Digital Commons Network^™

Creating A Collaborative Trauma-Informed Interdisciplinary Citywide Victim Services Model Focused On Health Care For Survivors Of Human Trafficking, Juhi Jain, Mackenzie Bennett, Mark D Bailey, Daniel Liaou, Sheri-Ann O Kaltiso, Jordan Greenbaum, Kimberly Williams, Mollie R Gordon, Melissa I M Torres, Phuong T Nguyen, John H Coverdale, Victor Williams, Cayla Hari, Samantha Rodriguez, Temilola Salami, Jonell E Potter

Center for Medical Ethics and Health Policy Staff Publications

Although human trafficking is recognized as a public health issue, research on the health effects of human trafficking and best intervention practices is limited. We describe 2 citywide collaborative victim services models, the THRIVE (Trafficking, Healthcare, Resources, and Interdisciplinary Victim Services and Education) Clinic at the University of Miami and Jackson Health System in Miami, Florida, and the Greater Houston Area Pathways for Advocacy-based, Trauma-Informed Healthcare (PATH) Collaborative at Baylor College of Medicine, CommonSpirit Health, and San Jose Clinic in Houston, Texas, funded in part by the Office for Victims of Crime, which focus on trauma-informed health care delivery for …

Investigation Of Urinary Metabolomics In A Phase I Hookworm Vaccine Trial In Gabon, Madeleine Eunice Betouke Ongwe, Yoanne D Mouwenda, Koen A Stam, Peter G Kremsner, Bertrand Lell, David Diemert, Jeff Bethony, Maria E Bottazzi, Peter J Hotez, Remko V Leeuwen, Martin P Grobusch, Ayola A Adegnika, Oleg A Mayboroda, Maria Yazdanbakhsh

Center for Medical Ethics and Health Policy Staff Publications

Metabolomics provides a powerful tool to study physiological changes in response to various perturbations such as vaccination. We explored whether metabolomic changes could be seen after vaccination in a phase I trial where Gabonese adults living either in rural or semi-urban areas received the subunit hookworm vaccine candidates (Na-GST-1 and Na-APR-1 (M74) adjuvanted with Alhydrogel plus GLA-AF (n = 24) or the hepatitis B vaccine (n = 8) as control. Urine samples were collected and assayed using targeted 1H NMR spectroscopy. At baseline, a set of metabolites significantly distinguished rural from semi-urban individuals. The pre- and post-vaccination comparisons indicated significant …

Rev-Erb Is Essential In Cardiac Fibroblasts Homeostasis, Xiaokang Luo, Shiyang Song, Lei Qi, Chih-Liang Tien, Hui Li, Weiyi Xu, Theodore Lemuel Mathuram, Thomas Burris, Yuanbiao Zhao, Zheng Sun, Lilei Zhang

Faculty, Staff and Students Publications

REV-ERB agonists have shown antifibrotic effects in the heart and other organs. The function of REV-ERB in the cardiac fibroblasts remains unstudied. Here, we characterize the functional difference of REV-ERB in mouse embryonic fibroblasts and cardiac fibroblasts using genetic deletion of REV-ERBα and ß in vitro. We show that REV-ERB α/β double deleted cardiac fibroblasts have reduced viability and proliferation, but increased migration and myofibroblasts activation. Thus, REV-ERB α/β has essential cell-autonomous role in cardiac fibroblasts in maintaining them in a healthy, quiescent state. We also show that existing REV-ERB agonist SR9009 strongly suppresses cardiac fibroblasts activation but in …

Metastatic Insulinoma Presenting With Postprandial Hypoglycemia, Monique Debrah Maher, Dimpi Nitin Desai, Mandeep Bajaj

Faculty, Staff and Students Publications

BACKGROUND/OBJECTIVE: Patients with an insulinoma, a type of pancreatic neuroendocrine tumor, typically present with fasting hypoglycemia but can rarely present exclusively with postprandial hypoglycemia.

