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Cardiovascular Health Is Associated With Physical Function Among Older Community Dwelling Men And Women., Yichen Jin, Toshiko Tanaka, Yan Ma, Stefania Bandinelli, Luigi Ferrucci, Sameera A Talegawkar

Exercise and Nutrition Sciences Faculty Publications

Background

Age related decline in physical function is a significant concern affecting the quality of life of older individuals.

Methods

We examined the associations between baseline overall cardiovascular health (CVH), its components, and physical function in 906 men and women from the InCHIANTI cohort. Physical function was assessed using the Short Performance Physical Battery and poor physical function was defined as an Short Performance Physical Battery score less than 10. Overall CVH score, ranging from 0 to 12 in the cohort, was operationalized using adherence to ideal levels for health behaviors including smoking status, physical activity, body mass index, and …

Precision Newborn Screening For Lysosomal Disorders, Melissa M. Minter Baerg, Stephanie D. Stoway, Jeremy Hart, Lea Mott, Dawn S. Peck, Stephanie L. Nett, Jason S. Eckerman, Jean M. Lacey, Coleman T. Turgeon, Dimitar Gavrilov, Devin Oglesbee, Kimiyo Raymond, Silvia Tortorelli, Dietrich Matern, Lars Mørkrid, Piero Rinaldo

Pathology and Laboratory Medicine Faculty Publications

Purpose: The implementation of newborn screening for lysosomal disorders has uncovered overall poor specificity, psychosocial harm experienced by caregivers, and costly follow-up testing of false-positive cases. We report an informatics solution proven to minimize these issues.

Methods: The Kentucky Department for Public Health outsourced testing for mucopolysaccharidosis type I (MPS I) and Pompe disease, conditions recently added to the recommended uniform screening panel, plus Krabbe disease, which was added by legislative mandate. A total of 55,161 specimens were collected from infants born over 1 year starting from February 2016. Testing by tandem mass spectrometry was integrated with multivariate pattern recognition …

Differential Impact Of Serial Measurement Of Nonplatelet Thromboxane Generation On Long-Term Outcome After Cardiac Surgery., Nikolaos Kakouros, Tyler J Gluckman, John V Conte, Thomas S Kickler, Katherine Laws, Bruce A Barton, Jeffrey J Rade

Articles, Abstracts, and Reports

BACKGROUND: Systemic thromboxane generation, not suppressible by standard aspirin therapy and likely arising from nonplatelet sources, increases the risk of atherothrombosis and death in patients with cardiovascular disease. In the RIGOR (Reduction in Graft Occlusion Rates) study, greater nonplatelet thromboxane generation occurred early compared with late after coronary artery bypass graft surgery, although only the latter correlated with graft failure. We hypothesize that a similar differential association exists between nonplatelet thromboxane generation and long-term clinical outcome.

METHODS AND RESULTS: Five-year outcome data were analyzed for 290 RIGOR subjects taking aspirin with suppressed platelet thromboxane generation. Multivariable modeling was performed to …

B Cell-Derived Il-4 Acts On Podocytes To Induce Proteinuria And Foot Process Effacement, Alfred Hj Kim, Jun-Jae Chung, Shreeram Akilesh, Ania Koziell, Sanjay Jain, Jeffrey B. Hodgin, Mark J. Miller, Thaddeus S. Stappenbeck, Jeffrey H. Miner, Andrey S. Shaw

Open Access Publications

The efficacy of B cell depletion therapies in diseases such as nephrotic syndrome and rheumatoid arthritis suggests a broader role in B cells in human disease than previously recognized. In some of these diseases, such as the minimal change disease subtype of nephrotic syndrome, pathogenic antibodies and immune complexes are not involved. We hypothesized that B cells, activated in the kidney, might produce cytokines capable of directly inducing cell injury and proteinuria. To directly test our hypothesis, we targeted a model antigen to the kidney glomerulus and showed that transfer of antigen-specific B cells could induce glomerular injury and proteinuria. …

This Means War: Female Choice In Guppies, Nathan Payne, Zac Talbot, Garrett Rydalch, Kim Sullivan

Biology Posters

In many organisms, including guppies, females choose with whom they mate. This is called female selection. For our experiment male and female guppies have been isolated from each other and then we tested to see if females preferred similar looking males in a bright environment more than a male in a neutral colored environment. We hypothesized that the female would prefer the male in the brighter colored environment over the males in the neutral colored environment. We predicted that the female would touch the glass on the brighter side more frequently.

