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All-In-One Adeno-Associated Virus Delivery And Genome Editing By Neisseria Meningitidis Cas9 In Vivo, Raed Ibraheim, Chun-Qing Song, Aamir Mir, Nadia Amrani, Wen Xue, Erik J. Sontheimer 2018 University of Massachusetts Medical School

All-In-One Adeno-Associated Virus Delivery And Genome Editing By Neisseria Meningitidis Cas9 In Vivo, Raed Ibraheim, Chun-Qing Song, Aamir Mir, Nadia Amrani, Wen Xue, Erik J. Sontheimer

RNA Therapeutics Institute Publications

BACKGROUND: Clustered, regularly interspaced, short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) have recently opened a new avenue for gene therapy. Cas9 nuclease guided by a single-guide RNA (sgRNA) has been extensively used for genome editing. Currently, three Cas9 orthologs have been adapted for in vivo genome engineering applications: Streptococcus pyogenes Cas9 (SpyCas9), Staphylococcus aureus Cas9 (SauCas9), and Campylobacter jejuni (CjeCas9). However, additional in vivo editing platforms are needed, in part to enable a greater range of sequences to be accessed via viral vectors, especially those in which Cas9 and sgRNA are combined into a single vector genome.

RESULTS: Here ...


Macular Phototoxicity After Corneal Cross-Linking, Paulo Rodolfo Barbisan Tagliari, Marina Goncalves Viturino Monteiro, Fernanda Maria Souto Silveira, Bo Tian, Roberto Damian Pacheco Pinto, Lucas Barasnevicius Quagliato, Mauricio Abujamra Nascimento, Rosane Silvestre de Castro, Carlos Eduardo Arieta Leite 2018 State University of Campinas, Brazil

Macular Phototoxicity After Corneal Cross-Linking, Paulo Rodolfo Barbisan Tagliari, Marina Goncalves Viturino Monteiro, Fernanda Maria Souto Silveira, Bo Tian, Roberto Damian Pacheco Pinto, Lucas Barasnevicius Quagliato, Mauricio Abujamra Nascimento, Rosane Silvestre De Castro, Carlos Eduardo Arieta Leite

Open Access Articles

Purpose: To assess potential vascular, structural, and functional changes to the macula in patients with keratoconus that underwent ultraviolet A (UVA)-riboflavin-mediated corneal collagen cross-linking (CXL) therapy.

Patients and methods: Seventeen eyes from 17 patients of age 16 years or older with keratoconus undergoing CXL treatment were studied. The same eye served as its own control (before CXL vs after CXL). Eyes were evaluated in terms of best-corrected visual acuity (BCVA), refractive error, intraocular pressure, Amsler grid, retinography, fluorescein angiography, autofluorescence, and spectral domain optical coherence tomography (SD-OCT) prior to CXL and 7 and 30 days after treatment. Multifocal electroretinography ...


Treatment Of Triple-Negative Breast Cancer Cells With The Canady Cold Plasma Conversion System: Preliminary Results, Xiaoqian Cheng, Warren Rowe, Lawan Ly, Alexey Shashurin, Taisen Zhuang, Shruti Wigh, Giacomo Basadonna, Barry Trink, Michael Keidar, Jerome Canady 2018 Jerome Canady Research Institute for Advanced Biological and Technological Sciences

Treatment Of Triple-Negative Breast Cancer Cells With The Canady Cold Plasma Conversion System: Preliminary Results, Xiaoqian Cheng, Warren Rowe, Lawan Ly, Alexey Shashurin, Taisen Zhuang, Shruti Wigh, Giacomo Basadonna, Barry Trink, Michael Keidar, Jerome Canady

Open Access Articles

Triple-negative breast cancer is a phenotype of breast cancer where the expression level of estrogen, progesterone and human epidermal growth factor receptor 2 (HER2) receptors are low or absent. It is more frequently diagnosed in younger and premenopausal women, among which African and Hispanic have a higher rate. Cold atmospheric plasma has revealed its promising ant-cancer capacity over the past two decades. In this study, we report the first cold plasma jet delivered by the Canady Cold Plasma Conversion Unit and characterization of its electric and thermal parameters. The unit effectively reduced the viability of triple-negative breast cancer up to ...


Pneumatic Balloon Dilation Versus Myotomy For The Treatment Of Achalsia, Benjamin E. Ueberroth 2018 Wayne State University School of Medicine

Pneumatic Balloon Dilation Versus Myotomy For The Treatment Of Achalsia, Benjamin E. Ueberroth

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Moonen A, Annese V, Belmans A, et al. Long-term results of the European achalasia trial: A multicentre randomised controlled trial comparing pneumatic dilation versus laparoscopic Heller myotomy. Gut. 2016 May;65(5):732-9. doi: 10.1136/gutjnl-2015-310602.