CASE REPORT: A 69-year-old man presented with episodes of postprandial blurry vision, sweating, and confusion for the last 2 years that were becoming more frequent over the last several weeks. Home blood glucose measurements revealed postprandial hypoglycemia (glucose level, 45-70 mg/dL), and symptoms were consistent with the Whipple triad. Continuous glucose monitoring revealed only postprandial hypoglycemia within 2 hours following meals. An outpatient fast was conducted with detectable insulin (6 μIU/mL) and C-peptide (2.0 ng/mL) levels …

Lessons Learned From An Enterprise-Wide Clinical Datathon, Andrew J Zimolzak, Jessica A Davila, Vamshi Punugoti, Ashok Balasubramanyam, Paul E Klotman, Laura A Petersen, Ryan H Rochat, Gloria Liao, Rory R Laubscher, Lee Leiber, Christopher I Amos

Faculty, Staff and Students Publications

In 2020, Baylor College of Medicine held a datathon to inform potential users of a new data warehouse, allow users to address clinical questions, identify warehouse capabilities and limitations, foster collaborations, and engage trainees. Senior faculty selected proposals based on feasibility and impact. Selectees worked with Information Technology for 2 months and presented findings. A survey of participants showed diverse levels of experience, high perceived value of the datathon, high rates of collaboration, and significant increases in knowledge. A datathon can promote familiarity with a new data warehouse, guide data warehouse improvement, and promote collaboration.

Esophageal Perforation Successfully Treated With Evt, Kavea Panneerselvam, Ronald Samuel, Robert J Sealock

Faculty, Staff and Students Publications

Esophageal perforation is rare and carries high morbidity and mortality. A high degree of suspicion is needed for timely diagnosis and treatment. A 54-year-old man presented with fever and confusion. Imaging revealed air in the hepatic inferior vena cava and concern for a fistula between the distal esophagus and the inferior vena cava. An upper endoscopic evaluation revealed a dental floss pick penetrating the distal esophagus. The foreign body was removed, and endoluminal vacuum therapy was used to close the perforation. Endoluminal vacuum therapy is an emerging therapy to treat full-thickness gastrointestinal injuries.

Widening Health Disparities: Increasing Cholangiocarcinoma Incidence In An Underserved Population, Disha Kumar, Varun Bansal, Syed A Raza, Aaron P Thrift, Hoda M Malaty, Robert J Sealock

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Cholangiocarcinoma is a relatively rare malignancy with high mortality. In the U.S., incidence rates of cholangiocarcinoma have increased, particularly affecting younger age groups and Hispanic and Asian individuals. We investigated the incidence of cholangiocarcinoma in a largely under-represented, minority population.

METHODS: We performed a retrospective cohort study from 2005 to 2017 among adults in a county-funded healthcare system in Harris County, Texas. Incidence rate ratios were computed to compare age-standardized rates using U.S. standard population between 2 time periods: 2005-2011 and 2012-2017.

RESULTS: We identified 139 cholangiocarcinoma cases (64% intrahepatic, 36% extrahepatic). The median age at diagnosis …

Mental Health And Access To Medical Care In Patients With Chronic Cardiovascular Conditions: An Analysis Of The Behavior Risk Factor Surveillance System, Riyad Y Kherallah, Mahmoud Al Rifai, Jing Liu, Sina Kianoush, Arunima Misra, Salim S Virani

Faculty, Staff and Students Publications

INTRODUCTION: Poor mental health is associated with worse outcomes for chronic diseases. It is unclear whether mental illness predisposes to difficulties with healthcare access.

METHODS: Using a combined dataset of the 2016-2019 Behavioral Risk Factor Surveillance System, this study focused on individuals who reported a chronic cardiovascular condition. Weighted multivariable logistic regression analyses were used to explore the association between domains of mental health and measures of healthcare access including delaying medical care, more than one year since last routine checkup, lack of a primary care physician, and cost-related medication nonadherence.

