Transcriptome Analysis Of Neisseria Gonorrhoeae During Natural Infection Reveals Differential Expression Of Antibiotic Resistance Determinants Between Men And Women, Kathleen Nudel, Ryan Mcclure, Matthew Moreau, Emma Briars, A. Jeanine Abrams, Brian Tjaden, Xiao-Hong Su, David Trees, Peter A. Rice, Paola Massari, Caroline A. Genco
Open Access Articles
Neisseria gonorrhoeae is a bacterial pathogen responsible for the sexually transmitted infection gonorrhea. Emergence of antimicrobial resistance (AMR) of N. gonorrhoeae worldwide has resulted in limited therapeutic choices for this infection. Men who seek treatment often have symptomatic urethritis; in contrast, gonococcal cervicitis in women is usually minimally symptomatic, but may progress to pelvic inflammatory disease. Previously, we reported the first analysis of gonococcal transcriptome expression determined in secretions from women with cervical infection. Here, we defined gonococcal global transcriptional responses in urethral specimens from men with symptomatic urethritis and compared these with transcriptional responses in specimens obtained from women ...
Therapeutic Benefit Of Apremilast On Enthesitis And Dactylitis In Patients With Psoriatic Arthritis: A Pooled Analysis Of The Palace 1-3 Studies, Dafna D. Gladman, Arthur Kavanaugh, Juan J. Gomez-Reino, Jurgen Wollenhaupt, Maurizio Cutolo, Georg Schett, Eric Lespessailles, Benoit Guerette, Nikolay Delev, Lichen Teng, Christopher J. Edwards, Charles Birbara, Philip J. Mease
Open Access Articles
Objective: The Psoriatic Arthritis Long-term Assessment of Clinical Efficacy (PALACE) clinical trial programme findings demonstrated that apremilast, an oral phosphodiesterase 4 inhibitor, is effective for treating psoriatic arthritis (PsA). Enthesitis and dactylitis are difficult-to-treat features of PsA leading to disability and affecting quality of life. PALACE 1, 2 and 3 data were pooled to assess the efficacy of apremilast on enthesitis and dactylitis outcomes in patients with these conditions at baseline.
Methods: Patients with enthesitis (n=945) or dactylitis (n=633) at baseline were analysed after receiving double-blind treatment with placebo, apremilast 30 mg two times per day or apremilast ...
A Pilot Professional Development Program For Occupational Therapy Practitioners Who Work In Home Settings: Knowledge Translation On Urinary Incontinence, Jaimee Betts Hegge
Occupational Therapy Faculty Publications
The purpose of this project was to increase the knowledge and confidence of home based occupational therapy practitioners working with adults and older adults who have urinary incontinence. The knowledge translation model of education is used to educate health care providers to improve integration of new information. The Reflective Questioning Framework for coaching can be effective with increasing knowledge and confidence of practitioners that are integrating new learning into their daily home care practice. This project investigated how these two approaches to education impacted occupational therapy practitioners perceived level of knowledge and confidence treating urinary incontinence in adult and older ...
Editorial: Controversies In The Local Management Of Lung Cancer, 2018 University of Massachusetts Medical School
Editorial: Controversies In The Local Management Of Lung Cancer, John M. Varlotto, Giulia Veronesi
Open Access Articles
At the time we agreed to edit this special edition of Frontiers in early 2017, the immunotherapy revolution was already established in the second-line treatment of metastatic non-small cell lung cancer (NSCLC) and even to a select group of patients (those whose tumor cells expressed PD-L1 of ≥50%) in the first-line treatment of metastatic disease. We felt that the summarization and understanding of the strengths and benefits of our local modalities were needed prior to the possible integration of immunotherapy into the treatment paradigms of Stages I–III NSCLC and small cell lung cancer (SCLC).
A Rationally Engineered Capsid Variant Of Aav9 For Systemic Cns-Directed And Peripheral Tissue-Detargeted Gene Delivery In Neonates, 2018 University of Massachusetts Medical School
A Rationally Engineered Capsid Variant Of Aav9 For Systemic Cns-Directed And Peripheral Tissue-Detargeted Gene Delivery In Neonates, Dan Wang, Shaoyong Li, Dominic J. Gessler, Jun Xie, Li Zhong, Jia Li, Karen Tran, Kim Van Vliet, Lingzhi Ren, Qin Su, Ran He, Jason E. Goetzmann, Terence R. Flotte, Mavis Agbandje-Mckenna, Guangping Gao
Open Access Articles
Adeno-associated virus (AAV) has provided the gene therapy field with the most powerful in vivo gene delivery vector to realize safe, efficacious, and sustainable therapeutic gene expression. Because many clinically relevant properties of AAV-based vectors are governed by the capsid, much research effort has been devoted to the development of AAV capsids for desired features. Here, we combine AAV capsid discovery from nature and rational engineering to report an AAV9 capsid variant, designated as AAV9.HR, which retains AAV9's capability to traverse the blood-brain barrier and transduce neurons. This variant shows reduced transduction in peripheral tissues when delivered through ...
