Digital Commons Network^™

Reflections Of The Angiotensin Receptor Blocker Recall By The Fda And Repercussions On Healthcare, Michael Gillette, Addison Taylor, Djenita Butulija, Himabindu Kadiyala, Hani Jneid

Faculty, Staff and Students Publications

PURPOSE: Beginning in July of 2018, the FDA issued a voluntary recall regarding the presence of a contaminant found in the manufacturing of valsartan. What would ensue has become a largely unprecedented sequence of alarming events since the FDA began reporting public recalls, withdrawals and safety alerts on their website in 2016. Since then, the United States has been significantly impacted by drug recalls affecting angiotensin receptor blockers. This report arms clinicians with additional guidance and provides a framework for responding appropriately to future similar incidents and includes an overview of the angiotensin receptor blockers, and their effects and safety …

Post-Registration Experience Of Nivolumab In Advanced Hepatocellular Carcinoma: An International Study, Petros Fessas, Ahmed Kaseb, Yinghong Wang, Anwaar Saeed, David Szafron, Tomi Jun, Sirish Dharmapuri, Abdul Rafeh Naqash, Mahvish Muzaffar, Musharraf Navaid, Uqba Khan, Chiehju Lee, Anushi Bulumulle, Bo Yu, Sonal Paul, Neil Nimkar, Dominik Bettinger, Francesca Benevento, Hannah Hildebrand, Tiziana Pressiani, Yehia I Abugabal, Nicola Personeni, Yi-Hsiang Huang, Lorenza Rimassa, Celina Ang, Thomas Marron, David J Pinato

Faculty, Staff and Students Publications

BACKGROUND: Nivolumab is Food and Drug Administration approved in sorafenib-experienced, advanced hepatocellular carcinoma (HCC). Post-registration data of treatment in a real-world setting is lacking.

PATIENTS AND METHODS: We performed an international, multicenter observational study to confirm safety and efficacy of nivolumab in 233 patients treated outside clinical trials from eight centers in North America, Europe and Asia.

RESULTS: Patients received nivolumab for Barcelona Clinic Liver Cancer stage C (n=191, 92.0%) and Child-Pugh (CP) A (n=158, 67.8%) or B (n=75, 32.2%) HCC as first (n=85, 36.5%) or second to fourth systemic therapy line …

Modulation Of Hedgehog Signaling By Kappa Opioids To Attenuate Osteoarthritis, Alexander E Weber, Omid Jalali, Sean Limfat, Ruzanna Shkhyan, Robert Van Der Horst, Siyoung Lee, Yucheng Lin, Liangliang Li, Erik N Mayer, Liming Wang, Nancy Q Liu, Frank A Petrigliano, Jay R Lieberman, Denis Evseenko

Faculty, Staff and Students Publications

OBJECTIVE: Inhibition of hedgehog (HH) signaling prevents cartilage degeneration and promotes repair in animal models of osteoarthritis (OA). This study, undertaken in OA models and in human OA articular cartilage, was designed to explore whether kappa opioid receptor (KOR) modulation via the inhibition of HH signaling may have therapeutic potential for achieving disease-modifying activity in OA.

METHODS: Primary human articular cartilage and synovial tissue samples from patients with knee OA undergoing total joint replacement and from healthy human subjects were obtained from the National Disease Research Interchange. For in vivo animal studies, a partial medial meniscectomy (PMM) model of knee …

Low-Dose Versus High-Dose Carfilzomib With Dexamethasone (S1304) In Patients With Relapsed-Refractory Multiple Myeloma, Sikander Ailawadhi, Rachael Sexton, Suzanne Lentzsch, Muneer H Abidi, Peter M Voorhees, Adam D Cohen, Eric M Rohren, Stephen Heitner, Kevin Kelly, Niklas J Mackler, David M Baer, Antje Hoering, Brian Durie, Robert Z Orlowski

Faculty, Staff and Students Publications

PURPOSE: Treatment of multiple myeloma has evolved tremendously and optimal utilization of available therapies will ensure maximal patient benefits.