Prevalence And Management Of Iron Overload In Pyruvate Kinase Deficiency: Report From The Pyruvate Kinase Deficiency Natural History Study, Eduard J. van Beers, Peter E. Newburger, Rachael F. Grace 2018 University Medical Center Utrecht

Prevalence And Management Of Iron Overload In Pyruvate Kinase Deficiency: Report From The Pyruvate Kinase Deficiency Natural History Study, Eduard J. Van Beers, Peter E. Newburger, Rachael F. Grace

Open Access Articles

Pyruvate kinase (PK) deficiency is the most common red cell glycolytic enzyme defect causing hereditary non-spherocytic hemolytic anemia. Current treatments are mainly supportive and include red cell transfusions and splenectomy.11 Regular red cell transfusions are known to result in iron overload; however, the prevalence and spectrum of transfusion-independent iron overload in the overall PK deficient population has not been well defined. This analysis describes the prevalence and clinical characteristics of iron overload in patients enrolled in the PK Deficiency Natural History Study (NHS) with a focus on those patients who are not regularly transfused.2


Icatibant Is Not An Appropriate Treatment Option For Ace-Inhibitor Induced Angioedema Of The Head And Neck, Faiz Khaja 2018 Wayne State University School of Medicine

Icatibant Is Not An Appropriate Treatment Option For Ace-Inhibitor Induced Angioedema Of The Head And Neck, Faiz Khaja

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Sinert T, Levy P, Bernstein JA, et al. Randomized trial of icatibant for angiotensin-converting enzyme inhibitor-induced upper airway angioedema. J Allergy Clin Immunol Pract. 2017;5(5):1402-9. doi: 10.1016/j.jaip.2017.03.003


The Canady Helios Cold Plasma Scalpel Significantly Decreases Viability In Malignant Solid Tumor Cells In A Dose-Dependent Manner, Warren Rowe, Xiaoqian Cheng, Lawan Ly, Taisen Zhuang, Giacomo Basadonna, Barry Trink, Michael Keidar, Jerome Canady 2018 Jerome Canady Research Institute for Advanced Biological and Technological Sciences

The Canady Helios Cold Plasma Scalpel Significantly Decreases Viability In Malignant Solid Tumor Cells In A Dose-Dependent Manner, Warren Rowe, Xiaoqian Cheng, Lawan Ly, Taisen Zhuang, Giacomo Basadonna, Barry Trink, Michael Keidar, Jerome Canady

Open Access Articles

To determine appropriate treatment doses of cold atmospheric plasma (CAP), the Canady Helios Cold Plasma Scalpel was tested across numerous cancer cell types including renal adenocarcinoma, colorectal carcinoma, pancreatic adenocarcinoma, ovarian adenocarcinoma, and esophageal adenocarcinoma. Various CAP doses were tested consisting of both high (3 L/min) and low (1 L/min) helium flow rates, several power settings, and a range of treatment times up to 5 min. The impact of cold plasma on the reduction of viability was consistently dose-dependent; however, the anti-cancer capability varied significantly between cell lines. While the lowest effective dose varied from cell line to ...


Support-Af: Piloting A Multi-Faceted, Electronic Medical Record-Based Intervention To Improve Prescription Of Anticoagulation, Alok Kapoor, Azraa Amroze, Jessica G. Golden, Sybil L. Crawford, Kevin O'Day, Rasha Elhag, Ahmed Nagy, Steve A. Lubitz, Jane S. Saczynski, Jomol Mathew, David D. McManus 2018 Boston University School of Medicine

Support-Af: Piloting A Multi-Faceted, Electronic Medical Record-Based Intervention To Improve Prescription Of Anticoagulation, Alok Kapoor, Azraa Amroze, Jessica G. Golden, Sybil L. Crawford, Kevin O'Day, Rasha Elhag, Ahmed Nagy, Steve A. Lubitz, Jane S. Saczynski, Jomol Mathew, David D. Mcmanus

Open Access Articles

Background: Only 50% of eligible atrial fibrillation ( AF ) patients receive anticoagulation ( AC ). Feasibility and effectiveness of electronic medical record (EMR)-based interventions to profile and raise provider AC percentage is poorly understood. The SUPPORT-AF (Supporting Use of AC Through Provider Profiling of Oral AC Therapy for AF) study aims to improve rates of adherence to AC guidelines by developing and delivering supportive tools based on the EMR to providers treating patients with AF.