Adeno-Associated Virus Genome Population Sequencing Achieves Full Vector Genome Resolution And Reveals Human-Vector Chimeras, 2018 University of Massachusetts Medical School
Adeno-Associated Virus Genome Population Sequencing Achieves Full Vector Genome Resolution And Reveals Human-Vector Chimeras, Phillip W. L. Tai, Jun Xie, Kaiyuen Fong, Matthew Seetin, Cheryl Heiner, Qin Su, Michael Weiand, Daniella Wilmot, Maria L. Zapp, Guangping Gao
Open Access Articles
Recombinant adeno-associated virus (rAAV)-based gene therapy has entered a phase of clinical translation and commercialization. Despite this progress, vector integrity following production is often overlooked. Compromised vectors may negatively impact therapeutic efficacy and safety. Using single molecule, real-time (SMRT) sequencing, we can comprehensively profile packaged genomes as a single intact molecule and directly assess vector integrity without extensive preparation. We have exploited this methodology to profile all heterogeneic populations of self-complementary AAV genomes via bioinformatics pipelines and have coined this approach AAV-genome population sequencing (AAV-GPseq). The approach can reveal the relative distribution of truncated genomes versus full-length genomes in ...
Pd-L1 Is Expressed On Human Platelets And Is Affected By Immune Checkpoint Therapy, 2018 University of Bonn
Pd-L1 Is Expressed On Human Platelets And Is Affected By Immune Checkpoint Therapy, Verena Rolfes, Christian Idel, Ralph Pries, Kirstin Plotze-Martin, Jens Habermann, Timo Gemoll, Sabine Bohnet, Eicke Latz, Julika Ribbat-Idel, Bernardo S. Franklin, Barbara Wollenberg
Open Access Articles
Cancer immunotherapy has been revolutionised by drugs that enhance the ability of the immune system to detect and fight tumors. Immune checkpoint therapies that target the programmed death-1 receptor (PD-1), or its ligand (PD-L1) have shown unprecedented rates of durable clinical responses in patients with various cancer types. However, there is still a large fraction of patients that do not respond to checkpoint inhibitors, and the challenge remains to find cellular and molecular cues that could predict which patients would benefit from these therapies. Using a series of qualitative and quantitative methods we show here that PBMCs and platelets from ...
A Fresh Look At Huntingtin Mrna Processing In Huntington's Disease, 2018 University of Massachusetts Medical School
A Fresh Look At Huntingtin Mrna Processing In Huntington's Disease, Lindsay S. Romo, Emily S. Mohn, Neil Aronin
RNA Therapeutics Institute Publications
Huntington's disease (HD) is an inherited neurodegenerative disorder caused by a mutation that expands the polyglutamine (CAG) repeat in exon 1 of the huntingtin (HTT) gene. Wild-type HTT protein interacts with other proteins to protect cells against toxic stimuli, mediate vesicle transport and endocytosis, and modulate synaptic activity. Mutant HTT protein disrupts autophagy, vesicle transport, neurotransmitter signaling, and mitochondrial function. Although many of the activities of wild-type HTT protein and the toxicities of mutant HTT protein are characterized, less is known about the activities of HTT mRNA. Most putative HD therapies aim to target mutant HTT mRNA before it ...
Cognitive And Emotional Correlates Of Improved Gait Distance During The Course Of Physical Therapy Treatment For An Incomplete Spinal Cord Injury, Danielle Miller
The focus of spinal cord injury rehabilitation over the past four decades has shifted from medical management to issuses that affect quality of life and community participation (Gómara- Toldrà, Sliwinski, & Dijkers, 2014). However, the care team for spinal cord injury patients still need to collaberate in order to design and implement interventions that result in maximum participation to provide an individual with a spinal cord injury an effective rehabilitation program. In order to create such a rehablitation program, the care team must know how certain psychological and cognitive aspects, such as depression and implict memory, are related to the ...
Integration Of Complementary And Alternative Medicine Into The Healthcare System In The United States, 2018 University of Washington – Tacoma
Integration Of Complementary And Alternative Medicine Into The Healthcare System In The United States, Nikki Lu
Global Honors Theses
Chronic diseases are a prevalent issue around the world and chronic diseases are hard to prevent due to various systemic factors in the healthcare system. This paper mainly focused on socioeconomic issues and highlighted a few systemic factors in the US healthcare system. These factors have created various health disparities, inequities among socially constructed groups, and financial expenditures in the US healthcare system. Socioeconomic factors significantly impact the health and healthcare among socially constructed groups. Additionally, in this paper there are current approaches in addressing these healthcare factors such as social determinants of health and precision medicine as well as ...
