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A Millifluidic Perfusion Cassette For Studying The Pathogenesis Of Enteric Infections Using Ex-Vivo Organoids, Reid L Wilson, Sarah A Hewes, Anubama Rajan, Shih-Ching Lin, Carolyn Bomidi, Takanori Iida, Mary K Estes, Anthony W Maresso, K Jane Grande-Allen Apr 2021

A Millifluidic Perfusion Cassette For Studying The Pathogenesis Of Enteric Infections Using Ex-Vivo Organoids, Reid L Wilson, Sarah A Hewes, Anubama Rajan, Shih-Ching Lin, Carolyn Bomidi, Takanori Iida, Mary K Estes, Anthony W Maresso, K Jane Grande-Allen

Faculty, Staff and Students Publications

To generate physiologically-relevant experimental models, the study of enteric diarrheal diseases is turning increasingly to advanced in vitro models that combine ex vivo, stem cell-derived "organoid" cell lines with bioengineered culture environments that expose them to mechanical stimuli, such as fluid flow. However, such approaches require considerable technical expertise with both microfabrication and organoid culture, and are, therefore, inaccessible to many researchers. For this reason, we have developed a perfusion system that is simple to fabricate, operate, and maintain. Its dimensions approximate the volume and cell culture area of traditional 96-well plates and allow the incorporation of fastidious primary, stem …


An Inactivated Bacterium (Paraprobiotic) Expressing Bacillus Thuringiensis Cry5b As A Therapeutic For Ascaris And Parascaris Spp. Infections In Large Animals, Joseph F. Urban, Martin K. Nielsen, David Gazzola, Yue Xie, Ethiopia Beshah, Yan Hu, Hanchen Li, Florentina Rus, Kelly Flanagan, Austin Draper, Sridhar Vakalapudi, Robert W. Li, Gary R. Ostroff, Raffi V. Aroian Mar 2021

An Inactivated Bacterium (Paraprobiotic) Expressing Bacillus Thuringiensis Cry5b As A Therapeutic For Ascaris And Parascaris Spp. Infections In Large Animals, Joseph F. Urban, Martin K. Nielsen, David Gazzola, Yue Xie, Ethiopia Beshah, Yan Hu, Hanchen Li, Florentina Rus, Kelly Flanagan, Austin Draper, Sridhar Vakalapudi, Robert W. Li, Gary R. Ostroff, Raffi V. Aroian

Maxwell H. Gluck Equine Research Center Faculty Publications

Ascaris and Parascaris are important parasites in the family Ascarididae, large, ubiquitous intestinal-dwelling nematodes infecting all classes of vertebrates. Parasitic nematode drug resistance in veterinary medicine and drug recalcitrance in human medicine are increasing worldwide, with few if any new therapeutic classes on the horizon. Some of these parasites are zoonotic, e.g., Ascaris is passed from humans to pigs and vice versa. The development of new therapies against this family of parasites would have major implications for both human and livestock health. Here we tested the therapeutic ability of a paraprobiotic or dead probiotic that expresses the Bacillus …


Inactivated Rabies Virus Vectored Sars-Cov-2 Vaccine Prevents Disease In A Syrian Hamster Model., Drishya Kurup, Delphine C Malherbe, Christoph Wirblich, Rachael Lambert, Adam J Ronk, Leila Zabihi Diba, Alexander Bukreyev, Matthias J. Schnell Mar 2021

Inactivated Rabies Virus Vectored Sars-Cov-2 Vaccine Prevents Disease In A Syrian Hamster Model., Drishya Kurup, Delphine C Malherbe, Christoph Wirblich, Rachael Lambert, Adam J Ronk, Leila Zabihi Diba, Alexander Bukreyev, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent coronavirus that has caused a worldwide pandemic. Although human disease is often asymptomatic, some develop severe illnesses such as pneumonia, respiratory failure, and death. There is an urgent need for a vaccine to prevent its rapid spread as asymptomatic infections accounting for up to 40% of transmission events. Here we further evaluated an inactivated rabies vectored SARS-CoV-2 S1 vaccine CORAVAX in a Syrian hamster model. CORAVAX adjuvanted with MPLA-AddaVax, a TRL4 agonist, induced high levels of neutralizing antibodies and generated a strong Th1-biased immune response. Vaccinated hamsters were protected from …


Characteristics And Comparative Clinical Outcomes Of Prisoner Versus Non-Prisoner Populations Hospitalized With Covid-19, Ahmed M. Altibi, Bhargava Pallavi, Hassan Liaqat, Alexander A. Slota, Radhika Sheth, Lama N. Al Jebbawi, Matt E. George, Allison Leduc, Enas Abdallah, Luke R. Russell, Saniya Jain, Nariné Shirvanian, Ahmad Masri, Vivek Kak Mar 2021

