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2022

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Full-Text Articles in Chemicals and Drugs

Role Of Adenylyl Cyclase Type 7 In Functions Of Bv-2 Microglia, Yawen Hu, Rebecca A. Hill, Masami Yoshimura Dec 2022

Role Of Adenylyl Cyclase Type 7 In Functions Of Bv-2 Microglia, Yawen Hu, Rebecca A. Hill, Masami Yoshimura

School of Medicine Faculty Publications

To assess the role of adenylyl cyclase type 7 (AC7) in microglia’s immune function, we generated AC7 gene knockout (AC7 KO) clones from a mouse microglial cell line, BV-2, using the CRISPR-Cas9 gene editing system. The ability of BV-2 cells to generate cAMP and their innate immune functions were examined in the presence or absence of ethanol. The parental BV-2 cells showed robust cAMP production when stimulated with prostaglandin-E1 (PGE1) and ethanol increased cAMP production in a dose-dependent manner. AC7 KO clones of BV-2 cells showed diminished and ethanol-insensitive cAMP production. The phagocytic activity of the parental BV-2 cells was …

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Therapies For Mitochondrial Disorders, Kayli Sousa Smyth, Anne Mulvihill Dec 2022

Therapies For Mitochondrial Disorders, Kayli Sousa Smyth, Anne Mulvihill

SURE Journal: Science Undergraduate Research Experience Journal

Mitochondria are cytoplasmic, double-membrane organelles that synthesise adenosine triphosphate (ATP). Mitochondria contain their own genome, mitochondrial DNA (mtDNA), which is maternally inherited from the oocyte. Mitochondrial proteins are encoded by either nuclear DNA (nDNA) or mtDNA, and both code for proteins forming the mitochondrial oxidative phosphorylation (OXPHOS) complexes of the respiratory chain. These complexes form a chain that allows the passage of electrons down the electron transport chain (ETC) through a proton motive force, creating ATP from adenosine diphosphate (ADP). This study aims to explore current and prospective therapies for mitochondrial disorders (MTDS). MTDS are clinical syndromes coupled with abnormalities …

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Gutka Consumption And Dietary Partialities Explaining Anemia In Women Of A Coastal Slum Of Karachi, Pakistan: A Mixed-Method Study, Ameer Muhammad, Sarah Saleem, Daniyaal Ahmad, Eleze Tariq, Yasir Shafiq Oct 2022

Gutka Consumption And Dietary Partialities Explaining Anemia In Women Of A Coastal Slum Of Karachi, Pakistan: A Mixed-Method Study, Ameer Muhammad, Sarah Saleem, Daniyaal Ahmad, Eleze Tariq, Yasir Shafiq

Community Health Sciences

Background: Limited literature is available on the dietary pattern and its consequences on health of women living in coastal slums of Karachi, Pakistan.
Material and methods: The study employed a mixed-method approach where concurrent quantitative and qualitative assessments were carried out. An analytical cross-sectional survey was conducted to collect information on demographic, household, obstetrics characteristics, and dietary pattern of married women of reproductive age (MWRA). Blood samples were collected to identify the hemoglobin level to determine anemia. For the qualitative component, focus group discussions were carried out with women and in-depth interviews with shopkeepers to understand the availability of food …

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Detailing The Effects Of Cbd On Parp And Survivin Expression In Ewing Sarcoma, Tyler Carter Oct 2022

Detailing The Effects Of Cbd On Parp And Survivin Expression In Ewing Sarcoma, Tyler Carter

Theses

Ewing sarcoma (ES) is an aggressive pediatric bone cancer with low five-year survival rates, particularly with recurrent disease because ES often becomes resistant to chemotherapy in these recurrences. Cannabidiol (CBD) has been identified as a potentially promising therapeutic for patients with ES. In other cancer types, CBD has demonstrated effects on two major proteins that contribute to chemotherapy resistance. The first, Poly (ADP-ribose) Polymerase I (PARP1), is a DNA damage repair enzyme that is overexpressed in recurrent ES. Though chemotherapy induces DNA damage in these cancer cells, the high levels of PARP1 facilitate repair of the DNA, allowing the mutated …

