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Healthcare Workers' Well-Being: A Systematic Review Of Positive Psychology Interventions, Alexandra P Townsley, Jenny Li-Wang, Rajani Katta Jan 2023

Healthcare Workers' Well-Being: A Systematic Review Of Positive Psychology Interventions, Alexandra P Townsley, Jenny Li-Wang, Rajani Katta

Faculty, Staff and Students Publications

Given persistent occupational stressors and multiple challenges in the delivery of healthcare, there is an increased focus on the well-being of healthcare workers. Responding to these challenges will require a multipronged approach, focusing on system level, organization, and individual actions. Positive psychology interventions (PPIs) represent a promising area for individual action. This systematic review indicates that PPI, delivered via many methods, holds promise for improving the well-being of healthcare workers, although there is a clear need for additional randomized controlled trials utilizing defined and standardized outcome measures. In this review, the most commonly evaluated PPIs were mindfulness-based or gratitude-based interventions. …


The Current Burden And Future Solutions For Preoperative Cataract-Refractive Evaluation Diagnostic Devices: A Modified Delphi Study, Bonnie An Henderson, Jaime Aramberri, Robin Vann, Adi Abulafia, Margaret Ainslie-Garcia, John Berdahl, Nicole Ferko, Kjell Gunnar Gundersen, So Goto, Preeya Gupta, Samuel Multack, Elizabeth Persaud, Duna Raoof, Giacomo Savini, H John Shammas, Li Wang, Wendy Zhi Wang Jan 2023

The Current Burden And Future Solutions For Preoperative Cataract-Refractive Evaluation Diagnostic Devices: A Modified Delphi Study, Bonnie An Henderson, Jaime Aramberri, Robin Vann, Adi Abulafia, Margaret Ainslie-Garcia, John Berdahl, Nicole Ferko, Kjell Gunnar Gundersen, So Goto, Preeya Gupta, Samuel Multack, Elizabeth Persaud, Duna Raoof, Giacomo Savini, H John Shammas, Li Wang, Wendy Zhi Wang

Faculty, Staff and Students Publications

Purpose: To obtain consensus on the key areas of burden associated with existing devices and to understand the requirements for a comprehensive next-generation diagnostic device to be able to solve current challenges and provide more accurate prediction of intraocular lens (IOL) power and presbyopia correction IOL success.

Patients and methods: Thirteen expert refractive cataract surgeons including three steering committee (SC) members constituted the voting panel. Three rounds of voting included a Round 1 structured electronic questionnaire, Round 2 virtual face-to-face meeting, and Round 3 electronic questionnaire to obtain consensus on topics related to current limitations and future solutions for preoperative …


Editorial: Hemostasis In Ecmo And Vad, Volume Ii, Jun Teruya, Jean M Connors, Barbara Zieger Jan 2023

Editorial: Hemostasis In Ecmo And Vad, Volume Ii, Jun Teruya, Jean M Connors, Barbara Zieger

Faculty, Staff and Students Publications

No abstract provided.


Atrial Standstill In The Pediatric Population: A Multi-Institution Collaboration, Taylor S Howard, David Y Chiang, Scott R Ceresnak, Virginie Beausejour Ladouceur, Robert D Whitehill, Richard J Czosek, Timothy K Knilans, Agnethe M Ahnfeldt, Malene Lando Borresen, Edgar Jaeggi, Sharmila Udupa, Robert Gow, Jeremy P Moore, Roberto G Galloti, Doug Y Mah, Jeffrey J Kim, Santiago O Valdes, Dianna M Milewicz, Christina Y Miyake Jan 2023

Atrial Standstill In The Pediatric Population: A Multi-Institution Collaboration, Taylor S Howard, David Y Chiang, Scott R Ceresnak, Virginie Beausejour Ladouceur, Robert D Whitehill, Richard J Czosek, Timothy K Knilans, Agnethe M Ahnfeldt, Malene Lando Borresen, Edgar Jaeggi, Sharmila Udupa, Robert Gow, Jeremy P Moore, Roberto G Galloti, Doug Y Mah, Jeffrey J Kim, Santiago O Valdes, Dianna M Milewicz, Christina Y Miyake

Faculty, Staff and Students Publications

Background: Atrial standstill (AS) is a rare condition characterized by absence of electrical activity within the atria. Studies to date have been limited.

Objectives: The authors sought to describe the clinical characteristics, genetics, and outcomes of patients with AS.

Methods: This was a retrospective multicenter study of patients < 18 years at AS diagnosis, defined as absence of atrial activity documented during an electrophysiology study, device placement, or noninvasive rhythm tracings and confirmed by echocardiogram. Patients with acquired disorders were excluded. Clinical details and genetic variants were recorded and analyzed.

