Analytical, Diagnostic and Therapeutic Techniques and Equipment Commons^™

5 Year Expression And Neutrophil Defect Repair After Gene Therapy In Alpha-1 Antitrypsin Deficiency, Christian Mueller, Gwladys Gernoux, Alisha M. Gruntman, Florie Borel, Emer P. Reeves, Roberto Calcedo, Farshid N. Rouhani, Anthony Yachnis, Margaret Humphries, Martha Campbell-Thompson, Louis M. Messina, Jeffrey D. Chulay, Bruce Trapnell, James M. Wilson, Noel G. Mcelvaney, Terence R. Flotte

Christian Mueller

Alpha-1 antitrypsin deficiency is a monogenic disorder resulting in emphysema due principally to the unopposed effects of neutrophil elastase. We previously reported achieving plasma wild-type alpha-1 antitrypsin concentrations at 2.5%-3.8% of the purported therapeutic level at 1 year after a single intramuscular administration of recombinant adeno-associated virus serotype 1 alpha-1 antitrypsin vector in alpha-1 antitrypsin deficient patients. We analyzed blood and muscle for alpha-1 antitrypsin expression and immune cell response. We also assayed previously reported markers of neutrophil function known to be altered in alpha-1 antitrypsin deficient patients. Here, we report sustained expression at 2.0%-2.5% of the target level from …

Effects Of Phosphodiesterase 3a Modulation On Murine Cerebral Microhemorrhages, Rachita K. Sumbria, Vitaly Vasilevko, Mher Mahoney Grigoryan, Annlia Paganini-Hill, Ronald Kim, David H. Cribbs, Mark J. Fisher

Pharmacy Faculty Articles and Research

Background: Cerebral microbleeds (CMB) are MRI-demonstrable cerebral microhemorrhages (CMH) which commonly coexist with ischemic stroke. This creates a challenging therapeutic milieu, and a strategy that simultaneously protects the vessel wall and provides anti-thrombotic activity is an attractive potential approach. Phosphodiesterase 3A (PDE3A) inhibition is known to provide cerebral vessel wall protection combined with anti-thrombotic effects. As an initial step in the development of a therapy that simultaneously treats CMB and ischemic stroke, we hypothesized that inhibition of the PDE3A pathway is protective against CMH development.

Methods: The effect of PDE3A pathway inhibition was studied in the inflammation-induced and …

Identification Of A Nucleoside Analog Active Against Adenosine Kinase-Expressing Plasma Cell Malignancies, Utthara Nayar, Jouliana Sadek, Jonathan Reichel, Denise Hernandez-Hopkins, Gunkut Akar, Peter J. Barelli, Michelle A. Sahai, Hufeng Zhou, Jennifer Totonchy, David Jayabalan, Ruben Niesvizky, Ilaria Guasparri, Duane Hassane, Yifang Liu, Shizuko Sei, Robert H. Shoemaker, J. David Warren, Olivier Elemento, Kenneth M. Kaye, Ethel Cesarman

Pharmacy Faculty Articles and Research

Primary effusion lymphoma (PEL) is a largely incurable malignancy of B cell origin with plasmacytic differentiation. Here, we report the identification of a highly effective inhibitor of PEL. This compound, 6-ethylthioinosine (6-ETI), is a nucleoside analog with toxicity to PEL in vitro and in vivo, but not to other lymphoma cell lines tested. We developed and performed resistome analysis, an unbiased approach based on RNA sequencing of resistant subclones, to discover the molecular mechanisms of sensitivity. We found different adenosine kinase–inactivating (ADK-inactivating) alterations in all resistant clones and determined that ADK is required to phosphorylate and activate 6-ETI. Further, we …

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis And Management In Young People: A Primer, P Rowe, R Underhill, K Friedman, A Gurwitt, Marvin Medow, M Schwartz, N Speight, Julian Stewart, R Vallings, K Rowe