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Clinical Characteristics And Implications Of Bradycardia In Covid‐19 Patients Treated With Remdesivir: A Single‐Center Retrospective Cohort Study, Ariyon Schreiber, Justin S. Bauzon, Kavita Batra, Salman Mohammed, Kevin Lee, Nazanin Houshmand, Uyen Pham, Celica Cosme, Kim Inciong, Omar Al‑Taweel, Keaton Nasser, Jibran Rana, Chris Sossou, Ariel Go, Dalia Hawwass, Jimmy Diep, Chowdhury H. Ahsan Aug 2022

Clinical Characteristics And Implications Of Bradycardia In Covid‐19 Patients Treated With Remdesivir: A Single‐Center Retrospective Cohort Study, Ariyon Schreiber, Justin S. Bauzon, Kavita Batra, Salman Mohammed, Kevin Lee, Nazanin Houshmand, Uyen Pham, Celica Cosme, Kim Inciong, Omar Al‑Taweel, Keaton Nasser, Jibran Rana, Chris Sossou, Ariel Go, Dalia Hawwass, Jimmy Diep, Chowdhury H. Ahsan

School of Medicine Faculty Publications

Background and Objectives: Remdesivir is an antiviral drug used to treat coronavirus disease 2019 (COVID-19) with a relatively obscure cardiac efect profle. Previous studies have reported bradycardia associated with remdesivir, but few have examined its clinical characteristics. The objective of this study was to investigate remdesivir associated bradycardia and its associated clinical characteristics and outcomes. Methods: This is a single-institution retrospective study that investigated bradycardia in 600 patients who received remdesivir for treatment of COVID-19. A total of 375 patients were included in the study after screening for other known causes of bradycardia (atrioventricular [AV] nodal blockers). All patients were …

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Rna Isolation In Duchenne Muscular Dystrophy (Dmd) Mice Models, Salem Abu Al-Burak Aug 2022

Rna Isolation In Duchenne Muscular Dystrophy (Dmd) Mice Models, Salem Abu Al-Burak

Undergraduate Student Research Internships Conference

Fibrosis is a progressive and typically irreversible disease process characterized by the excessive deposition of collagen in organs and in tissues of the musculoskeletal (MSK) system1,2. This process, which causes loss of organ and tissue function, can be initiated by micro-traumas3, an excessive and/or prolonged immune response1, the activation and proliferation of fibrosis-inducing progenitor cells4, and a pro-fibrotic extra-cellular microenvironment5. In parallel with the events that initiate fibrosis, genetic or environmental influences may cause cells and tissues to become predisposed to fibrosis development prior to initiation. This suggests that these …

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Statins: Masked Anti-Epileptic Warriors, Govinda Khatri, Priya Kotak, Ayush Kumar, Mohammad Mehedi Hasan Aug 2022

Statins: Masked Anti-Epileptic Warriors, Govinda Khatri, Priya Kotak, Ayush Kumar, Mohammad Mehedi Hasan

Medical College Documents

No abstract provided.

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Expression And Purification Of The Bacterial Protein Curli Csga And Its Cross-Interactions With Amyloid-B, Leah Grace Cantrell Jun 2022

Expression And Purification Of The Bacterial Protein Curli Csga And Its Cross-Interactions With Amyloid-B, Leah Grace Cantrell

Honors Theses

One of the main causes of neurodegenerative diseases is aggregation of amyloid proteins that are toxic to the neurons. Proteins like amyloid-β (Aβ) and α-syneuclein (α-syn) form hallmark aggregate lesions that contribute to pathological processes in the brain in Alzheimer and Parkinson’s patients, respectively. Recent ground-breaking studies have suggested a link between the microbiota of the gut and neurodegenerative diseases, called the “gut-brain axis.” It has been long known that the protein, CsgA found in many enteric bacteria, forms amyloid fibers of its own called Curli. Curli fibrils are a structural component of bacterial colonies and maintain the integrity of …

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Development And Implementation Of A Protocol For Denosumab Administration In An Outpatient Infusion Clinic, Erin Stavrakas May 2022

Development And Implementation Of A Protocol For Denosumab Administration In An Outpatient Infusion Clinic, Erin Stavrakas

The Eleanor Mann School of Nursing Student Works

Denosumab, or Prolia, is a medication given to increase bone mineral density (BMD) and prevent fracture risk in patients with osteoporosis. Guidelines for monitoring of side effects, data on long-term effects, and appropriate precautions are still being researched and developed. Healthcare teams are often unaware of preventative care measures to guide informed clinical decision making and patient care management. The recognized gap in care also reduces the standardization of health care delivery in clinics administering Prolia; this gap can lead to errors and miscommunication between patients and healthcare teams an increased risk for side effects. The aim of this translation …