Methods and Results: We emailed cardiologists and community-based primary care providers affiliated with our institution reports of their AC percentage relative to peers. We also sent an ...


Relapsed Ovarian High-Grade Serous Carcinoma With Long-Term Survival Associated With Synchronous Primary Squamous Cell Carcinoma Of The Colon, Karla Sladoljev, Ena Perin, Ani Mihaljević Ferrari, Marko Klarić, Alemka Brnčić-Fischer, Senija Eminović, Danijela Vrdoljak-Mozetič, Emina Babarovic 2018 School of Medicine University of Rijeka, University of Rijeka, Croatia

Relapsed Ovarian High-Grade Serous Carcinoma With Long-Term Survival Associated With Synchronous Primary Squamous Cell Carcinoma Of The Colon, Karla Sladoljev, Ena Perin, Ani Mihaljević Ferrari, Marko Klarić, Alemka Brnčić-Fischer, Senija Eminović, Danijela Vrdoljak-Mozetič, Emina Babarovic

Proceedings in Obstetrics and Gynecology

High-grade serous ovarian cancer (HGSOC) is the most common and also the most aggressive subtype of ovarian cancer while squamous cell carcinoma (SCC) of the colon is an extremely rare histologic subtype of all colonic malignancies with poor prognosis.

Here we report a unique case of synchronous primary SCC of the colon and second recurrence of HGSOC in a patient with 15-years survival. Our patient developed two recurrent HGSOCs with disease-free survival time of five and nine years, respectively. The second recurrence of HGSOC was associated with the synchronous primary SCC of the ascending colon and was further complicated with ...


One Group's Historical Reflections On Dna Vaccine Development, Ellen F. Fynan, Shan Lu, Harriet L. Robinson 2018 Worcester State College

One Group's Historical Reflections On Dna Vaccine Development, Ellen F. Fynan, Shan Lu, Harriet L. Robinson

Open Access Articles

DNA vaccines were pioneered by several groups in the early 1990s. This article presents the reflections of one of these groups on their work with retroviral vectors in chickens that contributed to the discovery and early development of DNA vaccines. Although the findings were initially met with skepticism, the work presented here combined with that of others founded a new method of vaccination: the direct inoculation of purified DNA encoding the target antigen.


Coping With Chronic Fungal Rhinosinusitis: Diagnosis To Therapy, Veronica Corcino, Leslie Beavin, Shengli Lu, Ashley Ross, Carmen V. Sciortino Jr. 2018 University of Louisville

Coping With Chronic Fungal Rhinosinusitis: Diagnosis To Therapy, Veronica Corcino, Leslie Beavin, Shengli Lu, Ashley Ross, Carmen V. Sciortino Jr.

The University of Louisville Journal of Respiratory Infections

No abstract provided.


The Efficacy Of Equine Assisted Therapy In The Treatment Of Autism Spectrum Disorders, Amy Hofmann 2018 University of Maine

The Efficacy Of Equine Assisted Therapy In The Treatment Of Autism Spectrum Disorders, Amy Hofmann

Electronic Theses and Dissertations

This study examines the effects of equine-assisted psychotherapies in children with an autism spectrum disorder. The CARS-2 and Children’s Sleep Habits Questionnaire parent-report questionnaires were used for evaluation, as well open-ended questions. A single researcher contacted and visited many PATH-certified centers in the United States. Facilities that participated were all located in the Mid-Atlantic to Northeast region. There were 16 participants, from 11 different farms, that completed both the initial and follow-up questionnaires which were given 7 weeks apart. A $25 Amazon gift card was used as an incentive to increase participation. Participating facilities also completed a questionnaire.

Overall ...


Characterization Of Theranostic Peptides For Glioblastoma Multiforme, Aaron Mellesmoen 2018 Northern Michigan University

Characterization Of Theranostic Peptides For Glioblastoma Multiforme, Aaron Mellesmoen

All NMU Master's Theses

Glioblastoma multiforme (GBM) is a type of primary CNS tumor in which viable treatment options do not exist. Standard of care including tumor resection, chemotherapy, and radiation does little to extend the 5-year survival expectancy past 5.1%. Herein, two small-peptide molecules with inherent antitumor activity, blood-brain barrier permeability, and capability for tumor-specific drug deliverance and intraoperative visualization (termed theranostic) were of focus. Confocal microscopy was employed to characterize in vitro specificity of chlorotoxin, a 4 kDa scorpion venom peptide, and rBSG, the recombinant 25 kDa non-glycosylated extracellular domain of extracellular matrix metalloproteinase inducer (EMMPRIN; Basigin ...


