Publications by authors named "Karen Harris"

42 Publications

Rate of detecting CIN3+ among patients with ASC-US using digital colposcopy and dynamic spectral imaging.

Oncol Lett 2020 Oct 16;20(4):17. Epub 2020 Jul 16.

Department of Obstetrics/Gynecology, University of Central Florida, Orlando, FL 32827, USA.

The present study compared two methods for the detection of severe cervical dysplasia in women with atypical squamous cells of underdetermined significance (ASC-US) cytology; digital colposcopy with adjunctive dynamic spectral imaging (DSI) and conventional colposcopy. IMPROVE-COLPO was a two-arm cross-sectional study of US community-based colposcopy. The active (prospective) arm of this study recruited patients examined by digital colposcopy and adjunctive DSI. Preceding consecutive patients that had been examined with conventional methods were used as historical controls in the retrospective arm of the study after being matched in number to those in the prospective arm by a colposcopist. In the present study, the primary measure was the number of women detected with cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+) following punch biopsy. The study included 1,353 retrospective and 1,226 prospective patients eligible for this analysis who were examined by 146 colposcopists in 42 community-based clinics. The patient baseline characteristics were comparable between the two arms. The average number of biopsies taken per patient was higher among the prospective arm patients (including standard and DSI-assisted biopsies) compared with the retrospective arm control patients (1.21 vs. 0.97 respectively). Biopsy detected 31 patients with CIN3+ [2.29%; 95% confidence interval (CI), 1.56-3.24] in the retrospective arm, and 48 patients with CIN3+ (3.92%; 95% CI, 2.90-5.16) in the prospective arm. The difference in the number of patients detected with CIN3+ in the two arms of the study was 1.62% (95% CI, 0.30-3.04; P=0.022), which corresponds to a 70.9% relative increase in the prospective compared with the retrospective arm. Biopsy appeared less efficient in detecting patients with CIN3+ in the retrospective arm compared with the prospective arm. However, there was no statistically significant difference between the retrospective arm and the prospective arm in terms of: i) Biopsies taken (over the entire population) per patient detected with CIN3+ (42.2 in the retrospective arm vs. 30.8 in the prospective arm; P=0.164) and ii) positive predictive value of using biopsies to identify patients with CIN3+ (2.83 vs. 3.92; P=0.118). Adoption of digital colposcopy with DSI increased the number of biopsies collected from ASC-US patients compared with retrospective controls of standard colposcopy and detected a significantly higher number of patients who were CIN3+. The number of additional biopsies taken in the prospective arm compared with the retrospective arm was too small to explain the increased detection of patients with CIN3+ observed in the prospective arm, suggesting that biopsies in the prospective arm were better at identifying CIN3+.
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http://dx.doi.org/10.3892/ol.2020.11878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406885PMC
October 2020

Circular Permutation of the Native Enzyme-Mediated Cyclization Position in Cyclotides.

ACS Chem Biol 2020 04 30;15(4):962-969. Epub 2020 Mar 30.

Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.

Cyclotides are a class of cyclic disulfide-rich peptides found in plants that have been adopted as a molecular scaffold for pharmaceutical applications due to their inherent stability and ability to penetrate cell membranes. For research purposes, they are usually produced and cyclized synthetically, but there are concerns around the cost and environmental impact of large-scale chemical synthesis. One strategy to improve this is to combine a recombinant production system with native enzyme-mediated cyclization. Asparaginyl endopeptidases (AEPs) are enzymes that can act as peptide ligases in certain plants to facilitate cyclotide maturation. One of these ligases, OaAEP1b, originates from the cyclotide-producing plant, , and can be produced recombinantly for use as an alternative to chemical cyclization of recombinant substrates. However, not all engineered cyclotides are compatible with AEP-mediated cyclization because new pharmaceutical epitopes often replace the most flexible region of the peptide, where the native cyclization site is located. Here we redesign a popular cyclotide grafting scaffold, MCoTI-II, to incorporate an AEP cyclization site located away from the usual grafting region. We demonstrate the incorporation of a bioactive peptide sequence in the most flexible region of MCoTI-II while maintaining AEP compatibility, where the two were previously mutually exclusive. We anticipate that our AEP-compatible scaffold, based on the most popular cyclotide for pharmaceutical applications, will be useful in designing bioactive cyclotides that are compatible with AEP-mediated cyclization and will therefore open up the possibility of larger scale enzyme-mediated production of recombinant or synthetic cyclotides alike.
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http://dx.doi.org/10.1021/acschembio.9b00996DOI Listing
April 2020

Herpes Simplex Virus Keratitis.

Authors:
Karen D Harris

Home Healthc Now 2019 Sep/Oct;37(5):281-284

Karen D. Harris, MSN, RN, ACNS-BC, is an Assistant Professor, McAuley School of Nursing, University of Detroit Mercy, Detroit, Michigan.

Herpes simplex virus (HSV) is a highly prevalent infection in the United States. One complication of HSV is HSV keratitis, an ocular HSV infection thought to be the leading cause of corneal blindness in the United States. Home care clinicians with knowledge of the signs and symptoms of HSV and HSV keratitis can aid in early detection and treatment of this potentially serious infection. This article discusses signs and symptoms of HSV keratitis, preventive measures, and treatment.
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http://dx.doi.org/10.1097/NHH.0000000000000791DOI Listing
February 2020

A suite of kinetically superior AEP ligases can cyclise an intrinsically disordered protein.