Do Female Guppies Really Know What They Want?, Jennica Blasi, Abby Keuhl-Coe, Hanna Kirkland, Michael Larson

Biology Posters

• Hypothesis: Female guppies do not influence each other’s choice of male guppy

• Predictions: If female guppies do not influence each other’s choice in males, then most females guppies will choose the same male whether alone or in the presence of other females

• Choice is defined as which pane of glass the female interacts more with from 1 to 3 minutes after being introduced to the tank

• 34 Females were used, 17 small and 17 large

Guppies: Sexy And You Know It?, Leslie Bredthauer, Katelin Boettcher, Landon Keller, Kim Sullivan

Biology Posters

We were curious to know if female guppies are more interested in the quality or quantity of males.

Is Beauty Only Skin Deep? Mate Selection In Guppies, Tyson Alles, Amanda Cook, Alex Kunz, Jeff Merkley

Biology Posters

Our experiment sought to understand mate preference in female guppies, Poecilia reticulata. We observed behavioral differences between wild-type males caught from a local indoor pond and vibrant pet store males, who exhibited higher stress levels, likely due in part to being shipped long distances. Observing these behavioral differences, we hypothesized that females would prefer the less stressed males regardless of color. When a female guppy was presented with both a wild type and a pet store male, we predicted that she would prefer the wild-type male on account of their lower stress.

Identification Of A Novel Synaptic Protein, Tmtc3, Involved In Periventricular Nodular Heterotopia With Intellectual Disability And Epilepsy, Sali M K Farhan, Kevin C J Nixon, Michelle Everest, Tara N Edwards, Shirley Long, Dmitri Segal, Maria J Knip, Heleen H Arts, Rana Chakrabarti, Jian Wang, John F Robinson, Donald Lee, Seyed M Mirsattari, C Anthony Rupar, Victoria M Siu, Forge Canada Consortium, Michael O Poulter, Robert A Hegele, Jamie M Kramer

Paediatrics Publications

Defects in neuronal migration cause brain malformations, which are associated with intellectual disability (ID) and epilepsy. Using exome sequencing, we identified compound heterozygous variants (p.Arg71His and p. Leu729ThrfsTer6) in TMTC3, encoding transmembrane and tetratricopeptide repeat containing 3, in four siblings with nocturnal seizures and ID. Three of the four siblings have periventricular nodular heterotopia (PVNH), a common brain malformation caused by failure of neurons to migrate from the ventricular zone to the cortex. Expression analysis using patient-derived cells confirmed reduced TMTC3 transcript levels and loss of the TMTC3 protein compared to parental and control cells. As TMTC3 function is currently …

Suppurative Complications Of Acute Hematogenous Osteomyelitis In Children, Jennifer J. Johnston, Cristina Murray-Krezan, Walter N. Dehority

Pediatrics Research and Scholarship

We carried out a case-control study in children with acute hematogenous osteomyelitis (AHO) with and without suppurative complications discharged from our institution over an 11-year period to test the hypothesis that abscess formation was associated with a delayed presentation to care. Of 102 children with AHO, 54 abscesses were documented in 46 patients (25 bone, 29 muscle). A delay in presentation was not associated with abscess formation (6.5 vs. 5.0 days, P=0.26). Overall, 78% of all bone abscesses were visible on initial MRI. Consistent use of MRI at presentation may identify children with suppurative complications of AHO.