RESULTS: Among 1,747,397 participants, 27% had a chronic cardiovascular …

Endpoints In Heart Failure Drug Development, Aliza Hussain, Arunima Misra, Biykem Bozkurt

Faculty, Staff and Students Publications

Heart failure (HF) is a major health problem worldwide. The development of effective drug and/or device therapy is crucial to mitigate the significant morbidity, mortality and healthcare costs associated with HF. The choice of endpoint in clinical trials has important practical and clinical implications. Outcomes of interest including mortality and HF hospitalisations provide robust evidence for regulatory approval granted there is sufficiency of safety data. At the same time, it is important to recognise that HF patients experience significant impairments in functional capacity and quality of life, underscoring the need to incorporate parameters of symptoms and patient-reported outcomes in clinical …

Management Of A Novel Autoimmune Disease, Copa Syndrome, In Pregnancy, Archana Ayyar, Rachel D Seaman, Kalpalatha Guntupalli, Mary C Tolcher

Faculty, Staff and Students Publications

BACKGROUND: COPA syndrome is a rare autoimmune disease, demonstrating an autosomal dominant inheritance pattern with variable penetration that occurs more frequently in females than males. This disease manifests in childhood as pulmonary hemorrhage, arthritis, and renal disease.

CASE: We present a case of obstetric management of a 20-year-old nulligravida patient with a diagnosis of COPA syndrome. Her case was further complicated by multiple antepartum admissions for hypoxemia and a complex psychosocial history of substance use. On her first antepartum admission, rheumatology recommended management with hydroxychloroquine, inhaled corticosteroids (budesonide), and bronchodilators (albuterol inhaler) as needed. On admission for induction of labor, …

Meta-Analysis Comparing Outcomes Of High-Power Short-Duration And Low-Power Long-Duration Radiofrequency Ablation For Atrial Fibrillation, Dibbendhu Khanra, Abdul Hamid, Saurabh Deshpande, Anindya Mukherjee, Sanjiv Petkar, Mohammad Saeed, Indranill Basu-Ray

Faculty, Staff and Students Publications

OBJECTIVE: High power short duration (HPSD) ablation strategy is proposed to be more effective than low power long duration (LPLD) for radiofrequency ablation of atrial fibrillation. Although small trials abound, data from a large cohort are lacking. This meta-analysis compares all the existing studies comparing these two approaches to evaluate perceived advantages of one over the other.

METHODS: A systematic search of PubMed, EMBASE, and Cochrane databases identified studies comparing HPSD to LPLD ablation. All the analyses used the random-effects model.

RESULTS: Ablation settings varied widely across 20 studies comprising 2,136 patients who underwent HPSD and 1,753 patients who underwent …

Foxo1 Is Present In Stomach Epithelium And Determines Gastric Cell Distribution, Wendy M Mckimpson, Taiyi Kuo, Takumi Kitamoto, Sei Higuchi, Jason C Mills, Rebecca A Haeusler, Domenico Accili

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Stomach cells can be converted to insulin-producing cells by Neurog3, MafA, and Pdxl over-expression. Enteroendocrine cells can be similarly made to produce insulin by the deletion of FOXO1. Characteristics and functional properties of FOXO1-expressing stomach cells are not known.

METHODS: Using mice bearing a FOXO1-GFP knock-in allele and primary cell cultures, we examined the identity of FOXO1-expressing stomach cells and analyzed their features through loss-of-function studies with red-to-green fluorescent reporters.

RESULTS: FOXO1 localizes to a subset of Neurog3 and parietal cells. FOXO1 deletion ex vivo or in vivo using Neurog3-cre or Atp4b-cre increased numbers of parietal cells, …

Severe Inflammatory Colitis Related To Encorafenib And Binimetinib Following Immune Checkpoint Inhibitor Therapy, Aaron G Issac, David Szafron, Dongguang Wei, Jennifer L Mcquade, Yinghong Wang

Faculty, Staff and Students Publications

Encorafenib, a BRAF kinase inhibitor, in combination with binimetinib, a selective MEK inhibitor have known gastrointestinal adverse events; however, adverse colitis events have not been well studied. We report a case series of 4 patients with melanoma who developed inflammatory colitis after BRAF and MEK inhibition with encorafenib and binimetinib, respectively. In the setting of immune checkpoint inhibitor use, BRAF and MEK inhibitors can cause significant inflammatory colitis with endoscopic patterns of predominant right colon ulcerations. It can lead to significant morbidity and frequent interruption of cancer treatment. Early recognition and prompt intervention are critical to improving patient outcomes.

