Investigating The Effects Of Brainstem Neuronal Adaptation On Cardiovascular Homeostasis., 2020 Institute for Systems Biology, Seattle, WA, United States.
Investigating The Effects Of Brainstem Neuronal Adaptation On Cardiovascular Homeostasis., James H Park, Jonathan Gorky, Babatunde Ogunnaike, Rajanikanth Vadigepalli, James S Schwaber
Articles, Abstracts, and Reports
Central coordination of cardiovascular function is accomplished, in part, by the baroreceptor reflex, a multi-input multi-output physiological control system that regulates the activity of the parasympathetic and sympathetic nervous systems via interactions among multiple brainstem nuclei. Recent single-cell analyses within the brain revealed that individual neurons within and across brain nuclei exhibit distinct transcriptional states contributing to neuronal function. Such transcriptional heterogeneity complicates the task of understanding how neurons within and across brain nuclei organize and function to process multiple inputs and coordinate cardiovascular functions within the larger context of the baroreceptor reflex. However, prior analysis of brainstem neurons revealed …
Glycogen Storage Diseases-Time To Flip The Outdated Diagnostic Approach Centered On Liver Biopsy With The Molecular Testing, 2020 Aga Khan University
Glycogen Storage Diseases-Time To Flip The Outdated Diagnostic Approach Centered On Liver Biopsy With The Molecular Testing, Sibtain Ahmed, Bushra Afroze
Department of Pathology and Laboratory Medicine
The glycogen storage diseases (GSDs) are a group of inherited metabolic disorders that result from a defect in any one of several enzymes required for either glycogen synthesis or glycogen degradation. The traditional diagnostic approach is based on the invasive hepatic or muscle biopsies, which are neither cost effective nor convenient. Molecular (gene testing) has emerged over the course of past few years as a robust alternative diagnostic tool, which not only confirms the diagnosis of GSDs but also clearly differentiates the types of GSDs allowing the initiation of the type-specific appropriate treatment for the particular type of GSDs. The …
Kidney Stone Analysis And Spiritual Guides (Pir Faqir): The Known-Unknowns, 2020 Aga Khan University
Kidney Stone Analysis And Spiritual Guides (Pir Faqir): The Known-Unknowns, Lena Jafri, Aysha Habib Khan, Humaira Asif
Department of Pathology and Laboratory Medicine
No abstract provided.
Monocyte Metabolic Reprogramming Promotes Pro-Inflammatory Activity And Staphylococcus Aureus Biofilm Clearance, 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 biofilm …
Kidney Stone Analysis And Spiritual Guides (Pir Faqir): The Known-Unknowns, 2020 Aga Khan University
Kidney Stone Analysis And Spiritual Guides (Pir Faqir): The Known-Unknowns, Lena Jafri, Aysha Habib Khan, Humaira Asif
Department of Pathology and Laboratory Medicine
No abstract provided.
Use Of Pefloxacin As A Surrogate Marker To Detect Ciprofloxacin Susceptibility In Salmonella Enterica Serotypes Typhi And Paratyphi A, 2020 Aga Khan University
Use Of Pefloxacin As A Surrogate Marker To Detect Ciprofloxacin Susceptibility In Salmonella Enterica Serotypes Typhi And Paratyphi A, Safia Moin, Mohammad Zeeshan, Sidra Laiq, Ahmed Raheem, Afia Zafar
Department of Pathology and Laboratory Medicine
Objective: To determine the use of pefloxacin as a surrogate marker to detect fluoroquinolone (ciprofloxacin) susceptibility against Salmonella enterica serotypes Typhi and Paratyphi A.
Methods: The prospective, descriptive cross-sectional study was conducted at the Aga Khan University Hospital, Karachi, from September 2016 to March 2018, and comprised Salmonella Typhi and Paratyphi A isolates of blood cultures. Disk susceptibility tests and broth microdilution to test minimum inhibitory concentration were performed as per standard guidelines. Data was analysed using SPSS 21.
