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Bispecific Human Il2-Ccr4 Immunotoxin Targets Human Cutaneous T-Cell Lymphoma, Haoyu Wang, Zhaohui Wang, Huiping Zhang, Zeng Qi, Ariel C Johnson, David Mathes, Elizabeth A Pomfret, Erin Rubin, Christene A Huang, Zhirui Wang May 2020

Bispecific Human Il2-Ccr4 Immunotoxin Targets Human Cutaneous T-Cell Lymphoma, Haoyu Wang, Zhaohui Wang, Huiping Zhang, Zeng Qi, Ariel C Johnson, David Mathes, Elizabeth A Pomfret, Erin Rubin, Christene A Huang, Zhirui Wang

Faculty, Staff and Student Publications

The majority of clinically diagnosed cutaneous T‐cell lymphomas (CTCL) highly express the cell‐surface markers CC chemokine receptor 4 (CCR4) and/or CD25. Recently, we have developed diphtheria toxin‐based recombinant Ontak®‐like human IL2 fusion toxin (IL2 fusion toxin) and anti‐human CCR4 immunotoxin (CCR4 IT). In this study, we first compared the efficacy of the CCR4 IT vs IL2 fusion toxin for targeting human CD25+CCR4+ CTCL. We demonstrated that CCR4 IT was more effective than IL2 fusion toxin. We further constructed an IL2‐CCR4 bispecific IT. The bispecific IT was significantly more effective than either IL2 fusion toxin or CCR4 IT alone. The bispecific …


Dietary Fat And Sugar Differentially Affect Β-Adrenergic Stimulation Of Cardiac Erk And Akt Pathways In C57bl/6 Male Mice Subjected To High-Calorie Feeding, Sadia Ashraf, Gizem Yilmaz, Xu Chen, Romain Harmancey May 2020

Dietary Fat And Sugar Differentially Affect Β-Adrenergic Stimulation Of Cardiac Erk And Akt Pathways In C57bl/6 Male Mice Subjected To High-Calorie Feeding, Sadia Ashraf, Gizem Yilmaz, Xu Chen, Romain Harmancey

Faculty, Staff and Student Publications

BACKGROUND: High dietary fat and sugar promote cardiac hypertrophy independently from an increase in blood pressure. The respective contribution that each macronutrient exerts on cardiac growth signaling pathways remains unclear.

OBJECTIVE: The goal of this study was to investigate the mechanisms by which high amounts of dietary fat and sugar affect cardiac growth regulatory pathways.

METHODS: Male C57BL/6 mice (9 wk old; n = 20/group) were fed a standard rodent diet (STD; kcal% protein-fat-carbohydrate, 29-17-54), a high-fat diet (HFD; 20-60-20), a high-fat and high-sugar Western diet (WD; 20-45-35), a high-sugar diet with mixed carbohydrates (HCD; 20-10-70), or a high-sucrose diet …


Oral Localization Of Scardovia Wiggsiae, Graydon Ramos Carr May 2020

Oral Localization Of Scardovia Wiggsiae, Graydon Ramos Carr

UNLV Theses, Dissertations, Professional Papers, and Capstones

Early childhood caries is one of the most prevalent diseases in the United States among children. The formation of caries is a complex, multifactorial process that is still being studied. Researchers have thought for years that Streptococcus mutans was the primary causative agent of early childhood caries. The recent discovery of a novel cariogenic pathogen, Scardovia wiggsiae and its significant contribution to the etiology of early childhood caries has led oral health researchers to re-evaluate this microorganism and its link to this disease. While there have been several projects undertaken within the University of Nevada, Las Vegas School of Dental …


The Effects Of Total Body Proton Irradiation On Mouse Myometrium, Lillith Bulawa May 2020

The Effects Of Total Body Proton Irradiation On Mouse Myometrium, Lillith Bulawa

Undergraduate Honors Theses

The boundaries of human space exploration continue to expand with new technology and discoveries making it even more important to investigate the effects of space on biological systems. Although humans have explored space in small increments, reproductive studies must be conducted to determine if stable short- or long-term residences for humans can exist in space. This study explored the effects of whole-body proton radiation on uterine smooth muscle known as the myometrium. Two types of mice utilized in this study were C57BL/6 and B6.129S6Cybbtm1Din/J NOX2 knockout mice. C57BL/6 mice are standard laboratory mice that were used to represent the wildtype …