Characteristics And Comparative Clinical Outcomes Of Prisoner Versus Non-Prisoner Populations Hospitalized With Covid-19, Ahmed M. Altibi, Bhargava Pallavi, Hassan Liaqat, Alexander A. Slota, Radhika Sheth, Lama N. Al Jebbawi, Matt E. George, Allison Leduc, Enas Abdallah, Luke R. Russell, Saniya Jain, Nariné Shirvanian, Ahmad Masri, Vivek Kak

Internal Medicine Articles

Prisons in the United States have become a hotbed for spreading COVID-19 among incarcerated individuals. COVID-19 cases among prisoners are on the rise, with more than 143,000 confirmed cases to date. However, there is paucity of data addressing clinical outcomes and mortality in prisoners hospitalized with COVID-19. An observational study of all patients hospitalized with COVID-19 between March 10 and May 10, 2020 at two Henry Ford Health System hospitals in Michigan. Clinical outcomes were compared amongst hospitalized prisoners and non-prisoner patients. The primary outcomes were intubation rates, in-hospital mortality, and 30-day mortality. Multivariable logistic regression and Cox-regression models were …


Passive Immunity Trial For Our Nation (Passiton): Study Protocol For A Randomized Placebo-Control Clinical Trial Evaluating Covid-19 Convalescent Plasma In Hospitalized Adults, Wesley H. Self, Thomas G. Stewart, Allison P. Wheeler, Wissam El Atrouni, Amanda J. Bistran-Hall, Jonathan D. Casey, Vince D. Cataldo, James D. Chappell, Claudia S. Cohn, Jessica B. Collins, Mark R. Denison, Marjolein De Wit, Sheri L. Dixon, Abhijit Duggal, Terri L. Edwards, Magali J. Fontaine, Adit A. Ginde, Michelle S. Harkins, Thelma Harrington, Estelle S. Harris, Daanish Hoda, Tina S. Ipe, Stuti J. Jaiswal, Nicholas J. Johnson, Alan E. Jones, Maryrose Laguio-Vila, Christopher J. Lindsell, Jason Mallada, Manoj J. Mammen, Ryan A. Metcalf, Elizabeth A. Middleton, Simon Mucha, Hollis R. O'Neal, Sonal R. Pannu, Jill M. Pulley, Xian Qiao, Jay S. Raval, Jillian P. Rhoads, Harry Schrager, Carl Shanholtz, Nathan I. Shapiro, Stephen J. Schrantz, Isaac Thomsen, Krista K. Vermillion, Gordon R. Bernard, Todd W. Rice Mar 2021

Passive Immunity Trial For Our Nation (Passiton): Study Protocol For A Randomized Placebo-Control Clinical Trial Evaluating Covid-19 Convalescent Plasma In Hospitalized Adults, Wesley H. Self, Thomas G. Stewart, Allison P. Wheeler, Wissam El Atrouni, Amanda J. Bistran-Hall, Jonathan D. Casey, Vince D. Cataldo, James D. Chappell, Claudia S. Cohn, Jessica B. Collins, Mark R. Denison, Marjolein De Wit, Sheri L. Dixon, Abhijit Duggal, Terri L. Edwards, Magali J. Fontaine, Adit A. Ginde, Michelle S. Harkins, Thelma Harrington, Estelle S. Harris, Daanish Hoda, Tina S. Ipe, Stuti J. Jaiswal, Nicholas J. Johnson, Alan E. Jones, Maryrose Laguio-Vila, Christopher J. Lindsell, Jason Mallada, Manoj J. Mammen, Ryan A. Metcalf, Elizabeth A. Middleton, Simon Mucha, Hollis R. O'Neal, Sonal R. Pannu, Jill M. Pulley, Xian Qiao, Jay S. Raval, Jillian P. Rhoads, Harry Schrager, Carl Shanholtz, Nathan I. Shapiro, Stephen J. Schrantz, Isaac Thomsen, Krista K. Vermillion, Gordon R. Bernard, Todd W. Rice

Pathology Research and Scholarship

BACKGROUND: Convalescent plasma is being used widely as a treatment for coronavirus disease 2019 (COVID-19). However, the clinical efficacy of COVID-19 convalescent plasma is unclear.

METHODS: The Passive Immunity Trial for Our Nation (PassITON) is a multicenter, placebo-controlled, blinded, randomized clinical trial being conducted in the USA to provide high-quality evidence on the efficacy of COVID-19 convalescent plasma as a treatment for adults hospitalized with symptomatic disease. Adults hospitalized with COVID-19 with respiratory symptoms for less than 14 days are eligible. Enrolled patients are randomized in a 1:1 ratio to 1 unit (200-399 mL) of COVID-19 convalescent plasma that has …


Neurological Manifestations As The Predictors Of Severity And Mortality In Hospitalized Individuals With Covid-19: A Multicenter Prospective Clinical Study, Man Amanat, Nima Rezaei, Mehrdad Roozbeh, Maziar Shojaei, Abbas Tafakhori, Anahita Zoghi, Ilad Alavi Darazam, Mona Salehi, Ehsan Karimialavijeh, Behnam Safarpour Lima, Amir Garakani, Alex R. Vaccaro, Mahtab Ramezani Mar 2021

