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A Case Series Of Hyponatremia And Management In Hospitalized Patients, Jake N. Cho MD, Rebecca Ong MD, Izuchukwu Nwakoby MD 2020 HCA Healthcare

A Case Series Of Hyponatremia And Management In Hospitalized Patients, Jake N. Cho Md, Rebecca Ong Md, Izuchukwu Nwakoby Md

Nephrology

No abstract provided.


A Systematic Re-Examination Of Processing Of Mhci-Bound Antigenic Peptide Precursors By Er Aminopeptidase 1, George Mavridis, Richa Arya, Alexander Domnick, Jerome Zoidakis, Manousos Makridakis, Antonia Vlahou, Anastasia Mpakali, Angelos Lelis, Dimitris Georgiadis, Robert Tampe, Athanasios Papakyriakou, Lawrence J. Stern, Efstratios Stratikos 2020 National Center for Scientific Research Demokritos

A Systematic Re-Examination Of Processing Of Mhci-Bound Antigenic Peptide Precursors By Er Aminopeptidase 1, George Mavridis, Richa Arya, Alexander Domnick, Jerome Zoidakis, Manousos Makridakis, Antonia Vlahou, Anastasia Mpakali, Angelos Lelis, Dimitris Georgiadis, Robert Tampe, Athanasios Papakyriakou, Lawrence J. Stern, Efstratios Stratikos

Open Access Articles

Endoplasmic reticulum aminopeptidase 1 (ERAP1) trims antigenic peptide precursors to generate mature antigenic peptides for presentation by major histocompatibility complex class I (MHCI) molecules and regulates adaptive immune responses. ERAP1 has been proposed to trim peptide precursors both in solution and in pre-formed MHCI-peptide complexes, but which mode is more relevant to its biological function remains controversial. Here, we compared ERAP1-mediated trimming of antigenic peptide precursors in solution or when bound to three MHCI alleles, HLA-B*58, HLA-B*08 and HLA-A*02. For all MHCI-peptide combinations, peptide binding onto MHCI protected against ERAP1-mediated trimming. In only a single MHCI-peptide combination ...


Methylation Of Srd5a2 Promoter Predicts A Better Outcome For Castration-Resistant Prostate Cancer Patients Undergoing Androgen Deprivation Therapy, Zongwei Wang, Tuo Deng, Xingbo Long, Xueming Lin, Shulin Wu, Hongbo Wang, Rongbin Ge, Zhenwei Zhang, Chin-Lee Wu, Mary-Ellen Taplin, Aria F. Olumi 2020 Harvard Medical School

Methylation Of Srd5a2 Promoter Predicts A Better Outcome For Castration-Resistant Prostate Cancer Patients Undergoing Androgen Deprivation Therapy, Zongwei Wang, Tuo Deng, Xingbo Long, Xueming Lin, Shulin Wu, Hongbo Wang, Rongbin Ge, Zhenwei Zhang, Chin-Lee Wu, Mary-Ellen Taplin, Aria F. Olumi

Open Access Articles

PURPOSE: To determine whether SRD5A2 promoter methylation is associated with cancer progression during androgen deprivation therapy (ADT) in CRPC.

PATIENTS AND METHODS: In a Local CRPC cohort, 42 prostatic specimens were collected from patients who were diagnosed as CRPC and underwent transurethral resection of the prostate (TURP) at Massachusetts General Hospital (MGH). In a metastatic CRPC (Met CRPC) cohort, 12 metastatic biopsies were collected from CRPC patients who would be treated with abiraterone plus dutasteride (Clinical Trial NCT01393730). As controls, 36 benign prostatic specimens were collected from patients undergoing prostate reduction surgery for symptoms of bladder outlet obstruction secondary to ...


