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A Study Of The Relationship Between Uric Acid And Substantia Nigra Brain Connectivity In Patients With Rem Sleep Behavior Disorder And Parkinson’S Disease, Timothy M. Ellmore, Jessika Suescun, Richard J. Castriotta, Mya C. Schiess Aug 2020

A Study Of The Relationship Between Uric Acid And Substantia Nigra Brain Connectivity In Patients With Rem Sleep Behavior Disorder And Parkinson’S Disease, Timothy M. Ellmore, Jessika Suescun, Richard J. Castriotta, Mya C. Schiess

Publications and Research

Low levels of the natural antioxidant uric acid (UA) and the presence of REM sleep behavior disorder (RBD) are both associated with an increased likelihood of developing Parkinson’s disease (PD). RBD and PD are also accompanied by basal ganglia dysfunction including decreased nigrostriatal and nigrocortical resting state functional connectivity. Despite these independent findings, the relationship between UA and substantia nigra (SN) functional connectivity remains unknown. In the present study, voxelwise analysis of covariance was used in a cross-sectional design to explore the relationship between UA and whole-brain SN functional connectivity using the eyes-open resting state fMRI method in controls without …


Considerations For Studying Sex As A Biological Variable In Spinal Cord Injury, Andrew N. Stewart, Steven M. Maclean, Arnold J. Stromberg, Jessica P. Whelan, William M. Bailey, John C. Gensel, Melinda E. Wilson Aug 2020

Considerations For Studying Sex As A Biological Variable In Spinal Cord Injury, Andrew N. Stewart, Steven M. Maclean, Arnold J. Stromberg, Jessica P. Whelan, William M. Bailey, John C. Gensel, Melinda E. Wilson

Physiology Faculty Publications

In response to NIH initiatives to investigate sex as a biological variable in preclinical animal studies, researchers have increased their focus on male and female differences in neurotrauma. Inclusion of both sexes when modeling neurotrauma is leading to the identification of novel areas for therapeutic and scientific exploitation. Here, we review the organizational and activational effects of sex hormones on recovery from injury and how these changes impact the long-term health of spinal cord injury (SCI) patients. When determining how sex affects SCI it remains imperative to expand outcomes beyond locomotor recovery and consider other complications plaguing the quality of …


Dha Modulates Manf And Trem2 Abundance, Enhances Neurogenesis, Reduces Infarct Size, And Improves Neurological Function After Experimental Ischemic Stroke, Ludmila Belayev, Sung Ha Hong, Raul S. Freitas, Hemant Menghani, Shawn J. Marcell, Larissa Khoutorova, Pranab K. Mukherjee, Madigan M. Reid, Reinaldo B. Oria, Nicolas G. Bazan Aug 2020

Dha Modulates Manf And Trem2 Abundance, Enhances Neurogenesis, Reduces Infarct Size, And Improves Neurological Function After Experimental Ischemic Stroke, Ludmila Belayev, Sung Ha Hong, Raul S. Freitas, Hemant Menghani, Shawn J. Marcell, Larissa Khoutorova, Pranab K. Mukherjee, Madigan M. Reid, Reinaldo B. Oria, Nicolas G. Bazan

School of Medicine Faculty Publications

Aims: Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a secretory neurotrophic factor protein that promotes repair after neuronal injury. The microglia cell surface receptor (triggering receptor expressed on myeloid cells-2; TREM2) regulates the production of pro- and antiinflammatory mediators after stroke. Here, we study MANF and TREM2 expression after middle cerebral artery occlusion (MCAo) and explore if docosahexaenoic acid (DHA) treatment exerts a potentiating effect. Methods: We used 2 hours of the MCAo model in rats and intravenously administered DHA or vehicle at 3 hours after the onset of MCAo. Neurobehavioral assessment was performed on days 1, 3, 7, and 14; …


Hepatic Stellate Cells And Hepatocarcinogenesis, Anna E Barry, Rajkumar Baldeosingh, Ryan Lamm, Keyur Patel, Kai Zhang, Dana A Dominguez, Kayla J Kirton, Ashesh P. Shah, Hien Dang Aug 2020

Hepatic Stellate Cells And Hepatocarcinogenesis, Anna E Barry, Rajkumar Baldeosingh, Ryan Lamm, Keyur Patel, Kai Zhang, Dana A Dominguez, Kayla J Kirton, Ashesh P. Shah, Hien Dang