Cytomegalovirus Infection Among Patients With Cancer Receiving Immune Checkpoint Inhibitors, Kavea Panneerselvam, David Szafron, Rajan N Amin, Dongguang Wei, Dongfeng Tan, Mehmet Altan, Pablo C Okhuysen, Malek Shatila, Gottumukkala Subba Raju, Anusha S Thomas, Yinghong Wang

Faculty, Staff and Students Publications

BACKGROUND: Immune checkpoint inhibitors (ICIs), used for the treatment of solid and hematologic malignancies, come with the risk of immune-related adverse events (irAEs). Opportunistic infections (e.g., cytomegalovirus [CMV]) mimic irAE symptoms and are understudied in this population. We aimed to describe the incidence, characteristics, treatment and outcomes of CMV infection in ICI-treated patients.

METHODS: We conducted a single-center retrospective review of all adult patients who were CMV-positive after ICI therapy between 06/2011 and 05/2020. A CMV-positive non-ICI cohort was matched to the ICI group based on age, sex and cancer type. Variables of interest were collected through electronic medical records. …

Inpatient Coding System And Opportunities For Documentation Optimization: An Interactive Session For Internal Medicine Residents, Lindsey Jordan Gay, Doris Lin, Ziba Colah, Glynda Raynaldo

Faculty, Staff and Students Publications

INTRODUCTION: The Inpatient Prospective Payment System, the framework for categorization of admissions, is based upon physician documentation leading to International Classification of Diseases, Tenth Revision code generation and Medical Severity Diagnosis-Related Group (MS-DRG) assignment. In this curriculum, we introduced internal medicine residents to this inpatient coding framework and its effects on hospital quality metrics and reimbursement. We focused on educating learners about the importance of physicians being proficient in providing thorough and specific clinical documentation to produce appropriate DRG assignment.

METHODS: Internal medicine residents participated in a 90-minute session that introduced the basic framework of inpatient coding, discussed effects of …

Dat3m: A Data Tracker For Multi-Faceted Management Of Multi-Site Clinical Research Data Submission, Curation, Master Inventorying, And Sharing, Shiqiang Tao, Licong Cui, Wei-Chun Chou, Samden Lhatoo, Guo-Qiang Zhang

Faculty, Staff and Student Publications

Managing research data is an important and challenging aspect of clinical studies, especially for multi-site collaboratives. To address this challenge, we designed, developed and deployed a multi-faceted, multi-level interactive data tracker (DaT3M) for multi-site clinical research data submission, curation, master inventorying, and sharing. Components of DaT3M include data overview, data portal, data status panel, data query engine, and data downloader. DaT3M managed clinical research data for the Center for SUDEP Research (CSR). The CSR instance of DaT3M includes 2,743 subjects from seven data contributing institutions, 7 data modalities and 10,678 data components: 3,398 Epilepsy Monitoring Unit reports, 3,440 electroencephalography recordings, …

An Evidence-Based, Structured, Expert Approach To Selecting Essential Indicators Of Primary Care Quality, Sylvia J Hysong, Kelley Arredondo, Ashley M Hughes, Houston F Lester, Frederick L Oswald, Laura A Petersen, Lechauncy Woodard, Edward Post, Shelly Deperalta, Daniel R Murphy, Jason Mcknight, Karin Nelson, Paul Haidet

Faculty, Staff and Students Publications

BACKGROUND: The purpose of this article is to illustrate the application of an evidence-based, structured performance measurement methodology to identify, prioritize, and (when appropriate) generate new measures of health care quality, using primary care as a case example. Primary health care is central to the health care system and health of the American public; thus, ensuring high quality is essential. Due to its complexity, ensuring high-quality primary care requires measurement frameworks that can assess the quality of the infrastructure, workforce configurations, and processes available. This paper describes the use of the Productivity Measurement and Enhancement System (ProMES) to compile a …