Labrad : Vol 46, Issue 1 - March 2020, Aga Khan University Hospital, Karachi 2020 Aga Khan University

Labrad : Vol 46, Issue 1 - March 2020, Aga Khan University Hospital, Karachi

LABRAD

  • Role of Immunofluorescence Studies in the Diagnosis of Autoimmune Disorders
  • Cystathionine Beta-Synthase Deficiency
  • Treatment of Factor VIII Inhibitor
  • Effective Internal Communication in Laboratories
  • Digital Breast Tomosynthesis
  • Overview of Common Myeloproliferative Neoplasms
  • Clinical Significance of free Androgen Index (FAI)
  • Radiology Quiz
  • The Best of the Past
  • Section Of Histopathology: Newer Horizons
  • A Webinar Series ‘Rare Links’
  • A Look into the Eye can Unleash Vital Diagnostic Pearls for 32 Rare Disorders
  • Lab & Rad Mesh up for the Early Recognition of Rare Disorders
  • Polaroid


Isolated Forefoot Juvenile Xanthogranuloma: Unique Case Study And Treatment In A Pediatric Patient, Brian Derner DPM, Kristine Hoffman, Amy Storfa MD, Dustin Kruse DPM, Paul A. Stone DPM, FACFAS 2020 HCA Healthcare

Isolated Forefoot Juvenile Xanthogranuloma: Unique Case Study And Treatment In A Pediatric Patient, Brian Derner Dpm, Kristine Hoffman, Amy Storfa Md, Dustin Kruse Dpm, Paul A. Stone Dpm, Facfas

Podiatry

Juvenile xanthogranulomas (JXG) are a benign histiocytic cell proliferative disorder in early childhood. They most commonly present within the first two years of life with papular or nodular changes to the skin on the head, neck or upper trunk. Xanthogranulomas are mostly self-limiting, can be singular or multiple, and rarely can infer a systemic disease process1. The purpose of this study was to publish a unique finding of an extra-tendinous solitary mass in an otherwise healthy 17-year old, with surgical and medical treatment after diagnosis.


B Cells Migrate Into Remote Brain Areas And Support Neurogenesis And Functional Recovery After Focal Stroke In Mice, Sterling B. Ortega, Vanessa O. Torres, Sarah E. Latchney, Cody W. Whoolery, Ibrahim Z. Noorbhai, Katie Poinsatte, Uma M. Selvaraj, Monica A. Benson, Anouk J. M. Meeuwissen, Erik J. Plautz, Xiangmei Kong, Denise M. Ramirez, Apoorva D. Ajay, Julian P. Meeks, Mark P. Goldberg, Nancy L. Monson, Amelia J. Eisch, Ann M. Stowe 2020 University of Iowa

B Cells Migrate Into Remote Brain Areas And Support Neurogenesis And Functional Recovery After Focal Stroke In Mice, Sterling B. Ortega, Vanessa O. Torres, Sarah E. Latchney, Cody W. Whoolery, Ibrahim Z. Noorbhai, Katie Poinsatte, Uma M. Selvaraj, Monica A. Benson, Anouk J. M. Meeuwissen, Erik J. Plautz, Xiangmei Kong, Denise M. Ramirez, Apoorva D. Ajay, Julian P. Meeks, Mark P. Goldberg, Nancy L. Monson, Amelia J. Eisch, Ann M. Stowe

Neurology Faculty Publications

Lymphocytes infiltrate the stroke core and penumbra and often exacerbate cellular injury. B cells, however, are lymphocytes that do not contribute to acute pathology but can support recovery. B cell adoptive transfer to mice reduced infarct volumes 3 and 7 d after transient middle cerebral artery occlusion (tMCAo), independent of changing immune populations in recipient mice. Testing a direct neurotrophic effect, B cells cocultured with mixed cortical cells protected neurons and maintained dendritic arborization after oxygen-glucose deprivation. Whole-brain volumetric serial two-photon tomography (STPT) and a custom-developed image analysis pipeline visualized and quantified poststroke B cell diapedesis throughout the brain, including ...