Polysubstance Exposure And Its Relationship To Pharmacological Treatment Characteristics, Parker Miller May 2020

Polysubstance Exposure And Its Relationship To Pharmacological Treatment Characteristics, Parker Miller

Undergraduate Honors Theses

Neonatal Abstinence Syndrome (NAS) remains an ever-growing public health issue and a continued avenue for future research. The research question for this retrospective study was whether polysubstance exposure is related to the dose of medication the infant received or to the number of opioid-medications required to treat the infants’ withdrawal symptoms? The hypothesis for the retrospective study was there will be a significant relationship between polysubstance exposure and the dose of medication the infant received as well as the number of opioid-medications required to treat the infants’ withdrawal symptoms. A bivariate correlational indicated that there was not a significant association …


Effects Of Alternative Chemotherapeutic Agents On Thyroid Cancer Cell Line Ml-1, Husref Rizvanovic May 2020

Effects Of Alternative Chemotherapeutic Agents On Thyroid Cancer Cell Line Ml-1, Husref Rizvanovic

Graduate Theses/Dissertations

Though differentiated thyroid carcinomas have decent prognosis when detected early, radioactive iodine (RAI) resistant and advanced thyroid cancers are still difficult to treat with existing therapies. Better therapeutic agents are needed. Studies have shown that aggressive thyroid cancers (ML-1) express the extracellular matrix protein, matrix metalloproteinase (MMP-2). MMP-2 has been linked to metastasis and aggressiveness of several cancers and has been shown to play a crucial role in tumor invasion. Chlorotoxin is a selective MMP-2 receptor agonist, and Saporin is a well-known ribosome-inactivating protein used for anti-cancer treatment; however, these two agents have never been studied when conjugated together. I …


Structure And Mechanism Of Human Diacylglycerol O-Acyltransferase 1, Lie Wang, Hongwu Qian, Yin Nian, Yimo Han, Zhenning Ren, Hanzhi Zhang, Liya Hu, B V Venkataram Prasad, Arthur Laganowsky, Nieng Yan, Ming Zhou May 2020

Structure And Mechanism Of Human Diacylglycerol O-Acyltransferase 1, Lie Wang, Hongwu Qian, Yin Nian, Yimo Han, Zhenning Ren, Hanzhi Zhang, Liya Hu, B V Venkataram Prasad, Arthur Laganowsky, Nieng Yan, Ming Zhou

Faculty, Staff and Students Publications

Diacylglycerol O-acyltransferase-1 (DGAT1) synthesizes triacylglycerides and is required for dietary fat absorption and fat storage in humans1. DGAT1 belongs to the superfamily of membrane-bound O-acyltransferases (MBOAT) that are found in all kingdoms of life and involved in acylation of lipids and proteins2,3. It remains unclear how human DGAT1 (hDGAT1) or other mammalian members of the MBOAT family recognize their substrates and catalyze their reactions. The absence of three-dimensional structures also hampers rational targeting of hDGAT1 for therapeutic purposes. Here we present the structure of hDGAT1 in complex with a substrate oleoyl Coenzyme A solved …


Prosthetic Valve Endocarditis From Trichosporon Asahii In An Immunocompetent Patient, Lizy Marial Paniagua, Deepthi Sudhakar, Lara Erika Perez, David Miranda, Pedro Urena, Igor Gregoric, Biswajit Kar, Hani Jneid, Jonalis Ramirez, David Paniagua May 2020

Prosthetic Valve Endocarditis From Trichosporon Asahii In An Immunocompetent Patient, Lizy Marial Paniagua, Deepthi Sudhakar, Lara Erika Perez, David Miranda, Pedro Urena, Igor Gregoric, Biswajit Kar, Hani Jneid, Jonalis Ramirez, David Paniagua

Faculty, Staff and Students Publications

Fungal endocarditis is a rare clinical entity. This report describes an unusual case of fungal endocarditis caused by infection with Trichosporon asahii in a 20-year-old immunocompetent man who received the diagnosis 1 year following biological aortic valve replacement. (Level of Difficulty: Beginner.)