Neurological Manifestations As The Predictors Of Severity And Mortality In Hospitalized Individuals With Covid-19: A Multicenter Prospective Clinical Study, Man Amanat, Nima Rezaei, Mehrdad Roozbeh, Maziar Shojaei, Abbas Tafakhori, Anahita Zoghi, Ilad Alavi Darazam, Mona Salehi, Ehsan Karimialavijeh, Behnam Safarpour Lima, Amir Garakani, Alex R. Vaccaro, Mahtab Ramezani

Department of Orthopaedic Surgery Faculty Papers

BACKGROUNDS: The reports of neurological symptoms are increasing in cases with coronavirus disease 2019 (COVID-19). This multi-center prospective study was conducted to determine the incidence of neurological manifestations in hospitalized cases with COVID-19 and assess these symptoms as the predictors of severity and death.

METHODS: Hospitalized males and females with COVID-19 who aged over 18 years were included in the study. They were examined by two neurologists at the time of admission. All survived cases were followed for 8 weeks after discharge and 16 weeks if their symptoms had no improvements.

RESULTS: We included 873 participants. Of eligible cases, 122 …


Original Antigenic Sin: The Downside Of Immunological Memory And Implications For Covid-19, Eric L Brown, Heather T Essigmann Mar 2021

Original Antigenic Sin: The Downside Of Immunological Memory And Implications For Covid-19, Eric L Brown, Heather T Essigmann

Faculty, Staff and Student Publications

The concept of original antigenic sin (OAS) was put forth many years ago to explain how humoral memory responses generated against one set of antigens can affect the nature of antibody responses elicited to challenge infections or vaccinations containing a similar but not identical array of antigens. Here, we highlight the link between OAS and the germinal center reaction (GCR), a process unique to activated B cells undergoing somatic hypermutation and class switch recombination. It is the powerful response of activated memory B cells and the accompanying GCR that establish the foundations of OAS. We apply these concepts to the …


Ap-1 And Nf-Κb Synergize To Transcriptionally Activate Latent Hiv Upon T-Cell Receptor Activation., Joseph Hokello, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi Mar 2021

Ap-1 And Nf-Κb Synergize To Transcriptionally Activate Latent Hiv Upon T-Cell Receptor Activation., Joseph Hokello, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi

Center for Translational Medicine Faculty Papers

Latent HIV-1 proviruses are capable of reactivating productive lytic infection, but the precise molecular mechanisms underlying emergence from latency are poorly understood. In this study, we determined the contribution of the transcription factors NF-κB, NFAT, and AP-1 in the reactivation of latent HIV following T-cell receptor (TCR) activation using Jurkat T-cell clones harboring single latent HIV proviruses. Our findings demonstrate that during reactivation from latency, NF-κB enhances HIV transcription while NFAT inhibits it by competing with NF-κB for overlapping binding sites on the HIV long terminal repeat (LTR). We have also demonstrated for the first time the molecular contribution of …


Severe Acute Respiratory Syndrome Coronavirus 2-Induced Acute Aortic Occlusion: A Case Report, Artem Minalyan, Franklin L. Thelmo, Vincent Chan, Stephanie Tzarnas, Faizan Ahmed Mar 2021

Severe Acute Respiratory Syndrome Coronavirus 2-Induced Acute Aortic Occlusion: A Case Report, Artem Minalyan, Franklin L. Thelmo, Vincent Chan, Stephanie Tzarnas, Faizan Ahmed

Department of Medicine Faculty Papers

Background: Severe acute respiratory syndrome coronavirus 2 infection can lead to a constellation of viral and immune symptoms called coronavirus disease 2019. Emerging literature increasingly supports the premise that severe acute respiratory syndrome coronavirus 2 promotes a prothrombotic milieu. However, to date there have been no reports of acute aortic occlusion, itself a rare phenomenon. We report a case of fatal acute aortic occlusion in a patient with coronavirus disease 2019.

Case report: A 59-year-old Caucasian male with past medical history of peripheral vascular disease presented to the emergency department for evaluation of shortness of breath, fevers, and dry cough. …


New Mexico's Covid-19 Experience, Nicole R. Jackson, Karen Zeigler, Mary Torrez, Yohsuke Makino, Natalie L. Adolphi, Sarah Lathrop, Lauren Decker, Lauren Dvorscak, Lori Proe, Ian D. Paul, Ross Zumwalt, Heather Jarrell Mar 2021

New Mexico's Covid-19 Experience, Nicole R. Jackson, Karen Zeigler, Mary Torrez, Yohsuke Makino, Natalie L. Adolphi, Sarah Lathrop, Lauren Decker, Lauren Dvorscak, Lori Proe, Ian D. Paul, Ross Zumwalt, Heather Jarrell