Sci Rep 2019 07 25;9(1):10820. Epub 2019 Jul 25.

La Trobe Institute for Molecular Science, Melbourne, Vic., 3086, Australia.

Asparaginyl endopeptidases (AEPs) are a class of enzymes commonly associated with proteolysis in the maturation of seed storage proteins. However, a subset of AEPs work preferentially as peptide ligases, coupling release of a leaving group to formation of a new peptide bond. These "ligase-type" AEPs require only short recognition motifs to ligate a range of targets, making them useful tools in peptide and protein engineering for cyclisation of peptides or ligation of separate peptides into larger products. Here we report the recombinant expression, ligase activity and cyclisation kinetics of three new AEPs from the cyclotide producing plant Oldenlandia affinis with superior kinetics to the prototypical recombinant AEP ligase OaAEP1. These AEPs work preferentially as ligases at both acidic and neutral pH and we term them "canonical AEP ligases" to distinguish them from other AEPs where activity preferences shift according to pH. We show that these ligases intrinsically favour ligation over hydrolysis, are highly efficient at cyclising two unrelated peptides and are compatible with organic co-solvents. Finally, we demonstrate the broad scope of recombinant AEPs in biotechnology by the backbone cyclisation of an intrinsically disordered protein, the 25 kDa malarial vaccine candidate Plasmodium falciparum merozoite surface protein 2 (MSP2).
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http://dx.doi.org/10.1038/s41598-019-47273-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658665PMC
July 2019

In Vitro and In Planta Cyclization of Target Peptides Using an Asparaginyl Endopeptidase from Oldenlandia affinis.

Methods Mol Biol 2019 ;2012:211-235

Hexima Limited, Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, Australia.

Cyclization of the peptide backbone by connecting the N- and C-terminus can endow target peptides with favorable properties, such as increased stability or potential oral bioavailability. However, there are few tools available for carrying out this modification. Asparaginyl endopeptidases (AEPs) are a class of enzymes that typically work as proteases, but a subset is highly efficient at cyclization of the peptide backbone. In this chapter we describe how to utilize a cyclizing AEP (OaAEP1) to produce backbone-cyclized peptides both in planta and in vitro. Using the in planta method, OaAEP1 and the target precursor peptide are coexpressed in the leaves of the model plant Nicotiana benthamiana, and cyclization of the target peptide occurs in planta. Using the in vitro method, purified recombinant OaAEP1 produced in bacteria is used to cyclize the target precursor peptide in vitro.
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http://dx.doi.org/10.1007/978-1-4939-9546-2_12DOI Listing
March 2020

Rapid and Scalable Plant-Based Production of a Potent Plasmin Inhibitor Peptide.

Front Plant Sci 2019 15;10:602. Epub 2019 May 15.

Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.

The backbone cyclic and disulfide bridged sunflower trypsin inhibitor-1 (SFTI-1) peptide is a proven effective scaffold for a range of peptide therapeutics. For production at laboratory scale, solid phase peptide synthesis techniques are widely used, but these synthetic approaches are costly and environmentally taxing at large scale. Here, we developed a plant-based approach for the recombinant production of SFTI-1-based peptide drugs. We show that transient expression in allows for rapid peptide production, provided that asparaginyl endopeptidase enzymes with peptide-ligase functionality are co-expressed with the substrate peptide gene. Without co-expression, no target cyclic peptides are detected, reflecting rapid degradation of non-cyclized substrate. We test this recombinant production system by expressing a SFTI-1-based therapeutic candidate that displays potent and selective inhibition of human plasmin. By using an innovative multi-unit peptide expression cassette, we show that yields reach ~60 μg/g dry weight at 6 days post leaf infiltration. Using nuclear magnetic resonance structural analysis and functional assays, we demonstrate the equivalence of plant and synthetically derived plasmin inhibitor peptide. The methods and insights gained in this study provide opportunities for the large scale, cost effective production of SFTI-1-based therapeutics.
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http://dx.doi.org/10.3389/fpls.2019.00602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530601PMC
May 2019

Optimizing preoperative requirements for outpatient cataract surgery at the Royal Alexandra Hospital.

Can J Ophthalmol 2019 06 19;54(3):306-313. Epub 2018 Oct 19.

Alberta Health Services, Edmonton, Alta; Department of Ophthalmology and Vision Sciences, University of Alberta, Edmonton, Alta.

Objective: To evaluate preoperative testing for cataract surgery, implement stakeholder-driven change, and increase the number of patients who arrived for surgery with complete preoperative requirements, for the purpose of delivering safe, high-quality, and cost-effective care for patients.

Design: Quality improvement.

Participants: Cataract surgery patients, health care staff in Ophthalmology Day Surgery, an Ophthalmology improvement team, the Clinical Section Heads of Ophthalmology and Anaesthesia, Quality Consultants, and members of the Quality Council participated in this study.

Methods: A lean quality improvement approach was used to define and build understanding of the problem. Between July and November 2016, a chart-based reporting system captured all patients who arrived for cataract surgery with expired or incomplete preoperative requirements. A cost analysis was completed, and evidence was reviewed to ensure alignment with best practice preoperative recommendations.

Results: On average, 25% (619/2451 over a 17-week period) of patients per day arrived at the Ophthalmology Day Surgery for cataract surgery with incomplete and/or expired physical history forms and ECGs. An improvement team worked to implement a radical improvement idea and relied on an existing questionnaire to ensure patient safety preoperatively.