Department of Surgery Faculty Papers

Hepatic stellate cells (HSCs) are a significant component of the hepatocellular carcinoma (HCC) tumor microenvironment (TME). Activated HSCs transform into myofibroblast-like cells to promote fibrosis in response to liver injury or chronic inflammation, leading to cirrhosis and HCC. The hepatic TME is comprised of cellular components, including activated HSCs, tumor-associated macrophages, endothelial cells, immune cells, and non-cellular components, such as growth factors, proteolytic enzymes and their inhibitors, and other extracellular matrix (ECM) proteins. Interactions between HCC cells and their microenvironment have become topics under active investigation. These interactions within the hepatic TME have the potential to drive carcinogenesis and create …


Ewing Sarcoma Family Of Tumors-Derived Small Extracellular Vesicle Proteomics Identify Potential Clinical Biomarkers., Glenson Samuel, Jennifer Crow, Jon B. Klein, Michael L. Merchant, Emily Nissen, Devin C. Koestler, Kris Laurence, Xiaobo Liang, Kathleen Neville, Vincent S. Staggs, Atif Ahmed, Safinur Atay, Andrew K. Godwin Aug 2020

Ewing Sarcoma Family Of Tumors-Derived Small Extracellular Vesicle Proteomics Identify Potential Clinical Biomarkers., Glenson Samuel, Jennifer Crow, Jon B. Klein, Michael L. Merchant, Emily Nissen, Devin C. Koestler, Kris Laurence, Xiaobo Liang, Kathleen Neville, Vincent S. Staggs, Atif Ahmed, Safinur Atay, Andrew K. Godwin

Manuscripts, Articles, Book Chapters and Other Papers

Purpose: Ewing Sarcoma Family of Tumors (ESFT), the second most common pediatric osseous malignancy, are characterized by the pathognomonic chromosomal EWS-ETS translocation. Outside of tumor biopsy, no clinically relevant ESFT biomarkers exist. Additionally, tumor burden assessment at diagnosis, monitoring of disease responsiveness to therapy, and detection of disease recurrence are limited to radiographic imaging. To identify new, clinically relevant biomarkers we evaluated the proteome of a subset of ESFT-derived small extracellular vesicles (sEVs).

Materials and methods: We performed the first high quality proteomic study of ESFT-derived sEVs from 5 ESFT cell lines representing the most common EWS-ETS fusion types and …


Fosl1 Is A Novel Mediator Of Endotoxin/Lipopolysaccharide-Induced Pulmonary Angiogenic Signaling., Christopher R. Nitkin, Sheng Xia, Heather Menden, Wei Yu, Min Xiong, Daniel P. Heruth, Shui Qing Ye, Venkatesh Sampath Aug 2020

Fosl1 Is A Novel Mediator Of Endotoxin/Lipopolysaccharide-Induced Pulmonary Angiogenic Signaling., Christopher R. Nitkin, Sheng Xia, Heather Menden, Wei Yu, Min Xiong, Daniel P. Heruth, Shui Qing Ye, Venkatesh Sampath

Manuscripts, Articles, Book Chapters and Other Papers

Systemic sepsis is a known risk factor for bronchopulmonary dysplasia (BPD) in premature infants, a disease characterized by dysregulated angiogenesis and impaired vascular and alveolar development. We have previoulsy reported that systemic endotoxin dysregulates pulmonary angiogenesis resulting in alveolar simplification mimicking BPD in neonatal mice, but the underlying mechanisms remain unclear. We undertook an unbiased discovery approach to identify novel signaling pathways programming sepsis-induced deviant lung angiogenesis. Pulmonary endothelial cells (EC) were isolated for RNA-Seq from newborn C57BL/6 mice treated with intraperitoneal lipopolysaccharide (LPS) to mimic systemic sepsis. LPS significantly differentially-regulated 269 genes after 6 h, and 1,934 genes after …


Hearing Loss In Mucopolysaccharidoses: Current Knowledge And Future Directions., Jeremy Wolfberg, Keerthana Chintalapati, Shunji Tomatsu, Kyoko Nagao Aug 2020

Hearing Loss In Mucopolysaccharidoses: Current Knowledge And Future Directions., Jeremy Wolfberg, Keerthana Chintalapati, Shunji Tomatsu, Kyoko Nagao

Department of Pediatrics Faculty Papers

Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by a deficiency of one of the enzymes involved in the degradation of glycosaminoglycans. Hearing loss is a common clinical presentation in MPS. This paper reviews the literature on hearing loss for each of the seven recognized subtypes of MPS. Hearing loss was found to be common in MPS I, II, III, IVA, VI, and VII, and absent from MPS IVB and MPS IX. MPS VI presents primarily with conductive hearing loss, while the other subtypes (MPS I, MPS II, MPS III, MPS IVA, and MPS VII) can present with …