Results: Twenty patients were diagnosed at a median age of 6.6 years (IQR: 2.9-10.8 years). Arrhythmias included 16 (80%) with atrial/supraventricular arrhythmias and 8 (40%) with ventricular tachycardia, including 4 with cardiac arrests. A type 1 Brugada pattern was documented in 4. Pacemakers were implanted in 18 (90%). Although atrial leads were …


Cumulative Comorbid Conditions Influence Mortality Risk After Staged Palliation For Hypoplastic Left Heart Syndrome And Variants, Emily R Backes, Natasha S Afonso, Danielle Guffey, James S Tweddell, Sarah Tabbutt, Nancy A Rudd, Ginny O'Harrow, Silvana Molossi, George M Hoffman, Garick Hill, Jeffrey S Heinle, Priya Bhat, Jeffrey B Anderson, Nancy S Ghanayem Jan 2023

Cumulative Comorbid Conditions Influence Mortality Risk After Staged Palliation For Hypoplastic Left Heart Syndrome And Variants, Emily R Backes, Natasha S Afonso, Danielle Guffey, James S Tweddell, Sarah Tabbutt, Nancy A Rudd, Ginny O'Harrow, Silvana Molossi, George M Hoffman, Garick Hill, Jeffrey S Heinle, Priya Bhat, Jeffrey B Anderson, Nancy S Ghanayem

Faculty, Staff and Students Publications

Objective: Prematurity, low birth weight, genetic syndromes, extracardiac conditions, and secondary cardiac lesions are considered high-risk conditions associated with mortality after stage 1 palliation. We report the impact of these conditions on outcomes from a prospective multicenter improvement collaborative.

Methods: The National Pediatric Cardiology Quality Improvement Collaborative Phase II registry was queried. Comorbid conditions were categorized and quantified to determine the cumulative burden of high-risk diagnoses on survival to the first birthday. Logistic regression was applied to evaluate factors associated with mortality.

Results: Of the 1421 participants, 40% (575) had at least 1 high-risk condition. The aggregate high-risk group had …


Acute Liver Failure And Unique Challenges Of Pediatric Liver Transplantation Amidst A Worldwide Cluster Of Adenovirus-Associated Hepatitis, Anna M Banc-Husu, Elizabeth A Moulton, Henry Shiau, Luz Helena Gutierrez Sanchez, Moreshwar S Desai, Dana Cerminara, Flor M Munoz, Leanne M Buffaloe, Kristen G Valencia-Deray, N Thao N Galvan, Julu Bhatnagar, Lindsey Estetter, Negar Rassaei, Sarah Reagan-Steiner, Jason Wicker, James J Dunn, Carl E Allen, Kalyani R Patel, Sanjiv Harpavat, John A Goss, Daniel H Leung Jan 2023

Acute Liver Failure And Unique Challenges Of Pediatric Liver Transplantation Amidst A Worldwide Cluster Of Adenovirus-Associated Hepatitis, Anna M Banc-Husu, Elizabeth A Moulton, Henry Shiau, Luz Helena Gutierrez Sanchez, Moreshwar S Desai, Dana Cerminara, Flor M Munoz, Leanne M Buffaloe, Kristen G Valencia-Deray, N Thao N Galvan, Julu Bhatnagar, Lindsey Estetter, Negar Rassaei, Sarah Reagan-Steiner, Jason Wicker, James J Dunn, Carl E Allen, Kalyani R Patel, Sanjiv Harpavat, John A Goss, Daniel H Leung

Faculty, Staff and Students Publications

Investigation into a recent cluster of acute hepatitis in children from the southeastern United States identified human adenovirus (HAdV) DNAemia in all 9 cases. Molecular genotyping in 5 of 9 (56%) children identified HAdV type 41 in all cases (100%). Importantly, 2 children from this cluster progressed rapidly to pediatric acute liver failure (PALF) and required liver transplantation. HAdV type 41, a known cause of self-limited gastroenteritis, has not previously been associated with severe cholestatic hepatitis and liver failure in healthy children. Adenovirus polymerase chain reaction assay and sequencing of amplicons performed on DNA extracted from formalin-fixed, paraffin-embedded liver tissue …


Emergency Department Presentations Of Diabetic Ketoacidosis In A Large Cohort Of Children, Lise E Nigrovic, Nathan Kuppermann, Simona Ghetti, Jeff E Schunk, Michael J Stoner, Arleta Rewers, Julie K Mcmanemy, Kimberly S Quayle, Jennifer L Trainor, Leah Tzimenatos, Jonathan E Bennett, Maria Y Kwok, Sage R Myers, Kathleen M Brown, T Charles Casper, Cody S Olsen, Nicole S Glaser Jan 2023

Emergency Department Presentations Of Diabetic Ketoacidosis In A Large Cohort Of Children, Lise E Nigrovic, Nathan Kuppermann, Simona Ghetti, Jeff E Schunk, Michael J Stoner, Arleta Rewers, Julie K Mcmanemy, Kimberly S Quayle, Jennifer L Trainor, Leah Tzimenatos, Jonathan E Bennett, Maria Y Kwok, Sage R Myers, Kathleen M Brown, T Charles Casper, Cody S Olsen, Nicole S Glaser

Faculty, Staff and Students Publications

Background: Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of childhood diabetes. However, the influence of demographic factors on presentation are not well-defined.

