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1. Chapter 3 Natural substrates and inhibitors of multidrug resistant pumps (MDRs) redefine the plant antimicrobials

Author

George P Tegos

Subjects
Multiple drug resistance, biology, business.industry, Drug discovery, biology.organism_classification, Antimicrobial, business, Bacteria, Biotechnology
Abstract

Publisher Summary This chapter describes the rationale for the characterization of natural substrates of multidrug resistant (MDR) pumps, reporting the identification of the first MDR substrates and inhibitors from plants against bacteria and yeasts. It discusses the methodology for the isolation of these compounds as well as the specificity of their activity. The chapter analyzes the current and future perspectives to natural drug discovery based on the classification of plant antimicrobials. The experimental data available demonstrate and reassure that plants produce MDR inhibitors against gram-positive bacteria and yeasts. An effective plant MDR inhibitor of gram-negative bacteria is still a missing part of the puzzle. Currently, there is only preliminary evidence for this, but the identification of such a compound is more than plausible. A comprehensive library of extracts from the National Cancer Institute (NCI), United States of America that consists of over 50,000 extracts from approximately 35,000 plants from all over the world is currently being screened. The collection represents most genera of vascular plants found in the tropics.

Published
2006
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2. Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: Results from the IMPACC study

Author

Al Ozonoff, Joanna Schaenman, Naresh Doni Jayavelu, Carly E. Milliren, Carolyn S. Calfee, Charles B. Cairns, Monica Kraft, Lindsey R. Baden, Albert C. Shaw, Florian Krammer, Harm van Bakel, Denise A. Esserman, Shanshan Liu, Ana Fernandez Sesma, Viviana Simon, David A. Hafler, Ruth R. Montgomery, Steven H. Kleinstein, Ofer Levy, Christian Bime, Elias K. Haddad, David J. Erle, Bali Pulendran, Kari C. Nadeau, Mark M. Davis, Catherine L. Hough, William B. Messer, Nelson I. Agudelo Higuita, Jordan P. Metcalf, Mark A. Atkinson, Scott C. Brakenridge, David Corry, Farrah Kheradmand, Lauren I.R. Ehrlich, Esther Melamed, Grace A. McComsey, Rafick Sekaly, Joann Diray-Arce, Bjoern Peters, Alison D. Augustine, Elaine F. Reed, Matthew C. Altman, Patrice M. Becker, Nadine Rouphael, Chris Bime, Mark M Davis, Kerry McEnaney, Brenda Barton, Claudia Lentucci, Mehmet Saluvan, Ana C. Chang, Annmarie Hoch, Marisa Albert, Tanzia Shaheen, Alvin T. Kho, Sanya Thomas, Jing Chen, Maimouna D. Murphy, Mitchell Cooney, Scott Presnell, Gabriela K. Fragiadakis, Ravi Patel, Leying Guan, Jeremy Gygi, Shrikant Pawar, Anderson Brito, Zain Khalil, Cole Maguire, Slim Fourati, James A. Overton, Randi Vita, Kerstin Westendorf, Ramin Salehi-Rad, Aleksandra Leligdowicz, Michael A. Matthay, Jonathan P. Singer, Kirsten N. Kangelaris, Carolyn M. Hendrickson, Matthew F. Krummel, Charles R. Langelier, Prescott G. Woodruff, Debra L. Powell, James N. Kim, Brent Simmons, I. Michael Goonewardene, Cecilia M. Smith, Mark Martens, Jarrod Mosier, Hiroki Kimura, Amy C. Sherman, Stephen R. Walsh, Nicolas C. Issa, Charles Dela Cruz, Shelli Farhadian, Akiko Iwasaki, Albert