Metabolism Of Jq1, An Inhibitor Of Bromodomain And Extra Terminal Bromodomain Proteins, In Human And Mouse Liver Microsomes†, Conrad Santini, Damian W Young, Martin M Matzuk Aug 2020

Metabolism Of Jq1, An Inhibitor Of Bromodomain And Extra Terminal Bromodomain Proteins, In Human And Mouse Liver Microsomes†, Conrad Santini, Damian W Young, Martin M Matzuk

Faculty, Staff and Students Publications

JQ1 is a small-molecule inhibitor of the bromodomain and extra terminal (BET) protein family that potently inhibits the bromodomain testis-specific protein (BRDT), which is essential for spermatogenesis. JQ1 treatment produces a reversible contraceptive effect by targeting the activity of BRDT in mouse male germ cells, validating BRDT as a male contraceptive target. Although JQ1 possesses favourable physical properties, it exhibits a short half-life. Because the details of xenobiotic metabolism play important roles in the optimization of drug candidates and in determining the role of metabolism in drug efficacy, we investigated the metabolism of JQ1 in human and mouse liver microsomes. …


The Landscape Of Rna Polymerase Ii-Associated Chromatin Interactions In Prostate Cancer, Susmita G Ramanand, Yong Chen, Jiapei Yuan, Kelly Daescu, Maryou Bk Lambros, Kathleen E Houlahan, Suzanne Carreira, Wei Yuan, Guemhee Baek, Adam Sharp, Alec Paschalis, Mohammed Kanchwala, Yunpeng Gao, Adam Aslam, Nida Safdar, Xiaowei Zhan, Ganesh V Raj, Chao Xing, Paul C Boutros, Johann De Bono, Michael Q Zhang, Ram S Mani Aug 2020

The Landscape Of Rna Polymerase Ii-Associated Chromatin Interactions In Prostate Cancer, Susmita G Ramanand, Yong Chen, Jiapei Yuan, Kelly Daescu, Maryou Bk Lambros, Kathleen E Houlahan, Suzanne Carreira, Wei Yuan, Guemhee Baek, Adam Sharp, Alec Paschalis, Mohammed Kanchwala, Yunpeng Gao, Adam Aslam, Nida Safdar, Xiaowei Zhan, Ganesh V Raj, Chao Xing, Paul C Boutros, Johann De Bono, Michael Q Zhang, Ram S Mani

College of Science & Mathematics Departmental Research

Transcriptional dysregulation is a hallmark of prostate cancer (PCa). We mapped the RNA polymerase II-associated (RNA Pol II-associated) chromatin interactions in normal prostate cells and PCa cells. We discovered thousands of enhancer-promoter, enhancer-enhancer, as well as promoter-promoter chromatin interactions. These transcriptional hubs operate within the framework set by structural proteins - CTCF and cohesins - and are regulated by the cooperative action of master transcription factors, such as the androgen receptor (AR) and FOXA1. By combining analyses from metastatic castration-resistant PCa (mCRPC) specimens, we show that AR locus amplification contributes to the transcriptional upregulation of the AR gene by increasing …


Expanding Pharmacotherapy Data Collection, Analysis, And Implementation In Eras® Programs—The Methodology Of An Exploratory Feasibility Study, Eric Johnson, Richard Parrish Ii, Gregg Nelson, Kevin Elias, Brian Kramer, Marian Gaviola Aug 2020

Expanding Pharmacotherapy Data Collection, Analysis, And Implementation In Eras® Programs—The Methodology Of An Exploratory Feasibility Study, Eric Johnson, Richard Parrish Ii, Gregg Nelson, Kevin Elias, Brian Kramer, Marian Gaviola

Pharmacy Practice and Science Faculty Publications

Surgical organizations dedicated to the improvement of patient outcomes have led to a worldwide paradigm shift in perioperative patient care. Since 2012, the Enhanced Recovery After Surgery (ERAS®) Society has published guidelines pertaining to perioperative care in numerous disciplines including elective colorectal and gynecologic/oncology surgery patients. The ERAS® and ERAS-USA® Societies use standardized methodology for collecting and assessing various surgical parameters in real-time during the operative process. These multi-disciplinary groups have constructed a bundled framework of perioperative care that entails 22 specific components of clinical interventions, which are logged in a central database, allowing a system …


Evaluation Of Aspirin And Statin Therapy Use And Adherence In Patients With Premature Atherosclerotic Cardiovascular Disease, Dhruv Mahtta, David J. Ramsey, Mahmoud Al Rifai, Khurram Nasir, Zainab Samad, David Aguilar, Hani Jneid, Christie M. Ballantyne, Laura A. Petersen, Salim S. Virani Aug 2020