Hierarchical Clustering Analyses Of Plasma Proteins In Subjects With Cardiovascular Risk Factors Identify Informative Subsets Based On Differential Levels Of Angiogenic And Inflammatory Biomarkers, Zachary Winder, Tiffany L. Sudduth, David W. Fardo, Qiang Cheng, Larry B. Goldstein, Peter T. Nelson, Frederick A. Schmitt, Gregory A. Jicha, Donna M. Wilcock 2020 University of Kentucky

Hierarchical Clustering Analyses Of Plasma Proteins In Subjects With Cardiovascular Risk Factors Identify Informative Subsets Based On Differential Levels Of Angiogenic And Inflammatory Biomarkers, Zachary Winder, Tiffany L. Sudduth, David W. Fardo, Qiang Cheng, Larry B. Goldstein, Peter T. Nelson, Frederick A. Schmitt, Gregory A. Jicha, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

Agglomerative hierarchical clustering analysis (HCA) is a commonly used unsupervised machine learning approach for identifying informative natural clusters of observations. HCA is performed by calculating a pairwise dissimilarity matrix and then clustering similar observations until all observations are grouped within a cluster. Verifying the empirical clusters produced by HCA is complex and not well studied in biomedical applications. Here, we demonstrate the comparability of a novel HCA technique with one that was used in previous biomedical applications while applying both techniques to plasma angiogenic (FGF, FLT, PIGF, Tie-2, VEGF, VEGF-D) and inflammatory (MMP1, MMP3, MMP9, IL8, TNFα) protein data to ...


Point-Of-Care Hpv Molecular Diagnostics For A Test-And-Treat Model In High-Risk Hiv Populations, Shahin Sayed, Michael Chung, Marleen Temmerman 2020 Aga Khan University

Point-Of-Care Hpv Molecular Diagnostics For A Test-And-Treat Model In High-Risk Hiv Populations, Shahin Sayed, Michael Chung, Marleen Temmerman

Pathology, East Africa

Strategies for cervical cancer prevention and control in low-income and middle-income countries (LMICs) require concerted efforts to improve screening and access to treatment, especially in high-risk HIV populations. LMICs bear the largest burden of HIV infection, human papillomavirus (HPV) infection is common among HIV-infected women, risk of cervical cancer is increased in women with HIV/AIDS, and HIV clinics provide opportunities to screen and treat for cervical cancer in this population.


Genetic And Functional Approaches To Understanding Autoimmune And Inflammatory Pathologies, Abbas Raza 2020 University of Vermont

Genetic And Functional Approaches To Understanding Autoimmune And Inflammatory Pathologies, Abbas Raza

Graduate College Dissertations and Theses

Our understanding of genetic predisposition to inflammatory and autoimmune diseases has been enhanced by large scale quantitative trait loci (QTL) linkage mapping and genome-wide association studies (GWAS). However, the resolution and interpretation of QTL linkage mapping or GWAS findings are limited. In this work, we complement genetic predictions for several human diseases including multiple sclerosis (MS) and systemic capillary leakage syndrome (SCLS) with genetic and functional data in model organisms to associate genes with phenotypes and diseases.

Focusing on MS, an autoimmune inflammatory disease of the central nervous system (CNS), we experimentally tested the effect of three of the GWAS ...


Tick-Borne Infections In New Hampshire: An Evaluation Of The Diagnostic Process In A Local Patient Population, Katherine Anderson 2020 University of New Hampshire, Durham

Tick-Borne Infections In New Hampshire: An Evaluation Of The Diagnostic Process In A Local Patient Population, Katherine Anderson

Honors Theses and Capstones

Overall, approximately 95 percent of reported cases of vector-borne disease were associated with ticks, making these the most medically important group of arthropods in the United States.1 Despite the prevalence of tick-borne infections, the process for the diagnosis of this condition is not well studied. This study aims to analyze data from a pool of 100 patients who underwent testing for tick-borne disease in the same institution in Dover, New Hampshire during the most recent peak tick season of 2019. Information utilized in this study included: patient age, sex, location of testing (inpatient versus outpatient), diagnostic testing methods used ...


Stochastic Expression Of Sae-Dependent Virulence Genes During Staphylococcus Aureus Biofilm Development Is Dependent On Saes, Elizabeth A. Delmain, Derek E. Moormeier, Jennifer L. Endres, Rebecca E. Hodges, Marat R. Sadykov, Alexander R. Horswill, Kenneth W. Bayles 2020 University of Nebraska Medical Center

Stochastic Expression Of Sae-Dependent Virulence Genes During Staphylococcus Aureus Biofilm Development Is Dependent On Saes, Elizabeth A. Delmain, Derek E. Moormeier, Jennifer L. Endres, Rebecca E. Hodges, Marat R. Sadykov, Alexander R. Horswill, Kenneth W. Bayles