Ubiquitination Of The Dna-Damage Checkpoint Kinase Chk1 By Traf4 Is Required For Chk1 Activation, Xinfang Yu, Wei Li, Haidan Liu, Qipan Deng, Xu Wang, Hui Hu, Zijun Y Xu-Monette, Wei Xiong, Zhongxin Lu, Ken H Young, Wei Wang, Yong Li May 2020

Ubiquitination Of The Dna-Damage Checkpoint Kinase Chk1 By Traf4 Is Required For Chk1 Activation, Xinfang Yu, Wei Li, Haidan Liu, Qipan Deng, Xu Wang, Hui Hu, Zijun Y Xu-Monette, Wei Xiong, Zhongxin Lu, Ken H Young, Wei Wang, Yong Li

Faculty, Staff and Students Publications

BACKGROUND: Aberrant activation of DNA damage response (DDR) is a major cause of chemoresistance in colorectal cancer (CRC). CHK1 is upregulated in CRC and contributes to therapeutic resistance. We investigated the upstream signaling pathways governing CHK1 activation in CRC.

METHODS: We identified CHK1-binding proteins by mass spectrometry analysis. We analyzed the biologic consequences of knockout or overexpression of TRAF4 using immunoblotting, immunoprecipitation, and immunofluorescence. CHK1 and TRAF4 ubiquitination was studied in vitro and in vivo. We tested the functions of TRAF4 in CHK1 phosphorylation and CRC chemoresistance by measuring cell viability and proliferation, anchorage-dependent and -independent cell growth, and mouse …


Metabolic-Sensing Of The Skeletal Muscle Clock Coordinates Fuel Oxidation, Hongshan Yin, Weini Li, Somik Chatterjee, Xuekai Xiong, Pradip Saha, Vijay Yechoor, Ke Ma May 2020

Metabolic-Sensing Of The Skeletal Muscle Clock Coordinates Fuel Oxidation, Hongshan Yin, Weini Li, Somik Chatterjee, Xuekai Xiong, Pradip Saha, Vijay Yechoor, Ke Ma

Faculty, Staff and Students Publications

Circadian clock confers temporal control in metabolism, with its disruption leading to the development of insulin resistance. Metabolic substrate utilization in skeletal muscle is coordinated with diurnal nutrient cycles. However, whether the molecular clock is involved in this coordination is largely unknown. Using a myocyte-selective genetic ablation mouse model of the essential clock activator Bmal1, here we identify muscle-intrinsic clock as a sensor of feeding cues to orchestrate skeletal muscle oxidation required for global nutrient flux. Bmal1 in skeletal muscle responds robustly to feeding in vivo and insulin induces its expression. Muscle Bmal1 deficiency impaired the transcriptional control of glucose …


Diabetic Retinopathy: Targeting Bigh3 To Develop Novel Molecular Therapies, Reanna Rodriguez, Anjalee Choudhury, Daniela Gonzalez, Cristian Mercado, Andrew Tsin May 2020

Diabetic Retinopathy: Targeting Bigh3 To Develop Novel Molecular Therapies, Reanna Rodriguez, Anjalee Choudhury, Daniela Gonzalez, Cristian Mercado, Andrew Tsin

School of Medicine Publications

Diabetic retinopathy (DR) is a complication of diabetes due to damage of blood vessels in the retina. Aside from being a major cause of blindness in the world, DR also has a significant impact on quality of life. Although there are methods to delay the progression of DR, there are no existing therapeutic regimens for early intervention. Thus, it is critical to develop cost-effective therapies towards preventing DR development.


When Treating Sick Joints Harms Lungs, Ixekizumab Induced Pleural Effusion, Rami Batarseh, Kyle Smith, Mohammed Al-Ourani, Amro K. Al-Astal Apr 2020

When Treating Sick Joints Harms Lungs, Ixekizumab Induced Pleural Effusion, Rami Batarseh, Kyle Smith, Mohammed Al-Ourani, Amro K. Al-Astal

Marshall Journal of Medicine

Immunological therapies have provided a multitude of new and effective treatment strategies for various disease states. While monoclonal antibody therapy benefits many patients, side effects are widely variable. here we present a case of pleural effusion complicating psoriatic arthritis treatment.