NYMC Faculty Publications

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease that affects children and adolescents as well as adults. The etiology has not been established. While many pediatricians and other health-care providers are aware of ME/CFS, they often lack essential knowledge that is necessary for diagnosis and treatment. Many young patients experience symptoms for years before receiving a diagnosis. This primer, written by the International Writing Group for Pediatric ME/CFS, provides information necessary to understand, diagnose, and manage the symptoms of ME/CFS in children and adolescents. ME/CFS is characterized by overwhelming fatigue with a substantial loss of physical and mental stamina. …

Recombinant Aav Serotype And Capsid Mutant Comparison For Pulmonary Gene Transfer Of Alpha-1-Antitrypsin Using Invasive And Noninvasive Delivery, Rejean Liqun Wang, Thomas J. Mclaughlin, Travis Cossette, Qiushi Tang, Kevin Foust, Martha Campbell-Thompson, Ashley Martino, Pedro Cruz, Scott Loiler, Christian Mueller, Terence R. Flotte

Christian Mueller

Recombinant adeno-associated viral (rAAV) vectors have been widely used in pulmonary gene therapy research. In this study, we evaluated the transduction and expression efficiencies of several AAV serotypes and AAV2 capsid mutants with specific pulmonary targeting ligands in the mouse lung. The noninvasive intranasal delivery was compared with the traditional intratracheal lung delivery. The rAAV8 was the most efficient serotype at expressing alpha-1-antitrypsin (AAT) in the lung among all the tested serotypes and mutants. A dose of 1 x 1010 vg of rAAV8-CB-AAT transduced a high percentage of cells in the lung when delivered intratrachealy. The serum and the broncho-alveolar …

An Objective Assessment Of The Variability In Number Of Drops Per Bottle Of Glaucoma Medication, Daniel B. Moore, Judy Beck, Richard J. Kryscio

Ophthalmology and Visual Science Faculty Publications

Background: The purpose of this study is to evaluate the number of eyedrops available per bottle of a variety of commonly prescribed glaucoma medications.

Methods: Six bottles of each glaucoma medication were tested: three each in the vertical and horizontal orientations. Bottles were housed in a customized force gauge apparatus designed to mimic ballpoint fingertip contact with a bottle. At a standard rate, all drops were expressed from each bottle and counted with an automated drop counter. Simultaneously, bottle volume was measured and drop size and number were also estimated. The main outcome measures were: total number of drops, volume …

Modeling Hiv Dynamics Following 3bnc117 Antibody Infusion, Samantha Erwin

Biology and Medicine Through Mathematics Conference

No abstract provided.

Clinical Applications Of Pd-L1 Bioassays For Cancer Immunotherapy, Delong Liu, Shuhang Wang, Wendy Bindeman

NYMC Faculty Publications

Programmed death ligand 1 (PD-L1) has emerged as a biomarker that can help to predict responses to immunotherapies targeted against PD-L1 and its receptor (PD-1). Companion tests for evaluating PD-L1 expression as a biomarker of response have been developed for many cancer immunotherapy agents. These assays use a variety of detection platforms at different levels (protein, mRNA), employ diverse biopsy and surgical samples, and have disparate positivity cutoff points and scoring systems, all of which complicate the standardization of clinical decision-making. This review summarizes the current understanding and ongoing investigations regarding PD-L1 expression as a potential biomarker for clinical outcomes …

Healing Touch: Enhancing Quality Of Life, Julia Mccann-Khludenev

Evidence-Based Practice Project Reports

Healing touch (HT) is a non-invasive energy therapy used in the management of symptoms of various health conditions. HT utilization has demonstrated enhanced comfort and relief of symptoms such as chronic pain, post-traumatic-stress, depression, and anxiety. The purpose of this evidence-based practice (EBP) project was to promote awareness and appointment compliance rate of HT amongst veterans, and also to determine effectiveness of HT intervention on symptom relief and well-being. The PICO question was: “For Veterans, what is the effect of HT education material and mail notification on appointment compliance rate, and HT delivery on symptom relief and well-being as compared …

Tumor Necrosis Factor Α Inhibition For Alzheimer's Disease, Rudy Chang, Kei-Lwun Yee, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Tumor necrosis factor α (TNF-α) plays a central role in the pathophysiology of Alzheimer’s disease (AD). Food and Drug Administration–approved biologic TNF-α inhibitors are thus a potential treatment for AD, but they do not cross the blood-brain barrier. In this short review, we discuss the involvement of TNF-α in AD, challenges associated with the development of existing biologic TNF-α inhibitors for AD, and potential therapeutic strategies for targeting TNF-α for AD therapy.