Efficacy And Safety Of Pembrolizumab In Patients Enrolled In Keynote-030 In The United States: An Expanded Access Program., Tara C Gangadhar, Wen-Jen Hwu, Michael A Postow, Omid Hamid, Adil Daud, Roxana Dronca, Richard Joseph, Steven J O'Day, F S Hodi, Anna C Pavlick, Harriet Kluger, Romina P Oxborough, Aiming Yang, Mihaela Gazdoiu, Debra A Kush, Scot Ebbinghaus, April K S Salama

Articles, Abstracts, and Reports

KEYNOTE-030 (ClinicalTrials.gov ID, NCT02083484) was a global expanded access program that allowed access to pembrolizumab, an antiprogrammed death 1 antibody, for patients with advanced melanoma before its regulatory approval. Patients with unresectable stage III/IV melanoma that progressed after standard-of-care therapy, including ipilimumab and, if BRAF mutant, a BRAF inhibitor, were eligible to receive pembrolizumab 2 mg/kg every 3 weeks. Response was assessed by immune-related response criteria by investigator review. Adverse events (AEs) were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. In the United States, 979 patients enrolled between April and September 2014. …

Second Primary Malignant Neoplasms And Survival In Adolescent And Young Adult Cancer Survivors., Theresa H M Keegan, Archie Bleyer, Aaron S Rosenberg, Qian Li, Melanie Goldfarb

Articles, Abstracts, and Reports

Importance: Although the increased incidence of second primary malignant neoplasms (SPMs) is a well-known late effect after cancer, few studies have compared survival after an SPM to survival of the same cancer occurring as first primary malignant neoplasm (PM) by age.

Objective: To assess the survival impact of SPMs in adolescents and young adults (AYAs) (15-39 years) compared with that of pediatric (<15 >years) and older adult (≥40 years) patients with the same SPMs.

Design, Setting, and Participants: This was a population-based, retrospective cohort study of patients with cancer in 13 Surveillance, Epidemiology and End Results regions in the United …

Oral Apolipoprotein A-I Mimetic D-4f Lowers Hdl-Inflammatory Index In High-Risk Patients: A First-In-Human Multiple-Dose, Randomized Controlled Trial., Richard L. Dunbar, Rajesh Movva, Leanne T. Bloedon, Danielle Duffy, Robert B. Norris, Mohamad Navab, Alan M. Fogelman, Daniel J. Rader

Department of Medicine Faculty Papers

A single dose of the apolipoprotein (apo)A-I mimetic peptide D-4F rendered high-density lipoprotein (HDL) less inflammatory, motivating the first multiple-dose study. We aimed to assess safety/tolerability, pharmacokinetics, and pharmacodynamics of daily, orally administered D-4F. High-risk coronary heart disease (CHD) subjects added double-blinded placebo or D-4F to statin for 13 days, randomly assigned 1:3 to ascending cohorts of 100, 300, then 500 mg (n = 62; 46 men/16 women). D-4F was safe and well-tolerated. Mean ± SD plasma D-4F area under the curve (AUC, 0-8h) was 6.9 ± 5.7 ng/mL*h (100 mg), 22.7 ± 19.6 ng/mL*h (300 mg), and 104.0 ± …

Multisite Evaluation Of The Bd Max Extended Enteric Bacterial Panel For Detection Of Yersinia Enterocolitica, Enterotoxigenic Escherichia Coli, Vibrio, And Plesiomonas Shigelloides From Stool Specimens., Patricia J Simner, Margret Oethinger, Kathleen A Stellrecht, Dylan R Pillai, Ram Yogev, Helene Leblond, Joel Mortensen

Articles, Abstracts, and Reports

The purpose of this study was to perform a multisite evaluation to establish the performance characteristics of the BD Max extended enteric bacterial panel (xEBP) assay directly from unpreserved or Cary-Blair-preserved stool specimens for the detection of Yersinia enterocolitica, enterotoxigenic Escherichia coli (ETEC), Vibrio, and Plesiomonas shigelloides The study included prospective, retrospective, and prepared contrived specimens from 6 clinical sites. BD Max xEBP results were compared to the reference method, which included standard culture techniques coupled with alternate PCR and sequencing, except for ETEC, for which the reference method was two alternate PCRs and sequencing. Alternate PCR was …