Temporal Cohort Logic, Guo-Qiang Zhang, Xiaojin Li, Yan Huang, Licong Cui

Faculty, Staff and Student Publications

We introduce a new logic, called Temporal Cohort Logic (TCL), for cohort specification and discovery in clinical and population health research. TCL is created to fill a conceptual gap in formalizing temporal reasoning in biomedicine, in a similar role that temporal logics play for computer science and its applications. We provide formal syntax and semantics for TCL and illustrate the various logical constructs using examples related to human health. Relationships and distinctions with existing temporal logical frameworks are discussed. Applications in electronic health record (EHR) and in neurophysiological data resource are provided. Our approach differs from existing temporal logics, in …

Diagnosis And Interpretation Of Testing For Cat Scratch Disease, Nasim Khalfe, Doris Lin

Faculty, Staff and Students Publications

Cat scratch disease (CSD) is an infectious disease caused by Bartonella henselae that presents as regional lymphadenopathy which can appear within weeks after a cat scratch. There is no gold standard for diagnosis. Rather, clinicians rely on an amalgam of criteria to make a definitive diagnosis. We describe a case of a 44-year-old woman with six cats who presented with a painful left inguinal mass, had splenic lesions on imaging, and had positive serology but a negative polymerase chain reaction test for B. henselae.

Causal Inference Of Genetic Variants And Genes In Amyotrophic Lateral Sclerosis, Siyu Pan, Xinxuan Liu, Tianzi Liu, Zhongming Zhao, Yulin Dai, Yin-Ying Wang, Peilin Jia, Fan Liu

Faculty, Staff and Student Publications

Amyotrophic lateral sclerosis (ALS) is a fatal progressive multisystem disorder with limited therapeutic options. Although genome-wide association studies (GWASs) have revealed multiple ALS susceptibility loci, the exact identities of causal variants, genes, cell types, tissues, and their functional roles in the development of ALS remain largely unknown. Here, we reported a comprehensive post-GWAS analysis of the recent large ALS GWAS (n = 80,610), including functional mapping and annotation (FUMA), transcriptome-wide association study (TWAS), colocalization (COLOC), and summary data-based Mendelian randomization analyses (SMR) in extensive multi-omics datasets. Gene property analysis highlighted inhibitory neuron 6, oligodendrocytes, and GABAergic neurons (Gad1/Gad2) as …

A Novel Framework To Estimate Cognitive Impairment Via Finger Interaction With Digital Devices, Ashley A Holmes, Shikha Tripathi, Emily Katz, Ijah Mondesire-Crump, Rahul Mahajan, Aaron Ritter, Teresa Arroyo-Gallego, Luca Giancardo

Faculty, Staff and Student Publications

Measuring cognitive function is essential for characterizing brain health and tracking cognitive decline in Alzheimer's Disease and other neurodegenerative conditions. Current tools to accurately evaluate cognitive impairment typically rely on a battery of questionnaires administered during clinical visits which is essential for the acquisition of repeated measurements in longitudinal studies. Previous studies have shown that the remote data collection of passively monitored daily interaction with personal digital devices can measure motor signs in the early stages of synucleinopathies, as well as facilitate longitudinal patient assessment in the real-world scenario with high patient compliance. This was achieved by the automatic discovery …

Sr9009 Improves Heart Function After Pressure Overload Independent Of Cardiac Rev-Erb, Hui Li, Shiyang Song, Chih-Liang Tien, Lei Qi, Andrea Graves, Eleni Nasiotis, Thomas P Burris, Yuanbiao Zhao, Zheng Sun, Lilei Zhang

Faculty, Staff and Students Publications

The core clock component REV-ERB is essential for heart function. Previous studies show that REV-ERB agonist SR9009 ameliorates heart remodeling in the pressure overload model with transverse aortic constriction (TAC). However, it is unknown whether SR9009 indeed works through cardiac REV-ERB, given that SR9009 might target other proteins and that REV-ERB in non-cardiac tissues might regulate cardiac functions indirectly. To address this question, we generated the REV-ERBα/β cardiac-specific double knockout mice (cDKO). We found that REV-ERB cardiac deficiency leads to profound dilated cardiac myopathy after TAC compared to wild-type (WT) control mice, confirming the critical role of REV-ERB in protecting …