Pathology Research and Scholarship

The 2019 novel coronavirus disease (COVID-19) has spread worldwide, infiltrating, infecting, and devastating communities in all locations of varying demographics. An overwhelming majority of published literature on the pathologic findings associated with COVID-19 is either from living clinical cohorts or from autopsy findings of those who died in a medical care setting, which can confound pure disease pathology. A relatively low initial infection rate paired with a high biosafety level enabled the New Mexico Office of the Medical Investigator to conduct full autopsy examinations on suspected COVID-19-related deaths. Full autopsy examination on the first 20 severe acute respiratory syndrome coronavirus …


Surveillance Systems For Monitoring Cervical Cancer Elimination Efforts: Focus On Hpv Infection, Cervical Dysplasia, Cervical Screening And Treatment., Julia M L Brotherton, Cosette Wheeler, Gary M. Clifford, Miriam Elfström, Marion Saville, John Kaldor, Dorothy A. Machalek Mar 2021

Surveillance Systems For Monitoring Cervical Cancer Elimination Efforts: Focus On Hpv Infection, Cervical Dysplasia, Cervical Screening And Treatment., Julia M L Brotherton, Cosette Wheeler, Gary M. Clifford, Miriam Elfström, Marion Saville, John Kaldor, Dorothy A. Machalek

Pathology Research and Scholarship

In order to achieve the global elimination of cervical cancer as a public health problem, close surveillance of progress in public health and clinical activities and outcomes across the three pillars of vaccination, screening and treatment will be required. Surveillance should ideally occur within an integrated system that is planned, funded, and regularly evaluated to ensure it is providing timely, accurate and relevant feedback for action. In this paper, we conceptualise the main public health surveillance objectives as process and outcome measures in each of the three pillars. Process measures include coverage/participation measures for vaccination, screening and treatment alongside the …


Point-Of-Care Lung Ultrasound For Covid-19: Findings And Prognostic Implications From 105 Consecutive Patients, Kosuke Yasukawa, Taro Minami, David R Boulware, Ayako Shimada, Ernest A Fischer Mar 2021

Point-Of-Care Lung Ultrasound For Covid-19: Findings And Prognostic Implications From 105 Consecutive Patients, Kosuke Yasukawa, Taro Minami, David R Boulware, Ayako Shimada, Ernest A Fischer

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Background: The prognostic value of point-of-care lung ultrasound has not been evaluated in a large cohort of patients with COVID-19 admitted to general medicine ward in the United States. The aim of this study was to describe lung ultrasound findings and their prognostic value in patients with COVID-19 admitted to internal medicine ward.

Method: This prospective observational study consecutively enrolled 105 hospitalized participants with COVID-19 at 2 tertiary care centers. Ultrasound was performed in 12 lung zones within 24 hours of admission. Findings were assessed relative to 4 outcomes: intensive care unit (ICU) need, need for intensive respiratory support, length …


The Structure And Diversity Of Strain-Level Variation In Vaginal Bacteria, Brett A Tortelli, Amanda L Lewis, Justin C Fay Mar 2021

The Structure And Diversity Of Strain-Level Variation In Vaginal Bacteria, Brett A Tortelli, Amanda L Lewis, Justin C Fay

2020-Current year OA Pubs

The vaginal microbiome plays an important role in human health and species of vaginal bacteria have been associated with reproductive disease. Strain-level variation is also thought to be important, but the diversity, structure and evolutionary history of vaginal strains is not as well characterized. We developed and validated an approach to measure strain variation from metagenomic data based on SNPs within the core genomes for six species of vaginal bacteria:


Covid-19 In Solid Organ Transplantation: Disease Severity And Clinical Update., Akanksha Arya, Michael Li, Nana Aburjania, Pooja Singh, Tricia. Royer, Sean Moss, Katherine A. Belden Feb 2021

Covid-19 In Solid Organ Transplantation: Disease Severity And Clinical Update., Akanksha Arya, Michael Li, Nana Aburjania, Pooja Singh, Tricia. Royer, Sean Moss, Katherine A. Belden

Department of Medicine Faculty Papers

BACKGROUND: Solid organ transplant (SOT) recipients are a complex, immunocompromised population in whom greater coronavirus disease 2019 (COVID-19) mortality has been reported compared with the general population.

METHODS: We examined a retrospective cohort of 58 SOT recipients with first-wave COVID-19, comparing patients with severe and nonsevere illness. Additionally, SOT recipients are compared with general patients with first-wave COVID-19.