Dynamic Range Of Frontoparietal Functional Modulation Is Associated With Working Memory Capacity Limitations In Older Adults, Jonathan G. Hakun, Nathan F. Johnson

Physical Therapy Faculty Publications

Older adults tend to over-activate regions throughout frontoparietal cortices and exhibit a reduced range of functional modulation during WM task performance compared to younger adults. While recent evidence suggests that reduced functional modulation is associated with poorer task performance, it remains unclear whether reduced range of modulation is indicative of general WM capacity-limitations. In the current study, we examined whether the range of functional modulation observed over multiple levels of WM task difficulty (N-Back) predicts in-scanner task performance and out-of-scanner psychometric estimates of WM capacity. Within our sample (60–77 years of age), age was negatively associated with frontoparietal modulation range. …

Pro-Inflammatory Chemokines And Cytokines Dominate The Blister Fluid Molecular Signature In Patients With Epidermolysis Bullosa And Affect Leukocyte And Stem Cell Migration., Vitali Alexeev, Julio Cesar Salas-Alanis, Francis Palisson, Lila Mukhtarzada, Giulio Fortuna, Jouni Uitto, Andrew P. South, Olga Igoucheva

Department of Dermatology and Cutaneous Biology Faculty Papers

Hereditary epidermolysis bullosa (EB) is associated with skin blistering and the development of chronic nonhealing wounds. Although clinical studies have shown that cell-based therapies improve wound healing, the recruitment of therapeutic cells to blistering skin and to more advanced skin lesions remains a challenge. Here, we analyzed cytokines and chemokines in blister fluids of patients affected by dystrophic, junctional, and simplex EB. Our analysis revealed high levels of CXCR1, CXCR2, CCR2, and CCR4 ligands, particularly dominant in dystrophic and junctional EB. In vitro migration assays demonstrated the preferential recruitment of CCR4⁺ lymphocytes and CXCR1⁺, CXCR2⁺, …

Endothelial Cell-Derived Microparticles From Patients With Obstructive Sleep Apnea Hypoxia Syndrome And Coronary Artery Disease Increase Aortic Endothelial Cell Dysfunction., Lixin Jia, Jingyao Fan, Wei Cui, Sa Liu, Na Li, Wayne Bond Lau, Xin-Liang Ma, Jie Du, Shaoping Nie, Yongxiang Wei

Department of Emergency Medicine Faculty Papers

BACKGROUND/AIMS: Obstructive sleep apnea hypoxia syndrome (OSAHS) is an independent risk factor for coronary artery disease (CAD). Treatment of OSAHS improves clinical outcome in some CAD patients, but the relationship between OSAHS and CAD is complex. Microparticles (MPs) are shed by the plasma membrane by either physiologic or pathologic stimulation. In the current study, we investigated the role of MPs in the context of OSAHS.

METHODS AND RESULTS: 54 patients with both suspected coronary artery stenosis and OSAHS were recruited and underwent both coronary arteriography and polysomnography. Circulating MPs were isolated and analyzed by flow cytometry. CAD+OSAHS patients exhibited greater …

Vitamin D, Heidi D Moretti, Vincent J Colucci, Bradley D Berry

Articles, Abstracts, and Reports

BACKGROUND: Vitamin D status may influence heart failure (HF) patient outcomes by affecting b-type natriuretic peptide (BNP), parathyroid hormone (PTH), and enhancing cardiac contractility. Vitamin D deficiency is associated with morbidity and mortality in HF patients. The objective of this study was to determine if vitamin D3 at a comparatively high dose would replete 25-hydroxyvitamin D (25(OH)D) stores, improve BNP, PTH, cardiopulmonary function, reduce inflammatory markers, and improve quality of life (QOL) in HF patients.