PATIENTS AND METHODS: We report the Southwest Oncology Group randomized phase II trial (S1304) comparing twice weekly low-dose (27 mg/m

RESULTS: Among 143 enrolled patients, of whom 121 were eligible and analyzable, the overall response rate was 42.8%, with no significant difference between the arms (

CONCLUSIONS: This randomized trial did not support a benefit of fixed duration, twice weekly 56 mg/m

Gut Microbiota-Derived Short-Chain Fatty Acids Promote Poststroke Recovery In Aged Mice, Juneyoung Lee, John D'Aigle, Louise Atadja, Victoria Quaicoe, Pedram Honarpisheh, Bhanu P Ganesh, Ahmad Hassan, Joerg Graf, Joseph Petrosino, Nagireddy Putluri, Liang Zhu, David J Durgan, Robert M Bryan, Louise D Mccullough, Venugopal Reddy Venna

Faculty, Staff and Students Publications

RATIONALE: The elderly experience profound systemic responses after stroke, which contribute to higher mortality and more severe long-term disability. Recent studies have revealed that stroke outcomes can be influenced by the composition of gut microbiome. However, the potential benefits of manipulating the gut microbiome after injury is unknown.

OBJECTIVE: To determine if restoring youthful gut microbiota after stroke aids in recovery in aged subjects, we altered the gut microbiome through young fecal transplant gavage in aged mice after experimental stroke. Further, the effect of direct enrichment of selective bacteria producing short-chain fatty acids (SCFAs) was tested as a more targeted …

Screening Tests For Active Pulmonary Tuberculosis In Children, Bryan Vonasek, Tara Ness, Yemisi Takwoingi, Alexander W. Kay, Susanna S. Van Wyk, Lara Ouellette, Ben J. Marais, Karen R. Steingart, Anna M. Mandalakas

Library Staff Publications

Background: Globally, children under 15 years represent approximately 12% of new tuberculosis cases, but 16% of the estimated 1.4 million deaths. This higher share of mortality highlights the urgent need to develop strategies to improve case detection in this age group and identify children without tuberculosis disease who should be considered for tuberculosis preventive treatment. One such strategy is systematic screening for tuberculosis in high-risk groups.

Objectives: To estimate the sensitivity and specificity of the presence of one or more tuberculosis symptoms, or symptom combinations; chest radiography (CXR); Xpert MTB/RIF; Xpert Ultra; and combinations of these as screening tests for …

A Substitution In Cgmp-Dependent Protein Kinase 1 Associated With Aortic Disease Induces An Active Conformation In The Absence Of Cgmp, Matthew H Chan, Sahar Aminzai, Tingfei Hu, Amatya Taran, Sheng Li, Choel Kim, Renate B Pilz, Darren E Casteel

Faculty, Staff and Students Publications

Type 1 cGMP-dependent protein kinases (PKGs) play important roles in human cardiovascular physiology, regulating vascular tone and smooth-muscle cell phenotype. A mutation in the human PRKG1 gene encoding cGMP-dependent protein kinase 1 (PKG1) leads to thoracic aortic aneurysms and dissections. The mutation causes an arginine-to-glutamine (RQ) substitution within the first cGMP-binding pocket in PKG1. This substitution disrupts cGMP binding to the pocket, but it also unexpectedly causes PKG1 to have high activity in the absence of cGMP via an unknown mechanism. Here, we identified the molecular mechanism whereby the RQ mutation increases basal kinase activity in the human PKG1α and …

Measuring Teacher Identity During The Transition From Medical School To Residency, Stephanie Sherman, Shelley Kumar, Jonathan Lim, Zaven Sargsyan, Bani Ratan, Teri Turner

Faculty, Staff and Students Publications

Residents undergo professional identity formation during training, and the integration of a teacher identity into that of a clinician is part of this process. We aimed to measure the teacher identity of incoming interns of various specialties. In this cross-sectional, survey-based study, we modified a validated teacher identity scale and distributed it to residents attending orientation at a large, academic institution. A total of 297 residents took the survey, including 272 interns; 80% (218/272) of interns completed the survey and permitted use of their data. The mean score for global teacher identity was 4.16 (SD 0.67) on a 1 to …