Methods: We included children from 12 centers who were < 18 years with DKA (glucose > 300 mg/dL, serum pH < 7.25, or serum bicarbonate < 15 mEq/L) enrolled in the Pediatric Emergency Care Applied Research Network (PECARN) Fluid Therapies Under Investigation in DKA (FLUID) Trial. Data were also collected for children who presented to the centers during the enrollment period but were not enrolled due to disease or treatment-related reasons. We compared demographic, clinical, and biochemical findings among children with newly and previously diagnosed diabetes and children in different age groups.

Results: Of the 1,679 DKA episodes in 1,553 children, 799 (47.5%) episodes occurred in children with newly diagnosed diabetes and 396 (23.6%) were severe (pH < 7.1). Newly diagnosed children < 6 years of age were not more likely to have severe DKA in terms of pH, but had more severe hypocarbia and higher blood urea nitrogen levels, factors previously associated with the risk of cerebral injury. Lower socioeconomic status (SES) (based on family income and maternal education level) were associated with more severe DKA in new onset children, and recurrent DKA in the previously diagnosed children.

Conclusions: Greater efforts are needed to identify the children with diabetes early and to prevent recurrent DKA, particularly among children in low-SES groups. Young children with DKA may need more intensive monitoring due to higher risk of cerebral injury.


Gut Check: Assessing The Role Of The Gut Microbiota In The Adverse Cardiovascular Effects Of Obstructive Sleep Apnoea, David J Durgan, Ramon Farré Jan 2023

Gut Check: Assessing The Role Of The Gut Microbiota In The Adverse Cardiovascular Effects Of Obstructive Sleep Apnoea, David J Durgan, Ramon Farré

Faculty, Staff and Students Publications

No abstract provided.


Camkiiδ Gene Editing- A Base Hit For The Heart, Christopher J Walkey, William R Lagor Jan 2023

Camkiiδ Gene Editing- A Base Hit For The Heart, Christopher J Walkey, William R Lagor

Faculty, Staff and Students Publications

No abstract provided.


Cardiac Function, Structural, And Electrical Remodeling By Microgravity Exposure, Mary R Sy, Joshua A Keefe, Jeffrey P Sutton, Xander H T Wehrens Jan 2023

Cardiac Function, Structural, And Electrical Remodeling By Microgravity Exposure, Mary R Sy, Joshua A Keefe, Jeffrey P Sutton, Xander H T Wehrens

Faculty, Staff and Students Publications

Space medicine is key to the human exploration of outer space and pushes the boundaries of science, technology, and medicine. Because of harsh environmental conditions related to microgravity and other factors and hazards in outer space, astronauts and spaceflight participants face unique health and medical challenges, including those related to the heart. In this review, we summarize the literature regarding the effects of spaceflight on cardiac structure and function. We also provide an in-depth review of the literature regarding the effects of microgravity on cardiac calcium handling. Our review can inform future mechanistic and therapeutic studies and is applicable to …


Role Of Ca2+ In Healthy And Pathologic Cardiac Function: From Normal Excitation–Contraction Coupling To Mutations That Cause Inherited Arrhythmia, Joshua A Keefe, Oliver M Moore, Kevin S Ho, Xander H T Wehrens Jan 2023

Role Of Ca2+ In Healthy And Pathologic Cardiac Function: From Normal Excitation–Contraction Coupling To Mutations That Cause Inherited Arrhythmia, Joshua A Keefe, Oliver M Moore, Kevin S Ho, Xander H T Wehrens

Faculty, Staff and Students Publications

Calcium (Ca2+) ions are a key second messenger involved in the rhythmic excitation and contraction of cardiomyocytes throughout the heart. Proper function of Ca2+-handling proteins is required for healthy cardiac function, whereas disruption in any of these can cause cardiac arrhythmias. This comprehensive review provides a broad overview of the roles of Ca2+-handling proteins and their regulators in healthy cardiac function and the mechanisms by which mutations in these proteins contribute to inherited arrhythmias. Major Ca2+ channels and Ca2+-sensitive regulatory proteins involved in cardiac excitation–contraction coupling are discussed, with special emphasis on the function of the RyR2 macromolecular complex. Inherited …


A Novel Interaction Between Extracellular Vimentin And Fibrinogen In Fibrin Formation, Marina Martinez-Vargas, Adrian Cebula, Lisa S Brubaker, Nitin Seshadri, Fong W Lam, Michele Loor, Todd K Rosengart, Andrew Yee, Rolando E Rumbaut, Miguel A Cruz Jan 2023

A Novel Interaction Between Extracellular Vimentin And Fibrinogen In Fibrin Formation, Marina Martinez-Vargas, Adrian Cebula, Lisa S Brubaker, Nitin Seshadri, Fong W Lam, Michele Loor, Todd K Rosengart, Andrew Yee, Rolando E Rumbaut, Miguel A Cruz

Faculty, Staff and Students Publications

INTRODUCTION: Thrombosis is frequently manifested in critically ill patients with systemic inflammation, including sepsis and COVID-19. The coagulopathy in systemic inflammation is often associated with increased levels of fibrinogen and D-dimer. Because elevated levels of vimentin have been detected in sepsis, we sought to investigate the relationship between vimentin and the increased fibrin formation potential observed in these patients.

