Medical Specialties Commons^™

Genetic Modification Of Human Mesenchymal Stem Cells Helps To Reduce Adiposity And Improve Glucose Tolerance In An Obese Diabetic Mouse Model., Sabyasachi Sen, Cleyton C Domingues, Carol Rouphael, Cyril Chou, Chul Kim, Nagendra Yadava

Medicine Faculty Publications

INTRODUCTION: Human mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into fat, muscle, bone and cartilage cells. Exposure of subcutaneous abdominal adipose tissue derived AD-MSCs to high glucose (HG) leads to superoxide accumulation and up-regulation of inflammatory molecules. Our aim was to inquire how HG exposure affects MSCs differentiation and whether the mechanism is reversible.

METHODS: We exposed human adipose tissue derived MSCs to HG (25 mM) and compared it to normal glucose (NG, 5.5 mM) exposed cells at 7, 10 and 14 days. We examined mitochondrial superoxide accumulation (Mitosox-Red), cellular oxygen consumption rate (OCR, Seahorse) and gene …

Enhanced Fitness And Renal Function In Type 2 Diabetes., Eric S. Nylen, S. M. Gandhi, Raya E. Kheirbek, Peter Kokkinos

Medicine Faculty Publications

Aims

To investigate the renal effects of fitness in people with diabetes with mild renal dysfunction.

Methods

The effect of a 12-week exercise programme on estimated GFR in 128 people with diabetes was evaluated.

Results

All cardiometabolic variables improved after 12 weeks of supervised exercise. Although there was a modest 3.9% increase in estimated GFR from baseline in the 128 people who completed the study, those with baseline chronic kidney disease stages 2 and 3 were found to have significant (6 and 12%, respectively; p < 0.01) improvements in post-exercise estimated GFR. Moreover, 42% of the people with chronic kidney disease stage 3 improved to chronic kidney disease stage 2 after the intervention.

Conclusion

Short-term exercise improves renal function in those with more moderate baseline chronic kidney disease. …

New-Onset Diabetes Mellitus With Exposure To Ledipasvir And Sofosbuvir., Resmi Premji, Nira Roopnarinesingh, Nazia Qazi, Eric S. Nylen

Medicine Faculty Publications

The combination therapy of ledipasvir/sofosbuvir was approved by the Food and Drug Administration in 2014 for the treatment of chronic hepatitis C. Although hyperglycemia is not well known to occur with its use, we present 2 cases of new-onset diabetes mellitus and a review of the literature suggesting an adverse event association. In the first patient with HIV, we postulate that ledipasvir/sofosbuvir increased the levels of tenofovir and thereby potentiated hyperglycemia. In the second case of a patient with prediabetes, ledipasvir/sofosbuvir appeared to increase insulin resistance. A literature review further supported an association of hyperglycemia and the use of ledipasvir/sofosbuvir. …

Race And Ethnicity, Obesity, Metabolic Health, And Risk Of Cardiovascular Disease In Postmenopausal Women, Michelle D. Schmiegelow, Haley Hedlin, Rachel H. Mackey, Lisa W. Martin, Mara Z. Vitolins, Marcia L. Stefanick, Marco V. Perez, Matthew Allison, Mark A. Hlatky

Medicine Faculty Publications

Background It is unclear whether obesity unaccompanied by metabolic abnormalities is associated with increased cardiovascular disease risk across racial and ethnic subgroups.

Methods and Results We identified 14 364 postmenopausal women from the Women's Health Initiative who had data on fasting serum lipids and serum glucose and no history of cardiovascular disease or diabetes at baseline. We categorized women by body mass index (in kg/m²) as normal weight (body mass index 18.5 to P=0.05). Obese black women without metabolic syndrome had higher adjusted risk (HR 1.95) than obese white women (HR 1.07; interaction P=0.02). Among women with …

Association Between Inflammation And Cardiac Geometry In Chronic Kidney Disease: Findings From The Cric Study., Jayanta Gupta, Elizabeth Dominic, Jeffrey C. Fink, Akinlolu O. Ojo, Ian R. Barrows, Muredach Reilly, Raymond R. Townsend, Marshall Joffe, Sylvia Rosas, Melanie Wolman, Samir Patel, Martin Keane, Harold I. Feldman, John W. Kusek, Dominic S. Raj

Medicine Faculty Publications

Background

Left ventricular hypertrophy (LVH) and myocardial contractile dysfunction are independent predictors of mortality in patients with chronic kidney disease (CKD). The association between inflammatory biomarkers and cardiac geometry has not yet been studied in a large cohort of CKD patients with a wide range of kidney function.