Evaluation Of Aspirin And Statin Therapy Use And Adherence In Patients With Premature Atherosclerotic Cardiovascular Disease, Dhruv Mahtta, David J. Ramsey, Mahmoud Al Rifai, Khurram Nasir, Zainab Samad, David Aguilar, Hani Jneid, Christie M. Ballantyne, Laura A. Petersen, Salim S. Virani

Section of Cardiology

Importance: Studies on the use of and adherence to secondary prevention therapies in patients with premature and extremely premature atherosclerotic cardiovascular disease (ASCVD) are lacking.
Objective: To evaluate and compare aspirin use, any statin use, high-intensity statin use, and statin adherence among patients with premature or extremely premature ASCVD compared with patients with nonpremature ASCVD.
Design, setting, and participants: This multicenter cross-sectional study used the clinical and administrative data sets of the US Department of Veterans Affairs (VA) to identify adult patients with at least 1 primary care visit in the VA health care system between October 1, 2014, and …


Vitamin C As An Adjunct Therapy In Sepsis Management, Nicholas Becker Aug 2020

Vitamin C As An Adjunct Therapy In Sepsis Management, Nicholas Becker

Theses and Graduate Projects

In the United States, sepsis afflicts nearly one in three ICU patients, is associated with monumental healthcare costs, and is among the leading causes of death. The burden of sepsis is felt globally, and efforts are underway to discover an effective adjunctive therapy. Vitamin C is a novel treatment showing promising early evidence. Additionally, vitamin C's use in combination therapy with hydrocortisone and thiamine has been postulated. These components are thought to work congruently to attenuate the pathophysiologic process of sepsis.

To answer whether vitamin C improves septic patient outcomes, a variety of methods were used to obtain information. Primarily, …


Factors That Impact Glycemic Control In Adolescents With Type 1 Diabetes, Kelsey Mcfarling Aug 2020

Factors That Impact Glycemic Control In Adolescents With Type 1 Diabetes, Kelsey Mcfarling

Theses and Graduate Projects

The incidence of Type 1 Diabetes (T1D) is increasing worldwide and is diagnosed disproportionately in adolescent populations. Additionally, studies show that adolescents with T1D experience worse glycemic control during this developmental period. Maintaining glycemic control in patients with T1D decreases the risk of developing future diabetic-related complications. Factors such as race, ethnicity, gender identity, sexual orientation, socioeconomic status, and medical comorbidities influence disparities in maintaining glycemic control in adolescents. The recognition of these factors on the management of T1D through an integrative team approach leads to increased glycemic control and decreased diabetic- related complications. This paper explores the effects of …


Microrna-16, Programmed Cell Death Protein-4 (Pdcd-4) And Polycystic Ovarian Syndrome, Naseem Zehra, Arfa Azhar, Rehana Rehman Aug 2020

Microrna-16, Programmed Cell Death Protein-4 (Pdcd-4) And Polycystic Ovarian Syndrome, Naseem Zehra, Arfa Azhar, Rehana Rehman

Department of Biological & Biomedical Sciences

No abstract provided.


Dermatology Journals And The Impact Factor, Lawrence Charles Parish, W Clark Lambert Aug 2020

Dermatology Journals And The Impact Factor, Lawrence Charles Parish, W Clark Lambert

Department of Dermatology and Cutaneous Biology Faculty Papers

The noted informatics authority, Eugene Garfield (1925-2017), while working at the Johns Hopkins Medical Library, decided to assist medical librarians in selecting the publications to which they should subscribe. Not only at issue was the expense of subscribing and binding the periodicals, but there was also the physical space for shelving them. This was the birth of the Science Citation Index (SCI), the Impact Factor (IF), and the Institute for Scientific Information (ISI)in Philidelphia.

The role of the SCI has expanded over the years. Libraries may still continue to select journals on the basis of their IF, with many institutions …


Heart Failure In Humans Reduces Contractile Force In Myocardium From Both Ventricles, Cheavar A. Blair, Elizabeth A Brundage, Katherine L. Thompson, Arnold J. Stromberg, Maya Guglin, Brandon J Biesiadecki, Kenneth S. Campbell Aug 2020

Heart Failure In Humans Reduces Contractile Force In Myocardium From Both Ventricles, Cheavar A. Blair, Elizabeth A Brundage, Katherine L. Thompson, Arnold J. Stromberg, Maya Guglin, Brandon J Biesiadecki, Kenneth S. Campbell

