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5. Modulating Integrin αIIbβ3 Activity through Mutagenesis of Allosterically Regulated Intersubunit Contacts

Author

Tan, Sophia K, Fong, Karen P, Polizzi, Nicholas F, Sternisha, Alex, Slusky, Joanna SG, Yoon, Kyungchul, DeGrado, William F, and Bennett, Joel S

Subjects
Biochemistry and Cell Biology, Biological Sciences, Alanine, Allosteric Regulation, Animals, CHO Cells, Cricetinae, Cricetulus, Humans, Mutagenesis, Platelet Glycoprotein GPIIb-IIIa Complex, Protein Binding, Protein Structure, Secondary, Protein Structure, Tertiary, Protein Subunits, Medicinal and Biomolecular Chemistry, Medical Biochemistry and Metabolomics, Biochemistry & Molecular Biology, Biochemistry and cell biology, Medical biochemistry and metabolomics, Medicinal and biomolecular chemistry
Abstract

Integrin αIIbβ3, a transmembrane heterodimer, mediates platelet aggregation when it switches from an inactive to an active ligand-binding conformation following platelet stimulation. Central to regulating αIIbβ3 activity is the interaction between the αIIb and β3 extracellular stalks, which form a tight heterodimer in the inactive state and dissociate in the active state. Here, we demonstrate that alanine replacements of sensitive positions in the heterodimer stalk interface destabilize the inactive conformation sufficiently to cause constitutive αIIbβ3 activation. To determine the structural basis for this effect, we performed a structural bioinformatics analysis and found that perturbing intersubunit contacts with favorable interaction geometry through substitutions to alanine quantitatively accounted for the degree of constitutive αIIbβ3 activation. This mutational study directly assesses the relationship between favorable interaction geometry at mutation-sensitive positions and the functional activity of those mutants, giving rise to a simple model that highlights the importance of interaction geometry in contributing to the stability between protein-protein interactions.

Published
2019

8. Impact of COVID-19 pandemic on accredited programs and graduates who sat for the American Society for Clinical Pathology Board of Certification examination: graduates' perspective.

Author

Duzan, Dana, Fong, Karen, Freeman, Vicki S, Goodyear, Nancy, Nadder, Teresa S, Spiczka, Amy, Taff, Teresa, and Tanabe, Patricia

Subjects
*GRADUATE education, *ACCREDITATION, *SCHOOL environment, *STRESS management, *HEALTH occupations students, *EVALUATION of human services programs, *SOCIOECONOMIC factors, *EDUCATIONAL tests & measurements, *CERTIFICATION, *DESCRIPTIVE statistics, *CONFIDENCE, *TEACHING methods, *ANXIETY, *EXPERIENCE, *STUDENTS, *EDUCATION of medical technologists, *RESEARCH methodology, *ACADEMIC achievement, *ONLINE education, *ABILITY, *MEDICAL laboratory science, *HOSPITAL health promotion programs, *SOCIAL support, *STUDENT attitudes, *COVID-19 pandemic, *PSYCHOSOCIAL factors, *TRAINING, *MENTAL depression
Abstract

Objective Students in health profession education programs were severely affected by the COVID-19 pandemic at both didactic and clinical training levels. The purpose for this American Society for Clinical Pathology Board of Certification (ASCP BOC) study was to determine the impact of the COVID-19 pandemic on graduates. This study represents the perspectives of laboratory professional graduates who sat for the BOC certification in their respective professional disciplines. Methods A survey was sent to all graduates from the National Accrediting Agency for Clinical Laboratory Science (NAACLS), Accrediting Bureau of Health Education Schools (ABHES), and Commission on Accreditation of Allied Health Education Programs (CAAHEP) accredited programs who sat for the ASCP BOC examination in 2020 and 2021 to determine the impact of COVID-19 on laboratory professional graduates during the pandemic. Results A total of 180 graduates responded to the survey. The majority of graduates indicated that at least 1 didactic program component was shifted to an online system during the pandemic and that both clinical and nonclinical student laboratories were affected. Although program completion for most graduates was not delayed, one-third of graduates delayed taking their respective BOC exam. Due to the lack of knowledge application through practical hands-on laboratory experience in their educational programs, graduates reported feeling a lack of readiness with regards to preparing for the national certification examination as well as for employment. Conclusion The study results showed the pandemic greatly impacted the education experience and readiness for the ASCP BOC examinations for graduates. Factors such as the absence of in-person learning and hands-on experience—both crucial aspects in laboratory training—and the ripple effects as a result of the pandemic, such as job loss, financial constraints, and health concerns, contributed to the decreased quality of education for graduates. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Transition to Oral Antibiotic Therapy for Hospitalized Adults With Gram-Negative Bloodstream Infections