Conclusions: Based on the literature, best practice guidelines, and a cost analysis, it was decided that patients undergoing routine cataract surgery in Edmonton Zone Hospitals under regional anaesthesia would no longer require physician history and physicals and ECGs. Elimination of the preoperative requirements for all but select high-risk patients meant that 100% of patients who arrived for cataract surgery would not have outstanding presurgery requirements.
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http://dx.doi.org/10.1016/j.jcjo.2018.07.010DOI Listing
June 2019

Advocating for Early-Career Nurse Innovators: Modeling the Institute of Medicine Report.

Creat Nurs 2019 Feb;25(1):10-16

was published by the of Medicine (IOM) of the National Academies in 2011. The Missouri Nurses Foundation and Missouri nurses modeled a sustainable project, the Early Career Nurse Innovator Project, exemplifying the intent of that report. The Missouri Nurses Foundation Executive Board comprises experienced nurses, nurse educators, nurses in other leadership roles, retired nurses, public members of the board, and administrative support staff. This article describes a project that was developed, implemented, and evaluated to recognize and encourage early-career nurses who have designed and led innovations to improve and promote the health of Missourians. Five of these early-career nurses were the recipients of monetary awards to encourage future innovations; the second recognition cycle is in the planning phase. Through the work of the Missouri Nurses Foundation, the scholarship of bedside nurses was recognized.
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http://dx.doi.org/10.1891/1078-4535.25.1.10DOI Listing
February 2019

Etiology of teacher knowledge and instructional skills for literacy at the upper elementary grades.

Ann Dyslexia 2019 04;69(1):5-20

Mary Emily Warner Professor of Education, Arizona State University, 1050 S. Forest Mall, 434E Farmer Bldg, Tempe, AZ, 85287, USA.

The purpose of this research was to study the etiology of teacher knowledge about and factors that influence implementation of evidence-based reading and writing interventions at the upper elementary grade levels. Five data sources are used in this study: first, we used teacher surveys about their pre-service preparation on reading comprehension and literacy practices gathered during a recent cluster randomized control trial on a reading comprehension intervention conducted with 280 fourth and fifth-grade teachers and their classroom students. We also conducted focus group interviews with 43% of the teachers and observed 90% of the teachers once during the implementation years. For writing, we used data collected from 32 teachers during a 3-year design project for a teacher-led computer-supported writing intervention. We also collected data from groups of school administrators using structured interviews during both studies. Finally, we conducted an artifact review of school curricula and posted professional development (PD) plans. Our results show that in both reading comprehension and writing, all teachers reported not receiving sound evidence-based pre-service preparation and they were not currently employing any evidence-based approaches. Most teachers reported using the basal reading series with very little variation from the lesson scope and sequence. Teachers and administrators frequently reported that skills were being taught in isolation (e.g., skill of the week is summarizing) and that writing was neglected. The interviews showed very interesting patterns of curricula decision-making by school administrators and these findings were further confirmed through the artifact reviews. Based on these results, we recommend that any review of teacher practices focus also on administrator decision-making and school level factors that are driving what happens in the classrooms. The review showed that the teachers themselves do not feel empowered to learn and deliver evidence-based literacy practices and feel constrained by the system.
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http://dx.doi.org/10.1007/s11881-018-00170-6DOI Listing
April 2019

Gottesfeld-Hohler Memorial Foundation Zika Virus Think Tank Summary.

Obstet Gynecol 2018 04;131(4):661-665

Department of Obstetrics and Gynecology, University of Colorado Denver School of Medicine, Aurora, Colorado; the Departments of Obstetrics, Gynecology and Reproductive Sciences and Pediatrics, Yale School of Medicine, New Haven, Connecticut; the Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, California; the Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Texas Children's Hospital, Baylor College of Medicine, Department of Obstetrics and Gynecology, Houston, Texas; Maternal-Fetal Medicine, Eastern Virginia School of Medicine, Norfolk, Virginia; Obstetrics and Gynecology, University of California, San Francisco, San Francisco, California; North Florida Women's Physicians, Gainesville, Florida; Maternal Fetal Medicine Department, Colsanitas Clinic, Columbia University Clinic, Bogota, Colombia; Maternal Fetal Medicine and Gynecology, San Juan, Puerto Rico; Professor Joaquim Amorim Neto Research Institute, Campina Grande, Brazil; Johns Hopkins University/Jhpiego and Department of Obstetrics and Gynecology, Johns Hopkins University, Baltimore, Maryland; The Federal University of Rio de Janeiro, Brazil; and the American Institute of Ultrasound in Medicine, Laurel, Maryland.

At a think tank bringing together experts on fetal neuroimaging, obstetric infectious diseases, and public health, we discussed trends in all of these areas for Zika virus. There is a wide variety of imaging findings in affected fetuses, influenced by timing of infection and probably host factors. The resources for diagnosis and interventions also vary by location with the hardest hit areas often having the fewest resources. We identified potential areas for both research and clinical collaboration as the Zika virus epidemic continues to evolve.
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http://dx.doi.org/10.1097/AOG.0000000000002538DOI Listing
April 2018

Co-expression of a cyclizing asparaginyl endopeptidase enables efficient production of cyclic peptides in planta.

J Exp Bot 2018 01;69(3):633-641

Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia.

