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Impact Of Rituximab On Patient-Reported Outcomes In Patients With Rheumatoid Arthritis From The Us Corrona Registry, Leslie R. Harrold, Ani John, Jennie Best, Steve Zlotnick, Chitra Karki, YouFu Li, Jeffrey D. Greenberg, Joel M. Kremer 2018 University of Massachusetts Medical School

Impact Of Rituximab On Patient-Reported Outcomes In Patients With Rheumatoid Arthritis From The Us Corrona Registry, Leslie R. Harrold, Ani John, Jennie Best, Steve Zlotnick, Chitra Karki, Youfu Li, Jeffrey D. Greenberg, Joel M. Kremer

Leslie R. Harrold

To evaluate the impact of rituximab on patient-reported outcomes (PROs) in a US-based observational cohort of patients with rheumatoid arthritis (RA). Patients with active RA, prior exposure to > /=1 tumor necrosis factor inhibitor (TNFi) and who newly initiated rituximab were identified. Changes in PROs were assessed 1 year after rituximab initiation. PRO measures included Clinical Disease Activity Index (CDAI); patient global disease activity, pain and fatigue (visual analog score; 0-100); morning stiffness (hours); modified Health Assessment Questionnaire (mHAQ; 0-3); and EuroQoL EQ-5D. Of the 667 patients who newly initiated rituximab, baseline PRO and clinical measures indicated that patients were substantially ...


Survival Advantage Of Both Human Hepatocyte Xenografts And Genome-Edited Hepatocytes For Treatment Of Alpha-1 Antitrypsin Deficiency, Florie Borel, Qiushi Tang, Gwladys Gernoux, Cynthia Greer, Ziqiong Wang, Adi Barzel, Mark A. Kay, Leonard D. Shultz, Dale L. Greiner, Terence R. Flotte, Michael A. Brehm, Christian Mueller 2017 University of Massachusetts Medical School

Survival Advantage Of Both Human Hepatocyte Xenografts And Genome-Edited Hepatocytes For Treatment Of Alpha-1 Antitrypsin Deficiency, Florie Borel, Qiushi Tang, Gwladys Gernoux, Cynthia Greer, Ziqiong Wang, Adi Barzel, Mark A. Kay, Leonard D. Shultz, Dale L. Greiner, Terence R. Flotte, Michael A. Brehm, Christian Mueller

Christian Mueller

Hepatocytes represent an important target for gene therapy and editing of single-gene disorders. In alpha-1 antitrypsin (AAT) deficiency, one missense mutation results in impaired secretion of AAT. In most patients, lung damage occurs due to a lack of AAT-mediated protection of lung elastin from neutrophil elastase. In some patients, accumulation of misfolded PiZ mutant AAT protein triggers hepatocyte injury, leading to inflammation and cirrhosis. We hypothesized that correcting the Z mutant defect in hepatocytes would confer a selective advantage for repopulation of hepatocytes within an intact liver. A human PiZ allele was crossed onto an immune-deficient (NSG) strain to create ...


Cancer Survivorship: Promoting A Lifetime Of Health, Janelle Coleman-Smith 2017 The University of San Francisco

Cancer Survivorship: Promoting A Lifetime Of Health, Janelle Coleman-Smith

Master's Projects and Capstones

Abstract

Introduction Cancer survivors can face post-cancer treatment effects that need addressing throughout their care trajectory. Education provided to stakeholders and patients will be beneficial in preventing fragmented care, increasing patient satisfaction, and expanding ongoing supportive clinical survivorship care. Methods An adapted Dr. Joanne Lester survivorship needs survey was given to n=7 post-cancer treatment patients within a northern California cancer patient advisory committee. The survey results were analyzed to identify common underserved chronic long-term survivorship needs. Based on the data, an evidence-based educational component was included within a booklet to enhance future survivorship care. Additional surveys were sent to ...


The Effects Of Continuous Insulin Pump Therapy On Glycemic Control In Pregnant Type 1 Diabetics, Kimberly Kelsey 2017 Dominican University of California

The Effects Of Continuous Insulin Pump Therapy On Glycemic Control In Pregnant Type 1 Diabetics, Kimberly Kelsey

Senior Theses and Capstone Projects

Type 1 Diabetics have various ways of managing their diabetes that have been studied for their effectiveness. Pregnancy in the Type 1 Diabetic has been understudied. It is known that Diabetics in general have poorer pregnancy outcomes because of poor glycemic control. This coupled with the fact that the body needs 3-4 times more insulin as pregnancy comes to an end makes managing blood glucose levels challenging for diabetics (Lowdermilk, 2016, p. 689). For the Type 1 Diabetic, there are two main ways to control diabetes: multiple daily injections using at least two type of insulin and continuous subcutaneous insulin ...