Rna-Gps Predicts Sars-Cov-2 Rna Residency To Host Mitochondria And Nucleolus, Kevin E Wu, Furqan M Fazal, Kevin R Parker, James Zou, Howard Y Chang

Faculty, Staff and Students Publications

SARS-CoV-2 genomic and subgenomic RNA (sgRNA) transcripts hijack the host cell's machinery. Subcellular localization of its viral RNA could, thus, play important roles in viral replication and host antiviral immune response. We perform computational modeling of SARS-CoV-2 viral RNA subcellular residency across eight subcellular neighborhoods. We compare hundreds of SARS-CoV-2 genomes with the human transcriptome and other coronaviruses. We predict the SARS-CoV-2 RNA genome and sgRNAs to be enriched toward the host mitochondrial matrix and nucleolus, and that the 5' and 3' viral untranslated regions contain the strongest, most distinct localization signals. We interpret the mitochondrial residency signal as an …

Improved Outcomes In The Treatment Of Post-Myocardial Infarction Ventricular Septal Defect With Percutaneous Tandemheart Left Ventricular Mechanical Circulatory Support, Pranav Loyalka, Angelo Nascimbene, Sriram S. Nathan, Rajko Radovancevic, Ajay S. Raman, Manish K. Patel, Keshava Rajagopal, Biswajit Kar, Igor D. Gregoric

The VAD Journal

Background

Post-myocardial infarction (MI) ventricular septal defect (VSD) is associated with 40% - 50% of peri-procedural mortalities; however, it is amenable to catheter-based therapies. We retrospectively investigated the impact of state-of-the-art bridging percutaneous left ventricular mechanical circulatory support (MCS) using the TandemHeart® (TH) ventricular assist device (VAD) on a patient with post-MI VSD.

Results

From July 2008 to March 2014, 23 patients were referred for treatment of post-MI VSD. Initially, 18/23 patients required MCS; 12 received an intra-aortic balloon pump (IABP), while 6 received initial TH support. Seven of the IABP patients later required TH support. Catheter-based device VSD closure …

Critical Micrornas And Regulatory Motifs In Cleft Palate Identified By A Conserved Mirna-Tf-Gene Network Approach In Humans And Mice

Faculty, Staff and Student Publications

Cleft palate (CP) is the second most common congenital birth defect. The etiology of CP is complicated, with involvement of various genetic and environmental factors. To investigate the gene regulatory mechanisms, we designed a powerful regulatory analytical approach to identify the conserved regulatory networks in humans and mice, from which we identified critical microRNAs (miRNAs), target genes and regulatory motifs (miRNA-TF-gene) related to CP. Using our manually curated genes and miRNAs with evidence in CP in humans and mice, we constructed miRNA and transcription factor (TF) co-regulation networks for both humans and mice. A consensus regulatory loop (miR17/miR20a-FOXE1-PDGFRA) and eight …

Metformin Enhances Autophagy And Normalizes Mitochondrial Function To Alleviate Aging-Associated Inflammation, Leena P Bharath, Madhur Agrawal, Grace Mccambridge, Dequina A Nicholas, Hatice Hasturk, Jing Liu, Kai Jiang, Rui Liu, Zhenheng Guo, Jude Deeney, Caroline M Apovian, Jennifer Snyder-Cappione, Gregory S Hawk, Rebecca M Fleeman, Riley M F Pihl, Katherine Thompson, Anna C Belkina, Licong Cui, Elizabeth A Proctor, Philip A Kern, Barbara S Nikolajczyk

Faculty, Staff and Student Publications

Age is a non-modifiable risk factor for the inflammation that underlies age-associated diseases; thus, anti-inflammaging drugs hold promise for increasing health span. Cytokine profiling and bioinformatic analyses showed that Th17 cytokine production differentiates CD4+ T cells from lean, normoglycemic older and younger subjects, and mimics a diabetes-associated Th17 profile. T cells from older compared to younger subjects also had defects in autophagy and mitochondrial bioenergetics that associate with redox imbalance. Metformin ameliorated the Th17 inflammaging profile by increasing autophagy and improving mitochondrial bioenergetics. By contrast, autophagy-targeting siRNA disrupted redox balance in T cells from young subjects and activated the Th17 …