In Vivo And In Vitro Studies Of Cry5b And Nicotinic Acetylcholine Receptor Agonist Anthelmintics Reveal A Powerful And Unique Combination Therapy Against Intestinal Nematode Parasites, 2018 University of Massachusetts Medical School
In Vivo And In Vitro Studies Of Cry5b And Nicotinic Acetylcholine Receptor Agonist Anthelmintics Reveal A Powerful And Unique Combination Therapy Against Intestinal Nematode Parasites, Yan Hu, Melanie Miller, Bo Zhang, Thanh-Thanh Nguyen, Martin K. Nielsen, Raffi V. Aroian
Open Access Articles
BACKGROUND: The soil-transmitted nematodes (STNs) or helminths (hookworms, whipworms, large roundworms) infect the intestines of ~1.5 billion of the poorest peoples and are leading causes of morbidity worldwide. Only one class of anthelmintic or anti-nematode drugs, the benzimidazoles, is currently used in mass drug administrations, which is a dangerous situation. New anti-nematode drugs are urgently needed. Bacillus thuringiensis crystal protein Cry5B is a powerful, promising new candidate. Drug combinations, when properly made, are ideal for treating infectious diseases. Although there are some clinical trials using drug combinations against STNs, little quantitative and systemic work has been performed to define ...
El Impacto De Las Artes Visuales En Personas Afectadas Por Cáncer, 2018 EXPLORARTE
El Impacto De Las Artes Visuales En Personas Afectadas Por Cáncer, Bettina Ingham
ICOT 18 - International Conference on Thinking - Cultivating Mindsets for Global Citizens
El impacto de las artes visuales en el bienestar y la mejora de la calidad de vida de personas afectadas por cáncer.
Un programa diseñado para poner en práctica e investigar el alcance que tienen las artes visuales y el método de Estrategias de Pensamiento Visual para el desarrollo de habilidades de pensamiento que promueven la identificación y expresión verbal de las emociones, minimizando, en el caso de las personas convalecientes, el sufrimiento que va desde el dolor de la enfermedad hasta el miedo a la muerte.
Los efectos que la contemplación (percepción estética), el análisis y la práctica(proceso ...
Engineered Exosomes For Delivery Of Therapeutic Sirnas To Neurons, 2018 University of Massachusetts Medical School
Engineered Exosomes For Delivery Of Therapeutic Sirnas To Neurons, Reka A. Haraszti
GSBS Dissertations and Theses
Extracellular vesicles (EVs), exosomes and microvesicles, transfer endogenous RNAs between neurons over short and long distances. We have explored EVs for siRNA delivery to brain. (1) We optimized siRNA chemical modifications and siRNA conjugation to lipids for EV-mediated delivery. (2) We developed a GMP-compatible, scalable method to manufacture active EVs in bulk. (3) We characterized lipid and protein content of EVs in detail. (4) We established how protein and lipid composition relates to siRNA delivering activity of EVs, and we reverse engineered natural exosomes (small EVs) into artificial exosomes based on these data.
We established that cholesterol-conjugated siRNAs passively associate ...
Precision Gene Therapy For Charcot-Marie-Tooth Disease: From Identifying Genetic Modifiers To Developing Allele-Specific Therapies, Kathryn H. Morelli Ph.D.
Electronic Theses and Dissertations
Charcot-Marie-Tooth Disease (CMT) is a clinically and genetically heterogeneous collection of inherited peripheral neuropathies generally characterized by progressive muscle atrophy, weakness, and loss of sensation in the distal extremities. This inherited disorder, for which there is currently no curative treatment, is the most common inherited disease of the peripheral nervous system, affecting 1:2,500 individuals worldwide.
Clinically, CMT is broadly divided into demyelinating (type 1) and axonal (type 2) forms. Although the clinical presentation can vary greatly in severity and progression within individual patients. Genetically, over 1,000 mutations in over 80 loci in the human genome have been ...
Structure Determination Of A Bioengineered Human/Porcine Factor Viii For Hemophilia A Treatment, And Improvements To The Human Factor Viii Model, 2018 Western Washington University
Structure Determination Of A Bioengineered Human/Porcine Factor Viii For Hemophilia A Treatment, And Improvements To The Human Factor Viii Model, Ian Smith
Graduate Student Symposium
Blood coagulation factor VIII (FVIII), is a non-enzymatic cofactor which plays a crucial role in the formation of a stable blood clot. Absence or deficiency of FVIII results in the blood disorder hemophilia A; with symptoms including internal hemorrhaging and the inability to stop bleeding from open wounds. Treatment of hemophilia A relies on infusions of blood, plasma, or protein concentrates to replace FVIII. Unfortunately, approximately 30% of patients receiving replacement FVIII generate pathologic anti-FVIII inhibitory antibodies, which both reduce the effectiveness of the FVIII therapeutic and increase the severity of hemophilia A symptoms.
