Medical Specialties Commons^™

Using Digital Assessment Technology To Detect Neuropsychological Problems In Primary Care Settings, David J Libon, Emily Frances Matusz, Stephanie Cosentino, Catherine C Price, Rod Swenson, Meagan Vermeulen, Terrie Beth Ginsberg, Adaora Obiageli Okoli-Umeweni, Leonard Powell, Robert Nagele, Sean Tobyne, Joyce Rios Gomes-Osman, Alvaro Pascual-Leone

Rowan-Virtua School of Osteopathic Medicine Departmental Research

INTRODUCTION: Screening for neurocognitive impairment and psychological distress in ambulatory primary and specialty care medical settings is an increasing necessity. The Core Cognitive Evaluation™ (CCE) is administered/scored using an iPad, requires approximately 8 min, assesses 3- word free recall and clock drawing to command and copy, asks questions about lifestyle and health, and queries for psychological distress. This information is linked with patients' self- reported concerns about memory and their cardiovascular risks.

METHODS: A total of 199 ambulatory patients were screened with the CCE as part of their routine medical care. The CCE provides several summary indices, and scores on …

Embryological Basis Of Polydactyly In 56 Years Old Male Patient, Sarayu M

Digital Journal of Clinical Medicine

Polydactyly is a common congenital hand deformity. The limb buds are the precursor structures of the limbs. Their formation begins in the 4th week, with the activation of mesenchymal cells in the somatic layer of lateral plate mesoderm. As mesenchyme cells enter the limb region, they secrete factors that induce the overlying ectoderm to form a structure called the apical ectodermal ridge (AER). Polydactyly is the congenital deformities which is seen in 1000 births. To observe and study the various type of polydactyly in relation to the preaxial polydactyly and postaxial polydactyly with other classification. So, thumb polydactyly is a …

Gonadotropin-Secreting And Thyrotropin-Secreting Pituitary Adenomas: A Single-Center Experience, Manjiri Karlekar, Chakra Diwaker, Vijaya Sarathi, Anurag Lila, Anima Sharma, Saba Samad Memon, Virendra Patil, Tushar Bandgar

Faculty, Staff and Student Publications

OBJECTIVE: Data regarding rare FPAs from India, a resource limited setting, are limited. We describe a case series of rare FPAs from a single center in western India.

MATERIALS AND METHODS: This was a retrospective case record review of patients diagnosed between January 2010 and July 2022. The diagnosis was based on biochemical(inappropriately elevated serum FSH/LH) and pathologic (positive immunostaining for FSH/LH) features in patients with FGA, and elevated serum thyroid hormones and normal/elevated TSH in patients with TSHomas.

RESULTS: We identified 11 patients with a total of six FGAs (median age 43.5 years, five men, one FGA cosecreting TSH, …

Pmca Screening Of Retropharyngeal Lymph Nodes In White-Tailed Deer And Comparisons With Elisa And Ihc, Rebeca Benavente, J Hunter Reed, Mitch Lockwood, Rodrigo Morales

Faculty, Staff and Student Publications

Chronic wasting disease (CWD) is a prion disease affecting cervids. CWD diagnosis is conducted through enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) in retropharyngeal lymph nodes. Unfortunately, these techniques have limited sensitivity against the biomarker (CWD-prions). Two in vitro prion amplification techniques, real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA), have shown promise in detecting CWD-prions in tissues and bodily fluids. Recent studies have demonstrated that RT-QuIC yields similar results compared to ELISA and IHC. Here, we analyzed 1003 retropharyngeal lymph nodes (RPLNs) from Texas white-tailed deer. PMCA detected CWD at a higher rate compared to ELISA/IHC, identified …

The 2022 American College Of Cardiology Expert Consensus On The Role Of Nonstatin Therapies: An Expert-Guided Tour, Mini G Varughese, Christie M Ballantyne

The Texas Heart Institute Journal

No abstract provided.

Circulating Metabolites May Illustrate Relationship Of Alcohol Consumption With Cardiovascular Disease, Yi Li, Mengyao Wang, Xue Liu, Jian Rong, Patricia Emogene Miller, Roby Joehanes, Tianxiao Huan, Xiuqing Guo, Jerome I Rotter, Jennifer A Smith, Bing Yu, Matthew Nayor, Daniel Levy, Chunyu Liu, Jiantao Ma

Faculty, Staff and Student Publications

BACKGROUND: Metabolite signatures of long-term alcohol consumption are lacking. To better understand the molecular basis linking alcohol drinking and cardiovascular disease (CVD), we investigated circulating metabolites associated with long-term alcohol consumption and examined whether these metabolites were associated with incident CVD.