Results: Of the 138 isolates, 91(66%) were intermediate resistant to ciprofloxacin but were resistant to pefloxacin, 42(30%) were resistant to both …
Is It T3 Thyrotoxicosis? A Case Of Falsely Elevated Tri-Iodothyronine (T3) Levels Leading To A Diagnosis Of Multiple Myeloma, 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 and spurious results. To …
Pbrm1 Acts As A P53 Lysine-Acetylation Reader To Suppress Renal Tumor Growth., 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 defective …
A Community Of Care: Patterns Of Pathology And Trauma With A Focus On The Bioarchaeology Of Care At Carrier Mills, Il (10,000 – 1000 Bp), 2019 University of Nevada, Las Vegas
A Community Of Care: Patterns Of Pathology And Trauma With A Focus On The Bioarchaeology Of Care At Carrier Mills, Il (10,000 – 1000 Bp), Alecia Schrenk
UNLV Theses, Dissertations, Professional Papers, and Capstones
Illness and injury are universal human experiences which are endowed with cultural meaning. Bioarchaeology has only recently begun to engage with the socioeconomic impacts of illness, injury, impairment, and healthcare provisioning in the past. This study examines how the Middle Archaic (6000 – 300 BC) and Early Woodland (1000 – 200 BC) hunter-gatherer community of Carrier Mills, Illinois was affected by and managed the socioeconomic burdens of poor health. The data presented in this study used bioarchaeological analyses to reveal patterns of poor health and healthcare provisioning within the Carrier Mills community. Bioarchaeology is ideally situated for such investigations since …
Sarcoidosis Of The Mandibular Condyle: A Rare Disease That Can Mimic Malignancy, 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 …
Multiple Mitochondrial Thioesterases Have Distinct Tissue And Substrate Specificity And Coa Regulation, Suggesting Unique Functional Roles., 2019 Thomas Jefferson University
Multiple Mitochondrial Thioesterases Have Distinct Tissue And Substrate Specificity And Coa Regulation, Suggesting Unique Functional Roles., Carmen Bekeova, Lauren Anderson-Pullinger, Kevin Boye, Felix Boos, Yana Sharpadskaya, Johannes M Herrmann, Erin L. Seifert
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Acyl-CoA thioesterases (Acots) hydrolyze fatty acyl-CoA esters. Acots in the mitochondrial matrix are poised to mitigate β-oxidation overload and maintain CoA availability. Several Acots associate with mitochondria, but whether they all localize to the matrix, are redundant, or have different roles is unresolved. Here, we compared the suborganellar localization, activity, expression, and regulation among mitochondrial Acots (Acot2, -7, -9, and -13) in mitochondria from multiple mouse tissues and from a model of Acot2 depletion. Acot7, -9, and -13 localized to the matrix, joining Acot2 that was previously shown to localize there. Mitochondria from heart, skeletal muscle, brown adipose tissue, and …
Image Restoration Using Automatic Damaged Regions Detection And Machine Learning-Based Inpainting Technique, 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 …
Worldwide Network For Blood And Marrow Transplantation Recommendations For Establishing A Hematopoietic Stem Cell Transplantation Program In Countries With Limited Resources, Part Ii: Clinical, Technical, And Socioeconomic Considerations, 2019 King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
Worldwide Network For Blood And Marrow Transplantation Recommendations For Establishing A Hematopoietic Stem Cell Transplantation Program In Countries With Limited Resources, Part Ii: Clinical, Technical, And Socioeconomic Considerations, Mahmoud Aljurf, Daniel Weisdorf, Shahrukh Hashmi, Amr Nassar, Eliane Gluckman, Mohamad Mohty, Doug Rizzo, Marcelo Pasquini, Mehdi Hamadani, Salman Adil
Department of Pathology and Laboratory Medicine