The Regulation Of Rotavirus–Infected Ht29.F8 And Ma104 Cells Treated With Arachidin 1 Or Arachidin 3, Caleb M. Witcher

Electronic Theses and Dissertations

Rotavirus (RV) infections cause severe life threatening diarrhea in young children and immunocompromised individuals. Several effective vaccines have been developed for young children but are not protective against all strains of RV, and there are no anti-RV therapeutics. Our laboratory has discovered a decrease in the number of infectious simian RV particles (SA114f) in human intestinal cell line, HT29.f8 cells with the addition of either of two stilbenoids, arachidin-1 (A1) or arachidin-3 (A3). This suggests effects on the host cell and RV replication. We examined the cellular effects of human RV strain (Wa) on a human intestinal cell line (HT29.f8) …

Perceptions Of Ncaa Division I Baseball Pitchers On Treatment Modalities For Pitching Arm Health, Thomas Williams

Graduate Theses

Throwing athletes of all sports have similarities, even if the sport itself is very different. Throwing an object creates a great amount of stress on the body, particularly at the shoulder and the elbow. A baseball pitcher should train and compete in all three planes of movement-sagittal, frontal and transverse. Training for throwing athletes has two main goals: to increase throwing power and to reduce throwing injuries. Analyzing training habits of a throwing athlete includes an understanding of the modalities they perform in order to prevent potential injuries from occurring. Baseball pitchers are extremely susceptible to throwing injuries, and must …

A Novel Distractive And Mobility-Enabling Lumbar Spinal Orthosis For Treating Mechanical Low Back Pain, Daniel Clay Hillyard

Theses and Dissertations (ETD)

Introduction: Lumbar spinal orthoses (LSOs) are often used as non-surgical treatment and serve to support the spine and alleviate low back pain. More recently, dynamic orthoses claiming to decompress the spine have been introduced. Currently, there is an unserved population of people that suffer from mechanical low back pain (LBP) conditions, such as degenerative disc disease or lumbar foraminal stenosis, that would benefit from spinal decompression and mobility. A previously-developed prototype of dynamic mobility orthosis (DMO1) was designed that provided a distractive load across the lumbar spine but required higher sagittal bending moments and was unable to maintain spinal off-loading …

Quantifying Joint Coordination Variability In Anterior Cruciate Ligament-Reconstructed Individuals During Walking, Kylie Davis

Theses and Dissertations (ETD)

The knee is the second most common joint to sustain injury. An estimated 200,000 anterior cruciate ligament (ACL) ruptures occur each year in the United States alone, and about 100,000 ACL reconstruction (ACLR) surgeries are performed annually. There is a significant risk of developing osteoarthritis of the knee after incurring an ACL injury, and the incidence of ipsilateral or contralateral injury is six times greater in individuals who have a surgically repaired ACL. Past studies have analyzed kinetic and kinematic characteristics of individual lower extremity joints to reveal differences between subjects with and without ACLR. Despite reports of altered kinematic …

Design, Validation, And Clinical Testing Of A Novel Fastening Device For A Scoliosis Brace, Cody Keith Bateman

Theses and Dissertations (ETD)

Each year, thirty thousand children in the US were put into a scoliosis brace. The primary function of scoliosis braces was to reduce and prevent progression of the spinal deformity as the patient grew by application of corrective forces to the spine. Straps, often made of Velcro, were attached to the back of the brace that applied forces to the spine when the straps were tightened. Braces were prescribed to be worn up to 23 hours a day. Studies have concluded that discomfort increased with increasing strap tension and pad pressure. They have also shown an increase in strap tension …