METHODS: Cumulative average alcohol consumption (g/day) was derived from the total consumption of beer, wine, and liquor on average of 19 years in 2428 Framingham Heart Study Offspring participants (mean age 56 years, 52% women). We used linear mixed models to investigate the associations of alcohol consumption with 211 log-transformed plasma metabolites, adjusting for age, sex, batch, smoking, diet, …

Endoscopic Retrograde Cholangiopancreatography-Related Early Perforations: A Study Of Effects Of Procedure Duration, Complexity, And Endoscopist Experience, Mark Aloysius, Hemant Goyal, Tejas Nikumbh, Niraj James Shah, Ghassan M Hammoud, Pritesh Mutha, Mairin Joseph-Talreja, Savio John, Ganesh Aswath, Vaibhav Wadhwa, Nirav Thosani

Faculty, Staff and Student Publications

BACKGROUND: Perforations (Perf) during endoscopic retrograde cholangiopancreatography (ERCP) are rare (< 1%) but potentially fatal events (up to 20% mortality). Given its rarity, most data is through case series studies from centers or analysis of large databases. Although a meta-analysis has shown fewer adverse events as a composite (bleeding, pancreatitis, Perf) during ERCP performed at high-volume centers, there is very little real-world data on endoscopist and center procedural volumes, ERCP duration and complexity on the occurrence of Perf.

AIM: To study the profile of Perf related to ERCP by center and endoscopist procedure volume, ERCP time, and complexity from a national endoscopic repository.

METHODS: Patients from clinical outcomes research initiative-national endoscopic database (2000-2012) who underwent ERCP were stratified based on the endoscopist and center volume (quartiles), and total procedure duration and complexity grade of the ERCP based on procedure details. The effects of these variables on the Perf that occurred were studied. Continuous variables were compared between Perf and no perforations (NoPerf) using the Mann-Whitney U test …

Utilizing Stakeholder Input Within The Tennessee Heart Health Network To Improve Cardiovascular Health Outcomes In Tennessee, Abigail C. Bennett

Longitudinal Scholar's Project

Background: Tennessee ranks sixth nationwide for most deaths related to heart disease. The Tennessee Heart Health Network (TN-HHN), an initiative coordinated by the Tennessee Population Health Consortium (TN-PHC), was created to combat this issue. The TN-HHN is a statewide network of primary care practices, health systems, and academic centers committed to implementing patient-centered outcomes research (PCOR) approaches to demonstrably improve cardiovascular disease (CVD) health outcomes and health equity across Tennessee.

Objective: Evaluate stakeholder experiences in participating in the Network in an effort to assess partner satisfaction and improve the TN-HHN as a whole.

Methods: Eligible stakeholders were invited via …

Acute Myocardial Infarction From A Lower-Middle Income Country-A Comprehensive Report On Performance Measures And Quality Metrics Using National Cardiovascular Data Registry, Farhala Mari Baloch, Ainan Arshad, Sher Sethi, Javed Tai

Section of Cardiology

Introduction: Epidemic of cardiovascular disease (CVD) is widely projected in South Asian population and estimated to get double in two decades. Ischemic heart disease (IHD) is one of the spectrums of CVD and acute myocardial infarction (AMI) being the common manifestations of IHD. National Cardiovascular Data Registry (NCDR) is a registry data that measure their practices and improve quality of care. In this project we aim to see our performance trends in the care of IHD including AMI patients over two year's period.
Material & methods: A cross sectional study conducted at the Aga Khan University Hospital, Karachi, Pakistan. All …

Importance Of Geriatrics In Psychiatric Postgraduate Education, Dr Anand R, Dr Kishor M, Dr Murali M R

Digital Journal of Clinical Medicine

Introduction

To assess the importance of Geriatrics in Psychiatric postgraduate education

Methodology

Marks allotted in question papers from Geriatrics in Psychiatry postgraduate examination from a university for a 5-year period was evaluated.

Discussion

1-6% of entire theory evaluation was related to Geriatric mental health topics predominantly on dementia and related disorders.