The development of hematopoietic stem cell transplantation (HSCT) programs can face significant challenges in most developing countries because such endeavors must compete with other government health care priorities, including the delivery of basic services. Although this is may be a limiting factor, these countries should prioritize development of the needed expertise to offer state-of-the-art treatments, including transplantation, by providing financial, technological, legal, ethical, and other needed support. This would prove beneficial in providing successful programs customized to the needs of their population and potentially provide long-term cost savings by circumventing the need for their citizens to seek care abroad. The …
New Insights Into The Lactate Shuttle: Role Of Mct4 In The Modulation Of The Exercise Capacity., 2019 Thomas Jefferson University
New Insights Into The Lactate Shuttle: Role Of Mct4 In The Modulation Of The Exercise Capacity., Sara Bisetto, Megan C Wright, Romana A Nowak, Angelo C Lepore, Tejvir S Khurana, Emanuele Loro, Nancy J Philp
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Lactate produced by muscle during high-intensity activity is an important end product of glycolysis that supports whole body metabolism. The lactate shuttle model suggested that lactate produced by glycolytic muscle fibers is utilized by oxidative fibers. MCT4 is a proton coupled monocarboxylate transporter preferentially expressed in glycolytic muscle fibers and facilitates the lactate efflux. Here we investigated the exercise capacity of mice with disrupted lactate shuttle due to global deletion of MCT4 (MCT4−/−) or muscle-specific deletion of the accessory protein Basigin (iMSBsg−/−). Although MCT4−/− and iMSBsg−/− mice have normal muscle morphology and contractility, only MCT4−/− mice exhibit an exercise intolerant …
Determinants Of Campylobacter Infection And Association With Growth And Enteric Inflammation In Children Under 2 Years Of Age In Low-Resource Settings, 2019 Nutrition and Clinical Services Division, icddr,b, Dhaka, Bangladesh
Determinants Of Campylobacter Infection And Association With Growth And Enteric Inflammation In Children Under 2 Years Of Age In Low-Resource Settings, Md Ahshanul Haque, James A. Platts-Mills, Estomih Mduma, Ladaporn Bodhidatta, Pascal Bessong, Sadia Shakoor, Gagandeep Kang, Margaret N. Kosek, Aldo A M Lima, Zulfiqar Ahmed Bhutta
Department of Pathology and Laboratory Medicine
Campylobacter species infections have been associated with malnutrition and intestinal inflammation among children in low-resource settings. However, it remains unclear whether that association is specific to Campylobacter jejuni/coli. The aim of this study was to assess the association between both all Campylobacter species infections and Campylobacter jejuni/coli infections on growth and enteric inflammation in children aged 1-24 months. We analyzed data from 1715 children followed from birth until 24 months of age in the MAL-ED birth cohort study, including detection of Campylobacter species by enzyme immunoassay and Campylobacter jejuni/coli by quantitative PCR in stool samples. Myeloperoxidase (MPO) concentration in stool, …
Plasma Cell Leukemia Mimicking Hairy Cell Leukemia: Extended Role Of Immunophenotyping In Correct Diagnosis, 2019 Aga Khan University
Plasma Cell Leukemia Mimicking Hairy Cell Leukemia: Extended Role Of Immunophenotyping In Correct Diagnosis, Ayesha Majeed Memon, Natasha Ali
Department of Pathology and Laboratory Medicine
No abstract provided.
Nearly Complete Genome Sequences Of 17 Enterovirus D68 Strains From Kansas City, Missouri, 2018, 2019 Vanderbilt University Medical Center
Nearly Complete Genome Sequences Of 17 Enterovirus D68 Strains From Kansas City, Missouri, 2018, Suman B. Pakala, Yi Tan, Ferdaus Hassan, Annie Mai, Robert H. Markowitz, Meghan H. Shilts, Seesandra V. Rajagopala, Rangaraj Selvarangan, Suman R. Das
Manuscripts, Articles, Book Chapters and Other Papers
Here, we report 17 nearly complete genome sequences of enterovirus D68 (EV-D68) isolated from Kansas City, MO, in 2018. Phylogenetic analysis suggests that these strains belong to subclade B3, similar to the ones that caused the 2016 epidemics in the United States but different from the 2014 outbreak B1 strains.