We have determined the molecular structure ...
Spectral Properties Of Doxorubicin Doped Rhdl Nanoparticles, 2018 University of North Texas Health Science Center at Fort Worth
Spectral Properties Of Doxorubicin Doped Rhdl Nanoparticles, Sunil Shah
Theses and Dissertations
Doxorubicin, also known as Adriamycin, is an anthracycline antibiotic which first gained clinical prominence in the early 1970’s as an effective antitumor agent. It is still used today to treat a spectrum of cancers like lymphoma, bladder, stomach, lung, breast, ovarian, and several others. Due to its production of free radicals to attack tumor cells, Doxorubicin interferes with mitochondrial phosphorylation and also induces cardiotoxicity. Thus, efficient and biocompatible delivery methods are needed for targeted drug delivery to overcome systemic toxicity. To maintain a high level of growth, tumor cells overexpress Scavenger receptors type B-1 (SR-B1). This cellular characteristic can ...
Failure Of Primary Total Knee Arthroplasty: Establishing A Baseline For Retrieval Analysis Using Well-Functioning Necropsy Specimens, 2018 University of Tennessee Health Science Center
Failure Of Primary Total Knee Arthroplasty: Establishing A Baseline For Retrieval Analysis Using Well-Functioning Necropsy Specimens, Meredith Perkins
Theses and Dissertations (ETD)
Introduction. Total knee arthroplasty (TKA) is an effective treatment for end-stage osteoarthritis of the knee. While many patients have positive functional and pain outcomes following primary TKA, a subset of patients have suboptimal outcomes, such as unexplained pain or aseptic loosening of the implant components necessitating revision of the index procedure. The understanding of the exact etiology of these suboptimal outcomes of primary TKA is in its infancy. In order to elucidate the etiology of failure in primary TKAs, a baseline for the factors contributing to arthroplasty failure and dissatisfaction must first be established. The purpose of this study was ...
The Dancing Nurse: Addressing Barriers To The Implementation Of Movement-Based Interventions In Holistic Patient Care, 2018 Oral Roberts University
The Dancing Nurse: Addressing Barriers To The Implementation Of Movement-Based Interventions In Holistic Patient Care, Jessica Collier, Audrey Thompson Phd
Nursing Undergraduate Work
The efficacy of dance movement therapy (DMT) is well demonstrated in contemporary nursing literature; however, implementation by healthcare professionals is often limited. Dance movement therapy was pioneered in the mid-20th century by classically trained modern dancer Marian Chace. Recent trends toward patient-centered care and interdisciplinary approaches render therapies such as DMT important modalities which nurses and other healthcare providers may become familiar with. This systematic research review focused on answering the question: “what are hindrances perceived by members of the healthcare team to implementing DMT as an alternative treatment modality?” Two variables were identified for the purposes of this ...
Maturation Of Human Induced Pluripotent Stem Cell Derived Engineered Cardiac Tissues Using Chief Transfection And Chronic Optical Pacing., Marc M. Dwenger
Electronic Theses and Dissertations
The immaturity of engineered cardiac tissues (ECTs) limits their ability to regenerate damaged myocardium and to serve as in vitro disease models and surrogates for drug toxicity testing. Several chronic biomimetic conditioning protocols, including mechanical stretch, perfusion, and electrical stimulation promote ECT maturation but have significant technical limitations. Non-contacting chronic light stimulation using heterologously expressed light-sensitive ChIEF ion channels, termed optogenetics, may be an advantageous alternative to chronic electrical stimulation. As a proof of principle, we transfected ECTs using an AAV packaged ChIEF and then verified acute optical pacing (OP) by patch clamp. We then chronically OP ECTs for 7 ...
The Systemic Quantification Of Immune Cell Populations In Various Murine Models: How Age, Tumor Burden, And Immunotherapy Affect The Immune Response, Kavita Sinha
Honors Scholar Theses
Immunotherapy as a form of cancer treatment has become increasingly popular in the past few decades. Researchers have worked to figure out how to best use the body’s natural defense mechanism, the immune system, to fight off and destroy cancer cells. In particular, the goal has been to manipulate checkpoint blockades such as CTLA-4 and PD-1 in order to take the breaks off of the immune system, allowing for a prolonged immune response to the cancer. This work has led to the development of human versions of anti-CTLA4 antibodies (ipilimumab, tremelimumab) and anti-PD1 antibodies (pembrolizumab and Nivolumab) that are ...