The Role Of Noncoding Rnas In Pancreatic Birth Defects, Ziyue Zoey Yang, Ronald J Parchem

Faculty, Staff and Students Publications

Congenital defects in the pancreas can cause severe health issues such as pancreatic cancer and diabetes which require lifelong treatment. Regenerating healthy pancreatic cells to replace malfunctioning cells has been considered a promising cure for pancreatic diseases including birth defects. However, such therapies are currently unavailable in the clinic. The developmental gene regulatory network underlying pancreatic development must be reactivated for in vivo regeneration and recapitulated in vitro for cell replacement therapy. Thus, understanding the mechanisms driving pancreatic development will pave the way for regenerative therapies. Pancreatic progenitor cells are the precursors of all pancreatic cells which use epigenetic changes …

Associations Between Birth Defects With Neural Crest Cell Origins And Pediatric Embryonal Tumors, Eugene C Wong, Philip J Lupo, Tania A Desrosiers, Hazel B Nichols, Susan M Smith, Charles Poole, Mark Canfield, Charles Shumate, Tiffany M Chambers, Jeremy M Schraw, Wendy N Nembhard, Mahsa M Yazdy, Eirini Nestoridi, Amanda E Janitz, Andrew F Olshan

Faculty, Staff and Students Publications

BACKGROUND: There are few assessments evaluating associations between birth defects with neural crest cell developmental origins (BDNCOs) and embryonal tumors, which are characterized by undifferentiated cells having a molecular profile similar to neural crest cells. The effect of BDNCOs on embryonal tumors was estimated to explore potential shared etiologic pathways and genetic origins.

METHODS: With the use of a multistate, registry-linkage cohort study, BDNCO-embryonal tumor associations were evaluated by generating hazard ratios (HRs) and 95% confidence intervals (CIs) with Cox regression models. BDNCOs consisted of ear, face, and neck defects, Hirschsprung disease, and a selection of congenital heart defects. Embryonal …

Retrieval Of Large Balloon Fragments During Transcatheter Pulmonary Valve Implantation Using A Novel Retrieval System, Anne C Taylor, Mohamed Ali H Ghandour, Asra Khan, Srinath T Gowda, Flora Nunez-Gallegos, Lynn F Peng, Jamil A Aboulhosn, Daniel S Levi, Doff B Mcelhinney, Athar M Qureshi

Faculty, Staff and Students Publications

The removal of balloon fragments from the pulmonary artery without damaging the pulmonary and tricuspid valves can be difficult. Four cases during transcatheter pulmonary valve replacement are described in which a novel retrieval system was used to facilitate safe removal. (Level of Difficulty: Advanced.)

Dhodh: A Promising Target In The Treatment Of T-Cell Acute Lymphoblastic Leukemia, Amy N Sexauer, Gabriela Alexe, Karin Gustafsson, Elizabeth Zanetakos, Jelena Milosevic, Mary Ayres, Varsha Gandhi, Yana Pikman, Kimberly Stegmaier, David B Sykes

Faculty, Staff and Student Publications

Patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) have a poor prognosis with few therapeutic options. With the goal of identifying novel therapeutic targets, we used data from the Dependency Map project to identify dihydroorotate dehydrogenase (DHODH) as one of the top metabolic dependencies in T-ALL. DHODH catalyzes the fourth step of de novo pyrimidine nucleotide synthesis. Small molecule inhibition of DHODH rapidly leads to the depletion of intracellular pyrimidine pools and forces cells to rely on extracellular salvage. In the absence of sufficient salvage, this intracellular nucleotide starvation results in the inhibition of DNA and RNA synthesis, …

Emergency Department Presentations Of Diabetic Ketoacidosis In A Large Cohort Of Children, Lisa 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

Department of Emergency Medicine Faculty Papers

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 …

Beyond Bacteria: How The Intratumor Mycobiome Modulates Lung Adenocarcinoma Progression, Zahraa Rahal, Humam Kadara

Faculty, Staff and Student Publications

Increasing evidence suggests that tumors harbor diverse microbiomes, adding complexity to the tumor microenvironment. In this issue of Cancer Cell, Liu et al. highlight the role of the intratumor mycobiome, specifically Aspergillus sydowii, in promoting lung adenocarcinoma progression. A. sydowii enhances the recruitment and activation of myeloid-derived suppressor cells via IL-1β signaling driven by the β-glucan-mediated Dectin-1/CARD9 pathway.