Teaching Joint Mobilizations In Physical Therapist Assistant Programs: Implications For Instruction And Policy, Renae H. Gorman

Student Dissertations

This research answers the question: Are physical therapist assistant programs teaching the manual therapy skill of joint mobilizations? This study also gathers information regarding how the joint mobilization techniques are being instructed and assessed within the Physical Therapist Assistant programs. This information could serve as the foundation for future research regarding developing instructional and evaluation strategies for manual therapy skills. The findings of this study may also affect the physical therapist assistants in clinical performance of manual therapy. The findings are pertinent due to conflicting statements by the professional organizations and the accrediting agency of physical therapist assistant educational programs. …

Mapping The Interaction Between Lrrc59 And Cip2a Oncoprotein, Tamika C. Reed

Graduate School of Biomedical Sciences Theses and Dissertations

The oncogene cancerous inhibitor of protein phosphatase 2A (CIP2A) has been shown to promote oncogenesis through numerous protein-protein interactions. CIP2A was initially found to be a direct inhibitor of the PP2A tumor suppressor protein; however, new research has demonstrated that CIP2A can act independently of PP2A through protein-protein interactions resulting in deregulation of the cell cycle and the development of therapeutic drug resistance, tumorigenesis, and cell proliferation. It has been shown that leucine rich repeat containing 59 protein (LRRC59) binds to and is required for the nuclear translocation of CIP2A, thereby making this interaction a target for drug therapy. Thus, …

Portosystemic Shunts In Cats: Management And Care, Rachael E. Konke

Master of Arts in Professional Writing Capstones

Portosystemic Shunts in Cats: Management and Care is an informative technical manual developed for veterinary professionals and caretakers of cats with portosystemic shunts. A portosystemic shunt is a complex and rare circulatory deformity in which unfiltered blood bypasses the liver and circulates throughout the body causing serious complications. Portosystemic Shunts in Cats: Management and Care details portosystemic specifics, symptoms, treatment, and proper everyday care for cats with portosystemic shunts.

Effects Of Therapeutic Music On Pain In Spinal Surgery Recovery, Michael Poulsen

Evidence-Based Practice Project Reports

Pain is one of the most common experienced symptoms reported by more than 80% of postoperative patients. Approximately 77-98% of postoperative patients report pain following their procedure with 40- 80% having moderate to severe pain. Pain is shown to elevate stress levels manifesting in increased heart rates, blood pressures, and oxygen demand. Inadequate pain control can develop into surgical complications causing surgical failure, blood clots, pneumonia, and chronic pain. Complimentary and alternative medicine such as music can be used in combination with opioid medication help improve pain control leading to successful surgical outcomes. The purpose of this evidence-based practice project …

High School Student Concussion Recovery Program: Teacher Involvement In Student Academic Transitions To Classroom And To Sports, Brittany Diego

Scholarly and Creative Works Conference (2015 - 2021)

Many symptoms of concussions can greatly interfere with the cognitive abilities and skills students use in school. Although students may have similar symptoms, they experience concussions differently. Students returning to the classroom from a concussion often have different needs and abilities.

Research shows that a formal, individualized protocol to treat suspected concussions, both academically and physically, is vital to the successful recovery of each student. Much research is available on concussions for professional athletes, specifically related to recovery and returning to their sport. However, there is little research about high school students regarding concussions. Concussion recovery programs for high school …

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

The Research and Scholarship Symposium (2013-2019)

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 …

Pilot Study Comparing The Childhood Arthritis & Rheumatology Research Alliance (Carra) Systemic Juvenile Idiopathic Arthritis Consensus Treatment Plans., Yukiko Kimura, Sriharsha Grevich, Timothy Beukelman, Esi Morgan, Peter A. Nigrovic, Kelly Mieszkalski, T Brent Graham, Maria Ibarra, Norman Ilowite, Marisa Klein-Gitelman, Karen Onel, Sampath Prahalad, Marilynn Punaro, Sarah Ringold, Dana Toib, Heather Van Mater, Jennifer E. Weiss, Pamela F. Weiss, Laura E. Schanberg, Carra Registry Investigators

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: To assess the feasibility of studying the comparative effectiveness of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) consensus treatment plans (CTPs) for systemic Juvenile Idiopathic Arthritis (JIA) using an observational registry.