Macrophage Activation Syndrome As A Complication Of Systemic Lupus Erythematosus In An Adult Male, Rajesh Gopalarathinam, Vamsee Chirumamilla, Balachandran Vaidyanathan Apr 2020

Macrophage Activation Syndrome As A Complication Of Systemic Lupus Erythematosus In An Adult Male, Rajesh Gopalarathinam, Vamsee Chirumamilla, Balachandran Vaidyanathan

Marshall Journal of Medicine

Macrophage activation syndrome (MAS) is a rare life-threatening complication that sometimes occurs in patients with systemic lupus erythematosus (SLE) and other connective tissue diseases. This syndrome is universally fatal without treatment, and therefore, prompt diagnosis and initiation of treatment is of vital importance.


The Spectrum Of Large Adrenal Masses: A Case Series, Jo Cooke-Barber, Sarah E. Hatef, Analise Mcgreal, Andrew Schwemmer, Christopher Senkowski Apr 2020

The Spectrum Of Large Adrenal Masses: A Case Series, Jo Cooke-Barber, Sarah E. Hatef, Analise Mcgreal, Andrew Schwemmer, Christopher Senkowski

HCA Healthcare Journal of Medicine

Background: Adrenocortical carcinoma (ACC) is a rare malignancy that is challenging to diagnose and has important implications for surgeons who approach this disease. Despite its rarity, it must always be in the differential diagnosis when investigating and treating large adrenal masses. We aim to demonstrate the complexities of this disease through a review of five recent patients at a single tertiary care center.

Methods: A series of five patients are described, each of whom presented to a single institution as referrals for "large adrenal mass" in the past sixteen months. Their pre-operative diagnosis, radiographic findings, the operative approach and the …


Acute Disseminated Encephalomyelitis, Ashan Hatharasinghe, Hossein Akhondi, Don Pepito Apr 2020

Acute Disseminated Encephalomyelitis, Ashan Hatharasinghe, Hossein Akhondi, Don Pepito

HCA Healthcare Journal of Medicine

Introduction: Acute Disseminated Encephalomyelitis (ADEM) is a rare autoimmune demyelinating disorder of the central nervous system. Clinical manifestations include encephalopathy, motor deficits, ataxia, and meningeal signs. In most cases, ADEM is preceded by either vaccination or viral illness. Here, we present a case with neither of the two predisposing elements.

Discussion: A 28-year-old Hispanic female presenting with substance use and suicidal ideation was placed on an involuntary psychiatric hold, started on olanzapine and scheduled for a psychiatric facility transfer. The following day, she was noted to have neurological deficits when ambulating. Computed tomography of the brain showed a right frontal …


The Precise (Pregnancy Care Integrating Translational Science, Everywhere) Database: Open-Access Data Collection In Maternal And Newborn Health, Laura A. Magee, Amber Strang, Larry Li, Domena Tu, Warancha Tumtaweetikul, Rachel Craik, Marina Daniele, Angela Koech, Umberto D’Alessandro, Marleen Temmerman Apr 2020

The Precise (Pregnancy Care Integrating Translational Science, Everywhere) Database: Open-Access Data Collection In Maternal And Newborn Health, Laura A. Magee, Amber Strang, Larry Li, Domena Tu, Warancha Tumtaweetikul, Rachel Craik, Marina Daniele, Angela Koech, Umberto D’Alessandro, Marleen Temmerman

Obstetrics and Gynaecology, East Africa

In less-resourced settings, adverse pregnancy outcome rates are unacceptably high. To effect improvement, we need accurate epidemiological data about rates of death and morbidity, as well as social determinants of health and processes of care, and from each country (or region) to contextualise strategies. The PRECISE database is a unique core infrastructure of a generic, unified data collection platform. It is built on previous work in data harmonisation, outcome and data field standardisation, open-access software (District Health Information System 2 and the Baobab Laboratory Information Management System), and clinical research networks. The database contains globally-recommended indicators included in Health Management …


Harnessing The Precise Network As A Platform To Strengthen Global Capacity For Maternal And Child Health Research In Sub-Saharan Africa, Meriel Flint-O’Kane, Peter Von Dadelszen, Prestige Tatenda Makanga, Esperança Sevene, Anna Roca, Peter Dukes, Saba Hinrichs-Krapels, Rachel Craik, Laura A. Magee, Marleen Temmerman, Angela Koech, The Precise Network Apr 2020

Harnessing The Precise Network As A Platform To Strengthen Global Capacity For Maternal And Child Health Research In Sub-Saharan Africa, Meriel Flint-O’Kane, Peter Von Dadelszen, Prestige Tatenda Makanga, Esperança Sevene, Anna Roca, Peter Dukes, Saba Hinrichs-Krapels, Rachel Craik, Laura A. Magee, Marleen Temmerman, Angela Koech, The Precise Network