Effects Of Lower Extremity Aerobic Exercise And Conditioned Pain Modulation On Evoked Shoulder Pain, Logan Lumpkins, Craig Wassinger 2017 East Tennessee State University

Effects Of Lower Extremity Aerobic Exercise And Conditioned Pain Modulation On Evoked Shoulder Pain, Logan Lumpkins, Craig Wassinger

Undergraduate Honors Theses

Background: Emerging evidence suggests that aerobic exercise and conditioned pain modulation may be advocated in treating patients with musculoskeletal pain. The effects of lower extremity aerobic exercise and conditioned pain modulation on evoked shoulder pain are not known.

Purpose: To determine the acute effects of lower extremity aerobic exercise and conditioned pain modulation on outcomes of evoked shoulder pain from pain pressure threshold measurements.

Study Design: Repeated measures.

Methods: Thirty (30) healthy volunteers were tested over the course of two sessions. Session 1 consisted of collecting pain pressure threshold measurements over the infraspinatus before and immediately following a conditioned pain ...


Decreasing Time To Broad Spectrum Antibiotics For Septic Patients In The Emergency Department, Joseph J. Zieminski, Emily E. Bryant 2017 Department of Pharmacy, Aurora St. Luke’s Medical Center

Decreasing Time To Broad Spectrum Antibiotics For Septic Patients In The Emergency Department, Joseph J. Zieminski, Emily E. Bryant

Journal of Patient-Centered Research and Reviews

Background: Timely administration of broad spectrum antibiotics has been shown to be directly correlated with decreased mortality for patients with severe sepsis and septic shock. As such, both the Surviving Sepsis Campaign and the SEP-1 CMS measure recognize timely antibiotic administration as a cornerstone of therapy for patients with severe sepsis or septic shock.

Purpose: Decrease time to broad spectrum antibiotic administration for septic patients in the emergency department (ED) of Aurora St. Luke’s Medical Center.

Methods: An alert within the electronic medical record was created to more rapidly identify potentially septic patients in the ED. After receiving the ...


Survival Advantage Of Both Human Hepatocyte Xenografts And Genome-Edited Hepatocytes For Treatment Of Alpha-1 Antitrypsin Deficiency, Florie Borel, Qiushi Tang, Gwladys Gernoux, Cynthia Greer, Ziqiong Wang, Adi Barzel, Mark A. Kay, Leonard D. Shultz, Dale L. Greiner, Terence R. Flotte, Michael A. Brehm, Christian Mueller 2017 University of Massachusetts Medical School

Survival Advantage Of Both Human Hepatocyte Xenografts And Genome-Edited Hepatocytes For Treatment Of Alpha-1 Antitrypsin Deficiency, Florie Borel, Qiushi Tang, Gwladys Gernoux, Cynthia Greer, Ziqiong Wang, Adi Barzel, Mark A. Kay, Leonard D. Shultz, Dale L. Greiner, Terence R. Flotte, Michael A. Brehm, Christian Mueller

Pediatric Publications and Presentations

Hepatocytes represent an important target for gene therapy and editing of single-gene disorders. In alpha-1 antitrypsin (AAT) deficiency, one missense mutation results in impaired secretion of AAT. In most patients, lung damage occurs due to a lack of AAT-mediated protection of lung elastin from neutrophil elastase. In some patients, accumulation of misfolded PiZ mutant AAT protein triggers hepatocyte injury, leading to inflammation and cirrhosis. We hypothesized that correcting the Z mutant defect in hepatocytes would confer a selective advantage for repopulation of hepatocytes within an intact liver. A human PiZ allele was crossed onto an immune-deficient (NSG) strain to create ...