Journal Articles: Pathology and Microbiology

The intricate process of biofilm formation in the human pathogen Staphylococcus aureus involves distinct stages during which a complex mixture of matrix molecules is produced and modified throughout the developmental cycle. Early in biofilm development, a subpopulation of cells detaches from its substrate in an event termed “exodus” that is mediated by SaePQRS-dependent stochastic expression of a secreted staphylococcal nuclease, which degrades extracellular DNA within the matrix, causing the release of cells and subsequently allowing for the formation of metabolically heterogenous microcolonies. Since the SaePQRS regulatory system is involved in the transcriptional control of multiple S. aureus virulence factors, the ...


Fluorescent Sensor Arrays Can Predict And Quantify The Composition Of Multicomponent Bacterial Samples, Denis Svechkarev, Marat Sadykov, Lucas J. Houser, Kenneth W. Bayles, Aaron M. Mohs 2020 University of Nebraska Medical Center

Fluorescent Sensor Arrays Can Predict And Quantify The Composition Of Multicomponent Bacterial Samples, Denis Svechkarev, Marat Sadykov, Lucas J. Houser, Kenneth W. Bayles, Aaron M. Mohs

Journal Articles: Pathology and Microbiology

Fast and reliable identification of infectious disease agents is among the most important challenges for the healthcare system. The discrimination of individual components of mixed infections represents a particularly difficult task. In the current study we further expand the functionality of a ratiometric sensor array technology based on small-molecule environmentally-sensitive organic dyes, which can be successfully applied for the analysis of mixed bacterial samples. Using pattern recognition methods and data from pure bacterial species, we demonstrate that this approach can be used to quantify the composition of mixtures, as well as to predict their components with the accuracy of ~80 ...


Tlr2 And Caspase-1 Signaling Are Critical For Bacterial Containment But Not Clearance During Craniotomy-Associated Biofilm Infection, Amy L. Aldrich, Cortney E. Heim, Wen Shi, Rachel W. Fallet, Bin Duan, Tammy Kielian 2020 Moffitt Cancer Center

Tlr2 And Caspase-1 Signaling Are Critical For Bacterial Containment But Not Clearance During Craniotomy-Associated Biofilm Infection, Amy L. Aldrich, Cortney E. Heim, Wen Shi, Rachel W. Fallet, Bin Duan, Tammy Kielian

Journal Articles: Pathology and Microbiology

BACKGROUND: A craniotomy is required to access the brain for tumor resection or epilepsy treatment, and despite precautionary measures, infectious complications occur at a frequency of 1-3%. Approximately half of craniotomy infections are caused by Staphylococcus aureus (S. aureus) that forms a biofilm on the bone flap, which is recalcitrant to antibiotics. Our prior work in a mouse model of S. aureus craniotomy infection revealed a critical role for myeloid differentiation factor 88 (MyD88) in bacterial containment and pro-inflammatory mediator production. Since numerous receptors utilize MyD88 as a signaling adaptor, the current study examined the importance of Toll-like receptor 2 ...


Monocyte Metabolic Reprogramming Promotes Pro-Inflammatory Activity And Staphylococcus Aureus Biofilm Clearance, Kelsey J. Yamada, Cortney E. Heim, Xinyuan Xi, Kuldeep S. Attri, Dezhen Wang, Wenting Zhang, Pankaj K. Singh, Tatiana K. Bronich, Tammy Kielian 2020 University of Nebraska Medical Center

Monocyte Metabolic Reprogramming Promotes Pro-Inflammatory Activity And Staphylococcus Aureus Biofilm Clearance, Kelsey J. Yamada, Cortney E. Heim, Xinyuan Xi, Kuldeep S. Attri, Dezhen Wang, Wenting Zhang, Pankaj K. Singh, Tatiana K. Bronich, Tammy Kielian

Journal Articles: Pathology and Microbiology

Biofilm-associated prosthetic joint infections (PJIs) cause significant morbidity due to their recalcitrance to immune-mediated clearance and antibiotics, with Staphylococcus aureus (S. aureus) among the most prevalent pathogens. We previously demonstrated that S. aureus biofilm-associated monocytes are polarized to an anti-inflammatory phenotype and the adoptive transfer of pro-inflammatory macrophages attenuated biofilm burden, highlighting the critical role of monocyte/macrophage inflammatory status in dictating biofilm persistence. The inflammatory properties of leukocytes are linked to their metabolic state, and here we demonstrate that biofilm-associated monocytes exhibit a metabolic bias favoring oxidative phosphorylation (OxPhos) and less aerobic glycolysis to facilitate their anti-inflammatory activity and ...