Statistics Faculty Publications

This study measured how heart failure affects the contractile properties of the human myocardium from the left and right ventricles. The data showed that maximum force and maximum power were reduced by approximately 30% in multicellular preparations from both ventricles, possibly because of ventricular remodeling (e.g., cellular disarray and/or excess fibrosis). Heart failure increased the calcium (Ca2+) sensitivity of contraction in both ventricles, but the effect was bigger in right ventricular samples. The changes in Ca2+ sensitivity were associated with ventricle-specific changes in the phosphorylation of troponin I, which indicated that adrenergic stimulation might induce different effects …


Clinicopathologic Features Predictive Of Distant Metastasis In Patients Diagnosed With Invasive Breast Cancer, Basim Ali, Fatima Mubarik, Nida Zahid, Abida K. Sattar Aug 2020

Clinicopathologic Features Predictive Of Distant Metastasis In Patients Diagnosed With Invasive Breast Cancer, Basim Ali, Fatima Mubarik, Nida Zahid, Abida K. Sattar

Department of Biological & Biomedical Sciences

Purpose: National Comprehensive Cancer Network and European Society for Medical Oncology guidelines suggest screening for distant metastasis (M1) in symptomatic patients or those with locally advanced breast cancer. These guidelines are based on studies that often used pathologic staging for analysis. Physician variability in screening for M1 has also resulted in overuse of diagnostic tests. We sought to identify clinicopathologic features at diagnosis that could guide testing for metastatic disease.
Methods: Patients diagnosed with invasive breast cancer between January 2014 and December 2015 were identified from our institutional database. Demographic and clinical variables were collected, including receptor profiles and clinical …


Biomarker Application For Precision Medicine In Stroke, Alexis N. Simpkins, Miroslaw Janowski, Helieh S. Oz, Jill Roberts, Gregory Bix, Sylvain Doré, Ann M. Stowe Aug 2020

Biomarker Application For Precision Medicine In Stroke, Alexis N. Simpkins, Miroslaw Janowski, Helieh S. Oz, Jill Roberts, Gregory Bix, Sylvain Doré, Ann M. Stowe

Neurosurgery Faculty Publications

Stroke remains one of the leading causes of long-term disability and mortality despite recent advances in acute thrombolytic therapies. In fact, the global lifetime risk of stroke in adults over the age of 25 is approximately 25%, with 24.9 million cases of ischemic stroke and 18.7 million cases of hemorrhagic stroke reported in 2015. One of the main challenges in developing effective new acute therapeutics and enhanced long-term interventions for stroke recovery is the heterogeneity of stroke, including etiology, comorbidities, and lifestyle factors that uniquely affect each individual stroke survivor. In this comprehensive review, we propose that future biomarker studies …


Development, Expansion And Role Of Myeloid-Derived Suppressor Cells In Post-Sepsis Immune Suppression, Tuqa Alkhateeb Aug 2020

Development, Expansion And Role Of Myeloid-Derived Suppressor Cells In Post-Sepsis Immune Suppression, Tuqa Alkhateeb

Electronic Theses and Dissertations

Myeloid-derived suppressor cells (MDSCs) numbers increase significantly in sepsis and are associated with high mortality rates. These myeloid cell precursors promote immunosuppression, especially in the late (post sepsis) stage. However, the mechanisms that underlie MDSC expansion and programming are not completely understood. To investigate these mechanisms, we used a cecal-ligation and puncture (CLP) mouse model of polymicrobial sepsis that progresses from an early/acute proinflammatory phase to a late/chronic immunosuppressive phase. Previous studies in our laboratory showed that microRNA (miR)-21 and miR-181b elevate levels of the transcription factor nuclear factor 1 (NFI-A) that promotes MDSC expansion. We report here that miR-21 …


Bdnf-Related Gene Expression Of Laser Capture Microdissected Glutamate Neurons From The Anterior Cingulate Cortex In Mouse Models Of Autism Spectrum Disorder, Misty Owens Aug 2020

Bdnf-Related Gene Expression Of Laser Capture Microdissected Glutamate Neurons From The Anterior Cingulate Cortex In Mouse Models Of Autism Spectrum Disorder, Misty Owens

Electronic Theses and Dissertations

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting social behaviors. ASD affects 1 in 59 children with males affected more frequently. ASD is postulated to result from excitatory and inhibitory neurotransmission imbalances. Brain-derived neurotrophic factor (BDNF) signaling affects ASD by influencing synaptogenesis, plasticity, and survival. Studying early in-utero neuropathological changes within ASD requires the use of animal models. Expression of BDNF-associated genes were analyzed within laser capture microdissected pyramidal neurons from the anterior cingulate cortex of male and female BTBR and valproic acid mouse models. No expression differences were found in any gene comparing the three groups. Gender comparisons …


Chronic Pain, Sleep Disruption, And Work Performance In The Military, Jeffrey Ransom Aug 2020

Chronic Pain, Sleep Disruption, And Work Performance In The Military, Jeffrey Ransom

Dissertations

Abstract

Background and Significance: Managing pain is a challenge for many organizations, including the U.S. military. The added complication of managing sleep disruption compounds the issue. Examining pain and sleep disruption in the context of work performance within the military is critical to understanding the impact of these conditions on our nation’s fighting forces.