MATERIALS AND METHODS: This hypothesis was examined by using recombinant human vimentin, anti-vimentin antibodies, plasma derived from healthy and critically ill patients, confocal microscopy, co-immunoprecipitation assays, and size exclusion chromatography.

RESULTS: The level of vimentin in plasma derived from critically ill …


A Novel Use Of Bar Code Medication Administration Data To Assess Nurse Staffing And Workload, Melissa K Knox, Paras D Mehta, Lynette E Dorsey, Christine Yang, Laura A Petersen Jan 2023

A Novel Use Of Bar Code Medication Administration Data To Assess Nurse Staffing And Workload, Melissa K Knox, Paras D Mehta, Lynette E Dorsey, Christine Yang, Laura A Petersen

Faculty, Staff and Students Publications

OBJECTIVE: The aim of the study is to introduce an innovative use of bar code medication administration (BCMA) data, medication pass analysis, that allows for the examination of nurse staffing and workload using data generated during regular nursing workflow.

METHODS: Using 1 year (October 1, 2014-September 30, 2015) of BCMA data for 11 acute care units in one Veterans Affairs Medical Center, we determined the peak time for scheduled medications and included medications scheduled for and administered within 2 hours of that time in analyses. We established for each staff member their daily peak-time medication pass characteristics (number of patients, …


A Rare Case Of Pancreatic Actinomyces, Marguerite Poche, Kyle Liu, Codey Pham, Shilpa Jain, Robert Sealock Jan 2023

A Rare Case Of Pancreatic Actinomyces, Marguerite Poche, Kyle Liu, Codey Pham, Shilpa Jain, Robert Sealock

Faculty, Staff and Students Publications

Actinomyces israelii is a filamentous, gram-positive anaerobic bacterium commonly found in the upper gastrointestinal tract, colon, and female genital tract. Rarely, actinomycosis can infect the pancreas most commonly after pancreatic instrumentation, often mimicking malignancy. We describe a case of a 26-year-old woman who presented with epigastric abdominal pain and nausea without prior pancreatic instrumentation. Abdominal imaging demonstrated a mass in the pancreatic head with fine-needle biopsy revealing Actinomyces. The patient was successfully treated with long-term antibiotic therapy resulting in resolution of the mass. Our case emphasizes the importance of considering nonmalignant etiologies in the differential diagnosis of pancreatic masses.


Neprilysin Inhibitors In Heart Failure: The Science, Mechanism Of Action, Clinical Studies, And Unanswered Questions, Biykem Bozkurt, Ajith P Nair, Arunima Misra, Claire Z Scott, Jamal H Mahar, Savitri Fedson Jan 2023

Neprilysin Inhibitors In Heart Failure: The Science, Mechanism Of Action, Clinical Studies, And Unanswered Questions, Biykem Bozkurt, Ajith P Nair, Arunima Misra, Claire Z Scott, Jamal H Mahar, Savitri Fedson

Faculty, Staff and Students Publications

This article provides a contemporary review and a new perspective on the role of neprilysin inhibition in heart failure (HF) in the context of recent clinical trials and addresses potential mechanisms and unanswered questions in certain HF patient populations. Neprilysin is an endopeptidase that cleaves a variety of peptides such as natriuretic peptides, bradykinin, adrenomedullin, substance P, angiotensin I and II, and endothelin. It has a broad role in cardiovascular, renal, pulmonary, gastrointestinal, endocrine, and neurologic functions. The combined angiotensin receptor and neprilysin inhibitor (ARNi) has been developed with an intent to increase vasodilatory natriuretic peptides and prevent counterregulatory activation …


Impact Of Gastrointestinal Polymerase Chain Reaction Panels On Antibiotic Utilization In Hospitalized Adult Patients, Gillean A Kelly, Roumen Iordanov, Alex Franklin, Amna Ahmed, Krithika Srinivasan, Jesica Hayon, Todd Lasco, Rosie Amini, Sabra Shay, Prathit A Kulkarni, Mayar Al Mohajer Jan 2023

Impact Of Gastrointestinal Polymerase Chain Reaction Panels On Antibiotic Utilization In Hospitalized Adult Patients, Gillean A Kelly, Roumen Iordanov, Alex Franklin, Amna Ahmed, Krithika Srinivasan, Jesica Hayon, Todd Lasco, Rosie Amini, Sabra Shay, Prathit A Kulkarni, Mayar Al Mohajer

Faculty, Staff and Students Publications

Multiplex stool polymerase chain reaction (PCR) panels offer rapid comprehensive testing for patients with infectious diarrhea. We compared antibiotic utilization among hospitalized patients with suspected infectious diarrhea who underwent diagnostic testing with either a stool culture or stool PCR panel. No significant differences in antibiotic utilization were identified.