An Integrated Computational And Experimental Study To Investigate Staphylococcus Aureus Metabolism, Mohammad Mazharul Islam, Vinai Chittezham Thomas, Matthew Van Beek, Jong-Sam Ahn, Abdulelah A. Alqarzaee, Chunyi Zhou, Paul D. Fey, Kenneth W. Bayles, Rajib Saha 2020 University of Nebraska - Lincoln

An Integrated Computational And Experimental Study To Investigate Staphylococcus Aureus Metabolism, Mohammad Mazharul Islam, Vinai Chittezham Thomas, Matthew Van Beek, Jong-Sam Ahn, Abdulelah A. Alqarzaee, Chunyi Zhou, Paul D. Fey, Kenneth W. Bayles, Rajib Saha

Journal Articles: Pathology and Microbiology

Staphylococcus aureus is a metabolically versatile pathogen that colonizes nearly all organs of the human body. A detailed and comprehensive knowledge of staphylococcal metabolism is essential to understand its pathogenesis. To this end, we have reconstructed and experimentally validated an updated and enhanced genome-scale metabolic model of S. aureus USA300_FPR3757. The model combined genome annotation data, reaction stoichiometry, and regulation information from biochemical databases and previous strain-specific models. Reactions in the model were checked and fixed to ensure chemical balance and thermodynamic consistency. To further refine the model, growth assessment of 1920 nonessential mutants from the Nebraska Transposon Mutant Library ...


Is It T3 Thyrotoxicosis? A Case Of Falsely Elevated Tri-Iodothyronine (T3) Levels Leading To A Diagnosis Of Multiple Myeloma, Nanik Ram, Saira Furqan, Sibtain Ahmed 2019 Aga Khan University

Is It T3 Thyrotoxicosis? A Case Of Falsely Elevated Tri-Iodothyronine (T3) Levels Leading To A Diagnosis Of Multiple Myeloma, Nanik Ram, Saira Furqan, Sibtain Ahmed

Section of Diabetes, Endocrinology and Metabolism

We are presenting a case of falsely elevated T3 levels in a patient due to interference from monoclonal immunoglobulins. A 56-year-old, clinically euthyroid man referred to the endocrinology clinic of the Aga Khan university, Karachi Pakistan, for possible T3 thyrotoxicosis after thyroid function tests revealed total T3 >12.32 nmol/L (reference range 0.6-2.79), normal TSH, and total T4 level. There was a mismatch in clinical and laboratory parameters and preliminary laboratory results were suggestive of thyroid binding globulin abnormalities. Further evaluation in this context unmasked multiple myeloma. The presence of monoclonal immunoglobulins can lead to assay interference ...


Pbrm1 Acts As A P53 Lysine-Acetylation Reader To Suppress Renal Tumor Growth., Weijia Cai, Liya Su, Lili Liao, Zongzhi Z Liu, Lauren Langbein, Essel Dulaimi, Joseph R Testa, Robert G Uzzo, Zhijiu Zhong, Wei Jiang, Qin Yan, Qing Zhang, Haifeng Yang 2019 Thomas Jefferson University

Pbrm1 Acts As A P53 Lysine-Acetylation Reader To Suppress Renal Tumor Growth., Weijia Cai, Liya Su, Lili Liao, Zongzhi Z Liu, Lauren Langbein, Essel Dulaimi, Joseph R Testa, Robert G Uzzo, Zhijiu Zhong, Wei Jiang, Qin Yan, Qing Zhang, Haifeng Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

p53 acetylation is indispensable for its transcriptional activity and tumor suppressive function. However, the identity of reader protein(s) for p53 acetylation remains elusive. PBRM1, the second most highly mutated tumor suppressor gene in kidney cancer, encodes PBRM1. Here, we identify PBRM1 as a reader for p53 acetylation on lysine 382 (K382Ac) through its bromodomain 4 (BD4). Notably, mutations on key residues of BD4 disrupt recognition of p53 K382Ac. The mutation in BD4 also reduces p53 binding to promoters of target genes such as CDKN1A (p21). Consequently, the PBRM1 BD4 mutant fails to fully support p53 transcriptional activity and is ...