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Regaining Effort-Based Food Motivation: The Drug Methylphenidate Reverses The Depressive Effects Of Tetrabenazine In Female Rats, Deanna Pietrorazio May 2022

Regaining Effort-Based Food Motivation: The Drug Methylphenidate Reverses The Depressive Effects Of Tetrabenazine In Female Rats, Deanna Pietrorazio

Honors Scholar Theses

Tetrabenazine (TBZ), a vesicular monoamine transporter type 2 (VMAT-2) inhibitor, depletes dopamine and induces motivational deficits and other depressive symptoms in humans. Methylphenidate (MPH) is a dopamine transport blocker that is used to enhance motivational function. Previous studies have shown that in male rats, TBZ induces a shift in effort-related choice such that a low-effort bias is induced. In male rats this occurs at a dose range of 0.75-1.0 mg/kg TBZ, and this effect is reversible with co-administration of MPH. Recent studies have shown that females need a higher dose of TBZ (2.0 mg/kg) to show the low-effort bias. The …

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Alternative Fixation Of Venous Valves For Bioprosthetic Applications, Makenzie Kapales May 2022

Alternative Fixation Of Venous Valves For Bioprosthetic Applications, Makenzie Kapales

Biomedical Engineering Undergraduate Honors Theses

Venous valve failure allows for the retrograde, or backward, flow of blood into the lower extremities, which leads to Chronic Venous Insufficiency (CVI). CVI infringes upon quality of life through ulceration and can result in death due to Deep Vein Thrombosis (DVT), or blood clots, causing pulmonary embolism. A successful treatment of CVI restores valve function and prevents retrograde blood flow; however, current bioprosthetic venous valves exhibit low patency and high calcification. To improve upon bioprosthetic venous valves and CVI treatment, the University of Arkansas’s Cardiovascular Biomechanics Lab conducts studies with the purpose of comparing the properties and performance of …

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Characterisation Of Drug-Resistant Mycobacterium Tuberculosis Mutations And Transmission In Pakistan, Gary Napier, Anwar Sheed Khan, Abdul Jabbar, Muhammad Tahir Khan, Sajid Ali, Muhammad Qasim, Noor Mohammad, Rumina Hasan, Zahra Hasan, Susana Campino Apr 2022

Characterisation Of Drug-Resistant Mycobacterium Tuberculosis Mutations And Transmission In Pakistan, Gary Napier, Anwar Sheed Khan, Abdul Jabbar, Muhammad Tahir Khan, Sajid Ali, Muhammad Qasim, Noor Mohammad, Rumina Hasan, Zahra Hasan, Susana Campino

Department of Pathology and Laboratory Medicine

Tuberculosis, caused by Mycobacterium tuberculosis, is a high-burden disease in Pakistan, with multi-drug (MDR) and extensive-drug (XDR) resistance, complicating infection control. Whole genome sequencing (WGS) of M. tuberculosis is being used to infer lineages (strain-types), drug resistance mutations, and transmission patterns-all informing infection control and clinical decision making. Here we analyse WGS data on 535 M. tuberculosis isolates sourced across Pakistan between years 2003 and 2020, to understand the circulating strain-types and mutations related to 12 anti-TB drugs, as well as identify transmission clusters. Most isolates belonged to lineage 3 (n = 397; 74.2%) strain-types, and were MDR (n = …

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Daclizumab (Zinbryta®): An Emerging Therapy For The Treatment Of Relapsing-Remitting Multiple Sclerosis, Morgan Homan, Sunitha Jones, Michaela Louden, Molly Wheeler, Anh Dao Le, Lindsey Peters Mar 2022

Daclizumab (Zinbryta®): An Emerging Therapy For The Treatment Of Relapsing-Remitting Multiple Sclerosis, Morgan Homan, Sunitha Jones, Michaela Louden, Molly Wheeler, Anh Dao Le, Lindsey Peters