Cyclotides are ultra-stable, backbone-cyclized plant defence peptides that have attracted considerable interest in the pharmaceutical industry. This is due to their range of native bioactivities as well as their ability to stabilize other bioactive peptides within their framework. However, a hindrance to their widespread application is the lack of scalable, cost-effective production strategies. Plant-based production is an attractive, benign option since all biosynthetic steps are performed in planta. Nonetheless, cyclization in non-cyclotide-producing plants is poor. Here, we show that cyclic peptides can be produced efficiently in Nicotiana benthamiana, one of the leading plant-based protein production platforms, by co-expressing cyclotide precursors with asparaginyl endopeptidases that catalyse peptide backbone cyclization. This approach was successful in a range of other plants (tobacco, bush bean, lettuce, and canola), either transiently or stably expressed, and was applicable to both native and engineered cyclic peptides. We also describe the use of the transgenic system to rapidly identify new asparaginyl endopeptidase cyclases and interrogate their substrate sequence requirements. Our results pave the way for exploiting cyclotides for pest protection in transgenic crops as well as large-scale production of cyclic peptide pharmaceuticals in plants.
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http://dx.doi.org/10.1093/jxb/erx422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5853369PMC
January 2018

Improving patient identification in an ophthalmology clinic using name alerts.

Can J Ophthalmol 2017 Dec 26;52(6):564-569. Epub 2017 Jun 26.

Department of Ophthalmology and Visual Sciences, University of Alberta, Alberta, Canada. Electronic address:

Objective: To develop a standardized process for reviewing daily patient lists and identifying potential risks of misidentification. Our goal was to develop a proactive approach to identify and eliminate risks of patient misidentification.

Methods: Assessment of current patient identification practices took place over a period of 4 weeks. Using a process map, a patient survey was developed to determine the encounter points when patient identification was confirmed. This information was used to develop a standardized protocol for review of daily appointment lists.

Results: Review of daily appointment lists was completed to identify potential similar/same name risks. A standardized manual process of chart review, flagging, and tracking was developed.

Conclusions: The name alert process resulted in a simple manual process for identifying which patients have a higher name risk and allowed care providers to take preventative action to decrease potential risk of incorrect diagnostic testing, procedure, or medication administration.
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http://dx.doi.org/10.1016/j.jcjo.2017.05.004DOI Listing
December 2017

Management of feline tibial diaphyseal fractures using orthogonal plates performed via minimally invasive plate osteosynthesis.

J Feline Med Surg 2018 01 1;20(1):6-14. Epub 2017 Feb 1.

Southern Counties Veterinary Specialists, Hangersley Ringwood, UK.

Objectives The objective was to assess the medium- and long-term outcomes (radiographic and owner questionnaire) of feline tibial diaphyseal fractures with orthogonal plate fixation via a minimally invasive plate osteosynthesis (MIPO) approach. Methods Medical records and radiographs of cats that had tibial diaphyseal fractures stabilised with orthogonal plates were obtained (2012-2016). Immediate postoperative radiographs were reviewed to assess the construct configuration and follow-up radiographs (where available) were used to assess bone healing and implant-related complications. An owner-completed questionnaire (feline musculoskeletal pain index [FMPI]) was used at a minimum of 6 months following surgery to assess the cats' ability to perform normal activities. Results Eight feline tibial diaphyseal fractures met the inclusion criteria. One major complication was observed, most likely due to an operative technical error. There were no further complications following revision surgery. Six of the eight cases that had radiographic follow-up either had clinical bone union or showed evidence of bone healing. All cases were classified as successful according to FMPI. Conclusions and relevance Orthogonal plating of feline tibial diaphyseal fractures via an MIPO approach resulted in successful outcomes and a lower complication rate compared with previously reported techniques.
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http://dx.doi.org/10.1177/1098612X17692470DOI Listing
January 2018

Pregnancy-Related Deaths, Florida, 1999-2012: Opportunities to Improve Maternal Outcomes.

Matern Child Health J 2018 02;22(2):204-215

College of Medicine, Obstetrics & Gynecology, University of Florida, 653-1 West 8th Street, LRC 3rd Floor, Jacksonville, FL, 32209-6511, USA.

Objectives To examine pregnancy-related deaths (PRDs) in Florida, to identify quality improvement (QI) opportunities, and to recommend strategies aimed at reducing maternal mortality. Methods The Florida Pregnancy-Associated Mortality Review (PAMR) Committee reviewed PRDs occurring between 1999 and 2012. The PAMR Committee determined causes of PRDs, identified contributing factors, and generated recommendations for prevention and quality improvement. Information from the PAMR data registry, and live births from Florida vital statistic data were used to calculate pregnancy-related mortality ratios (PRMR) and PRD univariate risk ratios (RR) with 95% confidence intervals (CI). Results Between 1999 and 2012, the PRMR fluctuated between 14.7 and 26.2 PRDs per 100,000 live births. The five leading causes of PRD were hypertensive disorders (15.5%), hemorrhage (15.2%), infection (12.7%), cardiomyopathy (11.1%), and thrombotic embolism (10.2%), which accounted for 65% of PRDs. Principal contributing factors were morbid obesity (RR = 7.0, 95% CI 4.9-10.0) and late/no prenatal care (RR = 4.2, 95% CI 3.1-5.6). The PRMR for black women was three-fold higher (RR = 3.3, 95% CI 2.7-4.0) than white women. Among the five leading causes of PRDs, 42.5% had at least one clinical care or health care system QI opportunity. Two-third of these were associated with clinical quality of care, which included standards of care, coordination, collaboration, and communication. The QI opportunities varied by PRD cause, but not by race/ethnicity. Conclusion Gaps in clinical care or health care systems were assessed as the primary factors in over 40% of PRDs leading the PAMR Committee to generate QI recommendations for clinical care and health care systems.
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http://dx.doi.org/10.1007/s10995-017-2392-yDOI Listing
February 2018

Clinical Nurse Specialist Perceptions' of Spiritual Care: Nurses Need Support, Care Falls Short.