Effects Of Covid-19 Vaccination On Pro-Coagulant State Of A Protein S-Deficient Pediatric Patient: New Hope For Treatment Of The Deficiency, Diana Polania-Villanueva, M. Kumar, Lekha Thangada, Jone Garai, Jovanny Zabaleta, Rinku Majumder

School of Medicine Faculty Publications

ISTH 2023 Congress, June 24 - 28, 2023, Montreal, Canada

Antiphosphatidylserine/Prothrombin Antibodies In Childhood Sle Are Associated With Lupus Anticoagulant Positivity, S. Chugh, R. Pilania, A. Kler, C. Hans, Narender Kumar, S. Singh, J. Ahluwalia

School of Medicine Faculty Publications

ISTH 2023 Congress, June 24 - 28, 2023, Montreal, Canada

Endoscopic Ultrasound-Guided Fiducial Placement For Stereotactic Body Radiation Therapy In Patients With Pancreatic Cancer, Irina M Cazacu, Ben S Singh, Rachael M Martin-Paulpeter, Sam Beddar, Stephen Chun, Emma B Holliday, Albert C Koong, Prajnan Das, Eugene J Koay, Cullen Taniguchi, Joseph M Herman, Manoop S Bhutani

Faculty, Staff and Student Publications

Accurate delivery of stereotactic body radiotherapy (SBRT) to pancreatic tumors relies on successful EUS-guided placement of fiducial markers. The aim of this study is to report the technical feasibility and safety of EUS-guided fiducial placement and to evaluate the characteristics and technical benefit of SBRT in a cohort of patients with pancreatic cancer (PC). A retrospective chart review was performed for all (n = 82) PC patients referred for EUS-guided fiducial placement by a single endosonographer at a tertiary cancer center. Data regarding EUS-related technical details, SBRT characteristics, adverse events, and continuous visibility of fiducials were recorded and analyzed. …

Ten Steps Toward Improving In-Hospital Cardiac Arrest Quality Of Care And Outcomes, Brahmajee K. Nallamothu, Robert Greif, Theresa Anderson, Huba Atiq, Thomaz Bittencourt Couto, Julie Considine, Allan R De Caen, Therese Djärv, Ann Doll, Matthew J. Douma

Department of Anaesthesia

No abstract provided.

Psychiatric Morbidity And Dental Problems Among Women From Institutional Care, Meghana Hanchate, Kishor M, Ashwini T S

Digital Journal of Clinical Medicine

No abstract provided.

Left Juxtaposition Of The Right Atrial Appendage: Pitfalls In Diagnosis, Kanya Singhapakdi, Wesam Sourour, Thomas Kimball

School of Medicine Faculty Publications

Several congenital anomalies of the right atrial appendage (RAA) have been described including aneurysm, herniation (in association with a pericardial defect), and left juxtaposition. The left juxtaposition of the RAA (LJRAA), first described by Birmingham in 1893 and subsequently introduced by Dixon in 1954, is usually associated with complex cardiac malformations such as obstruction of the left ventricular outflow tract. In this case report, we will describe an unusual variant of LJRAA in the absence of any other cardiac defects, which was initially misinterpreted as an aortic dissection. The correct diagnosis was made after careful reinterpretation and the use of …

Association Of Interleukin-6 And Interleukin-18 With Cardiovascular Disease In Older Adults: Atherosclerosis Risk In Communities Study, Xiaoming Jia, Leo Buckley, Caroline Sun, Mahmoud Al Rifai, Bing Yu, Vijay Nambi, Salim S Virani, Elizabeth Selvin, Kunihiro Matsushita, Ron C Hoogeveen, Josef Coresh, Amil M Shah, Christie M Ballantyne

Faculty, Staff and Students Publications

AIMS: Interleukin-6 (IL-6) and interleukin-18 (IL-18), important cytokines implicated in atherosclerosis and inflammaging, were assessed for associations with global cardiovascular disease (CVD), atrial fibrillation (AF), and death in older adults.