Obstetrics and Gynaecology, East Africa

It is widely acknowledged across the global health sector that research programmes need to be designed and implemented in a way that maximise opportunities for strengthening local capacity. This paper examines how the United Kingdom Research and Innovation (UKRI) Grand Challenges Research Fund (GCRF) funded PRECISE (PREgnancy Care Integrating translational Science, Everywhere) Network has been established as a platform to strengthen global capacity for research focused on the improvement of maternal, fetal and newborn health in subSaharan Africa. Best practice principles outlined in an ESSENCE on Health Research report have been considered in relation to the PRECISE Network capacity-building activities …


Precise Pregnancy Cohort: Challenges And Strategies In Setting Up A Biorepository In Sub-Saharan Africa, Rachel Craik, Donna Russell, Rachel M. Tribe, Marleen Temmerman, Angela Koech, Patricia Okiro, Geoffrey Omuse, Sikolia Wanyonyi Apr 2020

Precise Pregnancy Cohort: Challenges And Strategies In Setting Up A Biorepository In Sub-Saharan Africa, Rachel Craik, Donna Russell, Rachel M. Tribe, Marleen Temmerman, Angela Koech, Patricia Okiro, Geoffrey Omuse, Sikolia Wanyonyi

Obstetrics and Gynaecology, East Africa

Background and objective: PRECISE is a population-based, prospective pregnancy cohort study designed for deep phenotyping of pregnancies in women with placenta-related disorders, and in healthy controls. The PRECISE Network is recruiting ~ 10,000 pregnant women in three countries (The Gambia, Kenya, and Mozambique) representing sub-Saharan Africa. The principal aim is to improve our understanding of pre-eclampsia, fetal growth restriction and stillbirth. This involves the creation of a highly curated biorepository for state of the art discovery science and a rich database of antenatal variables and maternal and neonatal outcomes. Our overarching aim is to provide large sample numbers with …


The Precise (Pregnancy Care Integrating Translational Science, Everywhere) Network’S First Protocol: Deep Phenotyping In Three Sub-Saharan African Countries, Peter Von Dadelszen, Meriel Flint-O’Kane, Lucilla Poston, Rachel Craik, Donna Russell, Rachel M. Tribe, Umberto D’Alessandro, Marleen Temmerman, Angela Koech, Anna Roca Apr 2020

The Precise (Pregnancy Care Integrating Translational Science, Everywhere) Network’S First Protocol: Deep Phenotyping In Three Sub-Saharan African Countries, Peter Von Dadelszen, Meriel Flint-O’Kane, Lucilla Poston, Rachel Craik, Donna Russell, Rachel M. Tribe, Umberto D’Alessandro, Marleen Temmerman, Angela Koech, Anna Roca

Obstetrics and Gynaecology, East Africa

Background: The PRECISE (PREgnancy Care Integrating translational Science, Everywhere) Network is a new and broadly-based group of research scientists and health advocates based in the UK, Africa and North America.

Methods: This paper describes the protocol that underpins the clinical research activity of the Network, so that the investigators, and broader global health community, can have access to ‘deep phenotyping’ (social determinants of health, demographic and clinical parameters, placental biology and agnostic discovery biology) of women as they advance through pregnancy to the end of the puerperium, whether those pregnancies have normal outcomes or are complicated by one/more of the …


Transcriptional Upregulation Of Nlrc5 By Radiation Drives Sting- And Interferon-Independent Mhc-I Expression On Cancer Cells And T Cell Cytotoxicity., Lauren Zebertavage, Alejandro F Alice, Marka R Crittenden, Michael J. Gough Apr 2020

Transcriptional Upregulation Of Nlrc5 By Radiation Drives Sting- And Interferon-Independent Mhc-I Expression On Cancer Cells And T Cell Cytotoxicity., Lauren Zebertavage, Alejandro F Alice, Marka R Crittenden, Michael J. Gough