Treatment Of Severe Covid-19 Infection With Remdesivir In Peritoneal Dialysis, Ryan Geffin, Shazia Raheem, Lavannya M Pandit, Andrew S Hunter, Michael W Holliday, Aditya V Rao, Maulin K Shah Jan 2023

Treatment Of Severe Covid-19 Infection With Remdesivir In Peritoneal Dialysis, Ryan Geffin, Shazia Raheem, Lavannya M Pandit, Andrew S Hunter, Michael W Holliday, Aditya V Rao, Maulin K Shah

Faculty, Staff and Students Publications

End-stage kidney disease (ESKD) has been shown to be correlated with an increased risk of COVID-19 infection and mortality. Remdesivir is an effective non-EUA U.S. Food and Drug Administration (FDA)-approved antiviral agent for the treatment of COVID-19 in hospitalized adult and pediatric patients, though a lack of data has prevented its use in patients with severe kidney disease including dialysis patients. Some observational studies report the use of remdesivir in hemodialysis patients, but there are no reports of patients treated with remdesivir on peritoneal dialysis. Dialysis modalities may affect drug pharmacokinetics, and safety and efficiency of remdesivir in peritoneal dialysis …


Cerebral Microdialysis And Glucopenia In Traumatic Brain Injury: A Review, Himanshu Sharma, John P Mcginnis, Katherine E Kabotyanski, Shankar P Gopinath, Jerry C Goodman, Claudia Robertson, Jovany Cruz Navarro Jan 2023

Cerebral Microdialysis And Glucopenia In Traumatic Brain Injury: A Review, Himanshu Sharma, John P Mcginnis, Katherine E Kabotyanski, Shankar P Gopinath, Jerry C Goodman, Claudia Robertson, Jovany Cruz Navarro

Faculty, Staff and Students Publications

Traditionally, intracranial pressure (ICP) and partial brain tissue oxygenation (PbtO2) have been the primary invasive intracranial measurements used to guide management in patients with severe traumatic brain injury (TBI). After injury however, the brain develops an increased metabolic demand which may require an increment in the oxidative metabolism of glucose. Simultaneously, metabolic, and electrical dysfunction can lead to an inability to meet these demands, even in the absence of ischemia or increased intracranial pressure. Cerebral microdialysis provides the ability to accurately measure local concentrations of various solutes including lactate, pyruvate, glycerol and glucose. Experimental and clinical data demonstrate that such …


The Pathway To The Natural Gas Industry: Financial Development, Coal Consumption, And Carbon Dioxide Emissions In Pr China, Teng Tong, Jaime Ortiz, Haibo Wang Jan 2023

The Pathway To The Natural Gas Industry: Financial Development, Coal Consumption, And Carbon Dioxide Emissions In Pr China, Teng Tong, Jaime Ortiz, Haibo Wang

Faculty, Staff and Students Publications

This paper revisits the causal links between financial development, coal consumption, and CO2 emissions in P.R. China over the 1977–2017 period to validate the development of its natural gas industry. It uses a Bootstrap ARDL bound test with structural breaks to establish stationarity, short- and long-run dynamics, and causality of the series. The results show there are no long-run relationships among these three variables, but a Granger causality test does indicate the presence of both a two-way Granger causality between coal consumption and CO2 emissions, and a one-way Granger causality running from financial development to both coal consumption and CO2 …


Engineered Cd4 T Cells Expressing A Membrane Anchored Viral Inhibitor Restrict Hiv-1 Through Cis And Trans Mechanisms, Weiming Wang, Khanghy Truong, Chaobaihui Ye, Suman Sharma, Huan He, Lihong Liu, Michael Wen, Anisha Misra, Paul Zhou, Jason T Kimata Jan 2023

Engineered Cd4 T Cells Expressing A Membrane Anchored Viral Inhibitor Restrict Hiv-1 Through Cis And Trans Mechanisms, Weiming Wang, Khanghy Truong, Chaobaihui Ye, Suman Sharma, Huan He, Lihong Liu, Michael Wen, Anisha Misra, Paul Zhou, Jason T Kimata

Faculty, Staff and Students Publications

HIV-1 infection of target cells can occur through either cell-free virions or cell-cell transmission in a virological synapse, with the latter mechanism of infection reported to be 100- to 1,000-fold more efficient. Neutralizing antibodies and entry inhibitors effectively block cell-free HIV-1, but with few exceptions, they display much less inhibitory activity against cell-mediated HIV-1 transmission. Previously, we showed that engineering HIV-1 target cells by genetically linking single-chain variable fragments (scFvs) of antibodies to glycosyl phosphatidylinositol (GPI) potently blocks infection by cell-free virions and cell-mediated infection by immature dendritic cell (iDC)-captured HIV-1. Expression of scFvs on CD4


