Are A Cause Of Neurodevelopmental Disorders, Vincenzo Salpietro, Christine L. Dixon, Hui Guo, Oscar D. Bello, Jana Vandrovcova, Stephanie Efthymiou, Reza Maroofian, Gali Heimer, Salman Kirmani, Shahnaz H. Ibrahim

Department of Paediatrics and Child Health

AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca²⁺-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to …

Postpartum Psychosis In A Non-Native Language-Speaking Patient: A Perspective On Language Barriers And Cultural Competency., Tatsuhiko Naito, Justin Chin, Jun Lin, Pritesh J Shah, Christine M. Lomiguen

Touro College of Osteopathic Medicine (New York) Publications and Research

Postpartum psychosis is a condition characterised by rapid onset of psychotic symptoms several weeks after childbirth. Outside of its timing and descriptions of psychotic features, minimal research exists due to its relative rarity (1 to 2 per 1000 births in the USA), with greater emphasis on postpartum sadness and depression. With the existing literature, cultural differences and language barriers previously have not been taken into consideration as there are no documented cases of postpartum psychosis in a non-English-speaking patient. Correctly differentiating postpartum psychosis from other postpartum psychiatric disorders requires adeptly evaluating for the presence of psychotic symptoms with in-depth history …

Evaluating The Delivery Of Diabetes-Related Care Among The Asian Population, Lyly Bui

Dissertations

Purpose: This project evaluated current practices for Type 2 diabetes mellitus (T2DM) screening and management among Asian Americans (AAs) presenting to a primary care clinic and determined whether these practices adhered to the American Diabetes Association (ADA)’s 2018 guidelines.

Methods: A retrospective chart review was performed to extract data from clinical case records of AAs who visited the Vietnamese Health Center (VHC) between November 1, 2017 and November 1, 2018. Descriptive statistics were utilized to analyze the data.

Results: Of 173 charts reviewed, 76.3% of AAs had no previous T2DM diagnosis and 23.7% had a previous diagnosis. Among those without …

Malignant Distal Femur Tumors Management In Children, Low Cost Innovations With Affordable Care In A Tertiary Care Hospital, A Cross Sectional Study, Masood Umer, Javeria Saeed, Obada Hussein Hasan

Section of Orthopaedic Surgery

Introduction: Malignant musculoskeletal tumors in children are mostly comprised of Osteosarcoma and Ewing's sarcoma and distal femur is the most common site for primary bone tumors. This study examined the surgical management outcomes of pediatric patients (<18 years) presented in our setup with malignant distal femur tumors.
Methodology: We retrospectively reviewed the medical records of patients diagnosed with malignant sarcomas of distal femur and younger than 18 years of age who underwent limb salvage surgery during June 2009-June2017.
Results: There were 31 pediatric patients who had distal femur malignant tumors and out of them 20 patients were selected who underwent limb salvage as a primary surgery. The mean age (range) …

Blockade Of Tgf-Β Signaling To Enhance The Antitumor Response Is Accompanied By Dysregulation Of The Functional Activity Of Cd4, Magdalena J Polanczyk, Edwin Walker, Daniel Haley, Bella S Guerrouahen, Emmanuel T Akporiaye

Articles, Abstracts, and Reports

BACKGROUND: The pleiotropic cytokine, transforming growth factor (TGF)-β, and CD4

METHODS: Using BALB/c, FoxP3eGFP and Rag

RESULTS: SM16 abrogates TGF-β-induced Treg generation in vitro but does not prevent global homeostatic expansion of CD4

CONCLUSIONS: These findings suggest that blockade of TGF-β signaling is a potentially useful strategy for blunting Treg function to enhance the anti-tumor response. Our data further suggest that the overall dampening of Treg function may involve the expansion of a quiescent Treg precursor population, which is CD4

From Vaccine Vector To Oncomodulation: Understanding The Complex Interplay Between Cmv And Cancer., Nicole A. Wilski, Christopher M. Snyder