Articles, Abstracts, and Reports

Radiation therapy has been shown to enhance the efficacy of various T cell-targeted immunotherapies that improve antigen-specific T cell expansion, T regulatory cell depletion, or effector T cell function. Additionally, radiation therapy has been proposed as a means to recruit T cells to the treatment site and modulate cancer cells as effector T cell targets. The significance of these features remains unclear. We set out to determine, in checkpoint inhibitor resistant models, which components of radiation are primarily responsible for overcoming this resistance. In order to model the vaccination effect of radiation, we used a Listeria monocytogenes based vaccine to …


The Contribution Of Qualitative Research Within The Precise Study In Sub-Saharan Africa, Marina A. S. Daniele, Melisa Martinez-Alvarez, Angela Koech, Marianne Vidler, Tatiana Salisbury, Prestige Tatenda Makanga, Peris Musitia, Meriel Flint-O’Kane, Tanya Wells Brown, Brahima Amara Diallo, Marleen Temmerman, Geoffrey Omuse, Sikolia Wanyonyi, Patricia Okiro Apr 2020

The Contribution Of Qualitative Research Within The Precise Study In Sub-Saharan Africa, Marina A. S. Daniele, Melisa Martinez-Alvarez, Angela Koech, Marianne Vidler, Tatiana Salisbury, Prestige Tatenda Makanga, Peris Musitia, Meriel Flint-O’Kane, Tanya Wells Brown, Brahima Amara Diallo, Marleen Temmerman, Geoffrey Omuse, Sikolia Wanyonyi, Patricia Okiro

Obstetrics and Gynaecology, East Africa

The PRECISE Network is a cohort study established to investigate hypertension, fetal growth restriction and stillbirth (described as “placental disorders”) in Kenya, Mozambique and The Gambia. Several pregnancy or birth cohorts have been set up in low- and middle-income countries, focussed on maternal and child health. Qualitative research methods are sometimes used alongside quantitative data collection from these cohorts. Researchers affiliated with PRECISE are also planning to use qualitative methods, from the perspective of multiple subject areas. This paper provides an overview of the different ways in which qualitative research methods can contribute to achieving PRECISE’s objectives, and discusses the …


Designing An Antibiotic Eluting Trauma Screw To Reduce Short Term Infection In Bone Fractures, Dominic Lincoln Apr 2020

Designing An Antibiotic Eluting Trauma Screw To Reduce Short Term Infection In Bone Fractures, Dominic Lincoln

Honors Theses

Orthopedic infection in the United States is one of the most common and severe health risks faced by trauma patients. The most prevalent infection is orthopedic and trauma device-related infection (ORDI) and often occurs in long bones at the fracture site. The purpose of this paper is to explore this infection, its causes, and solutions currently on the market while providing novel solutions to the problem. The designs proposed will be evaluated for their effectiveness and value, while attempting to keep costs low for all stakeholders. The feasibility of patenting these ideas will also be considered, as will the testing …


Drugging Chemokine Receptors: Biased Cxcr3 Agonists Differentially Regulate Chemotaxis And Inflammation, Jeffrey Smith, Dylan Eiger, Chia-Feng Tsai, Lowell Nicholson, Rachel Glenn, Priya Alagesan, Amanda Macleod, John Jacobs, Tujin Shi, Sudarshan Rajagopal Apr 2020

Drugging Chemokine Receptors: Biased Cxcr3 Agonists Differentially Regulate Chemotaxis And Inflammation, Jeffrey Smith, Dylan Eiger, Chia-Feng Tsai, Lowell Nicholson, Rachel Glenn, Priya Alagesan, Amanda Macleod, John Jacobs, Tujin Shi, Sudarshan Rajagopal

Providence Portland Medical Center Internal Medicine 2020

Drugging Chemokine Receptors: Biased CXCR3 Agonists Differentially Regulate Chemotaxis And Inflammation

Jeffrey Smith, MD, PhD

Providence Portland Medical Center – Portland, OR

Additional Authors: Dylan Eiger, BS; Chia-Feng Tsai, PhD; Lowell Nicholson,MD; Rachel Glenn, BS; Priya Alagesan, BS; Amanda MacLeod, MD; John Jacobs, PhD; Tujin Shi, PhD; Sudarshan Rajagopal, MD,PhD

Introduction: G protein-coupled receptors (GPCRs) are the largest class of transmembrane receptors and the target of ~30% of FDA approved drugs. It is now well established that GPCRs can signal through multiple transducers, including classical heterotrimeric G proteins but also GPCR kinases and β-arrestins (1). While these signaling pathways can …