Simvastatin Does Not Sensitize Ibc3 Her2+ Inflammatory Breast Cancer Brain Metastases To Whole Brain Irradiation In An Immunocompromised Mouse Model, Swaminathan Kumar, Wendy A. Woodward 2018 The University of Texas M D Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Simvastatin Does Not Sensitize Ibc3 Her2+ Inflammatory Breast Cancer Brain Metastases To Whole Brain Irradiation In An Immunocompromised Mouse Model, Swaminathan Kumar, Wendy A. Woodward

UT GSBS Dissertations and Theses (Open Access)

Retrospective data analysis suggests that inflammatory breast cancer (IBC) patients who take statins have better locoregional control after radiotherapy than those who do not [23]. Our lab has previously demonstrated that simvastatin radiosensitizes IBC cells in vitro [23], and brain metastases have strong expression of cholesterol-regulation genes compared to lung metastases in vivo [unpublished]. Delaying whole-brain irradiation (WBI) beyond 21 days is insufficient to reduce the incidence of brain metastases (developed by injecting IBC3 cells through the tail vein) in our mouse model because even high rates of cell killing leave substantial cell volume in established metastases [unpublished].

With the ...


Citrullination Inactivates Nicotinamide-N-Methyltransferase, Venkatesh V. Nemmara, Ronak Tilvawala, Ari J. Salinger, Lacey Miller, Son Hong Nguyen, Eranthie Weerapana, Paul R. Thompson 2018 University of Massachusetts Medical School

Citrullination Inactivates Nicotinamide-N-Methyltransferase, Venkatesh V. Nemmara, Ronak Tilvawala, Ari J. Salinger, Lacey Miller, Son Hong Nguyen, Eranthie Weerapana, Paul R. Thompson

Thompson Lab Publications

Nicotinamide-N-methyl transferase (NNMT) catalyzes the irreversible methylation of nicotinamide (NAM) to form N-methyl nicotinamide (MeNAM) using SAM as a methyl donor. NNMT is implicated in several chronic disease conditions, including cancers, kidney disease, cardiovascular disease, and Parkinson's disease. Although phosphorylation of NNMT in gastric tumors is reported, the functional effects of this post-translational modification has not been investigated. We previously reported that citrullination of NNMT by Protein Arginine Deiminases (PADs) abolished its methyltransferase activity. Herein, we investigate the mechanism of inactivation. Using tandem MS, we identified three sites of citrullination in NNMT. With this information in hand, we used ...


Elevated Levels Of Matrix Metalloproteinases Reflect Severity And Extent Of Disease In Tuberculosis-Diabetes Co-Morbidity And Are Predominantly Reversed Following Standard Anti-Tuberculosis Or Metformin Treatment, Nathella P. Kumar, Kadar Moideen, Vijay Viswanathan, Basavaradhya S. Shruthi, Shanmugam Sivakumar, Pradeep A. Menon, Hardy Kornfeld, Subash Babu 2018 National Institutes of Health-NIH-NIRT-ICER

Elevated Levels Of Matrix Metalloproteinases Reflect Severity And Extent Of Disease In Tuberculosis-Diabetes Co-Morbidity And Are Predominantly Reversed Following Standard Anti-Tuberculosis Or Metformin Treatment, Nathella P. Kumar, Kadar Moideen, Vijay Viswanathan, Basavaradhya S. Shruthi, Shanmugam Sivakumar, Pradeep A. Menon, Hardy Kornfeld, Subash Babu

Open Access Articles

BACKGROUND: Matrix metalloproteinases (MMPs) are considered to be key mediators of tuberculosis (TB) pathology but their role in tuberculosis - diabetes comorbidity (TB-DM) is not well understood.

METHODS: To study the association of MMP levels with severity and extent of disease as well as bacterial burden in TB-DM, we examined the systemic levels of MMP-1, - 2, - 3, - 7, - 8, - 9, - 10, - 12 and - 13 in individuals with TB-DM and compared them to those with TB alone (TB) or healthy controls (HC). RESULTS: Circulating levels of MMP-1, - 2, - 3, - 7, - 10 and - 12 were significantly higher in TB-DM compared to both TB ...