Sulforaphane From Broccoli Reduces Symptoms Of Autism: A Follow-Up Case Series From A Randomized Double-Blind Study, Rhoda Lynch, Eileen Diggins, Susan Connors, Andrew W. Zimmerman, Kanwaljit Singh, Hua Liu, Paul Talalay, Jed W. Fahey 2017 University of Massachusetts Medical School

Sulforaphane From Broccoli Reduces Symptoms Of Autism: A Follow-Up Case Series From A Randomized Double-Blind Study, Rhoda Lynch, Eileen Diggins, Susan Connors, Andrew W. Zimmerman, Kanwaljit Singh, Hua Liu, Paul Talalay, Jed W. Fahey

Pediatric Publications and Presentations

Introduction: Autism spectrum disorder (ASD) affects 1 in 68 children, is characterized by impaired social interaction and communication as well as restricted or repetitive behaviors, and varies widely with respect to its causes and presentations. There are no validated pharmacologic treatments for the core symptoms of ASD. The social, medical, and economic burdens of ASD on families and caregivers are profound. We recently showed in a small clinical trial that sulforaphane (SF) from broccoli sprouts could significantly reduce the behavioral symptoms of ASD.

Methods: After we completed the intervention phase of the original trial (2011-2013), many caregivers used over-the-counter dietary ...


Disaggregating The Relative Influence Of Genetic, Environmental And Individual Factors On Lcl And Hdl Cholesterols And Bmi For A Sample Of African American (Aa) Mothers And Daughters, C. Jayne Brahler, Jewel Harden, Michelle McHone, Matthew Soules, Eric Evans, Ann Alyanak, Fred Diakpieng, Paul M. Vanderburgh 2017 University of Dayton

Disaggregating The Relative Influence Of Genetic, Environmental And Individual Factors On Lcl And Hdl Cholesterols And Bmi For A Sample Of African American (Aa) Mothers And Daughters, C. Jayne Brahler, Jewel Harden, Michelle Mchone, Matthew Soules, Eric Evans, Ann Alyanak, Fred Diakpieng, Paul M. Vanderburgh

Paul M. Vanderburgh

There are many reports about the associations between blood lipids, body mass index (BMI) and dietary cholesterol intakes both within the individual and between related individuals. The purpose of this descriptive research project was to investigate the relationships between LDL and HDL cholesterols, body mass index and dietary cholesterol intakes for a sample of African American (AA) mothers and their daughters and to attempt to separate the contribution of genetic versus environmental factors. Mother and daughter participants (n =42 and 66, respectively) were 12-14-hours fasted when blood samples were drawn, heights and weights measured, and 24 hour food recalls completed.


The Effect Of Photoactivated Tmp On Burkholderia Cepacia Biofilms, Reyna G. Osorio, Chandra N. Swiech, Tracy L. Collins 2017 Cedarville University

The Effect Of Photoactivated Tmp On Burkholderia Cepacia Biofilms, Reyna G. Osorio, Chandra N. Swiech, Tracy L. Collins

Tracy Collins, Ph.D.

Burkholderia cepacia is an opportunistic pathogen that causes infections in immunocompromised individuals such as cystic fibrosis patients. B. cepacia infections are typically characterized by the formation of complex communities of cells known as biofilms. Because B. cepacia biofilms are difficult to eradicate using antibiotics, it is important to pursue alternative treatment methods. Photodynamic therapy (PDT) is a type of therapy that uses light, a photosensitizer, and oxygen to elicit cell death through the production of reactive oxygen species. PDT has been shown in previous studies to be successful in killing both Pseudomonas aeruginosa and Staphylococcus aureus. In this study, we ...


Locked Nucleic Acid Gapmers And Conjugates Potently Silence Adam33, An Asthma-Associated Metalloprotease With Nuclear-Localized Mrna, Hannah M. Pendergraff, Pranathi Meda Krishnamurthy, Alexandre J. Debacker, Michael P. Moazami, Vivek K. Sharma, Liisa Niitsoo, Yong Yu, Yen Nee Tan, Hans Michael Haitchi, Jonathan K. Watts 2017 University of Southampton

Locked Nucleic Acid Gapmers And Conjugates Potently Silence Adam33, An Asthma-Associated Metalloprotease With Nuclear-Localized Mrna, Hannah M. Pendergraff, Pranathi Meda Krishnamurthy, Alexandre J. Debacker, Michael P. Moazami, Vivek K. Sharma, Liisa Niitsoo, Yong Yu, Yen Nee Tan, Hans Michael Haitchi, Jonathan K. Watts

Open Access Articles

Two mechanisms dominate the clinical pipeline for oligonucleotide-based gene silencing, namely, the antisense approach that recruits RNase H to cleave target RNA and the RNAi approach that recruits the RISC complex to cleave target RNA. Multiple chemical designs can be used to elicit each pathway. We compare the silencing of the asthma susceptibility gene ADAM33 in MRC-5 lung fibroblasts using four classes of gene silencing agents, two that use each mechanism: traditional duplex small interfering RNAs (siRNAs), single-stranded small interfering RNAs (ss-siRNAs), locked nucleic acid (LNA) gapmer antisense oligonucleotides (ASOs), and novel hexadecyloxypropyl conjugates of the ASOs. Of these designs ...