Purpose: Examine the associations of chronic pain and sleep disruption in the context of work performance among active duty military service members.

Research Aims: 1) Describe sociodemographic characteristics, military service characteristics, clinical characteristics, and work performance of active duty service members, 2) Examine relationships between these …


Epigenetic Targeting Of Mcl-1 Is Synthetically Lethal With Bcl-Xl/Bcl-2 Inhibition In Model Systems Of Glioblastoma, Enyuan Shang, Trang T. T. Nguyen, Chang Shu, Mike-Andrew Westhoff, Georg Karpel-Massler, Markus D. Siegelin Aug 2020

Epigenetic Targeting Of Mcl-1 Is Synthetically Lethal With Bcl-Xl/Bcl-2 Inhibition In Model Systems Of Glioblastoma, Enyuan Shang, Trang T. T. Nguyen, Chang Shu, Mike-Andrew Westhoff, Georg Karpel-Massler, Markus D. Siegelin

Publications and Research

Apoptotic resistance remains a hallmark of glioblastoma (GBM), the most common primary brain tumor in adults, and a better understanding of this process may result in more efficient treatments. By utilizing chromatin immunoprecipitation with next-generation sequencing (CHIP-seq), we discovered that GBMs harbor a super enhancer around the Mcl-1 locus, a gene that has been known to confer cell death resistance in GBM.We utilized THZ1, a known super-enhancer blocker, and BH3-mimetics, including ABT263, WEHI-539, and ABT199. Combined treatment with BH3-mimetics and THZ1 led to synergistic growth reduction in GBM models. Reduction in cellular viability was accompanied by significant cell death induction …


Dual X-Ray Absorptiometry Has Limited Utility In Detecting Bone Pathology In Children With Hypophosphatasia: A Pooled Post Hoc Analysis Of Asfotase Alfa Clinical Trial Data., Jill H. Simmons, Eric T. Rush, Anna Petryk, Shanggen Zhou, Gabriel Á. Martos-Moreno Aug 2020

Dual X-Ray Absorptiometry Has Limited Utility In Detecting Bone Pathology In Children With Hypophosphatasia: A Pooled Post Hoc Analysis Of Asfotase Alfa Clinical Trial Data., Jill H. Simmons, Eric T. Rush, Anna Petryk, Shanggen Zhou, Gabriel Á. Martos-Moreno

Manuscripts, Articles, Book Chapters and Other Papers

Asfotase alfa is an enzyme replacement therapy approved for treatment of patients with pediatric-onset hypophosphatasia (HPP), a rare, inherited, systemic disease causing impaired skeletal mineralization, short stature, and reduced physical function in children. The role of dual X-ray absorptiometry (DXA) in the assessment of children with HPP has been insufficiently explored. This post hoc analysis included pooled DXA data from 2 open-label, multicenter studies in 19 children with HPP. The study population was aged ≥5 to≤6.6 years at enrollment (male: 79%; median age at enrollment: 10.4 y [range: 5.9-16.7]; treatment duration: 6.3 y [range: 0.1-6.6]. Baseline height Z-scores indicated short …


Prevalence Of Risk Factors Of Acute Kidney Injury In A Tertiary Care Hospital In Pakistan, Ainan Arshad, Ahmed Ayaz Aug 2020

Prevalence Of Risk Factors Of Acute Kidney Injury In A Tertiary Care Hospital In Pakistan, Ainan Arshad, Ahmed Ayaz

Section of Internal Medicine

The objective of this study was to determine the prevalence of preventable risk factors of acute kidney injury in a tertiary care hospital in Pakistan. All patients admitted at Aga Khan University Hospital, Karachi with diagnosis of acute kidney injury were included out of which 134 were selected via random sampling. Patients with existing CKD were excluded. Data was then collected retrospectively from medical records of these patients. Mean age was 60±11.7 years while mean serum creatinine on admission was 2.4±1.3 (mg/dl). Sepsis played a role in almost half of the patients [60 (45%)]. Other factors included diarrhoea [23 (17%)], …