Cardiac Surgery During The Coronavirus Disease 2019 Pandemic: Perioperative Considerations And Triage Recommendations, Vivek Patel, Ernesto Jimenez, Lorraine Cornwell, Trung Tran, David Paniagua, Ali E Denktas, Andrew Chou, Samuel J Hankins, Biykem Bozkurt, Todd K Rosengart, Hani Jneid

Faculty, Staff and Students Publications

The coronavirus disease 2019 pandemic, caused by severe acute respiratory syndrome coronavirus-2, represents the third human affliction attributed to the highly pathogenic coronavirus in the current century. Because of its highly contagious nature and unprecedented global spread, its aggressive clinical presentation, and the lack of effective treatment, severe acute respiratory syndrome coronavirus-2 infection is causing the loss of thousands of lives and imparting unparalleled strain on healthcare systems around the world. In the current report, we discuss perioperative considerations for patients undergoing cardiac surgery and provide clinicians with recommendations to effectively triage and plan these procedures during the coronavirus disease …

Educational Case: Mantle Cell Lymphoma, Brenda Mai, Karan Saluja, Zhihong Hu, Nghia D Nguyen, Amer Wahed, Xiaohong Iris Wang, Lei Chen

Faculty, Staff and Student Publications

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.

Wellness Project Implementation Within Houston's Faith And Diabetes Initiative: A Mixed Methods Study

Faculty, Staff and Student Publications

BACKGROUND: Faith-based health promotion has shown promise for supporting healthy lifestyles, but has limited evidence of reaching scale or sustainability. In one recent such effort, volunteers from a diverse range of faith organizations were trained as peer educators to implement diabetes self-management education (DSME) classes within their communities. The purpose of this study was to identify factors associated with provision of these classes within six months of peer-educator training.

METHODS: This study used the Consolidated Framework for Implementation Research (CFIR) to identify patterns from interviews, observations, attendance records, and organizational background information. Two research team members thematically coded interview transcripts …

Using Spatial Methods To Better Understand Food Insecurity And Snap Under-Participation In Texas, Ryan Ramphul

Dissertations and Theses (Open Access)

The overall objective of this research is to use spatial methods to better understand food insecurity and SNAP under-participation in Texas. Paper 1 assesses whether a sample of community dwelling Medicare and Medicaid beneficiaries, who screen positive for food insecurity at healthcare locations in Harris County, exhibit a spatial pattern in terms of where they live. In other words, it tests whether or not there are statistically significant neighborhood hot spots or cold spots of food insecurity against a null hypothesis of complete spatial randomness. This approach is novel because it uses address-level data on patients who report being food …

Physician Burnout: Slowing The Burn Through Positive Deviance Strategies, Swapna Reddy

Dissertations and Theses (Open Access)

Introduction: Affecting 42% of physicians in the United States, “physician burnout” is considered a public health crisis with adverse impacts for personal providers, patients and organizations. Though much research has been devoted to the existence and causes of burnout, to date few studies have been conducted to identify factors associated with physician fulfillment. Aims: This dissertation research was intended to increase and improve knowledge of factors effective in contributing to physician professional fulfillment utilizing a Positive Deviance based approach. To that end, two studies were conducted: the first, a narrative review of the literature to identify specific correlates of physician …

Bayesian Modeling Of Censored Data With Application To Meta-Analysis Of Immunotherapy Trials, Xinyue Qi

Dissertations and Theses (Open Access)

My dissertation builds on a systematic review of 125 clinical trials reporting on treatment-related adverse events (AEs) associated with PD-1/PD-L1 inhibitors published from 2010 to 2018. The motivating dataset contained the following study-level components extracted from each publication: trial name, number of treated patients, selected immunotherapy drug, dosing schedule, cancer type, number of AEs within each category, and the pre-specified criteria for AE reporting. The number of AEs were reported based upon all-grade (Grade 1-5) and Grade 3 or higher (Grade 3-5) severity. My overall objective was to increase our understanding of the toxicity profiles of five most common cancer …