Impact Of Rituximab On Patient-Reported Outcomes In Patients With Rheumatoid Arthritis From The Us Corrona Registry, Leslie R. Harrold, Ani John, Jennie Best, Steve Zlotnick, Chitra Karki, YouFu Li, Jeffrey D. Greenberg, Joel M. Kremer 2017 University of Massachusetts Medical School

Impact Of Rituximab On Patient-Reported Outcomes In Patients With Rheumatoid Arthritis From The Us Corrona Registry, Leslie R. Harrold, Ani John, Jennie Best, Steve Zlotnick, Chitra Karki, Youfu Li, Jeffrey D. Greenberg, Joel M. Kremer

Open Access Articles

To evaluate the impact of rituximab on patient-reported outcomes (PROs) in a US-based observational cohort of patients with rheumatoid arthritis (RA). Patients with active RA, prior exposure to > /=1 tumor necrosis factor inhibitor (TNFi) and who newly initiated rituximab were identified. Changes in PROs were assessed 1 year after rituximab initiation. PRO measures included Clinical Disease Activity Index (CDAI); patient global disease activity, pain and fatigue (visual analog score; 0-100); morning stiffness (hours); modified Health Assessment Questionnaire (mHAQ; 0-3); and EuroQoL EQ-5D. Of the 667 patients who newly initiated rituximab, baseline PRO and clinical measures indicated that patients were substantially ...


Reframing Outcome Measures For Thrombolytics In Acute Ischemic Stroke, Brandon Baker, Charles W. Kropf, Nicholus Yee, James Peter Meza 2017 DMC-Sinai Grace Hospital Emergency Medicine Residency

Reframing Outcome Measures For Thrombolytics In Acute Ischemic Stroke, Brandon Baker, Charles W. Kropf, Nicholus Yee, James Peter Meza

Clinical Research in Practice: The Journal of Team Hippocrates

An informed consent conversation examining relevant research and discussing the potential benefits and harms of thrombolytic therapy in acute stroke.


Anticoagulation Increases Survival In Patients With Idiopathic Pulmonary Arterial Hypertension, Marvin L. Kajy 2017 Department of Internal Medicine, Detroit Receiving Hospital/Detroit Medical Center

Anticoagulation Increases Survival In Patients With Idiopathic Pulmonary Arterial Hypertension, Marvin L. Kajy

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Olsson KM, Delcroix M, Ghofrani HA, et al. Anticoagulation and survival in pulmonary arterial hypertension: Results from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA). Circulation, 2014;129(1):57-65. doi: 10.1161/CIRCULATIONAHA.113.004526


Alloimmune Responses Of Humanized Mice To Human Pluripotent Stem Cell Therapeutics, Nigel G. Kooreman, Michael A. Brehm, Dale L. Greiner, Leonard D. Shultz, Joseph C. Wu 2017 Stanford University

Alloimmune Responses Of Humanized Mice To Human Pluripotent Stem Cell Therapeutics, Nigel G. Kooreman, Michael A. Brehm, Dale L. Greiner, Leonard D. Shultz, Joseph C. Wu

Open Access Articles

There is growing interest in using embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) derivatives for tissue regeneration. However, an increased understanding of human immune responses to stem cell-derived allografts is necessary for maintaining long-term graft persistence. To model this alloimmunity, humanized mice engrafted with human hematopoietic and immune cells could prove to be useful. In this study, an in-depth analysis of graft-infiltrating human lymphocytes and splenocytes revealed that humanized mice incompletely model human immune responses toward allogeneic stem cells and their derivatives. Furthermore, using an "allogenized" mouse model, we show the feasibility of reconstituting immunodeficient mice with ...


Alcohol And Cancer: Mechanisms And Therapies, Anuradha Ratna, Pranoti Mandrekar 2017 University of Massachusetts Medical School

Alcohol And Cancer: Mechanisms And Therapies, Anuradha Ratna, Pranoti Mandrekar

Open Access Articles

Several scientific and clinical studies have shown an association between chronic alcohol consumption and the occurrence of cancer in humans. The mechanism for alcohol-induced carcinogenesis has not been fully understood, although plausible events include genotoxic effects of acetaldehyde, cytochrome P450 2E1 (CYP2E1)-mediated generation of reactive oxygen species, aberrant metabolism of folate and retinoids, increased estrogen, and genetic polymorphisms. Here, we summarize the impact of alcohol drinking on the risk of cancer development and potential underlying molecular mechanisms. The interactions between alcohol abuse, anti-tumor immune response, tumor growth, and metastasis are complex. However, multiple studies have linked the immunosuppressive effects ...