De Novo Variants Of Nr4a2 Are Associated With Neurodevelopmental Disorder And Epilepsy., Sakshi Singh, Aditi Gupta, Michael Zech, Ashley N. Sigafoos, Karl J. Clark, Yasemin Dincer, Matias Wagner, Jennifer B. Humberson, Sarah Green, Koen Van Gassen, Tracy Brandt, Rhonda E. Schnur, Francisca Millan, Yue Si, Volker Mall, Juliane Winkelmann, Ralitza H. Gavrilova, Eric W. Klee, Kendra Engleman, Nicole P. Safina, Rachel Slaugh, Emily M. Bryant, Wen-Hann Tan, Jorge Granadillo, Sunita N. Misra, G Bradley Schaefer, Shelley Towner, Eva H. Brilstra, Bobby P C Koeleman Aug 2020

De Novo Variants Of Nr4a2 Are Associated With Neurodevelopmental Disorder And Epilepsy., Sakshi Singh, Aditi Gupta, Michael Zech, Ashley N. Sigafoos, Karl J. Clark, Yasemin Dincer, Matias Wagner, Jennifer B. Humberson, Sarah Green, Koen Van Gassen, Tracy Brandt, Rhonda E. Schnur, Francisca Millan, Yue Si, Volker Mall, Juliane Winkelmann, Ralitza H. Gavrilova, Eric W. Klee, Kendra Engleman, Nicole P. Safina, Rachel Slaugh, Emily M. Bryant, Wen-Hann Tan, Jorge Granadillo, Sunita N. Misra, G Bradley Schaefer, Shelley Towner, Eva H. Brilstra, Bobby P C Koeleman

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: This study characterizes the clinical and genetic features of nine unrelated patients with de novo variants in the NR4A2 gene.

METHODS: Variants were identified and de novo origins were confirmed through trio exome sequencing in all but one patient. Targeted RNA sequencing was performed for one variant to confirm its splicing effect. Independent discoveries were shared through GeneMatcher.

RESULTS: Missense and loss-of-function variants in NR4A2 were identified in patients from eight unrelated families. One patient carried a larger deletion including adjacent genes. The cases presented with developmental delay, hypotonia (six cases), and epilepsy (six cases). De novo status was …


Lower Rates Of Heart Failure And All-Cause Hospitalizations During Pulmonary Artery Pressure-Guided Therapy For Ambulatory Heart Failure: One-Year Outcomes From The Cardiomems Post-Approval Study., David M Shavelle, Akshay S Desai, William T Abraham, Robert C Bourge, Nirav Raval, Lisa D Rathman, J Thomas Heywood, Rita A Jermyn, Jamie Pelzel, Orvar T Jonsson, Maria Rosa Costanzo, John D Henderson, Marie-Elena Brett, Philip B Adamson, Lynne W Stevenson, Cardiomems Post-Approval Study Investigators, Jacob Abraham (Cardiomems Post-Approval Study Investigator) Aug 2020

Lower Rates Of Heart Failure And All-Cause Hospitalizations During Pulmonary Artery Pressure-Guided Therapy For Ambulatory Heart Failure: One-Year Outcomes From The Cardiomems Post-Approval Study., David M Shavelle, Akshay S Desai, William T Abraham, Robert C Bourge, Nirav Raval, Lisa D Rathman, J Thomas Heywood, Rita A Jermyn, Jamie Pelzel, Orvar T Jonsson, Maria Rosa Costanzo, John D Henderson, Marie-Elena Brett, Philip B Adamson, Lynne W Stevenson, Cardiomems Post-Approval Study Investigators, Jacob Abraham (Cardiomems Post-Approval Study Investigator)

Articles, Abstracts, and Reports

BACKGROUND: Ambulatory hemodynamic monitoring with an implantable pulmonary artery (PA) sensor is approved for patients with New York Heart Association Class III heart failure (HF) and a prior HF hospitalization (HFH) within 12 months. The objective of this study was to assess the efficacy and safety of PA pressure-guided therapy in routine clinical practice with special focus on subgroups defined by sex, race, and ejection fraction.