RESULTS: Organs transplanted included 38 kidneys, 8 livers, 5 hearts, and 3 pancreases. Average SOT recipient age was 57.4 years; 62% were male; 46.6% were African American 36.2% were white. Comorbidities included hypertension (86%), chronic kidney disease (86%), diabetes mellitus (50%), coronary …


Drug Susceptibility Patterns Of Mycobacterium Tuberculosis From Adults With Multidrug-Resistant Tuberculosis And Implications For A Household Contact Preventive Therapy Trial, Anne-Marie Demers, Soyeon Kim, Sara Mccallum, Kathleen Eisenach, Michael Hughes, Linda Naini, Alberto Mendoza-Ticona, Neeta Pradhan, Kim Narunsky, Selvamuthu Poongulali, Sharlaa Badal-Faesen, Caryn Upton, Elizabeth Smith, N Sarita Shah, Gavin Churchyard, Amita Gupta, Anneke Hesseling, Susan Swindells, Actg A5300/Impaact I2003 Phoenix Feasibility Study Team Feb 2021

Drug Susceptibility Patterns Of Mycobacterium Tuberculosis From Adults With Multidrug-Resistant Tuberculosis And Implications For A Household Contact Preventive Therapy Trial, Anne-Marie Demers, Soyeon Kim, Sara Mccallum, Kathleen Eisenach, Michael Hughes, Linda Naini, Alberto Mendoza-Ticona, Neeta Pradhan, Kim Narunsky, Selvamuthu Poongulali, Sharlaa Badal-Faesen, Caryn Upton, Elizabeth Smith, N Sarita Shah, Gavin Churchyard, Amita Gupta, Anneke Hesseling, Susan Swindells, Actg A5300/Impaact I2003 Phoenix Feasibility Study Team

Journal Articles: Internal Medicine

BACKGROUND: Drug susceptibility testing (DST) patterns of Mycobacterium tuberculosis (MTB) from patients with rifampicin-resistant tuberculosis (RR-TB) or multidrug-resistant TB (MDR-TB; or resistant to rifampicin and isoniazid (INH)), are important to guide preventive therapy for their household contacts (HHCs).

METHODS: As part of a feasibility study done in preparation for an MDR-TB preventive therapy trial in HHCs, smear, Xpert MTB/RIF, Hain MTBDRplus, culture and DST results of index MDR-TB patients were obtained from routine TB programs. A sputum sample was collected at study entry and evaluated by the same tests. Not all tests were performed on all specimens due to variations …


Psychological Experience And Coping Strategies Of Patients In The Northeast Us Delaying Care For Infertility During The Covid-19 Pandemic., David B Seifer, William D Petok, Alisha Agrawal, Tanya L Glenn, Arielle H Bayer, Barry R Witt, Blair D Burgin, Harry J Lieman Feb 2021

Psychological Experience And Coping Strategies Of Patients In The Northeast Us Delaying Care For Infertility During The Covid-19 Pandemic., David B Seifer, William D Petok, Alisha Agrawal, Tanya L Glenn, Arielle H Bayer, Barry R Witt, Blair D Burgin, Harry J Lieman

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: On March 17, 2020 an expert ASRM task force recommended the temporary suspension of new, non-urgent fertility treatments during an ongoing world-wide pandemic of Covid-19. We surveyed at the time of resumption of fertility care the psychological experience and coping strategies of patients pausing their care due to Covid-19 and examined which factors were associated and predictive of resilience, anxiety, stress and hopefulness.

METHODS: Cross sectional cohort patient survey using an anonymous, self-reported, single time, web-based, HIPPA compliant platform (REDCap). Survey sampled two Northeast academic fertility practices (Yale Medicine Fertility Center in CT and Montefiore's Institute for Reproductive Medicine …


Circulating Mitochondrial Dna Is An Early Indicator Of Severe Illness And Mortality From Covid-19, Davide Scozzi, Marlene Cano, Lina Ma, Dequan Zhou, Ji Hong Zhu, Jane A. O'Halloran, Charles Goss, Adriana M. Rauseo, Zhiyi Liu, Sanjaya K. Sahu, Mohsen Ibrahim, Ramsey Hachem, Daniel Kreisel, Philip A. Mudd, Hrishikesh S. Kulkarni, Andrew E. Gelman, Et Al Feb 2021

Circulating Mitochondrial Dna Is An Early Indicator Of Severe Illness And Mortality From Covid-19, Davide Scozzi, Marlene Cano, Lina Ma, Dequan Zhou, Ji Hong Zhu, Jane A. O'Halloran, Charles Goss, Adriana M. Rauseo, Zhiyi Liu, Sanjaya K. Sahu, Mohsen Ibrahim, Ramsey Hachem, Daniel Kreisel, Philip A. Mudd, Hrishikesh S. Kulkarni, Andrew E. Gelman, Et Al

Open Access Publications

BackgroundMitochondrial DNA (MT-DNA) are intrinsically inflammatory nucleic acids released by damaged solid organs. Whether circulating cell-free MT-DNA quantitation could be used to predict the risk of poor COVID-19 outcomes remains undetermined.MethodsWe measured circulating MT-DNA levels in prospectively collected, cell-free plasma samples from 97 subjects with COVID-19 at hospital presentation. Our primary outcome was mortality. Intensive care unit (ICU) admission, intubation, vasopressor, and renal replacement therapy requirements were secondary outcomes. Multivariate regression analysis determined whether MT-DNA levels were independent of other reported COVID-19 risk factors. Receiver operating characteristic and area under the curve assessments were used to compare MT-DNA levels with …