Heavily And Fully Modified Rnas Guide Efficient Spycas9-Mediated Genome Editing, Aamir Mir, Julia F. Alterman, Matthew R. Hassler, Alexandre J. Debacker, Edward Hudgens, Dimas Echeverria, Michael H. Brodsky, Anastasia Khvorova, Jonathan K. Watts, Erik J. Sontheimer 2018 University of Massachusetts Medical School

Heavily And Fully Modified Rnas Guide Efficient Spycas9-Mediated Genome Editing, Aamir Mir, Julia F. Alterman, Matthew R. Hassler, Alexandre J. Debacker, Edward Hudgens, Dimas Echeverria, Michael H. Brodsky, Anastasia Khvorova, Jonathan K. Watts, Erik J. Sontheimer

Open Access Articles

RNA-based drugs depend on chemical modifications to increase potency and to decrease immunogenicity in vivo. Chemical modification will likely improve the guide RNAs involved in CRISPR-Cas9-based therapeutics as well. Cas9 orthologs are RNA-guided microbial effectors that cleave DNA. Here, we explore chemical modifications at all positions of the crRNA guide and tracrRNA cofactor. We identify several heavily modified versions of crRNA and tracrRNA that are more potent than their unmodified counterparts. In addition, we describe fully chemically modified crRNAs and tracrRNAs (containing no 2'-OH groups) that are functional in human cells. These designs will contribute to Cas9-based therapeutics since ...


Incidence Of Acute Kidney Injury Among Patients Treated With Piperacillin-Tazobactam Or Meropenem In Combination With Vancomycin, Wilbur Cliff Rutter, David S. Burgess 2018 University of Kentucky

Incidence Of Acute Kidney Injury Among Patients Treated With Piperacillin-Tazobactam Or Meropenem In Combination With Vancomycin, Wilbur Cliff Rutter, David S. Burgess

Pharmacy Practice and Science Faculty Publications

Acute kidney injury (AKI) increases during empirical antimicrobial therapy with the combination of piperacillin-tazobactam (TZP) and vancomycin (VAN) compared to the number of incidences with monotherapy or the combination of cefepime and VAN. Limited data regarding the impact of meropenem (MEM) combined with VAN exist. This study examined the AKI incidence among patients treated with MEM plus VAN (MEM+VAN) or TZP+VAN. Data were collected from the University of Kentucky Center for Clinical and Translational Science Enterprise Data Trust from September 2007 through October 2015. Adults without previous renal disease who received MEM+VAN or TZP+VAN for at ...


The Combination Of Human Urinary Kallidinogenase And Mild Hypothermia Protects Adult Rats Against Hypoxic-Ischemic Encephalopathy-Induced Injury By Promoting Angiogenesis And Regeneration, Xiaoya Gao, Haiting Xie, Shuzhen Zhu, Bin Yu, Ying Xian, Penghua Wang, Qing Wang 2018 New York Medical College

The Combination Of Human Urinary Kallidinogenase And Mild Hypothermia Protects Adult Rats Against Hypoxic-Ischemic Encephalopathy-Induced Injury By Promoting Angiogenesis And Regeneration, Xiaoya Gao, Haiting Xie, Shuzhen Zhu, Bin Yu, Ying Xian, Penghua Wang, Qing Wang

NYMC Faculty Publications

Objectives: Human Urinary Kallidinogenase (HUK) is a tissue kallikrein that plays neuroprotective role in ischemic conditions via different mechanisms. Mild hypothermia (MH) is another robust neuroprotectant that reduces mortality but does not profoundly ameliorate the neurological outcome in hypoxic-ischemic encephalopathy (HIE) patients. However, whether the combination of HUK and MH can be used as a promising neuroprotective treatment in HIE is unknown. Methods: One-hundred and forty-four adult Wistar rats were randomly divided into five groups: Sham, HIE, HUK, MH and a combination of HUK and MH treatment. The HIE rat model was established by right carotid dissection followed by hypoxia ...


Maximising The Global Health Impact Of Future Hiv Cure-Related Interventions Through Advance Planning, Regina Brown, Steven G. Deeks, Nir Eyal 2018 University of Massachusetts Medical School

Maximising The Global Health Impact Of Future Hiv Cure-Related Interventions Through Advance Planning, Regina Brown, Steven G. Deeks, Nir Eyal

Open Access Articles

Thinking about public health impact should inform HIV curative investigations. Should an effective HIV cure or sustained viral remission intervention emerge from ongoing investigations, implementation strategies aimed at ensuring global access will be needed if these approaches are to be impactful, and planning accordingly makes sense now. Specifically, we discuss three key access barriers to future cure-related interventions: high cost of the strategy; non-financial challenges to procurement, distribution and point-of-care delivery; and non-adherence and the need for long-term monitoring. As we argue, plans and decision-making for overcoming each of these barriers will need to be developed in advance. An evaluation ...


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