Association Of Aβ With Ceramide-Enriched Astrosomes Mediates Aβ Neurotoxicity, Ahmed Elsherbini, Alexander S. Kirov, Michael B. Dinkins, Guanghu Wang, Haiyan Qin, Zhihui Zhu, Priyanka Tripathi, Simone M. Crivelli, Erhard Bieberich Apr 2020

Association Of Aβ With Ceramide-Enriched Astrosomes Mediates Aβ Neurotoxicity, Ahmed Elsherbini, Alexander S. Kirov, Michael B. Dinkins, Guanghu Wang, Haiyan Qin, Zhihui Zhu, Priyanka Tripathi, Simone M. Crivelli, Erhard Bieberich

Physiology Faculty Publications

Amyloid-β (Aβ) associates with extracellular vesicles termed exosomes. It is not clear whether and how exosomes modulate Aβ neurotoxicity in Alzheimer's disease (AD). We show here that brain tissue and serum from the transgenic mouse model of familial AD (5xFAD) and serum from AD patients contains ceramide-enriched and astrocyte-derived exosomes (termed astrosomes) that are associated with Aβ. In Neuro-2a cells, primary cultured neurons, and human induced pluripotent stem cell-derived neurons, Aβ-associated astrosomes from 5xFAD mice and AD patient serum were specifically transported to mitochondria, induced mitochondrial clustering, and upregulated the fission protein Drp-1 at a concentration corresponding to 5 femtomoles …


It's In The Bag: Tidal Volumes In Adult And Pediatric Bag Valve Masks, Benjamin Dafilou, Daniel Schwester, Nathan Ruhl, Andreia Marques-Baptista Apr 2020

It's In The Bag: Tidal Volumes In Adult And Pediatric Bag Valve Masks, Benjamin Dafilou, Daniel Schwester, Nathan Ruhl, Andreia Marques-Baptista

College of Science & Mathematics Departmental Research

Introduction: A bag valve mask (BVM) is a life saving device used by all levels of health care professionals during resuscitative care. We focus most of our time optimizing the patient's position, firmly securing the mask, and frequency of ventilations. However, despite our best efforts to control these factors, we may still be precipitating harm to the patient. Multiple studies have shown the tidal volumes typically delivered by the adult BVM are often higher than recommended for lung-protective ventilation protocols. In this study we measure and compare the ventilation parameters delivered by the adult and pediatric BVM ventilators. Methods: A …


The Inflammatory Bowel Disease Questionnaire In Randomized Controlled Trials Of Treatment For Ulcerative Colitis: Systematic Review And Meta-Analysis, Aaron Yarlas, Stephen Maher, Martha Bayliss, Andrew Lovley, Joseph C. Cappelleri, Andrew G. Bushmakin, Marco D. Dibonaventura Apr 2020

The Inflammatory Bowel Disease Questionnaire In Randomized Controlled Trials Of Treatment For Ulcerative Colitis: Systematic Review And Meta-Analysis, Aaron Yarlas, Stephen Maher, Martha Bayliss, Andrew Lovley, Joseph C. Cappelleri, Andrew G. Bushmakin, Marco D. Dibonaventura

Journal of Patient-Centered Research and Reviews

Purpose: The 32-item Inflammatory Bowel Disease Questionnaire (IBDQ-32) is the most frequently used instrument to capture disease-specific quality of life in randomized clinical trials for ulcerative colitis. This review and meta-analysis provides the first synthesis of evidence regarding the sensitivity of IBDQ-32 total and domain scores to treatment efficacy.

Methods: A systematic literature search and risk-of-bias assessment yielded 14 articles that were included in the primary analysis. Treatments were categorized as efficacious if they met the primary efficacy endpoint (which was not the IBDQ-32); otherwise they were categorized as non-efficacious. A continuous measure of treatment efficacy was calculated for …


Giving Credence To The Experience Of X-Linked Hypophosphatemia In Adulthood: An Interprofessional Mixed-Methods Study, Melissa Hughes, Carolyn Macica, Catherine Meriano, Maya Doyle Apr 2020

Giving Credence To The Experience Of X-Linked Hypophosphatemia In Adulthood: An Interprofessional Mixed-Methods Study, Melissa Hughes, Carolyn Macica, Catherine Meriano, Maya Doyle

Journal of Patient-Centered Research and Reviews

Purpose: X-linked hypophosphatemia (XLH) is a rare X-linked dominant metabolic bone disease, often diagnosed in childhood but causing increasing physical debilitation and pain in adulthood. Physical comorbidities of XLH in adulthood include pervasive and early-onset degenerative arthritis, mineralizing enthesophytes and osteophytes, osteomalacia and pseudofracture, dental abscesses, and hearing loss.