Department of Microbiology and Immunology Faculty Papers

Cytomegalovirus (CMV) is a herpesvirus that establishes a persistent, but generally asymptomatic, infection in most people in the world. However, CMV drives and sustains extremely large numbers of antigen-specific T cells and is, therefore, emerging as an exciting platform for vaccines against infectious diseases and cancer. Indeed, pre-clinical data strongly suggest that CMV-based vaccines can sustain protective CD8+ T cell and antibody responses. In the context of vaccines for infectious diseases, substantial pre-clinical studies have elucidated the effcacy and protective mechanisms of CMV-based vaccines, including in non-human primate models of various infections. In the context of cancer vaccines, however, much …

Myc-Mediated Transcriptional Regulation Of The Mitochondrial Chaperone Trap1 Controls Primary And Metastatic Tumor Growth., Ekta Agarwal, Brian J. Altman, Jae Ho Seo, Jagadish C. Ghosh, Andrew V Kossenkov, Hsin-Yao Tang, Shiv Ram Krishn, Lucia R. Languino, Dmitry I. Gabrilovich, David W. Speicher, Chi V. Dang, Dario C. Altieri

Department of Cancer Biology Faculty Papers

The role of mitochondria in cancer continues to be debated, and whether exploitation of mitochondrial functions is a general hallmark of malignancy or a tumor- or context-specific response is still unknown. Using a variety of cancer cell lines and several technical approaches, including siRNA-mediated gene silencing, ChIP assays, global metabolomics and focused metabolite analyses, bioenergetics, and cell viability assays, we show that two oncogenic Myc proteins, c-Myc and N-Myc, transcriptionally control the expression of the mitochondrial chaperone TNFR-associated protein- 1 (TRAP1) in cancer. In turn, this Myc-mediated regulation preserved the folding and function of mitochondrial oxidative phosphorylation (OXPHOS) complex II …

Correction To: Toward A Comprehensive View Of Cancer Immune Responsiveness: A Synopsis From The Sitc Workshop., Davide Bedognetti, Michele Ceccarelli, Lorenzo Galluzzi, Rongze Lu, Karolina Palucka, Josue Samayoa, Stefani Spranger, Sarah Warren, Kwok-Kin Wong, Elad Ziv, Diego Chowell, Lisa M Coussens, Daniel D De Carvalho, David G Denardo, Jérôme Galon, Howard L Kaufman, Tomas Kirchhoff, Michael T Lotze, Jason J Luke, Andy J Minn, Katerina Politi, Leonard D Shultz, Richard Simon, Vésteinn Thorsson, Joanne B Weidhaas, Maria Libera Ascierto, Paolo Antonio Ascierto, James M Barnes, Valentin Barsan, Praveen K Bommareddy, Adrian Bot, Sarah E Church, Gennaro Ciliberto, Andrea De Maria, Dobrin Draganov, Winson S Ho, Heather M Mcgee, Anne Monette, Joseph F Murphy, Paola Nisticò, Wungki Park, Maulik Patel, Michael Quigley, Laszlo Radvanyi, Harry Raftopoulos, Nils-Petter Rudqvist, Alexandra Snyder, Randy F Sweis, Sara Valpione, Roberta Zappasodi, Lisa H Butterfield, Mary L Disis, Bernard A Fox, Alessandra Cesano, Francesco M Marincola

Articles, Abstracts, and Reports

Following publication of the original article [1], the author reported that an author name, Roberta Zappasodi, was missed in the authorship list.