Pharmacy and Wellness Review

Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system characterized by the deterioration of the myelin sheath, causing axonal damage which leads to debilitating symptoms. Most therapies for the treatment of MS, including daclizumab, primarily target relapsing-remitting multiple sclerosis (RRMS), a form of MS where patients experience periods of exacerbated symptoms as well as intermittent periods of remission. Daclizumab is a humanized monoclonal antibody that is administered as a once monthly subcutaneous injection. The SELECT trilogy of trials have been instrumental in providing safety and efficacy data for daclizumab. The DECIDE study was the first randomized controlled …

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Hsp90 Inhibitors Modulate Sars-Cov-2 Spike Protein Subunit 1-Induced Human Pulmonary Microvascular Endothelial Activation And Barrier Dysfunction, Ruben Manuel Luciano Colunga Biancatelli, Pavel Solopov, Betsy W. Gregory, Yara Khodour, John D. Catravas Mar 2022

Hsp90 Inhibitors Modulate Sars-Cov-2 Spike Protein Subunit 1-Induced Human Pulmonary Microvascular Endothelial Activation And Barrier Dysfunction, Ruben Manuel Luciano Colunga Biancatelli, Pavel Solopov, Betsy W. Gregory, Yara Khodour, John D. Catravas

Bioelectrics Publications

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused more than 5 million deaths worldwide. Multiple reports indicate that the endothelium is involved during SARS-Cov-2-related disease (COVID-19). Indeed, COVID-19 patients display increased thrombophilia with arterial and venous embolism and lung microcapillary thrombotic disease as major determinants of deaths. The pathophysiology of endothelial dysfunction in COVID-19 is not completely understood. We have investigated the role of subunit 1 of the SARS-CoV-2 spike protein (S1SP) in eliciting endothelial barrier dysfunction, characterized dose and time relationships, and tested the hypothesis that heat shock protein 90 (HSP90) inhibitors would prevent and repair such injury. S1SP …

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Use Of Steroids In Covid-19 Patients: What Is Known?, Syed Muhammad Mustahsan, Marzia Tahir, Emaduddin Siddiqui Mar 2022

Use Of Steroids In Covid-19 Patients: What Is Known?, Syed Muhammad Mustahsan, Marzia Tahir, Emaduddin Siddiqui

Department of Emergency Medicine

COVID-19 pandemic has exaggerated the role of steroids in the standard of care despite minimum direct evidence of their efficacy in COVID-19 patients and their well-known adverse effects. The literature abounds on the side effects of steroids affecting different organ systems of the body. COVID-19 patients, who are on long-term steroids, are more susceptible to their adverse effects. We, herein, briefly review the potential uses and the adverse effects of steroids on different organ systems of the body. Key Words: Steroids, COVID-19, Adverse effects.

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Endothelial Nitric Oxide Synthase (Enos) And The Cardiovascular System: In Physiology And In Disease States, N Tran, T Garcia, M Aniqa, S Ali, A Ally, Surya M. Nauli Jan 2022

Endothelial Nitric Oxide Synthase (Enos) And The Cardiovascular System: In Physiology And In Disease States, N Tran, T Garcia, M Aniqa, S Ali, A Ally, Surya M. Nauli

Pharmacy Faculty Articles and Research

Endothelial nitric oxide synthase (eNOS) plays a critical role in regulating and maintaining a healthy cardiovascular system. The importance of eNOS can be emphasized from the genetic polymorphisms of the eNOS gene, uncoupling of eNOS dimerization, and its numerous signaling regulations. The activity of eNOS on the cardiac myocytes, vasculature, and the central nervous system are discussed. The effects of eNOS on the sympathetic autonomic nervous system (SANS) and the parasympathetic autonomic nervous system (PANS), both of which profoundly influence the cardiovascular system, will be elaborated. The relationship between the eNOS protein with cardiovascular autonomic reflexes such as the baroreflex …

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Optimizing Antidotal Treatment With The Oral Hsp90 Inhibitor Tas-116 Against Hydrochloric Acid-Induced Pulmonary Fibrosis In Mice, Pavel A. Solopov, Ruben Manuel Luciano Colunga Biancatelli, Christiana Dimitropolou, Tierney Day, John Catravas Jan 2022

Optimizing Antidotal Treatment With The Oral Hsp90 Inhibitor Tas-116 Against Hydrochloric Acid-Induced Pulmonary Fibrosis In Mice, Pavel A. Solopov, Ruben Manuel Luciano Colunga Biancatelli, Christiana Dimitropolou, Tierney Day, John Catravas