Postsurgical Morbidity And Mortality Favorably Informs Deep Brain Stimulation For New Indications Including Schizophrenia And Schizoaffective Disorder, Judith M Gault, Patrick Hosokawa, Daniel Kramer, Elyn R Saks, Paul S Appelbaum, John A Thompson, Ann Olincy, Nicola Cascella, Akira Sawa, Wayne Goodman, Nidal Moukaddam, Sameer A Sheth, William S Anderson, Rachel A Davis Jan 2023

Postsurgical Morbidity And Mortality Favorably Informs Deep Brain Stimulation For New Indications Including Schizophrenia And Schizoaffective Disorder, Judith M Gault, Patrick Hosokawa, Daniel Kramer, Elyn R Saks, Paul S Appelbaum, John A Thompson, Ann Olincy, Nicola Cascella, Akira Sawa, Wayne Goodman, Nidal Moukaddam, Sameer A Sheth, William S Anderson, Rachel A Davis

Faculty, Staff and Students Publications

BACKGROUND: Deep brain stimulation (DBS) shows promise for new indications like treatment-refractory schizophrenia in early clinical trials. In the first DBS clinical trial for treatment refractory schizophrenia, despite promising results in treating psychosis, one of the eight subjects experienced both a symptomatic hemorrhage and an infection requiring device removal. Now, ethical concerns about higher surgical risk in schizophrenia/schizoaffective disorder (SZ/SAD) are impacting clinical trial progress. However, insufficient cases preclude conclusions regarding DBS risk in SZ/SAD. Therefore, we directly compare adverse surgical outcomes for all surgical procedures between SZ/SAD and Parkinson's disease (PD) cases to infer relative surgical risk relevant to …


Intermel: An International Biorepository And Clinical Database To Uncover Predictors Of Survival In Early-Stage Melanoma, Irene Orlow, Keimya D Sadeghi, Sharon N Edmiston, Jessica M Kenney, Cecilia Lezcano, James S Wilmott, Anne E Cust, Richard A Scolyer, Graham J Mann, Tim K Lee, Hazel Burke, Valerie Jakrot, Ping Shang, Peter M Ferguson, Tawny W Boyce, Jennifer S Ko, Peter Ngo, Pauline Funchain, Judy R Rees, Kelli O'Connell, Honglin Hao, Eloise Parrish, Kathleen Conway, Paul B Googe, David W Ollila, Stergios J Moschos, Eva Hernando, Douglas Hanniford, Diana Argibay, Christopher I Amos, Jeffrey E Lee, Iman Osman, Li Luo, Pei-Fen Kuan, Arshi Aurora, Bonnie E Gould Rothberg, Marcus W Bosenberg, Meg R Gerstenblith, Cheryl Thompson, Paul N Bogner, Ivan P Gorlov, Sheri L Holmen, Elise K Brunsgaard, Yvonne M Saenger, Ronglai Shen, Venkatraman Seshan, Eduardo Nagore, Marc S Ernstoff, Klaus J Busam, Colin B Begg, Nancy E Thomas, Marianne Berwick, Intermel Consortium Jan 2023

Intermel: An International Biorepository And Clinical Database To Uncover Predictors Of Survival In Early-Stage Melanoma, Irene Orlow, Keimya D Sadeghi, Sharon N Edmiston, Jessica M Kenney, Cecilia Lezcano, James S Wilmott, Anne E Cust, Richard A Scolyer, Graham J Mann, Tim K Lee, Hazel Burke, Valerie Jakrot, Ping Shang, Peter M Ferguson, Tawny W Boyce, Jennifer S Ko, Peter Ngo, Pauline Funchain, Judy R Rees, Kelli O'Connell, Honglin Hao, Eloise Parrish, Kathleen Conway, Paul B Googe, David W Ollila, Stergios J Moschos, Eva Hernando, Douglas Hanniford, Diana Argibay, Christopher I Amos, Jeffrey E Lee, Iman Osman, Li Luo, Pei-Fen Kuan, Arshi Aurora, Bonnie E Gould Rothberg, Marcus W Bosenberg, Meg R Gerstenblith, Cheryl Thompson, Paul N Bogner, Ivan P Gorlov, Sheri L Holmen, Elise K Brunsgaard, Yvonne M Saenger, Ronglai Shen, Venkatraman Seshan, Eduardo Nagore, Marc S Ernstoff, Klaus J Busam, Colin B Begg, Nancy E Thomas, Marianne Berwick, Intermel Consortium

Faculty, Staff and Students Publications

INTRODUCTION: We are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients. We also evaluated tissue-derived predictors of extracted nucleic acids' quality and success in downstream testing. This ongoing study will target 1,000 melanomas within the international InterMEL consortium.