Author

Engers, Drew W., primary, Tamma, Pranita D., additional, Fiawoo, Suiyini, additional, Fong, Karen, additional, Jariwala, Ripal, additional, Jenkins, Timothy C., additional, Kendall, Ronald E., additional, Lee, Jae Hyoung, additional, McCreary, Erin K., additional, Patel, Payal K., additional, Shihadeh, Katherine C., additional, Slish, Judianne, additional, Van Schooneveld, Trevor C., additional, and Malani, Anurag N., additional

Published
2024
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12. A Syst-OMICS Approach to Ensuring Food Safety and Reducing the Economic Burden of Salmonellosis.

Author

Emond-Rheault, Jean-Guillaume, Jeukens, Julie, Freschi, Luca, Kukavica-Ibrulj, Irena, Boyle, Brian, Dupont, Marie-Josée, Colavecchio, Anna, Barrere, Virginie, Cadieux, Brigitte, Arya, Gitanjali, Bekal, Sadjia, Berry, Chrystal, Burnett, Elton, Cavestri, Camille, Chapin, Travis K, Crouse, Alanna, Daigle, France, Danyluk, Michelle D, Delaquis, Pascal, Dewar, Ken, Doualla-Bell, Florence, Fliss, Ismail, Fong, Karen, Fournier, Eric, Franz, Eelco, Garduno, Rafael, Gill, Alexander, Gruenheid, Samantha, Harris, Linda, Huang, Carol B, Huang, Hongsheng, Johnson, Roger, Joly, Yann, Kerhoas, Maud, Kong, Nguyet, Lapointe, Gisèle, Larivière, Line, Loignon, Stéphanie, Malo, Danielle, Moineau, Sylvain, Mottawea, Walid, Mukhopadhyay, Kakali, Nadon, Céline, Nash, John, Ngueng Feze, Ida, Ogunremi, Dele, Perets, Ann, Pilar, Ana V, Reimer, Aleisha R, Robertson, James, Rohde, John, Sanderson, Kenneth E, Song, Lingqiao, Stephan, Roger, Tamber, Sandeep, Thomassin, Paul, Tremblay, Denise, Usongo, Valentine, Vincent, Caroline, Wang, Siyun, Weadge, Joel T, Wiedmann, Martin, Wijnands, Lucas, Wilson, Emily D, Wittum, Thomas, Yoshida, Catherine, Youfsi, Khadija, Zhu, Lei, Weimer, Bart C, Goodridge, Lawrence, and Levesque, Roger C

Subjects
Salmonella, antibiotic resistance, bacterial genomics, database, foodborne pathogen, next-generation sequencing, phylogeny, Genetics, Emerging Infectious Diseases, Biodefense, Infectious Diseases, Prevention, Vaccine Related, Foodborne Illness, Digestive Diseases, Human Genome, Infection, Good Health and Well Being, Environmental Science and Management, Soil Sciences, Microbiology
Abstract

The Salmonella Syst-OMICS consortium is sequencing 4,500 Salmonella genomes and building an analysis pipeline for the study of Salmonella genome evolution, antibiotic resistance and virulence genes. Metadata, including phenotypic as well as genomic data, for isolates of the collection are provided through the Salmonella Foodborne Syst-OMICS database (SalFoS), at https://salfos.ibis.ulaval.ca/. Here, we present our strategy and the analysis of the first 3,377 genomes. Our data will be used to draw potential links between strains found in fresh produce, humans, animals and the environment. The ultimate goals are to understand how Salmonella evolves over time, improve the accuracy of diagnostic methods, develop control methods in the field, and identify prognostic markers for evidence-based decisions in epidemiology and surveillance.

Published
2017

13. Directly Activating the Integrin αIIbβ3 Initiates Outside-In Signaling by Causing αIIbβ3 Clustering

Author

Fong, Karen P, Zhu, Hua, Span, Lisa M, Moore, David T, Yoon, Kyungchul, Tamura, Ryo, Yin, Hang, DeGrado, William F, and Bennett, Joel S

Subjects
Biochemistry and Cell Biology, Biological Sciences, Hematology, Blood Platelets, CSK Tyrosine-Protein Kinase, Humans, Immunoblotting, Immunoprecipitation, Peptide Fragments, Phosphorylation, Platelet Activation, Platelet Aggregation, Platelet Glycoprotein GPIIb-IIIa Complex, Syk Kinase, src-Family Kinases, Src, integrin, platelet, signal transduction, transmembrane domain, Chemical Sciences, Medical and Health Sciences, Biochemistry & Molecular Biology, Biological sciences, Biomedical and clinical sciences, Chemical sciences
Abstract