Sarcoidosis Of The Mandibular Condyle: A Rare Disease That Can Mimic Malignancy, Chad Sloan, Ben LaCrosse, Lei Yu, Alexander Braun, Scott Lauer, Timothy Donovan, John Baker, Jason Untrauer 2019 University of Nebraska Medical Center

Sarcoidosis Of The Mandibular Condyle: A Rare Disease That Can Mimic Malignancy, Chad Sloan, Ben Lacrosse, Lei Yu, Alexander Braun, Scott Lauer, Timothy Donovan, John Baker, Jason Untrauer

Graduate Medical Education Research Journal

Sarcoidosis can involve any of the organs, however intraosseous involvement is rare and ranges from 5 to 15%, with lesions of the mandible being even rarer – currently with few known cases reported. Intraosseous lesions involving the mandible have been noted to be asymptomatic or associated with chronic jaw pain. Additionally, mandibular involvement can present as a lytic bone lesion mimicking osseous malignancy. Chronic polyarthritis is commonly associated with the progression of sarcoidosis and intraosseous involvement has been considered a late-stage sequelae. We report a case of biopsy-proven sarcoidosis within the mandibular condyle in an asymptomatic 56-year-old Caucasian female who had ...


Orbit Image Analysis Machine Learning Software Can Be Used For The Histological Quantification Of Acute Ischemic Stroke Blood Clots, Sean Fitzgerald, Shunli Wang, Daying Dai, Dennis H. Murphree Jr., Abhay Pandit, Andrew Douglas, Asim Rizvi, Ramanathan Kadirvel, Michael Gilvarry, Ray McCarthy, Manuel Stritt, Matthew J. Gounis, Waleed Brinjikji, David F. Kallmes, Karen M. Doyle 2019 National University of Ireland, Galway

Orbit Image Analysis Machine Learning Software Can Be Used For The Histological Quantification Of Acute Ischemic Stroke Blood Clots, Sean Fitzgerald, Shunli Wang, Daying Dai, Dennis H. Murphree Jr., Abhay Pandit, Andrew Douglas, Asim Rizvi, Ramanathan Kadirvel, Michael Gilvarry, Ray Mccarthy, Manuel Stritt, Matthew J. Gounis, Waleed Brinjikji, David F. Kallmes, Karen M. Doyle

Open Access Articles

Our aim was to assess the utility of a novel machine learning software (Orbit Image Analysis) in the histological quantification of acute ischemic stroke (AIS) clots. We analyzed 50 AIS blood clots retrieved using mechanical thrombectomy procedures. Following HandE staining, quantification of clot components was performed by two different methods: a pathologist using a reference standard method (Adobe Photoshop CC) and an experienced researcher using Orbit Image Analysis. Following quantification, the clots were categorized into 3 types: RBC dominant (>/=60% RBCs), Mixed and Fibrin dominant ( > /=60% Fibrin). Correlations between clot composition and Hounsfield Units density on Computed Tomography (CT) were ...


Image Restoration Using Automatic Damaged Regions Detection And Machine Learning-Based Inpainting Technique, Chloe Martin-King 2019 Chapman University

Image Restoration Using Automatic Damaged Regions Detection And Machine Learning-Based Inpainting Technique, Chloe Martin-King

Computational and Data Sciences (PhD) Dissertations

In this dissertation we propose two novel image restoration schemes. The first pertains to automatic detection of damaged regions in old photographs and digital images of cracked paintings. In cases when inpainting mask generation cannot be completely automatic, our detection algorithm facilitates precise mask creation, particularly useful for images containing damage that is tedious to annotate or difficult to geometrically define. The main contribution of this dissertation is the development and utilization of a new inpainting technique, region hiding, to repair a single image by training a convolutional neural network on various transformations of that image. Region hiding is also ...


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