J Christ Nurs 2017 Jul/Sep;34(3):176-181

Mitzi M. Saunders, PhD, RN, is a certified adult clinical nurse specialist and associate professor at the University of Detroit Mercy, Detroit, Michigan. She coordinates and teaches in the adult-gerontology clinical nurse specialist program. Karen Harris, MSN, RN, is a certified adult clinical nurse specialist and clinical track nursing instructor at the University of Detroit Mercy. She has experience in medical/surgical, oncology, critical care, high-risk obstetrics, postpartum, and neonatal nursing care. Deborah L. Hale, MSN, RN, is a certified adult clinical nurse specialist. She has experience in nursing education, medical-surgical nursing, home healthcare, and faith community nursing.

The clinical nurse specialist (CNS) is positioned to influence spiritual care at three levels of practice: patient, nurse, and system. This study, the first to explore CNS spiritual care, reports on CNSs' perceptions in providing spiritual care. Four themes were extracted from interview data: 1) Providing direct spiritual support for patients, 2) Nurses need support in providing spiritual care, 3) Using existing resources, and 4) Spiritual care falls short. Not one CNS mentioned barriers to their direct provision of spiritual care. Results support that CNSs can improve spiritual care delivery.
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http://dx.doi.org/10.1097/CNJ.0000000000000394DOI Listing
October 2017

Clinical Nurse Specialists' Perceptions of Care for Vulnerable Patients.

Holist Nurs Pract 2016 Mar-Apr;30(2):64-9

College of Health Professions, McAuley School of Nursing, University of Detroit Mercy, Detroit, Michigan.

The vulnerable and underserved are populations that have higher risks in health care. A clinical nurse specialist is an advanced practice registered nurse who can help mitigate risks and provide holistic care for these patients. Researching clinical nurse specialists' perceptions of their role in caring for the vulnerable populations is important to ensuring quality care and filling in current practice weaknesses.
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http://dx.doi.org/10.1097/HNP.0000000000000132DOI Listing
September 2016

Efficient backbone cyclization of linear peptides by a recombinant asparaginyl endopeptidase.

Nat Commun 2015 Dec 18;6:10199. Epub 2015 Dec 18.

Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia.

Cyclotides are diverse plant backbone cyclized peptides that have attracted interest as pharmaceutical scaffolds, but fundamentals of their biosynthetic origin remain elusive. Backbone cyclization is a key enzyme-mediated step of cyclotide biosynthesis and confers a measure of stability on the resultant cyclotide. Furthermore, cyclization would be desirable for engineered peptides. Here we report the identification of four asparaginyl endopeptidases (AEPs), proteases implicated in cyclization, from the cyclotide-producing plant Oldenlandia affinis. We recombinantly express OaAEP1b and find it functions preferably as a cyclase by coupling C-terminal cleavage of propeptide substrates with backbone cyclization. Interestingly, OaAEP1b cannot cleave at the N-terminal site of O. affinis cyclotide precursors, implicating additional proteases in cyclotide biosynthesis. Finally, we demonstrate the broad utility of this enzyme by cyclization of peptides unrelated to cyclotides. We propose that recombinant OaAEP1b is a powerful tool for use in peptide engineering applications where increased stability of peptide products is desired.
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http://dx.doi.org/10.1038/ncomms10199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703859PMC
December 2015

An Infectious Diseases Physician-Led Antimicrobial Stewardship Program at a Small Community Hospital Associated With Improved Susceptibility Patterns and Cost-Savings After the First Year.

Open Forum Infect Dis 2015 Apr 12;2(2):ofv064. Epub 2015 May 12.

Division of Infectious Diseases and International Health, Department of Medicine ; Clinical Microbiology, Department of Pathology , University of Virginia Health System , Charlottesville ; Departments of Pharmacy.

The importance of antimicrobial stewardship is increasingly recognized, yet data from community hospitals are limited. Despite an initially low acceptance rate, an Infectious Diseases physician-led program at a 70-bed rural hospital was associated with a 42% decrease in anti-infective expenditures and susceptibility improvement in Pseudomonas aeruginosa over 3 years.
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http://dx.doi.org/10.1093/ofid/ofv064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4473105PMC
April 2015

Nursing Leader Collaboration to Drive Quality Improvement and Implementation Science.

Nurs Adm Q 2015 Jul-Sep;39(3):229-38

University of Alabama at Birmingham, University Hospital, Birmingham, Alabama (Mss Ryan, Harris, Mattox and Camp); UF Health Shands at the University of Florida, Gainesville, Florida (Ms Singh); and Clinical and Global Partnerships, University of Alabama at Birmingham, School of Nursing, Birmingham, Alabama (Dr Shirey).