METHODS: Untreated systemic JIA patients enrolled in the CARRA Registry were begun on one of 4 CTPs chosen by the treating physician and patient/family (glucocorticoid [GC] alone; methotrexate [MTX] ± GC; IL1 inhibitor [IL1i] ± GC; IL6 inhibitor [IL6i] ± GC). The primary outcome of clinical inactive disease (CID) without current GC use was assessed at 9 months.

TRIAL REGISTRATION: clinicaltrials.gov NCT01697254; first registered 9/28/12 (retrospectively enrolled). …

Nephrotoxicity In Patients With Or Without Cystic Fibrosis Treated With Polymyxin B Compared To Colistin, Ryan L. Crass, Wilbur Cliff Rutter, Donna R. Burgess, Craig A. Martin, David S. Burgess

Pharmacy Practice and Science Faculty Publications

Nephrotoxicity is the primary adverse effect of the polymyxins. The relative rates of toxicity of polymyxin B and colistin have not been fully elucidated, especially in patients with cystic fibrosis (CF). A retrospective cohort study of adults treated with polymyxin B or colistin for at least 48 h was conducted. The primary endpoint was the incidence of kidney injury assessed by RIFLE (i.e., risk, injury, failure, loss, end-stage renal disease) criteria. Risk factors for kidney injury were evaluated using multivariate Cox regression. A total of 414 patients were evaluated, 220 of whom had CF. In patients without CF, there was …

Toward A Research Agenda For Oncology Physical Therapy, Lucinda Pfalzer, Nicole L. Stout, Shana Harrington, Mary Insana Fisher

Physical Therapy Faculty Publications

Research Round-up: Cancer survivors frequently experience cancer treatment–related functional impairments and disability. While a growing body of evidence supports the effectiveness of rehabilitation interventions for these individuals, there are significant gaps in the existing literature and no interdisciplinary agreement on the priorities for cancer rehabilitation research. In 2016, the Oncology Section revised its strategic plan and set an objective to create an oncology rehabilitation research agenda for the physical therapy (PT) profession. To achieve this goal, the scope of the agenda, a development and review process, and dissemination plan need to be developed.

An Examination Of Step Frequency And The Running Readiness Scal As Predictors Of Running-Related Injury In Collegiate Cross-Country Athletes, Jenna D'Errico

Undergraduate Distinction Papers

The objective of this study was to determine the relationship between step frequency, the Running Readiness Scale, and Running-Related Injury rate among the Otterbein cross-country team during the Fall 2016 season. Step frequencies were calculated for each athlete at a preferred and pre-determined pace. As a part of the running Readiness Scale assessment, each athlete completed a series of screening tasks to assess body alignment, weight distribution, and muscular endurance. Each participant logged their running and injury history throughout the season using the Otterbein Run Tracker app. The researchers hypothesized that higher step frequencies and Running Readiness Scale pass rates …

A Comparative Study Of Three Different Types Of Stem Cells For Treatment Of Rat Spinal Cord Injury, Jiri Ruzicka, L Machova-Urdzikova, John Gillick, T Amemori, N Romanyuk, K Karova, K Zaviskova, J Dubisova, S Kubinova, Raj Murali, E Sykova, Meena Jhanwar-Uniyal, P Jendelova

NYMC Faculty Publications

Three different sources of human stem cells-bone marrow-derived mesenchymal stem cells (BM-MSCs), neural progenitors (NPs) derived from immortalized spinal fetal cell line (SPC-01), and induced pluripotent stem cells (iPSCs)-were compared in the treatment of a balloon-induced spinal cord compression lesion in rats. One week after lesioning, the rats received either BM-MSCs (intrathecally) or NPs (SPC-01 cells or iPSC-NPs, both intraspinally), or saline. The rats were assessed for their locomotor skills (BBB, flat beam test, and rotarod). Morphometric analyses of spared white and gray matter, axonal sprouting, and glial scar formation, as well as qPCR and Luminex assay, were conducted to …