I. Ko, Sharon Chinthrajah, Neera Ahuja, Angela J. Rogers, Maja Artandi, Sarah A.R. Siegel, Zhengchun Lu, Douglas A. Drevets, Brent R. Brown, Matthew L. Anderson, Faheem W. Guirgis, Rama V. Thyagarajan, Justin F. Rousseau, Dennis Wylie, Johanna Busch, Saurin Gandhi, Todd A. Triplett, George Yendewa, Olivia Giddings, Evan J. Anderson, Aneesh K. Mehta, Jonathan E. Sevransky, Bernard Khor, Adeeb Rahman, Daniel Stadlbauer, Jayeeta Dutta, Hui Xie, Seunghee Kim-Schulze, Ana Silvia Gonzalez-Reiche, Adriana van de Guchte, Keith Farrugia, Zenab Khan, Holden T. Maecker, David Elashoff, Jenny Brook, Estefania Ramires-Sanchez, Megan Llamas, Adreanne Rivera, Claudia Perdomo, Dawn C. Ward, Clara E. Magyar, Jennifer A. Fulcher, Yumiko Abe-Jones, Saurabh Asthana, Alexander Beagle, Sharvari Bhide, Sidney A. Carrillo, Suzanna Chak, Rajani Ghale, Ana Gonzalez, Alejandra Jauregui, Norman Jones, Tasha Lea, Deanna Lee, Raphael Lota, Jeff Milush, Viet Nguyen, Logan Pierce, Priya A. Prasad, Arjun Rao, Bushra Samad, Cole Shaw, Austin Sigman, Pratik Sinha, Alyssa Ward, Andrew Willmore, Jenny Zhan, Sadeed Rashid, Nicklaus Rodriguez, Kevin Tang, Luz Torres Altamirano, Legna Betancourt, Cindy Curiel, Nicole Sutter, Maria Tercero Paz, Gayelan Tietje-Ulrich, Carolyn Leroux, Jennifer Connors, Mariana Bernui, Michel A. Kutzler, Carolyn Edwards, Edward Lee, Edward Lin, Brett Croen, Nicholas C. Semenza, Brandon Rogowski, Nataliya Melnyk, Kyra Woloszczuk, Gina Cusimano, Mathew R. Bell, Sara Furukawa, Renee McLin, Pamela Marrero, Julie Sheidy, George P. Tegos, Crystal Nagle, Nathan Mege, Kristen Ulring, Vicki Seyfert-Margolis, Michelle Conway, Dave Francisco, Allyson Molzahn, Heidi Erickson, Connie Cathleen Wilson, Ron Schunk, Bianca Sierra, Trina Hughes, Kinga Smolen, Michael Desjardins, Simon van Haren, Xhoi Mitre, Jessica Cauley, Xiaofang Li, Alexandra Tong, Bethany Evans, Christina Montesano, Jose Humberto Licona, Jonathan Krauss, Jun Bai Park Chang, Natalie Izaguirre, Omkar Chaudhary, Andreas Coppi, John Fournier, Subhasis Mohanty, M. Catherine Muenker, Allison Nelson, Khadir Raddassi, Michael Rainone, William E. Ruff, Syim Salahuddin, Wade L. Schulz, Pavithra Vijayakumar, Haowei Wang, Elsio Wunder Jr., H. Patrick Young, Yujiao Zhao, Miti Saksena, Deena Altman, Erna Kojic, Komal Srivastava, Lily Q. Eaker, Maria C. Bermúdez-González, Katherine F. Beach, Levy A. Sominsky, Arman R. Azad, Juan Manuel Carreño, Gagandeep Singh, Ariel Raskin, Johnstone Tcheou, Dominika Bielak, Hisaaki Kawabata, Lubbertus CF Mulder, Giulio Kleiner, Alexandra S. Lee, Evan Do Do, Andrea Fernandes, Monali Manohar, Thomas Hagan, Catherine A. Blish, Hena Naz Din, Jonasel Roque, Samuel Yang, Amanda Brunton, Peter E. Sullivan, Matthew Strnad, Zoe L. Lyski, Felicity J. Coulter, J. Leland Booth, Lauren A. Sinko, Lyle L. Moldawer, Brittany Borresen, Brittney Roth-Manning, Li-Zhen Song, Ebony Nelson, Megan Lewis-Smith, Jacob Smith, Pablo Guaman Tipan, Nadia Siles, Sam Bazzi, Janelle Geltman, Kerin Hurley, Gio Gabriele, Scott Sieg, Tatyana Vaysman, Laurel Bristow, Laila Hussaini, Kieffer Hellmeister, Hady Samaha, Andrew Cheng, Christine Spainhour, Erin M. Scherer, Brandi Johnson, Amer Bechnak, Caroline R. Ciric, Lauren Hewitt, Erin Carter, Nina Mcnair, Bernadine Panganiban, Christopher Huerta, Jacob Usher, and Susan Pereira Ribeiro