αIIbβ3 activation in platelets is followed by activation of the tyrosine kinase c-Src associated with the carboxyl terminus of the β3 cytosolic tail. Exogenous peptides designed to interact with the αIIb transmembrane (TM) domain activate single αIIbβ3 molecules in platelets by binding to the αIIb TM domain and causing separation of the αIIbβ3 TM domain heterodimer. Here we asked whether directly activating single αIIbβ3 molecules in platelets using the designed peptide anti-αIIb TM also initiates αIIbβ3-mediated outside-in signaling by causing activation of β3-associated c-Src. Anti-αIIb TM caused activation of β3-associated c-Src and the kinase Syk, but not the kinase FAK, under conditions that precluded extracellular ligand binding to αIIbβ3. c-Src and Syk are activated by trans-autophosphorylation, suggesting that activation of individual αIIbβ3 molecules can initiate αIIbβ3 clustering in the absence of ligand binding. Consistent with this possibility, incubating platelets with anti-αIIb TM resulted in the redistribution of αIIbβ3 from a homogenous ring located at the periphery of discoid platelets into nodular densities consistent with clustered αIIbβ3. Thus, these studies indicate that not only is resting αIIbβ3 poised to undergo a conformational change that exposes its ligand-binding site, but it is poised to rapidly assemble into intracellular signal-generating complexes as well.

Published
2016

15. Diagnostic testing and antibiotic utilization among inpatients evaluated for coronavirus disease 2019 (COVID-19) pneumonia

Author

Wimmer, Megan R., primary, Griffin, Meggie, additional, Peterson-Weber, Alex, additional, Schulz, Lucas T., additional, Hamel, Ashlee G., additional, Schwei, Rebecca J., additional, Fong, Karen, additional, Burgess, Donna R., additional, Brett, Meghan, additional, Hale, Cory M., additional, Holubar, Marisa, additional, Jain, Rupali, additional, Larry, Rachel, additional, Spivak, Emily S., additional, Newland, Helen, additional, Njoku, Jessica, additional, Postelnick, Michael, additional, Walraven, Carla, additional, and Pulia, Michael S., additional

Published
2023
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22. Eligibility, Enrollment, and Completion of Exercise-Based Cardiac Rehabilitation Following Stroke Rehabilitation: What Are the Barriers?

Author

Marzolini, Susan, Fong, Karen, Jagroop, David, Neirinckx, Jennifer, Liu, Jean, Reyes, Rina, Grace, Sherry L., Oh, Paul, and Colella, Tracey J.F.

Subjects
Time, Physical therapists, Partnerships, Health, World Health Organization, University Health Network
Abstract

Background. People after stroke benefit from comprehensive secondary prevention programs including cardiac rehabilitation (CR), yet there is little understanding of eligibility for exercise and barriers to use. Objective. The aim of this study was to examine eligibility for CR; enrollment, adherence, and completion; and factors affecting use. Design. This was a prospective study of 116 consecutive people enrolled in a single outpatient stroke rehabilitation (OSR) program located in Toronto, Ontario, Canada. Methods. Questionnaires were completed by treating physical therapists for consecutive participants receiving OSR and included reasons for CR ineligibility, reasons for declining participation, demographics, and functional level. CR eligibility criteria included the ability to walk [greater than or equal to]100 m (no time restriction) and the ability to exercise at home independently or with assistance. People with or without hemiplegic gait were eligible for adapted or traditional CR, respectively. Logistic regression analyses were used to examine factors associated with use indicators. Results. Of 116 participants receiving OSR, 82 (70.7%) were eligible for CR; 2 became eligible later. Sixty (71.4%) enrolled in CR and 49 (81.7%) completed CR, attending 87.1% (SD = 16.6%) of prescribed sessions. The primary reasons for ineligibility included being nonambulatory or having poor ambulation (52.9%; 18/34 patients) and having severe cognitive deficits and no home exercise support (20.6%; 7/34). Frequently cited reasons for declining CR were moving or travel out of country (17.2%; 5/29 reasons), lack of interest (13.8%; 4/29), transportation issues (10.3%; 3/29), and desiring a break from therapy (10.3%; 3/29). In a multivariate analysis, people who declined CR were more likely to be women, have poorer attendance at OSR, and not diabetic. Compared with traditional CR, stroke-adapted CR resulted in superior attendance (66.1% [SD = 22.9%] vs 87.1% [SD = 16.6%], respectively) and completion (66.7% vs 89.7%, respectively). The primary reasons for dropping out were medical (45%) and moving (27%). Limitations. Generalizability to other programs is limited, and other, unmeasured factors may have affected outcomes. Conclusions. An OSR-CR partnership provided an effective continuum of care, with approximately 75% of eligible people participating and more than 80% completing. However, just over 1 of 4 eligible people declined participation; therefore, strategies should target lack of interest, transportation, women, and people without diabetes. An alternative program model is needed for people who have severe ambulatory or cognitive deficits and no home exercise support., Stroke is highly prevalent globally and a leading cause of adult neurological disability. (1) There is mounting evidence demonstrating the benefits and feasibility of comprehensive secondary prevention programs, particularly those [...]