Bioelectrics Publications

Exposure to high concentrations of hydrochloric acid (HCl) can lead to severe acute and chronic lung injury. In the aftermath of accidental spills, victims may be treated for the acute symptoms, but the chronic injury is often overlooked. We have developed a mouse model of acute and chronic lung injury, in which the peak of acute lung injury occurs on the day 4 after HCl exposure. We have also demonstrated that HSP90 inhibitors are effective antidotes when administered starting 24 h after HCl. In this study we examined the hypothesis that the novel oral HSP90 inhibitor TAS-116 can effectively ameliorate …

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Management Of Adult Growth Hormone Deficiency Related To Hypopituitarism, Kellie Jamin Jan 2022

Management Of Adult Growth Hormone Deficiency Related To Hypopituitarism, Kellie Jamin

Capstone Showcase

The treatment of growth hormone deficiency (GHD) is well-established in childhood but less understood in adults, given the more complex role that growth hormone (GH) assumes in this population. Decreased functionality of the pituitary gland, otherwise known as hypopituitarism, can present with an isolated GHD in adulthood, which may result from a number of factors including neoplasm, ischemia, infection, traumatic injury, or systemic disease. Adult GHD may be definitively diagnosed with a stimulation test, the insulin tolerance test (ITT) being the study of choice. With a positive ITT, the disorder can be treated with growth hormone replacement therapy (GHRT), which …

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Opioid Medication Use And Blood Dna Methylation: Epigenome-Wide Association Meta-Analysis, Mikyeong Lee, Roby Joehanes, Daniel L. Mccartney, Minjung Kho, Anke Hüls, Annah B. Wyss, Chunyu Liu, Rosie M. Walker, Sharon L.R. Kardia, Thomas S. Wingo, Adam Burkholder, Jiantao Ma, Archie Campbell, Aliza P. Wingo, Tianxiao Huan, Sinjini Sikdar, Amena Keshawarz, David A. Bennett, Jennifer A. Smith, Kathryn L. Evans, Daniel Levy, Stephanie J. London Jan 2022

Opioid Medication Use And Blood Dna Methylation: Epigenome-Wide Association Meta-Analysis, Mikyeong Lee, Roby Joehanes, Daniel L. Mccartney, Minjung Kho, Anke Hüls, Annah B. Wyss, Chunyu Liu, Rosie M. Walker, Sharon L.R. Kardia, Thomas S. Wingo, Adam Burkholder, Jiantao Ma, Archie Campbell, Aliza P. Wingo, Tianxiao Huan, Sinjini Sikdar, Amena Keshawarz, David A. Bennett, Jennifer A. Smith, Kathryn L. Evans, Daniel Levy, Stephanie J. London

Mathematics & Statistics Faculty Publications

Aim: To identify differential methylation related to prescribed opioid use. Methods: This study examined whether blood DNA methylation, measured using Illumina arrays, differs by recent opioid medication use in four population-based cohorts. We meta-analyzed results (282 users; 10,560 nonusers) using inverse-variance weighting. Results: Differential methylation (false discovery rate <0.05) was observed at six CpGs annotated to the following genes: KIAA0226, CPLX2, TDRP, RNF38, TTC23 and GPR179. Integrative epigenomic analyses linked implicated loci to regulatory elements in blood and/or brain. Additionally, 74 CpGs were differentially methylated in males or females. Methylation at significant CpGs correlated with gene expression in blood and/or brain. Conclusion: This study identified DNA …

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Effectiveness Of Stabilized Hypochlorous Acid In Acute Peritonitis Treatment: A Murine Surgical Study, Benjamin Michael Pomeroy Jan 2022

Effectiveness Of Stabilized Hypochlorous Acid In Acute Peritonitis Treatment: A Murine Surgical Study, Benjamin Michael Pomeroy

MSU Graduate Theses

Peritonitis is an inflammatory condition affecting the mesothelial cells that line the peritoneal cavity and is commonly induced by bowel perforations. This medical emergency is treated through antibiotic therapy and surgical intervention followed by tissue irrigation (lavage). Acute treatments aim to remove the bacterial burden, however recurring peritoneal infections occur at high rates and contribute to patient morbidity. These recurring infections are likely due to the inability of lavage solutions to remove the entire massive intra-abdominal bacterial load due to intestinal perforation. Numerous antiseptic solutions and antibiotic additives have been evaluated in their ability to improve source control by abdominal …

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