Benefits Derived From Full Laboratory Automation In Microbiology: A Tale Of Four Laboratories, Karissa Culbreath, Heather Piwonka, John Korver, Mir Noorbakhsh Feb 2021

Benefits Derived From Full Laboratory Automation In Microbiology: A Tale Of Four Laboratories, Karissa Culbreath, Heather Piwonka, John Korver, Mir Noorbakhsh

Pathology Research and Scholarship

Automation in clinical microbiology is starting to become more commonplace and reportedly offers several advantages over the manual laboratory. Most studies have reported on the rapid turnaround times for culture results, including times for identification of pathogens and their respective antimicrobial susceptibilities, but few have studied the benefits from a laboratory efficiency point of view. This is the first large, multicenter study in North America to report on the benefits derived from automation measured in full-time equivalents (FTE), FTE reallocation, productivity, cost per specimen, and cost avoidance. Pre- and post-full automation audits were done at 4 laboratories that have vastly …


Pharmacokinetic And Pharmacodynamic Profiling Of Minocycline For Injection Following A Single Infusion In Critically Ill Adults In A Phase Iv Open-Label Multicenter Study (Acumin), Thomas P Lodise, Yasir Hamad, Et Al Feb 2021

Pharmacokinetic And Pharmacodynamic Profiling Of Minocycline For Injection Following A Single Infusion In Critically Ill Adults In A Phase Iv Open-Label Multicenter Study (Acumin), Thomas P Lodise, Yasir Hamad, Et Al

Open Access Publications

Intravenous (i.v.) minocycline is increasingly used to treat infections caused by multidrug-resistant (MDR)


Neoadjuvant Anti-Ox40 (Medi6469) Therapy In Patients With Head And Neck Squamous Cell Carcinoma Activates And Expands Antigen-Specific Tumor-Infiltrating T Cells., Rebekka Duhen, Carmen Ballesteros-Merino, Alexandra K Frye, Eric Tran, Venkatesh Rajamanickam, Shu-Ching Chang, Yoshinobu Koguchi, Carlo Bifulco, Brady Bernard, Rom Leidner, Brendan Curti, Bernard A Fox, Walter Urba, Richard Bryan Bell, Andrew D Weinberg Feb 2021

Neoadjuvant Anti-Ox40 (Medi6469) Therapy In Patients With Head And Neck Squamous Cell Carcinoma Activates And Expands Antigen-Specific Tumor-Infiltrating T Cells., Rebekka Duhen, Carmen Ballesteros-Merino, Alexandra K Frye, Eric Tran, Venkatesh Rajamanickam, Shu-Ching Chang, Yoshinobu Koguchi, Carlo Bifulco, Brady Bernard, Rom Leidner, Brendan Curti, Bernard A Fox, Walter Urba, Richard Bryan Bell, Andrew D Weinberg

Articles, Abstracts, and Reports

Despite the success of checkpoint blockade in some cancer patients, there is an unmet need to improve outcomes. Targeting alternative pathways, such as costimulatory molecules (e.g. OX40, GITR, and 4-1BB), can enhance T cell immunity in tumor-bearing hosts. Here we describe the results from a phase Ib clinical trial (NCT02274155) in which 17 patients with locally advanced head and neck squamous cell carcinoma (HNSCC) received a murine anti-human OX40 agonist antibody (MEDI6469) prior to definitive surgical resection. The primary endpoint was to determine safety and feasibility of the anti-OX40 neoadjuvant treatment. The secondary objective was to assess the effect of …


Efficacy And Safety Of The Mrna-1273 Sars-Cov-2 Vaccine, Lindsey R Baden, Hana M El Sahly, Brandon Essink, Karen Kotloff, Sharon Frey, Rick Novak, David Diemert, Stephen A Spector, Nadine Rouphael, C Buddy Creech, John Mcgettigan, Shishir Khetan, Nathan Segall, Joel Solis, Adam Brosz, Carlos Fierro, Howard Schwartz, Kathleen Neuzil, Larry Corey, Peter Gilbert, Holly Janes, Dean Follmann, Mary Marovich, John Mascola, Laura Polakowski, Julie Ledgerwood, Barney S Graham, Hamilton Bennett, Rolando Pajon, Conor Knightly, Brett Leav, Weiping Deng, Honghong Zhou, Shu Han, Melanie Ivarsson, Jacqueline Miller, Tal Zaks, Cove Study Group Feb 2021

Efficacy And Safety Of The Mrna-1273 Sars-Cov-2 Vaccine, Lindsey R Baden, Hana M El Sahly, Brandon Essink, Karen Kotloff, Sharon Frey, Rick Novak, David Diemert, Stephen A Spector, Nadine Rouphael, C Buddy Creech, John Mcgettigan, Shishir Khetan, Nathan Segall, Joel Solis, Adam Brosz, Carlos Fierro, Howard Schwartz, Kathleen Neuzil, Larry Corey, Peter Gilbert, Holly Janes, Dean Follmann, Mary Marovich, John Mascola, Laura Polakowski, Julie Ledgerwood, Barney S Graham, Hamilton Bennett, Rolando Pajon, Conor Knightly, Brett Leav, Weiping Deng, Honghong Zhou, Shu Han, Melanie Ivarsson, Jacqueline Miller, Tal Zaks, Cove Study Group

Faculty, Staff and Students Publications

BACKGROUND: Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19.