A Physiologically-Based Pharmacokinetic Model For Targeting Calcitriol-Conjugated Quantum Dots To Inflammatory Breast Cancer Cells., 2019 University of Delaware
A Physiologically-Based Pharmacokinetic Model For Targeting Calcitriol-Conjugated Quantum Dots To Inflammatory Breast Cancer Cells., James Forder, Mallory Smith, Margot Wagner, Rachel J. Schaefer, Jonathan Gorky, Kenneth L. Van Golen, Anja Nohe, Prasad Dhurjati
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Quantum dots (QDs) conjugated with 1,25 dihydroxyvitamin D3 (calcitriol) and Mucin-1 (MUC-1) antibodies (SM3) have been found to target inflammatory breast cancer (IBC) tumors and reduce proliferation, migration, and differentiation of these tumors in mice. A physiologically-based pharmacokinetic model has been constructed and optimized to match experimental data for multiple QDs: control QDs, QDs conjugated with calcitriol, and QDs conjugated with both calcitriol and SM3 MUC1 antibodies. The model predicts continuous QD concentration for key tissues in mice distinguished by IBC stage (healthy, early-stage, and late-stage). Experimental and clinical efforts in QD treatment of IBC can be augmented by in …
Prevalence Of Malaria Reported During Summer And Winter At A Tertiary Care Hospital In Karachi, Pakistan, 2019 Aga Khan University
Prevalence Of Malaria Reported During Summer And Winter At A Tertiary Care Hospital In Karachi, Pakistan, Fazal M. Arain, Aisha Memon, Roohi Jamal, Ahmed Raheem Buksh, Mohammad Asim Beg
Department of Biological & Biomedical Sciences
This study was designed to determine the prevalence and type of malaria cases that presented throughout the year 2014 in a tertiary care hospital in Karachi, Pakistan. A total of 1099 cases, (377 females, 722 males) were reported. Plasmodium vivax (P. vivax) was discovered in 93.7% cases compared to 6.3% Plasmodium falciparum (P. falciparum). Based on the highest and lowest weather temperatures, in summer (June, July and August) and in winter (December, January and February) were differentiated. The number of cases were greater during summer months compared to winter. Interestingly, the ratio of P. falciparum to P. vivax during winter …
Outcomes Of Hematopoietic Cell Transplantation In Patients With Germline Samd9/Samd9l Mutations., 2019 Children's Mercy Hospital
Outcomes Of Hematopoietic Cell Transplantation In Patients With Germline Samd9/Samd9l Mutations., Ibrahim A. Ahmed, Midhat S. Farooqi, Mark T. Vander Lugt, Jessica Boklan, Melissa Rose, Erika D. Friehling, Brandon Triplett, Kenneth Lieuw, Blachy Davila Saldana, Christine M. Smith, Jason R. Schwartz, Rakesh K. Goyal
Manuscripts, Articles, Book Chapters and Other Papers
Germline mutations in SAMD9 and SAMD9L genes cause MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy) (OMIM: *610456) and ataxia-pancytopenia (OMIM: *611170) syndromes, respectively, and are associated with chromosome 7 deletions, myelodysplastic syndrome (MDS), and bone marrow failure. In this retrospective series, we report outcomes of allogeneic hematopoietic cell transplantation (HCT) in patients with hematologic disorders associated with SAMD9/SAMD9L mutations. Twelve patients underwent allogeneic HCT for MDS (n = 10), congenital amegakaryocytic thrombocytopenia (n = 1), and dyskeratosis congenita (n = 1). Exome sequencing revealed heterozygous mutations in SAMD9 (n = 6) or SAMD9L (n = …