Published
2020
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23. Status of Medical Laboratory Science Faculty and Programs

Author

Freeman, Vicki, primary, Brown, Karen, additional, Parker Fenn, JoAnn, additional, Fong, Karen, additional, Genzen, Jonathan, additional, Goodyear, Nancy, additional, Lunz Houston, Mary, additional, Taff, Terry, additional, and Tanabe, Patricia, additional

Published
2023
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24. Impact of COVID-19 pandemic on accredited programs and graduates who sat for the American Society for Clinical Pathology–Board of Certification Examination: program directors' perspective.

Author

Duzan, Dana, Fong, Karen, Freeman, Vicki S, Goodyear, Nancy, Nadder, Teresa S, Spiczka, Amy, Taff, Teresa, and Tanabe, Patricia

Subjects
*ONLINE education, *PATHOLOGICAL laboratories, *ACCREDITATION, *ACADEMIC medical centers, *PSYCHOLOGY of movement, *COLLEGE teacher attitudes, *SIMULATION methods in education, *LEARNING strategies, *ACADEMIC achievement, *DESCRIPTIVE statistics, *COMMUNICATION, *COVID-19 pandemic, *PROFESSIONAL licensure examinations, *MEDICAL education, *EMPLOYEE retention
Abstract

Objective Health professions education programs were severely affected by the COVID-19 pandemic at clinical and didactic training levels. The purpose for this American Society for Clinical Pathology–Board of Certification (BOC) study was to determine the impact of the COVID-19 pandemic on the graduates who sat for BOC certification in their respective professional disciplines from the perspective of program directors (PDs). A separate article will be published on the graduates' perspective. Methods A survey was sent to all PDs from the National Accrediting Agency for Clinical Laboratory Science, Accrediting Bureau of Health Education Schools, and Commission on Accreditation of Allied Health Education Programs, accredited programs whose graduates are certified by the BOC, to determine the impact of COVID-19 on healthcare graduates and education programs during the pandemic. Results A total of 201 PDs responded. All programs consistently reported that the pandemic had a negative impact on their students' BOC pass rate and scores. When asked what educational formats were used, all groups used virtual live lectures and recorded lectures. University programs were found to use more online student laboratories and simulation laboratory sessions than the hospital programs, affecting the psychomotor skills of their students. Conclusion The results indicated that the effects from the COVID-19 pandemic were related to the inherent differences between hospital and university programs. This study revealed that the pandemic affected university programs more than hospital programs. [ABSTRACT FROM AUTHOR]

Published
2023
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26. Diagnostic testing and antibiotic utilization among inpatients evaluated for coronavirus disease 2019 (COVID-19) pneumonia

Author

Wimmer, Megan R., Griffin, Meggie, Peterson-Weber, Alex, Schulz, Lucas T., Hamel, Ashlee G., Schwei, Rebecca J., Fong, Karen, Burgess, Donna R., Brett, Meghan, Hale, Cory M., Holubar, Marisa, Jain, Rupali, Larry, Rachel, Spivak, Emily S., Newland, Helen, Njoku, Jessica, Postelnick, Michael, Walraven, Carla, and Pulia, Michael S.

Abstract

AbstractWe evaluated diagnostic test and antibiotic utilization among 252 patients from 11 US hospitals who were evaluated for coronavirus disease 2019 (COVID-19) pneumonia during the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) omicron variant pandemic wave. In our cohort, antibiotic use remained high (62%) among SARS-CoV-2–positive patients and even higher among those who underwent procalcitonin testing (68%).