Subjects
COVID-19, SARS-CoV-2, Viral load, Antibody, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: Better understanding of the association between characteristics of patients hospitalized with coronavirus disease 2019 (COVID-19) and outcome is needed to further improve upon patient management. Methods: Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective, observational study of 1164 patients from 20 hospitals across the United States. Disease severity was assessed using a 7-point ordinal scale based on degree of respiratory illness. Patients were prospectively surveyed for 1 year after discharge for post-acute sequalae of COVID-19 (PASC) through quarterly surveys. Demographics, comorbidities, radiographic findings, clinical laboratory values, SARS-CoV-2 PCR and serology were captured over a 28-day period. Multivariable logistic regression was performed. Findings: The median age was 59 years (interquartile range [IQR] 20); 711 (61%) were men; overall mortality was 14%, and 228 (20%) required invasive mechanical ventilation. Unsupervised clustering of ordinal score over time revealed distinct disease course trajectories. Risk factors associated with prolonged hospitalization or death by day 28 included age ≥ 65 years (odds ratio [OR], 2.01; 95% CI 1.28–3.17), Hispanic ethnicity (OR, 1.71; 95% CI 1.13–2.57), elevated baseline creatinine (OR 2.80; 95% CI 1.63– 4.80) or troponin (OR 1.89; 95% 1.03–3.47), baseline lymphopenia (OR 2.19; 95% CI 1.61–2.97), presence of infiltrate by chest imaging (OR 3.16; 95% CI 1.96–5.10), and high SARS-CoV2 viral load (OR 1.53; 95% CI 1.17–2.00). Fatal cases had the lowest ratio of SARS-CoV-2 antibody to viral load levels compared to other trajectories over time (p=0.001). 589 survivors (51%) completed at least one survey at follow-up with 305 (52%) having at least one symptom consistent with PASC, most commonly dyspnea (56% among symptomatic patients). Female sex was the only associated risk factor for PASC. Interpretation: Integration of PCR cycle threshold, and antibody values with demographics, comorbidities, and laboratory/radiographic findings identified risk factors for 28-day outcome severity, though only female sex was associated with PASC. Longitudinal clinical phenotyping offers important insights, and provides a framework for immunophenotyping for acute and long COVID-19. Funding: NIH.

Published
2022
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3. Early network properties of the COVID-19 pandemic – The Chinese scenario

Author

Ariel L. Rivas, José L. Febles, Stephen D. Smith, Almira L. Hoogesteijn, George P. Tegos, Folorunso O. Fasina, and James B. Hittner

Subjects
Network-theory, Smallworld, COVID-19, Interdisciplinary, Geo-referenced, Infectious and parasitic diseases, RC109-216
Abstract

Objectives: To control epidemics, sites more affected by mortality should be identified. Methods: Defining epidemic nodes as areas that included both most fatalities per time unit and connections, such as highways, geo-temporal Chinese data on the COVID-19 epidemic were investigated with linear, logarithmic, power, growth, exponential, and logistic regression models. A z-test compared the slopes observed. Results: Twenty provinces suspected to act as epidemic nodes were empirically investigated. Five provinces displayed synchronicity, long-distance connections, directionality and assortativity – network properties that helped discriminate epidemic nodes. The rank I node included most fatalities and was activated first. Fewer deaths were reported, later, by rank II and III nodes, while the data from rank I–III nodes exhibited slopes, the data from the remaining provinces did not. The power curve was the best fitting model for all slopes. Because all pairs (rank I vs. rank II, rank I vs. rank III, and rank II vs. rank III) of epidemic nodes differed statistically, rank I–III epidemic nodes were geo-temporally and statistically distinguishable. Conclusions: The geo-temporal progression of epidemics seems to be highly structured. Epidemic network properties can distinguish regions that differ in mortality. This real-time geo-referenced analysis can inform both decision-makers and clinicians.

Published
2020
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