Systematic Review With Meta-Analysis: Prevalence Of Prior And Concurrent Barrett’S Oesophagus In Oesophageal Adenocarcinoma Patients, Mimi C Tan, Nabil Mansour, Donna L White, Amy Sisson, Hashem B El-Serag, Aaron P Thrift

Library Staff Publications

BACKGROUND: The proportions of patients with oesophageal adenocarcinoma (OAC) diagnosed by Barrett's oesophagus surveillance or with pre-existing Barrett's oesophagus are unclear.

AIM: To estimate the prevalence of prior and concurrent Barrett's oesophagus diagnosis among patients with OAC or oesophagogastric junction adenocarcinomas (OGJAC).

METHODS: We searched PubMed and Embase to identify studies published 1966-1/8/2020 that examined the prevalence of prior (≥6 months) or concurrent Barrett's diagnosis (at cancer diagnosis) among OAC and OGJAC patients. Random effects models estimated overall and stratified pooled prevalence rates.

RESULTS: A total of 69 studies, including 33 002 OAC patients (53 studies) and 2712 patients with …

Covid-19 Testnorm: A Tool To Normalize Covid-19 Testing Names To Loinc Codes, Xiao Dong, Jianfu Li, Ekin Soysal, Jiang Bian, Scott L Duvall, Elizabeth Hanchrow, Hongfang Liu, Kristine E Lynch, Michael Matheny, Karthik Natarajan, Lucila Ohno-Machado, Serguei Pakhomov, Ruth Madeleine Reeves, Amy M Sitapati, Swapna Abhyankar, Theresa Cullen, Jami Deckard, Xiaoqian Jiang, Robert Murphy, Hua Xu

Faculty, Staff and Student Publications

Large observational data networks that leverage routine clinical practice data in electronic health records (EHRs) are critical resources for research on coronavirus disease 2019 (COVID-19). Data normalization is a key challenge for the secondary use of EHRs for COVID-19 research across institutions. In this study, we addressed the challenge of automating the normalization of COVID-19 diagnostic tests, which are critical data elements, but for which controlled terminology terms were published after clinical implementation. We developed a simple but effective rule-based tool called COVID-19 TestNorm to automatically normalize local COVID-19 testing names to standard LOINC (Logical Observation Identifiers Names and Codes) …

Rna-Gps Predicts High-Resolution Rna Subcellular Localization And Highlights The Role Of Splicing, Kevin E Wu, Kevin R Parker, Furqan M Fazal, Howard Y Chang, James Zou

Faculty, Staff and Students Publications

Subcellular localization is essential to RNA biogenesis, processing, and function across the gene expression life cycle. However, the specific nucleotide sequence motifs that direct RNA localization are incompletely understood. Fortunately, new sequencing technologies have provided transcriptome-wide atlases of RNA localization, creating an opportunity to leverage computational modeling. Here we present RNA-GPS, a new machine learning model that uses nucleotide-level features to predict RNA localization across eight different subcellular locations-the first to provide such a wide range of predictions. RNA-GPS's design enables high-throughput sequence ablation and feature importance analyses to probe the sequence motifs that drive localization prediction. We find localization …

Impact Of Covid-19 On Pediatric Gastroenterology Fellow Training In North America, Daniel Mallon, John F Pohl, Uma P Phatak, Melissa Fernandes, John M Rosen, Sarah S Lusman, Cade M Nylund, Candi S Jump, Aliza B Solomon, Arvind Srinath, Andrew Singer, Rula Harb, Norberto Rodriguez-Baez, Kristin L Whitfield Van Buren, Shifra Koyfman, Riha Bhatt, Dellys M Soler-Rodriguez, Mamata Sivagnanam, Christine K Lee, Naspghan Training Committee Covid-19 Survey Working Group

Faculty, Staff and Students Publications

BACKGROUND: The COVID-19 pandemic has drastically changed healthcare systems and training around the world. The Training Committee of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition sought to understand how COVID-19 has affected pediatric gastroenterology fellowship training.