METHODS: Following a pre-established protocol, participating centers ship formalin-fixed paraffin embedded (FFPE) tissue sections to Memorial Sloan Kettering Cancer Center for …


Ai-Powered Discovery Of A Novel P53-Y220c Reactivator, Shan Zhou, Dafei Chai, Xu Wang, Praveen Neeli, Xinfang Yu, Aram Davtyan, Ken Young, Yong Li Jan 2023

Ai-Powered Discovery Of A Novel P53-Y220c Reactivator, Shan Zhou, Dafei Chai, Xu Wang, Praveen Neeli, Xinfang Yu, Aram Davtyan, Ken Young, Yong Li

Faculty, Staff and Students Publications

Introduction

The p53-Y220C mutation is one of the most common mutations that play a major role in cancer progression.

Methods

In this study, we applied artificial intelligence (AI)-powered virtual screening to identify small-molecule compounds that specifically restore the wild-type p53 conformation from p53-Y220C. From 10 million compounds, the AI algorithm selected a chemically diverse set of 83 high-scoring hits, which were subjected to several experimental assays using cell lines with different p53 mutations.

Results

We identified one compound, H3, that preferentially killed cells with the p53-Y220C mutation compared to cells with other p53 mutations. H3 increased the amount of folded …


Milder Loss Of Insulin-Containing Islets In Individuals With Type 1 Diabetes And Type 2 Diabetes-Associated Tcf7l2 Genetic Variants, Maria J Redondo, Sarah J Richardson, Daniel Perry, Charles G Minard, Alice L J Carr, Todd Brusko, Irina Kusmartseva, Alberto Pugliese, Mark A Atkinson Jan 2023

Milder Loss Of Insulin-Containing Islets In Individuals With Type 1 Diabetes And Type 2 Diabetes-Associated Tcf7l2 Genetic Variants, Maria J Redondo, Sarah J Richardson, Daniel Perry, Charles G Minard, Alice L J Carr, Todd Brusko, Irina Kusmartseva, Alberto Pugliese, Mark A Atkinson

Faculty, Staff and Students Publications

AIMS/HYPOTHESIS: TCF7L2 variants are the strongest genetic risk factor for type 2 diabetes. In individuals with type 1 diabetes, these variants are associated with a higher C-peptide AUC, a lower glucose AUC during an OGTT, single autoantibody positivity near diagnosis, particularly in individuals older than 12 years of age, and a lower frequency of type 1 diabetes-associated HLA genotypes. Based on initial observations from clinical cohorts, we tested the hypothesis that type 2 diabetes-predisposing TCF7L2 genetic variants are associated with a higher percentage of residual insulin-containing cells (ICI%) in pancreases of donors with type 1 diabetes, by examining genomic data …


Tanshinone Iia Inhibits Cell Viability And Promotes Puma-Mediated Apoptosis Of Oral Squamous Cell Carcinoma, Shuangze Han, Xinfang Yu, Ruirui Wang, Xiaocong Wang, Lulu Liu, Qing Zhao, Rongbo Xie, Ming Li, Zhong Su Zhou Jan 2023

Tanshinone Iia Inhibits Cell Viability And Promotes Puma-Mediated Apoptosis Of Oral Squamous Cell Carcinoma, Shuangze Han, Xinfang Yu, Ruirui Wang, Xiaocong Wang, Lulu Liu, Qing Zhao, Rongbo Xie, Ming Li, Zhong Su Zhou

Faculty, Staff and Students Publications

Apoptosis alteration is responsible for tumorigenesis and tumor resistance to therapies. The natural product Tanshinone IIA (Tan IIA) exhibits potent inhibitory effects against various tumors. However, the effect of Tan IIA on apoptosis and its underlying mechanism remains elusive in oral squamous cell carcinoma (OSCC). Here, we demonstrated that Tan IIA dose-dependently suppressed cell viability and colony formation in CAL27, SCC4, and SCC25 cells. Moreover, Tan IIA inhibited Akt activation from inducing Foxo3a dephosphorylation and PUMA-mediated apoptosis. PUMA or Foxo3a knockdown compromised the inhibitory effect of Tan IIA on OSCC cells. Tan IIA administration inhibited CAL27-deprived xenograft tumor growth and …


Trends And Outcomes In Patients With Coronary Artery Disease Undergoing Tavr: Insights From Va Cart, Khanjan B Shah, Colin O'Donnell, Dhruv Mahtta, Stephen W Waldo, Calvin Choi, Ki Park, Ali E Denktas, David Paniagua, Umair Khalid Jan 2023

Trends And Outcomes In Patients With Coronary Artery Disease Undergoing Tavr: Insights From Va Cart, Khanjan B Shah, Colin O'Donnell, Dhruv Mahtta, Stephen W Waldo, Calvin Choi, Ki Park, Ali E Denktas, David Paniagua, Umair Khalid

Faculty, Staff and Students Publications

BACKGROUND: Obstructive coronary artery disease (CAD) is common in patients with severe symptomatic aortic stenosis. The management and impact of obstructive CAD in patients undergoing transcatheter aortic valve replacement (TAVR) have not been fully evaluated. We aimed to determine the patient characteristics and clinical outcomes among veterans undergoing TAVR with and without obstructive CAD and to determine temporal trends and association of pre-TAVR percutaneous coronary intervention (PCI) with clinical outcomes.