Nursing leadership opportunities to improve quality and align resources in health care exist. An estimated 18% of United States gross domestic product is spent on health care delivery systems that produce poor outcomes. The purpose of this article was to describe how quality improvement and implementation science initiatives enhance outcomes using nursing leadership strategies that play an integral role in aligning key colleagues to drive the collaborative process. A critical appraisal of the literature was conducted, which supports the importance of evidenced-based practice improvement, collaborative change process, and professional role of nursing leadership. Limited evidence exists related to practice strategies for nursing leaders to implement sustainable change at the unit level for successful alignment of resources. Strategies based on Rogers' Diffusion of Innovation Theory are recommended to address the gap in the literature. The strategies aim to increase meaningful knowledge or the "why," create a tipping point, and implement sustainable change starting with the end in mind. Nurse leaders are a central component for driving alignment and implementing change at the unit level. Uses of the described evidenced-based strategies have implications for nursing practice, education, and scholarship.
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http://dx.doi.org/10.1097/NAQ.0000000000000111DOI Listing
December 2016

Nursing practice implications of the year of ethics.

Authors:
Karen T Harris

Nurs Womens Health 2015 Apr-May;19(2):119-22

e 2015 ANA Code of Ethics is foundational to professional nursing practice and is aligned with AWHONN’s core values, standards of care and position statement on ethical decision-making in the clinical setting. Understanding the roles and responsibilities of nurses to ensure an ethical practice environment is critical to perinatal health outcomes and sta engagement and to the prevention of moral distress.
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http://dx.doi.org/10.1111/1751-486X.12183DOI Listing
September 2016

Use of immunodampening to overcome diversity in the malarial vaccine candidate apical membrane antigen 1.

Infect Immun 2014 Nov 25;82(11):4707-17. Epub 2014 Aug 25.

Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Australia

Apical membrane antigen 1 (AMA1) is a leading malarial vaccine candidate; however, its polymorphic nature may limit its success in the field. This study aimed to circumvent AMA1 diversity by dampening the antibody response to the highly polymorphic loop Id, previously identified as a major target of strain-specific, invasion-inhibitory antibodies. To achieve this, five polymorphic residues within this loop were mutated to alanine, glycine, or serine in AMA1 of the 3D7 and FVO Plasmodium falciparum strains. Initially, the corresponding antigens were displayed on the surface of bacteriophage, where the alanine and serine but not glycine mutants folded correctly. The alanine and serine AMA1 mutants were expressed in Escherichia coli, refolded in vitro, and used to immunize rabbits. Serological analyses indicated that immunization with a single mutated form of 3D7 AMA1 was sufficient to increase the cross-reactive antibody response. Targeting the corresponding residues in an FVO backbone did not achieve this outcome. The inclusion of at least one engineered form of AMA1 in a biallelic formulation resulted in an antibody response with broader reactivity against different AMA1 alleles than combining the wild-type forms of 3D7 and FVO AMA1 alleles. For one combination, this extended to an enhanced relative growth inhibition of a heterologous parasite line, although this was at the cost of reduced overall inhibitory activity. These results suggest that targeted mutagenesis of AMA1 is a promising strategy for overcoming antigenic diversity in AMA1 and reducing the number of variants required to induce an antibody response that protects against a broad range of Plasmodium falciparum AMA1 genotypes. However, optimization of the immunization regime and mutation strategy will be required for this potential to be realized.
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http://dx.doi.org/10.1128/IAI.02061-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4249334PMC
November 2014

Standardized severe maternal morbidity review: rationale and process.

J Obstet Gynecol Neonatal Nurs 2014 Jul-Aug;43(4):403-8

Severe maternal morbidity and mortality have been rising in the United States. To begin a national effort to reduce morbidity, a specific call to identify all pregnant and postpartum women experiencing admission to an intensive care unit or receipt of four or more units of blood for routine review has been made. While advocating for review of these cases, no specific guidance for the review process was provided. Therefore, the aim of this expert opinion is to present guidelines for a standardized severe maternal morbidity interdisciplinary review process to identify systems, professional, and facility factors that can be ameliorated, with the overall goal of improving institutional obstetric safety and reducing severe morbidity and mortality among pregnant and recently pregnant women. This opinion was developed by a multidisciplinary working group that included general obstetrician–gynecologists, maternal–fetal medicine subspecialists, certified nurse–midwives, and registered nurses all with experience in maternal mortality reviews. A process for standardized review of severe maternal morbidity addressing committee organization, review process, medical record abstraction and assessment, review culture, data management, review timing, and review confidentiality is presented. Reference is made to a sample severe maternal morbidity abstraction and assessment form.
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http://dx.doi.org/10.1111/1552-6909.12478DOI Listing
November 2015

Standardized severe maternal morbidity review: rationale and process.

Obstet Gynecol 2014 Aug;124(2 Pt 1):361-366

Departments of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California, Montefiore Medical Center, Bronx, New York, University of Florida College of Medicine, Gainesville, Florida, Virginia Commonwealth University, Richmond, Virginia, California Pacific Hospital, San Francisco, California, Medical College of Wisconsin, Milwaukee, Wisconsin, and Wake Forest University, Winston-Salem, North Carolina; the Division of Reproductive Health, Centers for Disease Control and Prevention, Atlanta, Georgia; the Association of Women's Health, Obstetric and Neonatal Nurses and the American College of Obstetricians and Gynecologists, Washington, DC; the Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, California; the University of Colorado College of Nursing, Aurora, Colorado; and the Cooper University Hospital, Cooper Medical School, Rowan University, Camden, New Jersey.