METHODS AND RESULTS: Participants from Atherosclerosis Risk in Communities study Visit 5 (mean age 75.4 ± 5.1 years) with IL-6 and IL-18 measurements were included (n = 5672). Cox regression models were used to assess associations of IL-6 and IL-18 with coronary heart disease (CHD), ischaemic stroke, heart failure (HF) hospitalization, global CVD (composite of CHD, stroke, and HF), AF, and all-cause death. Over a median follow-up of 7.2 years, …

Novel Size-Based High-Density Lipoprotein Subspecies And Incident Vascular Events, Austin Deets, Parag H. Joshi, Alvin Chandra, Kavisha Singh, Amit Khera, Salim S. Virani, Christie M. Ballantyne, James D. Otvos, Robin P F. Dullaart, Eke G. Gruppen

Office of the Provost

Background: High‐density lipoprotein (HDL) particle concentration likely outperforms HDL cholesterol in predicting atherosclerotic cardiovascular events. Whether size‐based HDL subspecies explain the atheroprotective associations of HDL particle concentration remains unknown. Our objective was to assess whether levels of specific size‐based HDL subspecies associate with atherosclerotic cardiovascular disease in a multiethnic pooled cohort and improve risk prediction beyond traditional atherosclerotic cardiovascular disease risk factors.
Methods and Results: Seven HDL size‐based subspecies were quantified by nuclear magnetic resonance (LP4 algorithm; H1=smallest; H7=largest) among participants without prior atherosclerotic cardiovascular disease in ARIC (Atherosclerosis Risk in Communities), MESA (Multi‐Ethnic Study of Atherosclerosis), PREVEND (Prevention of …

Frequency Of Dysnatremia In Patients Admitted With Covid-19 Infection And Its Prognostic Implication, Farah Gul Khan, Saadia Sattar, Muhammad M. Yaqoob, Nida Vallani, Maryam Asad

Section of Nephrology

Objective: We aimed to investigate the frequency of dysnatremia among patients admitted with COVID-19 infection and its association with inpatient mortality.
Methods: This retrospective longitudinal study was conducted for 12 weeks. Serum sodium levels were recorded at admission, during the hospital stay, and within 48 hours of discharge or death. Logistic regression was used to determine the predictors of mortality.
Results: This study included 574 patients (69.7% men, age 55.6 ± 14.4 years). On admission, mean sodium was 135.9 ± 6.4 mEq/L; 39% had hyponatremia and 4.7% had hypernatremia. During admission, hypernatremia increased to 18.8%; maximum sodium in patients who …

A Randomized Phase Iii Study Of Standard Versus High-Dose Cytarabine With Or Without Vorinostat For Aml, Guillermo Garcia-Manero, Nikolai A Podoltsev, Megan Othus, John M Pagel, Jerald P Radich, Min Fang, David A Rizzieri, Guido Marcucci, Stephen A Strickland, Mark R Litzow, M Lynn Savoie, Bruno C Medeiros, Mikkael A Sekeres, Tara L Lin, Geoffrey L Uy, Bayard L Powell, Jonathan E Kolitz, Richard A Larson, Richard M Stone, David Claxton, James Essell, Selina M Luger, Sanjay R Mohan, Anna Moseley, Frederick R Appelbaum, Harry P Erba

Faculty, Staff and Student Publications

Prior experience indicated that use of higher doses of cytarabine during induction for acute myeloid leukemia (AML) with a histone deacetylase inhibitor resulted in high response rates. S1203 was a randomized multicenter trial for previously untreated patients aged 18-60 with AML which compared daunorubicin and cytarabine (DA), idarubicin with higher dose cytarabine (IA) and IA with vorinostat (IA + V). The primary endpoint was event free survival (EFS). 738 patients were randomized: 261 to each DA and IA arms and 216 to the IA + V arm. 96, 456, and 150 patients had favorable-, intermediate-, and unfavorable-risk cytogenetics, respectively. 152 …

Impact Of Receiving Hospital On Out‐Of‐Hospital Cardiac Arrest Outcome: Racial And Ethnic Disparities In Texas, Ryan Huebinger, Marina Del Rios, Benjamin S Abella, Bryan Mcnally, Carrie Bakunas, Richard Witkov, Micah Panczyk, Eric Boerwinkle, Bentley Bobrow

Faculty, Staff and Student Publications

Background Factors associated with out-of-hospital cardiac arrest (OHCA) outcome disparities remain poorly understood. We evaluated the role of receiving hospital on OHCA outcome disparities. Methods and Results We studied people with OHCA who survived to hospital admission from TX-CARES (Texas Cardiac Arrest Registry to Enhance Survival), 2014 to 2021. Using census data, we stratified OHCAs into majority (>50%) strata: non-Hispanic White race and ethnicity, non-Hispanic Black race and ethnicity, and Hispanic or Latino ethnicity. We stratified hospitals into performance quartiles based on the primary outcome, survival with good neurologic outcome. We evaluated the association between race and ethnicity and …