Methods: This mixed-methods analysis included physical findings, diagnostic imaging, occupational and physical therapy assessments, and semi-structured interviews by social work to understand the functional outcomes and lived experience of XLH in adulthood, through connections between qualitative data obtained by social work and occupational therapy with the quantitative findings from other disciplines. …


Does Patient-Provider Race/Ethnicity Concordance Impact Outcomes For Adults With Lupus?, Pamela C. Delis Phd, Rn, Cne, Inge B. Corless Phd, Rn, Fnap, Faan, Indigo Young Ms, Ccc-Slp, Mary W. Hildebrand Otd,Otr/L, Jessica G. Bell Ms, Amanda Tarbet Mslis Apr 2020

Does Patient-Provider Race/Ethnicity Concordance Impact Outcomes For Adults With Lupus?, Pamela C. Delis Phd, Rn, Cne, Inge B. Corless Phd, Rn, Fnap, Faan, Indigo Young Ms, Ccc-Slp, Mary W. Hildebrand Otd,Otr/L, Jessica G. Bell Ms, Amanda Tarbet Mslis

Journal of Health Disparities Research and Practice

Background: Health disparities exist among the 1.5 million Americans with lupus, with women of color bearing higher disease rates and burden. Complex reasons include genetics, comorbidities, and socioeconomics. These factors may lead to differences in health-related outcomes in lupus.

Aim: To determine if patient-provider racial/ethnic concordance plays a role in outcomes for adults with lupus.

Method: For this scoping review, the authors searched PubMed Medline and CINAHL using keywords and subject headings for lupus, race or ethnicity, and patient-health professional concordance.

Results: Despite an intentionally broadened search of literature, the authors identified a lack of studies examining the topic.

Conclusions: …


Meeting Radiation Dosimetry Capacity Requirements Of Population-Scale Exposures By Geostatistical Sampling., Peter K Rogan, Eliseos J Mucaki, Ruipeng Lu, Ben C Shirley, Edward Waller, Joan H M Knoll Apr 2020

Meeting Radiation Dosimetry Capacity Requirements Of Population-Scale Exposures By Geostatistical Sampling., Peter K Rogan, Eliseos J Mucaki, Ruipeng Lu, Ben C Shirley, Edward Waller, Joan H M Knoll

Biochemistry Publications

BACKGROUND: Accurate radiation dose estimates are critical for determining eligibility for therapies by timely triaging of exposed individuals after large-scale radiation events. However, the universal assessment of a large population subjected to a nuclear spill incident or detonation is not feasible. Even with high-throughput dosimetry analysis, test volumes far exceed the capacities of first responders to measure radiation exposures directly, or to acquire and process samples for follow-on biodosimetry testing.

AIM: To significantly reduce data acquisition and processing requirements for triaging of treatment-eligible exposures in population-scale radiation incidents.

METHODS: Physical radiation plumes modelled nuclear detonation scenarios of simulated exposures at …


Cardiovascular Recovery From Emotional Stress: An Operationalization Of Equanamity Following Mindfulness-Based Emotional Stress, Emma Mcbride Apr 2020

Cardiovascular Recovery From Emotional Stress: An Operationalization Of Equanamity Following Mindfulness-Based Emotional Stress, Emma Mcbride

Theses and Dissertations

Theoretical models of mindfulness suggest that meditation may improve health, in part, by regulating stress physiology, including faster recovery of heart rate (HR) and blood pressure (SBP/DBP) after emotional stress. Furthermore, improved cardiovascular recovery (CR) may be a marker of equanimity, defined as increased acceptance of and reduced reactivity to stress. No studies have tested this hypothesis, partly because methodology for assessing CR remains controversial. Using a novel operationalization of equanimity and several methods of measuring CR, this project investigated whether (1) equanimity is associated with improved CR, (2) Mindfulness-Based Stress Reduction (MBSR) is associated with improved CR, and (3) …