METHODS: A 21 question survey was distributed to all 77 pediatric gastroenterology fellowship program directors (PDs) in the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition program director database via email on April 7. Responses collected through April 19, 2020 were analyzed using descriptive statistics.

RESULTS: Fifty-one of 77 (66%) PDs from the United States, Canada, and Mexico responded to …

Association Analysis Of Driver Gene-Related Genetic Variants Identified Novel Lung Cancer Susceptibility Loci With 20,871 Lung Cancer Cases And 15,971 Controls, Yuzhuo Wang, Olga Y Gorlova, Ivan P Gorlov, Meng Zhu, Juncheng Dai, Demetrius Albanes, Stephen Lam, Adonina Tardon, Chu Chen, Gary E Goodman, Stig E Bojesen, Maria Teresa Landi, Mattias Johansson, Angela Risch, Heunz-Erich Wichmann, Heike Bickeboller, David C Christiani, Gad Rennert, Susanne M Arnold, Paul Brennan, John K Field, Sanjay Shete, Loïc Le Marchand, Olle Melander, Hans Brunnstrom, Geoffrey Liu, Rayjean J Hung, Angeline S Andrew, Lambertus A Kiemeney, Shanbeh Zienolddiny, Kjell Grankvist, Mikael Johansson, Neil E Caporaso, Penella J Woll, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Victoria L Stevens, Hongxia Ma, Guangfu Jin, Zhibin Hu, Christopher I Amos, Hongbing Shen

Faculty, Staff and Students Publications

BACKGROUND: A substantial proportion of cancer driver genes (CDG) are also cancer predisposition genes. However, the associations between genetic variants in lung CDGs and the susceptibility to lung cancer have rarely been investigated.

METHODS: We selected expression-related single-nucleotide polymorphisms (eSNP) and nonsynonymous variants of lung CDGs, and tested their associations with lung cancer risk in two large-scale genome-wide association studies (20,871 cases and 15,971 controls of European descent). Conditional and joint association analysis was performed to identify independent risk variants. The associations of independent risk variants with somatic alterations in lung CDGs or recurrently altered pathways were investigated using data …

Combined Lenvatinib And Pembrolizumab As Salvage Therapy In Advanced Adrenal Cortical Carcinoma, Sara Bedrose, Kevin Charles Miller, Lina Altameemi, Mohamed S Ali, Sameh Nassar, Naveen Garg, Marilyne Daher, Keith D Eaton, Jeffrey Thomas Yorio, Davey B Daniel, Matthew Campbell, Keith C Bible, Mabel Ryder, Ashish V Chintakuntlawar, Mouhammed Amir Habra

Faculty, Staff and Students Publications

BACKGROUND: There is no effective systemic therapy for metastatic adrenal cortical carcinoma (ACC) after failure of platinum-based chemotherapy. The efficacies of single-agent oral multikinase inhibitors (MKIs) or salvage immune checkpoint inhibitors (CPIs) have been very limited. It is unknown whether combining CPIs, such as pembrolizumab (PEM), with other therapies, such as MKIs, could yield higher response rates in ACC, yet this combination has shown promise in other cancers. Herein, we describe the first case series using PEM in combination with the MKI lenvatinib (LEN) in patients with progressive, metastatic ACC.

METHODS: A retrospective case series describing the use of LEN/PEM …

Renal Trajectory Patterns Are Associated With Postdischarge Mortality In Patients With Cirrhosis And Acute Kidney Injury, Ayse L Mindikoglu, Ruben Hernaez, Yan Liu, Jennifer R Kramer, Thomas Taylor, Abbas Rana, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Little is known about long-term outcomes of acute kidney injury (AKI) in patients with cirrhosis. Outcomes can vary with stage of AKI, chronic kidney disease, and trajectory of renal function.

METHODS: We collected data from the Department of Veterans Affairs and identified 6917 patients with cirrhosis who developed AKI during hospitalization at any of its 127 hospitals, from 2004 through 2014. We used latent class analysis of serial creatinine measurements during the index hospitalization to determine trajectories of renal function.