METHODS: This was a 6 month, parallel group, double-blind, placebo-controlled, single clinic center, randomized trial of supplemental vitamin D3 using a dose of 10,000 IU …

Ufm1 Founder Mutation In The Roma Population Causes Recessive Variant Of H-Abc., Eline M C Hamilton, Enrico Bertini, Luba Kalaydjieva, Bharti Morar, Dana Dojčáková, Adeline Vanderver, Recessive H-Abc Research Group.

Neurology Faculty Publications

OBJECTIVE: To identify the gene defect in patients with hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) who are negative for TUBB4A mutations.

METHODS: We performed homozygosity mapping and whole exome sequencing (WES) to detect the disease-causing variant. We used a Taqman assay for population screening. We developed a luciferase reporter construct to investigate the effect of the promoter mutation on expression.

RESULTS: Sixteen patients from 14 families from different countries fulfilling the MRI criteria for H-ABC exhibited a similar, severe clinical phenotype, including lack of development and a severe epileptic encephalopathy. The majority of patients had a …

Association Of Metabolic Syndrome And Change In Unified Parkinson's Disease Rating Scale Scores., Maureen Leehey, Sheng Luo, Saloni Sharma, Anne-Marie A. Wills, Jacquelyn L. Bainbridge, Pei Shieen Wong, David K. Simon, Jay S Schneider, Yunxi Zhang, Adriana Pérez, Rohit Dhall, Chadwick W. Christine, Carlos Singer, Franca Cambi, James T Boyd

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

OBJECTIVE: To explore the association between metabolic syndrome and the Unified Parkinson's Disease Rating Scale (UPDRS) scores and, secondarily, the Symbol Digit Modalities Test (SDMT).

METHODS: This is a secondary analysis of data from 1,022 of 1,741 participants of the National Institute of Neurological Disorders and Stroke Exploratory Clinical Trials in Parkinson Disease Long-Term Study 1, a randomized, placebo-controlled trial of creatine. Participants were categorized as having or not having metabolic syndrome on the basis of modified criteria from the National Cholesterol Education Program Adult Treatment Panel III. Those who had the same metabolic syndrome status at consecutive annual visits …

Intravesical Rad-Ifnα/Syn3 For Patients With High-Grade, Bacillus Calmette-Guerin-Refractory Or Relapsed Non-Muscle-Invasive Bladder Cancer: A Phase Ii Randomized Study., Neal D Shore, Stephen A Boorjian, Daniel J Canter, Kenneth Ogan, Lawrence I Karsh, Tracy M Downs, Leonard G Gomella, Ashish M Kamat, Yair Lotan, Robert S Svatek, Trinity J Bivalacqua, Robert L Grubb, Tracey L Krupski, Seth P Lerner, Michael E Woods, Brant A Inman, Matthew I Milowsky, Alan Boyd, F Peter Treasure, Gillian Gregory, David G Sawutz, Seppo Yla-Herttuala, Nigel R Parker, Colin P N Dinney

Department of Medicine Faculty Papers

Purpose Many patients with high-risk non-muscle-invasive bladder cancer (NMIBC) are either refractory to bacillus Calmette-Guerin (BCG) treatment or may experience disease relapse. We assessed the efficacy and safety of recombinant adenovirus interferon alfa with Syn3 (rAd-IFNα/Syn3), a replication-deficient recombinant adenovirus gene transfer vector, for patients with high-grade (HG) BCG-refractory or relapsed NMIBC. Methods In this open-label, multicenter (n = 13), parallel-arm, phase II study ( ClinicalTrials.gov identifier: NCT01687244), 43 patients with HG BCG-refractory or relapsed NMIBC received intravesical rAd-IFNα/Syn3 (randomly assigned 1:1 to 1 × 10(11) viral particles (vp)/mL or 3 × 10(11) vp/mL). Patients who responded at months 3, …

Nanoparticle Delivery Of Mir-34a Eradicates Long-Term-Cultured Breast Cancer Stem Cells Via Targeting C22orf28 Directly, Xiaoti Lin, Weiyu Chen, Fengqin Wei, Binhua P. Zhou, Mien-Chie Hung, Xiaoming Xie