Quantitative Dwi As An Early Imaging Biomarker Of The Response To Chemoradiation In Esophageal Cancer, Benjamin C. Musall 2017 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Quantitative Dwi As An Early Imaging Biomarker Of The Response To Chemoradiation In Esophageal Cancer, Benjamin C. Musall

UT GSBS Dissertations and Theses (Open Access)

For patients diagnosed with stages IIa-IIb esophageal cancer, the current standard of care treatment is tri-modality therapy (TMT), where neoadjuvant chemoradiation (nCRT) is followed by surgical resection. Histopathology of resected tumors reveals that pathological complete response (pCR) is achieved in 20-30% of patients through nCRT alone. Because of the high mortality and morbidity associated with esophagectomy, it may be advantageous for patients exhibiting pCR from nCRT alone to be placed under observation rather than completing their TMT. Therefore, a method for predicting response at an early time-point during nCRT is highly desirable. Conventional methods such as endoscopic ultrasound, re-biopsy, and ...


Biomechanical Testing Of An Exercise For Strengthening The Proximal Femur., Alyssa Osbourne 2017 University of Louisville

Biomechanical Testing Of An Exercise For Strengthening The Proximal Femur., Alyssa Osbourne

Electronic Theses and Dissertations

Based on the principles of cutting edge bone remodeling research, a unique therapeutic exercise device was designed specifically to improve bone quality at the most critical location of the proximal femur prone to fracture: the superior-lateral femoral neck where the fracture first initiates during a fall. The exercise/device is intended to work by inducing enough strain in the bone to stimulate the body’s natural bone remodeling mechanisms to increase bone density in the proximal femur and consequently prevent a fracture from arising if a fall to the side does occur.

In order to test the proposed exercise, experiments ...


Evolution Of The Alpha-1 Antitrypsin Muscle Gene Therapy: Translation From Clinical Trial To Benchtop And Back Again, Alisha M. Gruntman, Gwladys Gernoux, Gensheng Wang, Janet Benson, Jeff Chulay, Dave Knop, Christian Mueller, Terence R. Flotte 2017 University of Massachusetts Medical School

Evolution Of The Alpha-1 Antitrypsin Muscle Gene Therapy: Translation From Clinical Trial To Benchtop And Back Again, Alisha M. Gruntman, Gwladys Gernoux, Gensheng Wang, Janet Benson, Jeff Chulay, Dave Knop, Christian Mueller, Terence R. Flotte

Christian Mueller

Alpha-one antitrypsin (AAT) deficiency is a genetic disease affecting the lungs due to inadequate anti-protease activity in the pulmonary interstitium. On-going human trials use intra-muscular delivery of adeno-associated virus (rAAV1), allowing expressing myofibers to secrete normal (M)AAT protein. In the Phase IIa trial, patients in the highest dose cohort (6x1012vg/kg) were given 100 intra-muscular (IM) injections of undiluted vector, with serum AAT levels still substantially below target levels. Previous work has shown that delivering rAAV vector to the musculature via limb perfusion leads to widespread gene expression in myofibers. We hypothesize that widespread delivery would result in an ...


Alzheimer’S Disease: Dawn Of A New Era?, Farideh Amirrad, Emira Bousoik, Kiumars Shamloo, Hassan Al-Shiyab, Viet-Hong Nguyen, Hamidreza Montazeri Aliabadi 2017 Chapman University

Alzheimer’S Disease: Dawn Of A New Era?, Farideh Amirrad, Emira Bousoik, Kiumars Shamloo, Hassan Al-Shiyab, Viet-Hong Nguyen, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Alzheimer’s disease (AD) is an irreversible neurodegenerative disease characterized by a progressive decline in cognition and memory, leading to significant impairment in daily activities and ultimately death. It is the most common cause of dementia, the prevalence of which increases with age; however, age is not the only predisposing factor. The pathology of this cognitive impairing disease is still not completely understood, which has limited the development of valid therapeutic options. Recent years have witnessed a wide range of novel approaches to combat this disease, so that they greatly increased our understanding of the disease and of the unique ...


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