Key Inflammatory Pathway Activations In The Mci Stage Of Alzheimer’S Disease, Jagan A. Pillai, Sean Maxwell, Lynn M. Bekris, Stephen M. Rao, Mark R. Chance, James B. Leverenz

Faculty Scholarship

Objective: To determine the key inflammatory pathways that are activated in the peripheral and CNS compartments at the mild cognitive impairment (MCI) stage of Alzheimer’s disease (AD). Methods: A cross-sectional study of patients with clinical and biomarker characteristics consistent with MCI-AD in a discovery cohort, with replication in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Inflammatory analytes were measured in the CSF and plasma with the same validated multiplex analyte platform in both cohorts and correlated with AD biomarkers (CSF Aβ42, total tau (t-tau), phosphorylated tau (p-tau) to identify key inflammatory pathway activations. The pathways were additionally validated by evaluating …

Edb-Fn Targeted Peptide–Drug Conjugates For Use Against Prostate Cancer, Shang Eun Park, Kiumars Shamloo, Timothy A. Kristedja, Shaban Darwish, Marco Bisoffi, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

Prostate cancer (PCa) is the most common malignancy in men and is the leading cause of cancer-related male mortality. A disulfide cyclic peptide ligand [CTVRTSADC] 1 has been previously found to target extra domain B of fibronectin (EDB-FN) in the extracellular matrix that can dierentiate aggressive PCa from benign prostatic hyperplasia. We synthesized and optimized the stability of ligand 1 by amide cyclization to obtain [KTVRTSADE] 8 using Fmoc/tBu solid-phase chemistry. Optimized targeting ligand 8 was found to be stable in phosphate buered saline (PBS, pH 6.5, 7.0, and 7.5) and under redox conditions, with a half-life longer than 8 …

The Left Behind Generation: Instructional Practices To Increase The Technological Literacy Of Older Adults, Daphne Pace Phillips

USF Tampa Graduate Theses and Dissertations

This study sought to explore the utilization and perception of best practices by community-based technology training programs when instructing older adults to become technologically literate. The target population included adults age 55 years and older of the Baby Boomer generational cohort who ranged academically from possessing a high school diploma or General Education Diploma (GED) through a college degree and had enrolled in a local technology training program to improve their technological skill level with the goal of obtaining employment and/or to remain functionally independent. This study was conducted at three community technology training centers located in the southeast that …

Reporter's Occupation And Source Of Adverse Device Event Reports Contained In The Fda's Maude Database, Kevin T. Kavanagh, Raeford E. Brown, Steve S. Kraman, Lindsay E. Calderon, Sean P. Kavanagh

Anesthesiology Faculty Publications

Introduction: A review of the medical device adverse events submitted to the United States Food & Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database was undertaken to determine the major sources of the information.

Methods: The reporter’s occupation and source of the medical device report were determined for acquisition dates Jan 1, 1997 to Dec 31, 2018. A total of 7,766,737 adverse event records were analyzed.

Results: 96.6% of reports originated with the manufacturer. Patients (patients/family/friend) were the most frequent submitter of reports directly to the FDA, almost five times as often as physicians. Nurses submitted reports …

Plasticizer Interaction With The Heart: Chemicals Used In Plastic Medical Devices Can Interfere With Cardiac Electrophysiology., Rafael Jaimes, Damon Mccullough, Bryan Siegel, Luther Swift, Daniel Mcinerney, James Hiebert, Erick A Perez-Alday, Beatriz Trenor, Jiansong Sheng, Javier Saiz, Larisa G Tereshchenko, Nikki Gillum Posnack

Pediatrics Faculty Publications

BACKGROUND: Phthalates are used as plasticizers in the manufacturing of flexible, plastic medical products. Patients can be subjected to high phthalate exposure through contact with plastic medical devices. We aimed to investigate the cardiac safety and biocompatibility of mono-2-ethylhexyl phthalate (MEHP), a phthalate with documented exposure in intensive care patients.

METHODS: Optical mapping of transmembrane voltage and pacing studies were performed on isolated, Langendorff-perfused rat hearts to assess cardiac electrophysiology after MEHP exposure compared with controls. MEHP dose was chosen based on reported blood concentrations after an exchange transfusion procedure.

RESULTS: Thirty-minute exposure to MEHP increased the atrioventricular node (147 …

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 …

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 …

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 …

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 …

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 …