Molecular and Cellular Biochemistry Faculty Publications

Rationale: Cancer stem cells (CSCs) have been implicated as the seeds of therapeutic resistance and metastasis, due to their unique abilities of self-renew, wide differentiation potentials and resistance to most conventional therapies. It is a proactive strategy for cancer therapy to eradicate CSCs. Methods: Tumor tissue-derived breast CSCs (BCSC), including XM322 and XM607, were isolated by fluorescence-activated cell sorting (FACS); while cell line-derived BCSC, including MDA-MB-231.SC and MCF-7.SC, were purified by magnetic-activated cell sorting (MACS). Analyses of microRNA and mRNA expression array profiles were performed in multiple breast cell lines. The mentioned nanoparticles were constructed following the standard molecular cloning …

Detection Of Activating Estrogen Receptor Gene (Esr1) Mutations In Single Circulating Tumor Cells, Carmela Paolillo, Zhaomei Mu, Giovanna Rossi, Matthew J. Schiewer, Thomas Nguyen, Laura Austin, Ettore Capoluongo, Karen E. Knudsen, Massimo Cristofanilli, Paolo Fortina

Department of Cancer Biology Faculty Papers

Purpose: Early detection is essential for treatment plans before onset of metastatic disease. Our purpose was to demonstrate feasibility to detect and monitor estrogen receptor 1 (ESR1) gene mutations at the single circulating tumor cell (CTC) level in metastatic breast cancer (MBC). Experimental Design: We used a CTC molecular characterization approach to investigate heterogeneity of 14 hotspot mutations in ESR1 and their correlation with endocrine resistance. Combining the CellSearch and DEPArray technologies allowed recovery of 71 single CTCs and 12 WBC from 3 ER-positive MBC patients. Forty CTCs and 12 WBC were subjected to whole genome amplification by MALBAC and …

A Two-Biomarker Model Predicts Mortality In The Critically Ill With Sepsis., Carmen Mikacenic, Brenda L Price, Susanna Harju-Baker, D Shane O'Mahony, Cassianne Robinson-Cohen, Frank Radella, William O Hahn, Ronit Katz, David C Christiani, Jonathan Himmelfarb, W Conrad Liles, Mark M Wurfel

Articles, Abstracts, and Reports

RATIONALE: Improving the prospective identification of patients with systemic inflammatory response syndrome (SIRS) and sepsis at low risk for organ dysfunction and death is a major clinical challenge.

OBJECTIVES: To develop and validate a multibiomarker-based prediction model for 28-day mortality in critically ill patients with SIRS and sepsis.

METHODS: A derivation cohort (n = 888) and internal test cohort (n = 278) were taken from a prospective study of critically ill intensive care unit (ICU) patients meeting two of four SIRS criteria at an academic medical center for whom plasma was obtained within 24 hours. The validation cohort (n = …

Timing Of Pd-1 Blockade Is Critical To Effective Combination Immunotherapy With Anti-Ox40., David J Messenheimer, Shawn M. Jensen, Michael E Afentoulis, Keith W Wegman, Zipei Feng, David J Friedman, Michael J. Gough, Walter Urba, Bernard A Fox

Articles, Abstracts, and Reports

Purpose: Antibodies specific for inhibitory checkpoints PD-1 and CTLA-4 have shown impressive results against solid tumors. This has fueled interest in novel immunotherapy combinations to affect patients who remain refractory to checkpoint blockade monotherapy. However, how to optimally combine checkpoint blockade with agents targeting T-cell costimulatory receptors, such as OX40, remains a critical question.Experimental Design: We utilized an anti-PD-1-refractory, orthotopically transplanted MMTV-PyMT mammary cancer model to investigate the antitumor effect of an agonist anti-OX40 antibody combined with anti-PD-1. As PD-1 naturally aids in immune contraction after T-cell activation, we treated mice with concurrent combination treatment versus sequentially administering anti-OX40 …