METHODS: This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. …


Seroprevalence Of Sars-Cov-2 Antibodies In Children And Adults In St. Louis, Missouri, Usa, Brittany K Smith, Andrew B Janowski, Jonathan E Danis, Ian B Harvey, Haiyan Zhao, Ya-Nan Dai, Christopher W Farnsworth, Ann M Gronowski, Stephen Roper, Daved H Fremont, David Wang Feb 2021

Seroprevalence Of Sars-Cov-2 Antibodies In Children And Adults In St. Louis, Missouri, Usa, Brittany K Smith, Andrew B Janowski, Jonathan E Danis, Ian B Harvey, Haiyan Zhao, Ya-Nan Dai, Christopher W Farnsworth, Ann M Gronowski, Stephen Roper, Daved H Fremont, David Wang

Open Access Publications

Reported coronavirus disease 2019 (COVID-19) case counts likely underestimate the true prevalence because mild or asymptomatic cases often go untested. Here, we use a sero-survey to estimate the seroprevalence of IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the St. Louis, MO, metropolitan area in a symptom-independent manner. Five hundred three adult and 555 pediatric serum/plasma samples were collected from patients presenting to Barnes-Jewish Hospital or St. Louis Children's Hospital between 14 April 2020 and 12 May 2020. We developed protocols for in-house enzyme-linked immunosorbent assays (ELISAs) using spike and nucleoprotein and used the assays to estimate …


Pandemic Makes Chronic Disease Prevention A Priority., Karen S. Kmetik, Alexis Skoufalos, David B. Nash Feb 2021

Pandemic Makes Chronic Disease Prevention A Priority., Karen S. Kmetik, Alexis Skoufalos, David B. Nash

College of Population Health Faculty Papers

This article is the authors' final version prior to publication in Population Health Management, Volume 24, Issue 1, February 2021, Pages 1-2

Final publication is available from Mary Ann Liebert, Inc., publishers https://doi.org/10.1089/pop.2020.0126


Therapeutic Enhancement Of Radiation And Immunomodulation By Gold Nanoparticles In Triple Negative Breast Cancer, Brana Janic, Stephen L. Brown, Ryan Neff, Fangchao Liu, Guangzhao Mao, Yalei Chen, Latoya Jackson, Indrin J. Chetty, Benjamin Movsas, Ning Wen Feb 2021

Therapeutic Enhancement Of Radiation And Immunomodulation By Gold Nanoparticles In Triple Negative Breast Cancer, Brana Janic, Stephen L. Brown, Ryan Neff, Fangchao Liu, Guangzhao Mao, Yalei Chen, Latoya Jackson, Indrin J. Chetty, Benjamin Movsas, Ning Wen

Radiation Oncology Articles

Gold nanoparticles (AuNPs) have been shown to enhance cancer radiotherapy (RT) gain by localizing the absorption of radiation energy in the tumor while sparing surrounding normal tissue from radiation toxicity. Previously, we showed that AuNPs enhanced RT induced DNA damage and cytotoxicity in MCF7 breast cancer cells. Interestingly, we found that cancer cells exhibited a size-dependent AuNPs intracellular localization (4 nm preferentially in the cytoplasm and 14 nm in the nucleus). We extended those studies to an in vivo model and examined the AuNPs effects on RT cytotoxicity, survival and immunomodulation of tumor microenvironment (TME) in human triple negative breast …


Ccr5 Inhibition In Critical Covid-19 Patients Decreases Inflammatory Cytokines, Increases Cd8 T-Cells, And Decreases Sars-Cov2 Rna In Plasma By Day 14, Bruce K Patterson, Philip A Mudd, Et Al Feb 2021

Ccr5 Inhibition In Critical Covid-19 Patients Decreases Inflammatory Cytokines, Increases Cd8 T-Cells, And Decreases Sars-Cov2 Rna In Plasma By Day 14, Bruce K Patterson, Philip A Mudd, Et Al

Open Access Publications

OBJECTIVE: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now a global pandemic. Emerging results indicate a dysregulated immune response. Given the role of CCR5 in immune cell migration and inflammation, we investigated the impact of CCR5 blockade via the CCR5-specific antibody leronlimab on clinical, immunological, and virological parameters in severe COVID-19 patients.