Npy1 Receptor Agonist Modulates Development Of Depressive-Like Behavior And Gene Expression In Hypothalamus In Sps Rodent Ptsd Model, Lidia Serova, H Mulhall, Esther Sabban

NYMC Faculty Publications

Delivery of neuropeptide Y (NPY) to the brain by intranasal infusion soon after traumatic stress has shown therapeutic potential, and prevented development of many behavioral and neuroendocrine impairments in the single prolonged stress (SPS) animal model of PTSD. Therefore, we examined whether the Y1R preferring agonist [Leu(31)Pro(34)]NPY is sufficient to prevent development of SPS induced depressive-like behavioral changes, and hypothalamic gene expression as obtained with intranasal NPY intervention. Male Sprague-Dawely rats were given intranasal infusion of either NPY (150 mug/rat), a low (68 mug /rat), or high (132 mug/rat) dose of [Leu(31)Pro(34)]NPY or vehicle immediately following the last SPS stressor, …

Venoarterial Extracorporeal Membrane Oxygenation For Cardiogenic Shock: A Retrospective Analysis Based On The Etiology Of Shock, Andrew Burchett, Thomas Tribble, Richard Charnigo, Susan Smyth, Maya Guglin

The VAD Journal

Abstract:

Background: We performed a retrospective analysis to evaluate the efficacy of VA-ECMO support in cardiogenic shock based on various etiologies.

Methods: We retrospectively analyzed 99 patients supported with VA-ECMO from January 1, 2012 to January 1, 2015. Outcomes included survival to discontinuation of VA-ECMO support and survival to hospital discharge. The etiologies of cardiogenic shock included cardiac arrest (CPR), acute myocardial infarction (AMI), decompensated congestive heart failure (CHF), pulmonary embolism (PE), right ventricular failure (RVF) not secondary to an acute pulmonary embolism, and post-cardiotomy syndrome (PCS). The PCS group was used as a reference group; odds ratios were estimated …

Electrotransfer Of Plasmid Dna Radiosensitizes B16f10 Tumors Through Activation Of Immune Response, Richard Heller

School of Medical Diagnostics & Translational Sciences Faculty Publications

Background
Tumor irradiation combined with adjuvant treatments, either vascular targeted or immunomodulatory, is under intense investigation. Gene electrotransfer of therapeutic genes is one of these approaches. The aim of this study was to determine, whether gene electrotransfer of plasmid encoding shRNA for silencing endoglin, with vascular targeted effectiveness, can radiosensitize melanoma B16F10 tumors.

Materials and methods
The murine melanoma B16F10 tumors, growing on the back of C57Bl/6 mice, were treated by triple gene electrotransfer and irradiation. The antitumor effect was evaluated by determination of tumor growth delay and proportion of tumor free mice. Furthermore, histological analysis of tumors (necrosis, apoptosis, …

Family Strategies To Support Siblings Of Pediatric Hematopoietic Stem Cell Transplant Patients., Taylor E. White, Kristopher A. Hendershot, Margie D. Dixon, Wendy Pelletier, Ann Haight, Kristin Stegenga, Melissa A. Alderfer, Lydia Cox, Jeffrey M. Switchenko, Pamela Hinds, Rebecca D. Pentz

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To describe the strategies families report using to address the needs and concerns of siblings of children, adolescents, and young adults undergoing hematopoietic stem cell transplant (HSCT).

METHODS: A secondary semantic analysis was conducted of 86 qualitative interviews with family members of children, adolescents, and young adults undergoing HSCT at 4 HSCT centers and supplemented with a primary analysis of 38 additional targeted qualitative interviews (23 family members, 15 health care professionals) conducted at the primary center. Analyses focused on sibling issues and the strategies families use to address these issues.

RESULTS: The sibling issues identified included: (1) feeling …