Plasma Diaphanous Related Formin 1 Levels Are Associated With Altered Glucose Metabolism And Insulin Resistance In Patients With Polycystic Ovary Syndrome: A Case Control Study, Xing Li, Mingyu Liao, Jiaqing Shao, Weixin Li, Liu Shi, Dong Wang, Juan Ni, Qiuyue Shen, Fan Yang, Guiliang Peng, Ling Zhou, Yuling Zhang, Zheng Sun, Hongting Zheng, Min Long

Faculty, Staff and Students Publications

BACKGROUND: Diaphanous related formin 1 (DIAPH1) is a novel component of advanced glycation end product (AGE) signal transduction that was recently found to participate in diabetes-related disorders, obesity, and androgen hormones. We investigated whether plasma DIAPH1 levels were a potential prognostic predictor for polycystic ovary syndrome (PCOS).

METHODS: The levels of circulating plasma DIAPH1 and indicators of glucose, insulin, lipid metabolism, liver enzymes, kidney function, sex hormones, and inflammation were measured in 75 patients with PCOS and 77 healthy participants. All of the participants were divided into normal-weight (NW) and overweight/obese (OW) subgroups. Statistical analyses were performed with R studio. …

Selective Vulnerability Of The Intermediate Retinal Capillary Plexus Precedes Retinal Ganglion Cell Loss In Ocular Hypertension, Priyamvada M Pitale, Guofu Shen, Rohini R Sigireddi, Maria Polo-Prieto, Yong H Park, Solomon E Gibson, Peter D Westenskow, Roomasa Channa, Benjamin J Frankfort

Faculty, Staff and Students Publications

Introduction: Glaucoma, a disease of retinal ganglion cell (RGC) injury and potentially devastating vision loss, is associated with both ocular hypertension (OHT) and reduced ocular blood flow. However, the relationship between OHT and retinal capillary architecture is not well understood. In this project, we studied microvasculature damage in mice exposed to mild levels of induced OHT.

Methods: Mild OHT was induced with the microbead model for 2 weeks. At this time point, some retinas were immunostained with CD31 (endothelium), Collagen IV (basement membrane), and RBPMS (RGCs) for z-stack confocal microscopy. We processed these confocal images to distinguish the three retinal …

Problems In Csf And Ophthalmic Disease Research, Ryan Machiele, Benjamin Jay Frankfort, Hanspeter Esriel Killer, David Fleischman

Faculty, Staff and Students Publications

There has been significant interest and progress in the understanding of cerebrospinal fluid pressure and its relationship to glaucoma and other ophthalmic diseases. However, just as every physiologic fluid pressure fluctuates, cerebrospinal fluid pressure (CSFP) is similarly dynamic. Coupling this with the difficulty in measuring the pressure, there are many obstacles in furthering this field of study. This review highlights some of the difficulties in CSFP research, including fluid compartmentalization, estimation equations, and pressure fluctuation. Keeping these limitations in mind will hopefully improve the quality and context of this burgeoning field.

Systematic Profiling Of Dnmt3a Variants Reveals Protein Instability Mediated By The Dcaf8 E3 Ubiquitin Ligase Adaptor, Yung-Hsin Huang, Chun-Wei Chen, Venkatasubramaniam Sundaramurthy, Mikołaj Słabicki, Dapeng Hao, Caroline J Watson, Ayala Tovy, Jaime M Reyes, Olga Dakhova, Brielle R Crovetti, Christina Galonska, Minjung Lee, Lorenzo Brunetti, Yubin Zhou, Katrina Tatton-Brown, Yun Huang, Xiaodong Cheng, Alexander Meissner, Peter J M Valk, Lionel Van Maldergem, Mathijs A Sanders, Jamie R Blundell, Wei Li, Benjamin L Ebert, Margaret A Goodell