METHODS: This multi-center, prospective, open-label, observational, single-arm trial of 1200 patients across 104 centers within the United States with New York Heart Association class III HF and a prior HFH within 12 months evaluated …


The Great Debate At 'Immunotherapy Bridge', Naples, December 5, 2019., Paolo A Ascierto, Carlo Bifulco, Jerome Galon, Claus Garbe, Samir N Khleif, Jennifer Mcquade, Kunle Odunsi, Hideho Okada, Chrystal M Paulos, Sergio A Quezada, Hussein A Tawbi, John Timmerman, Giorgio Trinchieri, Lisa H Butterfield, Igor Puzanov Aug 2020

The Great Debate At 'Immunotherapy Bridge', Naples, December 5, 2019., Paolo A Ascierto, Carlo Bifulco, Jerome Galon, Claus Garbe, Samir N Khleif, Jennifer Mcquade, Kunle Odunsi, Hideho Okada, Chrystal M Paulos, Sergio A Quezada, Hussein A Tawbi, John Timmerman, Giorgio Trinchieri, Lisa H Butterfield, Igor Puzanov

Articles, Abstracts, and Reports

As part of the 2019 Immunotherapy Bridge congress (December 4-5, Naples, Italy), the Great Debate session featured counterpoint views from leading experts on six topical issues in immunotherapy today. These were the use of chimeric antigen receptor T cell therapy in solid tumors, whether the Immunoscore should be more widely used in clinical practice, whether antibody-dependent cellular cytotoxicity is important in the mode of action of anticytotoxic T-lymphocyte-associated protein 4 antibodies, whether the brain is immunologically unique or just another organ, the role of microbiome versus nutrition in affecting responses to immunotherapy, and whether chemotherapy is immunostimulatory or immunosuppressive. Discussion …


Lc-Ms Based Stability-Indicating Method For Studying The Degradation Of Lonidamine Under Physical And Chemical Stress Conditions, Ankit K. Rochani, Margaret A. Wheatley, Brian Oeffinger, John R. Eisenbrey, Gagan Kaushal Aug 2020

Lc-Ms Based Stability-Indicating Method For Studying The Degradation Of Lonidamine Under Physical And Chemical Stress Conditions, Ankit K. Rochani, Margaret A. Wheatley, Brian Oeffinger, John R. Eisenbrey, Gagan Kaushal

College of Pharmacy Faculty Papers

Background and purpose: Lonidamine is a hexokinase II inhibitor, works as an anticancer molecule, and is extensively explored in clinical trials. Limited information prevails about the stability-indicating methods which could determine the forced degradation of lonidamine under stressed conditions. Hence, we report the use of a rapid, sensitive, reproducible, and highly accurate liquid chromatography and mass spectrometry method to analyze lonidamine degradation. Experimental approach: The Xbridge BEH shield reverse phase C18 column (2.5 μm, 4.6 × 75 mm) using isocratic 50:50 water: acetonitrile with 0.1% formic acid can detect lonidamine with help of mass spectrometer in tandem with an ultraviolet …


Family Planning And Afghan Refugee Women And Men Living In Melbourne, Australia: New Opportunities And Transcultural Tensions, Alana Russo, Belinda Lewis, Razia Ali, Atiq Abed, Grant Russel, Stanley Luchters Aug 2020

Family Planning And Afghan Refugee Women And Men Living In Melbourne, Australia: New Opportunities And Transcultural Tensions, Alana Russo, Belinda Lewis, Razia Ali, Atiq Abed, Grant Russel, Stanley Luchters

Population Health, East Africa

This research aimed to explore the family planning perspectives and experiences of Afghan women and men living in Melbourne. A total of 57 Afghan women and men participated in six focus groups and 20 semi-structured interviews. The majority of participants indicated a preference for two or three children and were open to using modern contraception. However, many women described experiencing negative side effects when using hormone-based contraception and expressed difficulty negotiating condom use with their husbands as an alternative. Some women described how these difficulties resulted in inconsistent contraceptive practices and, at times, unintended pregnancy. Participants recognised that health professionals …


Symmetric Inverse Consistent Nonlinear Registration Driven By Mutual Information, Wen Fury, Keun Woo Park, Zhuhao Wu, Eunhee Kim, Moon-Sook Woo, Yu Bai, Lynn E Macdonald, Susan D Croll, Sunghee Cho Aug 2020

Symmetric Inverse Consistent Nonlinear Registration Driven By Mutual Information, Wen Fury, Keun Woo Park, Zhuhao Wu, Eunhee Kim, Moon-Sook Woo, Yu Bai, Lynn E Macdonald, Susan D Croll, Sunghee Cho

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: Stroke is a major cause of chronic neurological disability. There is considerable interest in understanding how acute transcriptome changes evolve into subacute and chronic patterns that facilitate or limit spontaneous recovery. Here we mapped longitudinal changes in gene expression at multiple time points after stroke in mice out to 6 months.

METHODS: Adult C57BL/6 mice were subjected to transient middle cerebral artery occlusion. Longitudinal transcriptome levels were measured at 10 time points after stroke from acute to recovery phases of ischemic stroke. Localization and the number of mononuclear phagocytes were determined in the postischemic brain. Whole-mount brain …