Late-Gadolinium Enhancement Is Common In Older Pediatric Heart Transplant Recipients And Is Associated With Lower Ejection Fraction, Andrew A Lawson, Kae Watanabe, Lindsay Griffin, Christina Laternser, Michael Markl, Cynthia K Rigsby, Melanie Sojka, Joshua D Robinson, Nazia Husain

Faculty, Staff and Students Publications

BACKGROUND: Chronic graft failure and cumulative rejection history in pediatric heart transplant recipients (PHTR) are associated with myocardial fibrosis on endomyocardial biopsy (EMB). Cardiovascular magnetic resonance imaging (CMR) is a validated, non-invasive method to detect myocardial fibrosis via the presence of late gadolinium enhancement (LGE). In adult heart transplant recipients, LGE is associated with increased risk of future adverse clinical events including hospitalization and death. We describe the prevalence, pattern, and extent of LGE on CMR in a cohort of PHTR and its associations with recipient and graft characteristics.

METHODS: This was a retrospective study of consecutive PHTR who underwent …

Plasma Metabolomics And Quantitative Interstitial Abnormalities In Ever-Smokers, Bina Choi, Raúl San José Estépar, Suneeta Godbole, Jeffrey L Curtis, Jennifer M Wang, Rubén San José Estépar, Ivan O Rosas, Jared R Mayers, Brian D Hobbs, Craig P Hersh, Samuel Y Ash, Meilan K Han, Russell P Bowler, Kathleen A Stringer, George R Washko, Wassim W Labaki

Faculty, Staff and Students Publications

BACKGROUND: Quantitative interstitial abnormalities (QIA) are an automated computed tomography (CT) finding of early parenchymal lung disease, associated with worse lung function, reduced exercise capacity, increased respiratory symptoms, and death. The metabolomic perturbations associated with QIA are not well known. We sought to identify plasma metabolites associated with QIA in smokers. We also sought to identify shared and differentiating metabolomics features between QIA and emphysema, another smoking-related advanced radiographic abnormality.

METHODS: In 928 former and current smokers in the Genetic Epidemiology of COPD cohort, we measured QIA and emphysema using an automated local density histogram method and generated metabolite profiles …

Discovery, Structure-Activity Relationship And In Vitro Anticancer Activity Of Small-Molecule Inhibitors Of The Protein-Protein Interactions Between Af9/Enl And Af4 Or Dot1l, Xin Li, Xiaowei Wu, Shenyou Nie, Jidong Zhao, Yuan Yao, Fangrui Wu, Chandra Bhushan Mishra, Md Ashraf-Uz-Zaman, Bala Krishna Moku, Yongcheng Song

Faculty, Staff and Students Publications

Simple Summary

Chromosomal translocations involving the mixed lineage leukemia (MLL) gene generate potent fusion oncogenes and cause acute myeloid leukemia or lymphocytic leukemia, which account for ~75% infant and 5–10% child/adult acute leukemia cases with a poor prognosis (5-year survival rates < 45%). Protein–protein interactions between the most frequent MLL fusion partner proteins AF9/ENL and AF4 or histone methyltransferase DOT1L are critical to malignant gene expression and are therefore a potential drug target for cancer. Compound screening followed by medicinal chemistry studies identified several novel small-molecule inhibitors showing strong inhibition of these protein–protein interactions, significant suppression of characteristic gene expression, and robust cellular anticancer activities with negligible cytotoxicity. These compounds are useful chemical probes for biological studies of these protein–protein interactions, as well as pharmacological leads for further drug development against MLL-rearranged and other leukemias.

Abstract

Chromosomal translocations involving the mixed lineage leukemia (MLL) gene cause 5–10% acute leukemias with poor clinical outcomes. Protein–protein interactions (PPI) between the most frequent MLL fusion partner proteins AF9/ENL and AF4 or histone methyltransferase DOT1L are drug targets for MLL-rearranged (MLL-r) leukemia. Several benzothiophene-carboxamide compounds were identified as novel inhibitors of these PPIs with IC₅₀ values as …