Faculty, Staff and Students Publications

Clonal hematopoiesis is a prevalent age-related condition associated with a greatly increased risk of hematologic disease; mutations in DNA methyltransferase 3A (DNMT3A) are the most common driver of this state. DNMT3A variants occur across the gene with some particularly associated with malignancy, but the functional relevance and mechanisms of pathogenesis of the majority of mutations are unknown. Here, we systematically investigated the methyltransferase activity and protein stability of 253 disease-associated DNMT3A mutations, and found that 74% were loss-of-function mutations. Half of these variants exhibited reduced protein stability and, as a class, correlated with greater clonal expansion and acute …

A Steroid Receptor Coactivator Small Molecule "Stimulator" Attenuates Post-Stroke Ischemic Brain Injury, Lisa K Mcclendon, Roberto L Garcia, Tyler Lazaro, Ariadna Robledo, Viren Vasandani, Zean Aaron Evan Luna, Abhijit S Rao, Aditya Srivatsan, David M Lonard, Clifford C Dacso, Peter Kan, Bert W O'Malley

Faculty, Staff and Students Publications

Introduction: Pathologic remodeling of the brain following ischemic stroke results in neuronal loss, increased inflammation, oxidative stress, astrogliosis, and a progressive decrease in brain function. We recently demonstrated that stimulation of steroid receptor coactivator 3 with the small-molecule stimulator MCB-613 improves cardiac function in a mouse model of myocardial ischemia. Since steroid receptor coactivators are ubiquitously expressed in the brain, we reasoned that an MCB-613 derivative (MCB-10-1), could protect the brain following ischemic injury. To test this, we administered MCB-10-1 to rats following middle cerebral artery occlusion and reperfusion.

Methods: Neurologic impairment and tissue damage responses were evaluated on day …

Steroid Receptor Coactivators – Their Role In Immunity, Yosi Gilad, David M Lonard, Bert W O'Malley

Faculty, Staff and Students Publications

Steroid Receptor Coactivators (SRCs) are essential regulators of transcription with a wide range of impact on human physiology and pathology. In immunology, SRCs play multiple roles; they are involved in the regulation of nuclear factor-κB (NF-κB), macrophage (MΦ) activity, lymphoid cells proliferation, development and function, to name just a few. The three SRC family members, SRC-1, SRC-2 and SRC-3, can exert their immunological function either in an independent manner or act in synergy with each other. In certain biological contexts, one SRC family member can compensate for lack of activity of another member, while in other cases one SRC can …

Glucocentric Drugs In Cardiovascular Disease Protection And Heart Failure, Khawaja M Talha, Gregg C Fonarow, Salim S Virani, Javed Butler

Faculty, Staff and Students Publications

Evidence for cardiovascular outcomes with older-generation antihyperglycemic drugs in the management of type 2 diabetes is based on aggregated data from prior randomized controlled trials and observational studies that were not focused on prespecified cardiovascular end points. Newer antihyperglycemic medications have undergone a rigorous evaluation of cardiovascular outcomes through randomized controlled trials since the US Food and Drug Administration imposed a mandatory requirement for all glucose-lowering drugs in 2008. The three classes of drugs that have been most extensively studied are dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter-2 (SGLT2) inhibitors, the latter two reporting significant …

Dual Orexin Receptor Antagonists For Treatment Of Insomnia: A Systematic Review And Meta-Analysis On Randomized, Double-Blind, Placebo-Controlled Trials Of Suvorexant And Lemborexant, Habibolah Khazaie, Masoud Sadeghi, Sepideh Khazaie, Max Hirshkowitz, Amir Sharafkhaneh

Faculty, Staff and Students Publications

Study objectives: Recent treatment guidelines for chronic insomnia recommend pharmacological and non-pharmacological therapies. One of the contemporary drug options for insomnia includes dual orexin receptor antagonist (DORA), such as suvorexant and lemborexant. We conducted a systematic review and meta-analysis for the treatment of insomnia with suvorexant and lemborexant based on randomized, double-blind, placebo-controlled Trials.

Methods: We conducted a comprehensive search on three databases (PubMed/Medline, Web of Science, and Cochrane Library) till August 14, 2021, without any restrictions to retrieve the relevant articles. The effect sizes were computed presenting the pooled mean difference or risk ratio along with 95% confidence interval …