METHODS: In March 2020, 10 terminally ill, critical COVID-19 patients received two doses of leronlimab via individual emergency use indication. We analyzed changes in clinical presentation, immune cell populations, inflammation, as well as SARS-CoV-2 plasma viremia before and 14 days after treatment.

RESULTS: Over the …


A Timely Call To Arms: Covid-19, The Circadian Clock, And Critical Care, Jeffrey Haspel, Minjee Kim, Phyllis Zee, Tanja Schwarzmeier, Sara Montagnese, Satchidananda Panda, Adriana Albani, Martha Merrow Feb 2021

A Timely Call To Arms: Covid-19, The Circadian Clock, And Critical Care, Jeffrey Haspel, Minjee Kim, Phyllis Zee, Tanja Schwarzmeier, Sara Montagnese, Satchidananda Panda, Adriana Albani, Martha Merrow

2020-Current year OA Pubs

We currently find ourselves in the midst of a global coronavirus disease 2019 (COVID-19) pandemic, caused by the highly infectious novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we discuss aspects of SARS-CoV-2 biology and pathology and how these might interact with the circadian clock of the host. We further focus on the severe manifestation of the illness, leading to hospitalization in an intensive care unit. The most common severe complications of COVID-19 relate to clock-regulated human physiology. We speculate on how the pandemic might be used to gain insights on the circadian clock but, more importantly, on …


Disparities In Sars-Cov-2 Positivity Rates: Associations With Race And Ethnicity, Harvey W Kaufman, Justin K Niles, David B. Nash Feb 2021

Disparities In Sars-Cov-2 Positivity Rates: Associations With Race And Ethnicity, Harvey W Kaufman, Justin K Niles, David B. Nash

College of Population Health Faculty Papers

Numerous reports indicate that African Americans and Latinos are being affected disproportionately by coronavirus disease 2019 (COVID-19). Positivity rates have not been analyzed on scale because only 4 states report race/ethnicity as part of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. Previous studies also have had little ability to control for many known risk factors to better identify the effects of COVID-19 on racial and ethnic communities. Using test results from a large national reference laboratory database that included patients from all 50 states and the District of Columbia, this study compared positivity rates for SARS-CoV-2 nucleic acid amplification …


The Quest For Conquering Covid-19: Updates From The Laboratory, David B. Nash Feb 2021

The Quest For Conquering Covid-19: Updates From The Laboratory, David B. Nash

College of Population Health Faculty Papers

No abstract provided.


Characterization And Localization Of Antigens For Serodiagnosis Of Human Paragonimiasis, Kurt C Curtis, Kerstin Fischer, Young-Jun Choi, Makedonka Mitreva, Gary J Weil, Peter U Fischer Feb 2021

Characterization And Localization Of Antigens For Serodiagnosis Of Human Paragonimiasis, Kurt C Curtis, Kerstin Fischer, Young-Jun Choi, Makedonka Mitreva, Gary J Weil, Peter U Fischer

2020-Current year OA Pubs

Paragonimiasis is a foodborne trematode infection that affects 23 million people, mainly in Asia. Lung fluke infections lead frequently to chronic cough with fever and hemoptysis, and are often confused with lung cancer or tuberculosis. Paragonimiasis can be efficiently treated with praziquantel, but diagnosis is often delayed, and patients are frequently treated for other conditions. To improve diagnosis, we selected five Paragonimus kellicotti proteins based on transcriptional abundance, recognition by patient sera, and conservation among trematodes and expressed them as His-fusion proteins in Escherichia coli. Sequences for these proteins have 76-99% identity with amino acid sequences for orthologs in the …


Prevalence Of Functional Limitation In Covid-19 Recovered Patients Using The Post Covid-19 Functional Status Scale, Pankaj Pant, Aishana Joshi, Babin Basnet, Bibek Man Shrestha, Navindra Raj Bista, Niraj Bam, Santa Kumar Das Jan 2021

Prevalence Of Functional Limitation In Covid-19 Recovered Patients Using The Post Covid-19 Functional Status Scale, Pankaj Pant, Aishana Joshi, Babin Basnet, Bibek Man Shrestha, Navindra Raj Bista, Niraj Bam, Santa Kumar Das

Faculty, Staff and Student Publications

INTRODUCTION: COVID-19 is an emerging global health pandemic causing tremendous morbidity and mortality worldwide. Chronic symptoms progressing to poor functional status have been reported in a substantial proportion of COVID-19 patients worldwide. This study aimed to determine the prevalence of functional limitation in COVID-19 recovered patients using the post-COVID-19 functional status scale.

METHODS: A descriptive cross-sectional study was conducted at Tribhuvan University Teaching Hospital. COVID-19 recovered patients with reverse transcription-polymerase chain reaction negative status were included and assessed using the post-COVID-19 functional status scale. Data entry and analysis was done in Statistical Package for the Social Sciences version 20.0. Descriptive …