RESULTS: Overall, 32% of patients died within 90 days of discharge from the hospital and 48% of …

Mechanism Of Ligand Activation Of A Eukaryotic Cyclic Nucleotide-Gated Channel, Xiangdong Zheng, Ziao Fu, Deyuan Su, Yuebin Zhang, Minghui Li, Yaping Pan, Huan Li, Shufang Li, Robert A Grassucci, Zhenning Ren, Zhengshan Hu, Xueming Li, Ming Zhou, Guohui Li, Joachim Frank, Jian Yang

Faculty, Staff and Students Publications

Cyclic nucleotide-gated (CNG) channels convert cyclic nucleotide (CN) binding and unbinding into electrical signals in sensory receptors and neurons. The molecular conformational changes underpinning ligand activation are largely undefined. We report both closed- and open-state atomic cryo-EM structures of a full-length Caenorhabditis elegans cyclic GMP-activated channel TAX-4, reconstituted in lipid nanodiscs. These structures, together with computational and functional analyses and a mutant channel structure, reveal a double-barrier hydrophobic gate formed by two S6 amino acids in the central cavity. cGMP binding produces global conformational changes that open the cavity gate located ~52 Å away but do not alter the structure …

Low Yield Of Hepatitis C Infection In An Outreach Screening Program In Harris County, Texas, Hyun-Seok Kim, Rosalia Guerrero, Shane W Reader, Maria Daheri, Maya Balakrishnan, Catherine L Troisi, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

A community outreach hepatitis C virus (HCV) infection screening program provided low yield of detecting HCV-infected patients, linking them to our hepatology clinic for treatment. Our data underscore that most of the yield was related to addiction centers and birth cohort; these groups should be targeted by future interventions.

Models For Small Area Estimation For Census Tracts, Fan Li

Faculty, Staff and Student Publications

This study examines issues of Small Area Estimation (SAE) that are raised by reliance on the American Community Survey (ACS), which reports tract-level data based on much smaller samples than the decennial census long-form that it replaced. We demonstrate the problem using a 100% transcription of microdata from the 1940 census. By drawing many samples from two major cities, we confirm a known pattern: random samples yield unbiased point estimates of means or proportions, but estimates based on smaller samples have larger average errors in measurement and greater risk of large error. Sampling variability also inflates estimates of measures of …

Nuclear Localization Of A Novel Calpain-2 Mediated Junctophilin-2 C-Terminal Cleavage Peptide Promotes Cardiomyocyte Remodeling, Satadru K Lahiri, Ann P Quick, Benoit Samson-Couterie, Mohit Hulsurkar, Ies Elzenaar, Ralph J Van Oort, Xander H T Wehrens

Faculty, Staff and Students Publications

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. Patients with HF exhibit a loss of junctophilin-2 (JPH2), a structural protein critical in forming junctional membrane complexes in which excitation-contraction takes place. Several mechanisms have been proposed to mediate the loss of JPH2, one being cleavage by the calcium-dependent protease calpain. The downstream mechanisms underlying HF progression after JPH2 cleavage are presently poorly understood. In this study, we used Labcas to bioinformatically predict putative calpain cleavage sites on JPH2. We identified a cleavage site that produces a novel C-terminal JPH2 peptide (JPH2-CTP) using several domain-specific antibodies. Western …

Lactate Dehydrogenase Rising: Bleeding Or Clotting?, Ashleigh Long, Amin Yehya, David Baran

The VAD Journal

Modern continuous-flow ventricular assist devices (VADs) have greatly improved the survival of patients with end stage heart failure. However, they are associated with adverse effects, including cerebrovascular accidents (CVA), bleeding, infection, and device thrombosis. Definitive measures to evaluate for pump thrombosis can be challenging; hence, multiple laboratory and imaging modalities have been studied to help guide decision making. Lactate dehydrogenase (LDH) has proven to be a reliable test when used in the appropriate clinical settings to help diagnose pump thrombosis. When a patient presents with both signs of life-threatening cerebral hemorrhage and VAD thrombosis, the clinical picture can be quite …