Severe maternal morbidity and mortality have been rising in the United States. To begin a national effort to reduce morbidity, a specific call to identify all pregnant and postpartum women experiencing admission to an intensive care unit or receipt of 4 or more units of blood for routine review has been made. While advocating for review of these cases, no specific guidance for the review process was provided. Therefore, the aim of this expert opinion is to present guidelines for a standardized severe maternal morbidity interdisciplinary review process to identify systems, professional, and facility factors that can be ameliorated, with the overall goal of improving institutional obstetric safety and reducing severe morbidity and mortality among pregnant and recently pregnant women. This opinion was developed by a multidisciplinary working group that included general obstetrician-gynecologists, maternal-fetal medicine subspecialists, certified nurse-midwives, and registered nurses all with experience in maternal mortality reviews. A process for standardized review of severe maternal morbidity addressing committee organization, review process, medical record abstraction and assessment, review culture, data management, review timing, and review confidentiality is presented. Reference is made to a sample severe maternal morbidity abstraction and assessment form.
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http://dx.doi.org/10.1097/AOG.0000000000000397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4293011PMC
August 2014

Idiopathic ischemic necrosis of an accessory carpal bone in a dog.

J Am Vet Med Assoc 2013 Dec;243(12):1746-50

Department of Veterinary Medicine, Cambridge Veterinary School, University of Cambridge, Cambridge, CB3 0ES, England.

Case Description: A 6-year-old neutered female mixed-breed dog was evaluated because of a 6-week history of left forelimb lameness that varied in severity.

Clinical Findings: Radiography revealed expansile and lytic changes of the left accessory carpal bone (ACB). Results of histologic evaluation of ACB core biopsy specimens indicated areas of bone necrosis. The entire left ACB was excised and submitted for histologic evaluation; results confirmed a diagnosis of idiopathic ischemic necrosis.

Treatment And Outcome: Left pancarpal arthrodesis was performed to treat carpal hyperextension and persistent lameness. The dog had an excellent functional outcome with no other problems related to the carpus until its death 4 years later, further decreasing suspicion that the problem was attributable to an undetected neoplasm or bacterial or fungal osteomyelitis.

Clinical Relevance: The radiographic and histologic findings for the dog of this report were similar to previously reported findings for dogs with ischemic femoral head necrosis and humans with ischemic carpal (pisiform or lunate bone) necrosis. The etiology of the ischemic ACB necrosis in this dog was not determined. To the authors' knowledge, this is the first report of a dog with idiopathic ischemic ACB necrosis. Idiopathic ischemic necrosis should be included as a differential diagnosis for dogs with lameness and destructive and expansile ACB radiographic lesions. An excellent functional outcome may be attained by means of ACB excision and pancarpal arthrodesis.
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http://dx.doi.org/10.2460/javma.243.12.1746DOI Listing
December 2013

A comparative study of hair removal at an NHS hospital: Luminette intense pulsed light versus electrolysis.

J Dermatolog Treat 2014 Apr 19;25(2):169-73. Epub 2012 Sep 19.

Withington Community Hospital , Manchester , UK.

Twenty-five women, referred for hair removal by electrolysis, were enrolled in a split face study to treat facial hirsutism. Each patient was treated on six occasions: one-half of the face with electrolysis and the other side with an intense pulsed light source. Patients were evaluated with respect to reduction in hair counts, side effects and discomfort during treatment. Re-growth was assessed at 3, 6 and 9 months following treatment. All patients, except one with very sparse, fair hair growth, preferred treatment with the Intense Pulsed Light and rated their average hair reduction with this method as 77% after five treatments. The overall patient satisfaction rates as determined by visual analogue scales were 8.3 out of 10 for IPL and 5.4 out of 10 for electrolysis.
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http://dx.doi.org/10.3109/09546634.2012.715239DOI Listing
April 2014

"An adjective is a word hanging down from a noun": learning to write and students with learning disabilities.

Ann Dyslexia 2013 Apr 13;63(1):65-79. Epub 2011 Oct 13.

Department of Special Education, Vanderbilt University, Nashville, TN 37069, USA.

By the upper elementary grades, writing becomes an essential tool both for learning and for showing what you know. Students who struggle significantly with writing are at a terrible disadvantage. Data from the National Assessment of Educational Progress indicate that only 25% of students can be classified as competent writers; students with learning disabilities (LD) have even greater problems with writing than their normally achieving peers and frequently demonstrate a deteriorating attitude toward writing after the primary grades. In this article, we focus on composing and the writing process, and examine the knowledge base about writing development and instruction among students with LD. We address what research tells us about skilled writers and the development of writing knowledge, strategies, skill, and the will to write, and how this relates to students with LD. Next, we summarize what has been learned from research on writing development, effective instruction, and the writing abilities of students with LD in terms of effective instruction for these students. Finally, we indicate critical areas for future research.
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http://dx.doi.org/10.1007/s11881-011-0057-xDOI Listing
April 2013

Peptide inhibitors of the malaria surface protein, apical membrane antigen 1: identification of key binding residues.

Biopolymers 2011 May 6;95(5):354-64. Epub 2011 Jan 6.

Structural Biology Division, The Walter & Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia.