METHODS: We identified all patients who underwent TAVR from 2012 to 2021 in the VA Health Care System. The sample population was divided into patients with and without obstructive CAD …


Stealing From The Heart: A Rare Case Of Chest Pain Post-Coronary Artery Bypass Grafting, Prasanti A Kotta, Joshua R Hirsch, Umair Khalid, Ali E Denktas Jan 2023

Stealing From The Heart: A Rare Case Of Chest Pain Post-Coronary Artery Bypass Grafting, Prasanti A Kotta, Joshua R Hirsch, Umair Khalid, Ali E Denktas

Faculty, Staff and Students Publications

A 70-year-old veteran with prior triple vessel coronary artery bypass grafting (CABG) presented with exertional chest pain. His work-up revealed > 40 mm Hg bilateral upper extremity blood pressure difference. Chest computed tomography and invasive angiography revealed severe stenosis at the ostium of the left subclavian artery, proximal to the origin of the left internal mammary artery to left anterior descending artery graft (LIMA-LAD). A diagnosis of coronary subclavian steal syndrome (CSSS) was made, and carotid-subclavian bypass was performed. This case outlines when to suspect CSSS, an approach to its diagnosis, and the importance of its timely management.


Is It Time To Switch To Bivalirudin For Ecmo Anticoagulation?, Amir Navaei, Vadim Kostousov, Jun Teruya Jan 2023

Is It Time To Switch To Bivalirudin For Ecmo Anticoagulation?, Amir Navaei, Vadim Kostousov, Jun Teruya

Faculty, Staff and Students Publications

For decades, unfractionated heparin (hereafter, heparin) has been the primary anticoagulant used for extracorporeal membrane oxygenation (ECMO) support. More recently, however, bivalirudin, a direct thrombin inhibitor, has emerged as an alternative. This systematic review based on PRISMA guidelines, aims to summarize 16 comparative studies and 8 meta-analysis and review articles published from January, 2011 till May, 2023 which directly compares ECMO courses using heparin versus bivalirudin as the anticoagulant. While this comparison is complicated by the lack of a standardized definition of major bleeding or thrombosis, our overall findings suggest there is no statistical difference between heparin and bivalirudin in …


Advances In Prosthetic Technology: A Perspective On Ethical Considerations For Development And Clinical Translation, Hayden Gavette, Cody L Mcdonald, Kristin Kostick-Quenet, Ashley Mullen, Bijan Najafi, M G Finco Jan 2023

Advances In Prosthetic Technology: A Perspective On Ethical Considerations For Development And Clinical Translation, Hayden Gavette, Cody L Mcdonald, Kristin Kostick-Quenet, Ashley Mullen, Bijan Najafi, M G Finco

Faculty, Staff and Students Publications

Technological advancements of prostheses in recent years, such as haptic feedback, active power, and machine learning for prosthetic control, have opened new doors for improved functioning, satisfaction, and overall quality of life. However, little attention has been paid to ethical considerations surrounding the development and translation of prosthetic technologies into clinical practice. This article, based on current literature, presents perspectives surrounding ethical considerations from the authors' multidisciplinary views as prosthetists (HG, AM, CLM, MGF), as well as combined research experience working directly with people using prostheses (AM, CLM, MGF), wearable technologies for rehabilitation (MGF, BN), machine learning and artificial intelligence …


Adeno-Associated Virus 8 Delivers An Immunomodulatory Peptide To Mouse Liver More Efficiently Than To Rat Liver, Yuqing Wang, Ayrea Hurley, Marco De Giorgi, Mark R Tanner, Rong-Chi Hu, Michael W Pennington, William R Lagor, Christine Beeton Jan 2023

Adeno-Associated Virus 8 Delivers An Immunomodulatory Peptide To Mouse Liver More Efficiently Than To Rat Liver, Yuqing Wang, Ayrea Hurley, Marco De Giorgi, Mark R Tanner, Rong-Chi Hu, Michael W Pennington, William R Lagor, Christine Beeton

Faculty, Staff and Students Publications

Targeting the Kv1.3 potassium channel has proven effective in reducing obesity and the severity of animal models of autoimmune disease. Stichodactyla toxin (ShK), isolated from the sea anemone Stichodactyla helianthus, is a potent blocker of Kv1.3. Several of its analogs are some of the most potent and selective blockers of this channel. However, like most biologics, ShK and its analogs require injections for their delivery, and repeated injections reduce patient compliance during the treatment of chronic diseases. We hypothesized that inducing the expression of an ShK analog by hepatocytes would remove the requirement for frequent injections and lead to a …