Published
2024
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27. Antimicrobial stewardship, procalcitonin testing, and rapid blood-culture identification to optimize sepsis care in critically ill adult patients: A quality improvement initiative

Author

Sligl, Wendy I., primary, Chen, Justin Z., additional, Wang, Xiaoming, additional, Boehm, Cheyanne, additional, Fong, Karen, additional, Crick, Katelynn, additional, Garrido Clua, Míriam, additional, Codan, Cassidy, additional, Dingle, Tanis C., additional, Gregson, Daniel, additional, Prosser, Connie, additional, Sadrzadeh, Hossein, additional, Yan, Charles, additional, Chen, Guanmin, additional, Tse-Chang, Alena, additional, Garros, Daniel, additional, Doig, Christopher J., additional, Zygun, David, additional, Opgenorth, Dawn, additional, Conly, John M., additional, and Bagshaw, Sean M, additional

Published
2023
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31. How does the antimicrobial stewardship provider role affect prospective audit and feedback acceptance for restricted antibiotics in a Canadian tertiary-care center?

Author

Hammond, Keely M., Kabbani, Dima, Doucette, Karen E., Smith, Stephanie W., Lau, Cecilia, Bains, Serena, Fong, Karen, Stewart, Jackson, and Chen, Justin Z.

Abstract

AbstractOf 731 restricted antimicrobial prescriptions subject to antimicrobial stewardship program (ASP) prospective audit and feedback (PAF) over a 3-year period, 598 PAF recommendations (82%) were fully accepted. Physician auditors had an increased odds of PAF recommendation acceptance, reinforcing the complementary role of the ASP physician in the multidisciplinary ASP team.

Published
2024
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36. The impact of coronavirus disease 2019 (COVID-19) on the antimicrobial stewardship pharmacist workforce: A multicenter survey

Author

Wimmer, Megan R., primary, Schulz, Lucas T., additional, Hamel, Ashlee G., additional, Schwei, Rebecca J., additional, Fong, Karen, additional, Burgess, Donna R., additional, Brett, Meghan, additional, Hale, Cory M., additional, Holubar, Marisa, additional, Jain, Rupali, additional, Larry, Rachel, additional, Spivak, Emily S., additional, Newland, Helen, additional, Njoku, Jessica, additional, Postelnick, Michael, additional, Walraven, Carla, additional, and Pulia, Michael S., additional

Published
2022
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38. Deciphering the human platelet sheddome

Author

Fong, Karen P., Barry, Colin, Tran, Anh N., Traxler, Elizabeth A., Wannemacher, Kenneth M., Tang, Hsin-Yao, Speicher, Kaye D., Blair, Ian A., Speicher, David W., Grosser, Tilo, and Brass, Lawrence F.

Published
2011
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46. Call for improvement in medical school training in genetics: results of a national survey

Author

Haspel, Richard L., primary, Genzen, Jonathan R., additional, Wagner, Jay, additional, Fong, Karen, additional, Haspel, Richard L., additional, Wilcox, Rebecca, additional, Adem, Patricia V., additional, Anderson, Hana, additional, Atkinson, James B., additional, Burke, Leah W., additional, Joseph, Loren, additional, LeGallo, Robin D., additional, Lew, Madelyn, additional, Lockwood, Christina M., additional, Naeem, Rizwan, additional, Rizvi, Hasan, additional, Ortega, Julian Sanz, additional, Shane-Carson, Kate, additional, Sobel, Mark E., additional, Suarez, Eric, additional, Tafe, Laura J., additional, Wang, Jason, additional, and Wilcox, Rebecca L., additional

Published
2021
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48. Multicenter point prevalence evaluation of the utilization and safety of drug therapies for COVID-19 at the onset of the pandemic timeline in the United States

Author

Rhodes, Nathaniel J, primary, Dairem, Atheer, additional, Moore, William J, additional, Shah, Anooj, additional, Postelnick, Michael J, additional, Badowski, Melissa E, additional, Michienzi, Sarah M, additional, Borkowski, Jaime L, additional, Polisetty, Radhika S, additional, Fong, Karen, additional, Spivak, Emily S, additional, Beardsley, James R, additional, Hale, Cory M, additional, Pallotta, Andrea M, additional, Srinivas, Pavithra, additional, and Schulz, Lucas T, additional

Published
2021
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49. Antibiotic Resistance in Shiga Toxigenic Escherichia coli Isolates from Surface Waters and Sediments in a Mixed Use Urban Agricultural Landscape

Author

Ma, Yvonne, primary, Chen, Jessica, additional, Fong, Karen, additional, Nadya, Stephanie, additional, Allen, Kevin, additional, Laing, Chad, additional, Ziebell, Kim, additional, Topp, Ed, additional, Carroll, Laura M., additional, Wiedmann, Martin, additional, Delaquis, Pascal, additional, and Wang, Siyun, additional

Published
2021
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