Apical membrane antigen 1 (AMA1) is essential for malaria parasite invasion of erythrocytes and is therefore an attractive target for drug development. Peptides that bind AMA1 have been identified from random peptide libraries expressed on the surface of phage. Of these, R1, which binds to a hydrophobic ligand binding site on AMA1, was a particularly potent inhibitor of parasite invasion of erythrocytes in vitro. The solution structure of R1 contains a turn-like conformation between residues 5-10. Here the importance of residues in this turn-like structure for binding to AMA1 was examined by site-directed mutagenesis and NMR spectroscopy. The peptide was expressed as a fusion protein following replacement of Met16 by Leu in order to accommodate cyanogen bromide cleavage. This modified peptide (R2) displayed the same affinity for AMA1 as R1, showing that the identity of the side chain at position 16 was not critical for binding. Substitution of Phe5, Pro7, Leu8, and Phe9 with alanine led to significant (7.5- to >350-fold) decreases in affinity for AMA1. Comparison of backbone amide and C(α) H chemical shifts for these R2 analogues with corresponding values for R2 showed no significant changes, with the exception of R2(P7A), where slightly larger differences were observed, particularly for residues flanking position 7. The absence of significant changes in the secondary chemical shifts suggests that these mutations had little effect on the solution conformation of R2. The identification of a nonpolar region of these peptides containing residues essential for AMA1 binding establishes a basis for the design of anti-malarial drugs based on R1 mimetics.
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http://dx.doi.org/10.1002/bip.21582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164155PMC
May 2011

Non-synonymous single nucleotide polymorphisms in the watermelon eIF4E gene are closely associated with resistance to zucchini yellow mosaic virus.

Theor Appl Genet 2009 Dec 10;120(1):191-200. Epub 2009 Oct 10.

U.S. Vegetable Laboratory, U.S. Department of Agriculture, Agriculture Research Service, Charleston, SC 29414, USA.

Zucchini yellow mosaic virus (ZYMV) is one of the most economically important potyviruses infecting cucurbit crops worldwide. Using a candidate gene approach, we cloned and sequenced eIF4E and eIF(iso)4E gene segments in watermelon. Analysis of the nucleotide sequences between the ZYMV-resistant watermelon plant introduction PI 595203 (Citrullus lanatus var. lanatus) and the ZYMV-susceptible watermelon cultivar 'New Hampshire Midget' ('NHM') showed the presence of single nucleotide polymorphisms (SNPs). Initial analysis of the identified SNPs in association studies indicated that SNPs in the eIF4E, but not eIF(iso)4E, were closely associated to the phenotype of ZYMV-resistance in 70 F(2) and 114 BC(1R) progenies. Subsequently, we focused our efforts in obtaining the entire genomic sequence of watermelon eIF4E. Three SNPs were identified between PI 595203 and NHM. One of the SNPs (A241C) was in exon 1 and the other two SNPs (C309A and T554G) were in the first intron of the gene. SNP241 which resulted in an amino acid substitution (proline to threonine) was shown to be located in the critical cap recognition and binding area, similar to that of several plant species resistance to potyviruses. Analysis of a cleaved amplified polymorphism sequence (CAPS) marker derived from this SNP in F(2) and BC(1R) populations demonstrated a cosegregation between the CAPS-2 marker and their ZYMV resistance or susceptibility phenotype. When we investigated whether such SNP mutation in the eIF4E was also conserved in several other PIs of C. lanatus var. citroides, we identified a different SNP (A171G) resulting in another amino acid substitution (D71G) from four ZYMV-resistant C. lanatus var. citroides (PI 244018, PI 482261, PI 482299, and PI 482322). Additional CAPS markers were also identified. Availability of all these CAPS markers will enable marker-aided breeding of watermelon for ZYMV resistance.
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http://dx.doi.org/10.1007/s00122-009-1169-0DOI Listing
December 2009

Successful treatment of an unusual cause of myocardial ischemia.

J Am Coll Cardiol 2009 Jul;54(3):277

Department of Cardiology, Gundersen Lutheran Health System, La Crosse, Wisconsin, USA.

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http://dx.doi.org/10.1016/j.jacc.2009.02.072DOI Listing
July 2009

Rapid optimization of a peptide inhibitor of malaria parasite invasion by comprehensive N-methyl scanning.

J Biol Chem 2009 Apr 21;284(14):9361-71. Epub 2009 Jan 21.

Department of Biochemistry, La Trobe University, Victoria 3086, Australia.

Apical membrane antigen 1 (AMA1) of the malaria parasite Plasmodium falciparum has been implicated in the invasion of host erythrocytes and is an important vaccine candidate. We have previously described a 20-residue peptide, R1, that binds to AMA1 and subsequently blocks parasite invasion. Because this peptide appears to target a site critical for AMA1 function, it represents an important lead compound for anti-malarial drug development. However, the effectiveness of this peptide inhibitor was limited to a subset of parasite isolates, indicating a requirement for broader strain specificity. Furthermore, a barrier to the utility of any peptide as a potential therapeutic is its susceptibility to rapid proteolytic degradation. In this study, we sought to improve the proteolytic stability and AMA1 binding properties of the R1 peptide by systematic methylation of backbone amides (N-methylation). The inclusion of a single N-methyl group in the R1 peptide backbone dramatically increased AMA1 affinity, bioactivity, and proteolytic stability without introducing global structural alterations. In addition, N-methylation of multiple R1 residues further improved these properties. Therefore, we have shown that modifications to a biologically active peptide can dramatically enhance activity. This approach could be applied to many lead peptides or peptide therapeutics to simultaneously optimize a number of parameters.
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http://dx.doi.org/10.1074/jbc.M808762200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2666588PMC
April 2009