Mir-181a Increases Foxo1 Acetylation And Promotes Granulosa Cell Apoptosis Via Sirt1 Downregulation., Mei Zhang, Qun Zhang, Yali Hu, Lu Xu, Yue Jiang, Chunxue Zhang, Lijun Ding, Ruiwei Jiang, Jianxin Sun, Haixiang Sun, Guijun Yan

Center for Translational Medicine Faculty Papers

Oxidative stress impairs follicular development by inducing granulosa cell (GC) apoptosis, which involves enhancement of the transcriptional activity of the pro-apoptotic factor Forkhead box O1 (FoxO1). However, the mechanism by which oxidative stress promotes FoxO1 activity is still unclear. Here, we found that miR-181a was upregulated in hydrogen peroxide (H

Interleukin-17 Limits Hypoxia-Inducible Factor 1Α And Development Of Hypoxic Granulomas During Tuberculosis, Racquel Domingo-Gonzalez, Shibali Das, Kristin L. Griffiths, Mushtaq Ahmed, Monika Bambouskova, Suhas Gondi, Noor Al-Hammadi, Reid Townsend, Maxim N. Artyomov, Shabaana A. Khader, Et Al.

Open Access Publications

Mycobacterium tuberculosis (Mtb) is a global health threat, compounded by the emergence of drug-resistant strains. A hallmark of pulmonary tuberculosis (TB) is the formation of hypoxic necrotic granulomas, which upon disintegration, release infectious Mtb. Furthermore, hypoxic necrotic granulomas are associated with increased disease severity and provide a niche for drug-resistant Mtb. However, the host immune responses that promote the development of hypoxic TB granulomas are not well described. Using a necrotic Mtb mouse model, we show that loss of Mtb virulence factors, such as phenolic glycolipids, decreases the production of the proinflammatory cytokine IL-17 (also referred to as IL-17A). IL-17 …

Clinician-Investigator Training And The Need To Pilot New Approaches To Recruiting And Retaining This Workforce., Alison K Hall, Sherry L Mills, P Kay Lund

Neurology Faculty Publications

Clinician–investigators, also called physician–scientists, offer critical knowledge and perspectives that benefit research on basic science mechanisms, improved diagnostic and therapeutic approaches, population and outcomes medicine, health policy, and health services, yet few clinically trained health professionals pursue a research career. Sustaining this workforce requires attention to the unique challenges faced by investigators who must achieve clinical and research competence during training and their careers. These challenges include the duration of required clinical training, limited or discontinuous research opportunities, high levels of educational debt, balancing the dual obligations and rewards of clinical care and research, competition for research funding, and the …

Circulating Early- And Mid-Pregnancy Micrornas And Risk Of Gestational Diabetes., Pandora L Wander, Edward J Boyko, Karin Hevner, Viraj J Parikh, Mahlet G Tadesse, Tanya K Sorensen, Michelle A Williams, Daniel A Enquobahrie

Articles, Abstracts, and Reports

AIMS: Epigenetic regulators, including microRNAs (miRNAs), are implicated in type 2 diabetes, but evidence linking circulating miRNAs in pregnancy and risk of gestational diabetes (GDM) is sparse. Potential modifiers, including pre-pregnancy overweight/obesity and offspring sex, are unexamined. We hypothesized that circulating levels of early-mid-pregnancy (range 7-23weeks of gestation) candidate miRNAs are related to subsequent development of GDM. We also hypothesized that miRNA-GDM associations might vary by pre-pregnancy body-mass index (ppBMI) or offspring sex.

METHODS: In a case-control analysis (36GDM cases/80 controls) from the Omega study, a prospective cohort study of pregnancy complications, we measured early-mid-pregnancy plasma levels of 10miRNAs chosen …

Exosomal Microrna For Detection Of Cardiac Sarcoidosis., Elliott D Crouser, Nabeel Y Hamzeh, Lisa A Maier, Mark W Julian, May Gillespie, Mohammad Rahman, David Baxter, Xiaogang Wu, S Patrick Nana-Sinkam, Kai Wang

Articles, Abstracts, and Reports

No abstract provided.