Methods

Plasma levels of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, high-sensitivity C-Reactive protein (hs-CRP), fibrinogen and serum albumin were measured in 3,939 Chronic Renal Insufficiency Cohort study participants. Echocardiography was performed according to the recommendations of the American Society of Echocardiography and interpreted …

Translation Initiation Complex Eif4f Is A Therapeutic Target For Dual Mtor Kinase Inhibitors In Non-Hodgkin Lymphoma., Christos Demosthenous, Jing Jing Han, Mary J Stenson, Matthew J Maurer, Linda E Wellik, Brian Link, Kristen Hege, Ahmet Dogan, Eduardo Sotomayor, Thomas Witzig, Mamta Gupta

Medicine Faculty Publications

Deregulated mRNA translation has been implicated in disease development and in part is controlled by a eukaryotic initiation complex eIF4F (composed of eIF4E, eIF4G and eIF4A). We demonstrate here that the cap bound fraction from lymphoma cells was enriched with eIF4G and eIF4E indicating that lymphoma cells exist in an activated translational state. Moreover, 77% (110/142) of diffuse large B cell lymphoma tumors expressed eIF4E and this was associated with an inferior event free survival. Over-expression of wild-type eIF4E (eIF4E(WT)) but not cap-mutant eIF4E (eIF4E(cap mutant)) increased the activation of the eIF4F complex. Treatment with the active-site dual mTOR inhibitor …

A Six-Week Home Exercise Program Improves Endothelial Function And Cd34+ Circulating Progenitor Cells In Patients With Pre-Diabetes, Sabyasachi Sen, Sarah Witkowski, Ann Lagoy, Ashequl Islam

Medicine Faculty Publications

Background: Pre-diabetes is associated with endothelial dysfunction and affects endothelium-associated stem cells. Lifestyle modification has been shown to prevent the progression from pre-diabetes to overt type 2 diabetes; however, the effect of such interventions on CD34⁺ progenitor cells in pre-diabetes participants has not been tested. The purpose of this study was to determine whether a home-based 6-week exercise intervention improved vascular function, circulating number, function, and gene expression of circulating CD34⁺progenitor cells in patients with pre-diabetes.

Methods: Patients (40 - 70 years, BMI of 25 - 39.9, n = 11) were enrolled in a 16-week randomized crossover …

Statin Use And Risk Of Haemorrhagic Stroke In A Community-Based Cohort Of Postmenopausal Women: An Observational Study From The Women's Health Initiative, Elena Salmoriago-Blotcher, Kathleen M. Hovey, Christopher A. Andrews, Jennifer G. Robinson, Karen C. Johnson, Sylvia Wassertheil-Smoller, Sybil Crawford, Lisa W. Martin, Judith Ockene, Joann E. Manson

Medicine Faculty Publications

Objectives To determine whether statin treatment is associated with increased risk of haemorrhagic stroke (HS) in older women. A secondary objective was to evaluate HS risk in users of combined statin and antiplatelet treatment.

Design Observational study: secondary data analysis from the Women's Health Initiative (WHI) clinical trials.

Setting Women were recruited from 40 participating sites.

Participants Cohort of 68 132 women followed through 2005 (parent study) and for an additional 5 years in the extension study.

Main outcome measures Statin use was assessed at baseline and at follow-up visits (1, 3, 6 and 9 years). Women brought medications in …

Clinical Significance Of A Point Mutation In Dna Polymerase Beta (Polb) Gene In Gastric Cancer., Xiaohui Tan, Hongyi Wang, Guangbin Luo, Shuyang Ren, Wenmei Li, Jiantao Cui, Harindarpal S. Gill, Sidney W. Fu, Youyong Lu

Medicine Faculty Publications

Gastric cancer (GC) is a major cause of global cancer mortality. Genetic variations in DNA repair genes can modulate DNA repair capability and, consequently, have been associated with risk of developing cancer. We have previously identified a T to C point mutation at nucleotide 889 (T889C) in DNA polymerase beta (POLB) gene, a key enzyme involved in base excision repair in primary GCs. The purpose of this study was to evaluate the mutation and expression of POLB in a larger cohort and to identify possible prognostic roles of the POLB alterations in GC. Primary GC specimens and their matched normal …

Integrating Spirituality As A Key Component Of Patient Care, Suzette Bremault-Phillips, Joanne Olson, Pamela Brett-Maclean, Doreen Oneschuk, Shane Sinclair, Ralph Magnus, Jeanne Weis, Marjan Abbasi, Jasneet Parmar, Christina M. Puchalski

Medicine Faculty Publications

Patient care frequently focuses on physical aspects of disease management, with variable attention given to spiritual needs. And yet, patients indicate that spiritual suffering adds to distress associated with illness. Spirituality, broadly defined as that which gives meaning and purpose to a person’s life and connectedness to the significant or sacred, often becomes a central issue for patients. Growing evidence demonstrates that spirituality is important in patient care. Yet healthcare professionals (HCPs) do not always feel prepared to engage with patients about spiritual issues. In this project, HCPs attended an educational session focused on using the FICA Spiritual History Tool …

Isolation Of Leclercia Adecarboxylata From A Patient With A Subungual Splinter., Rina Allawh, Brendan J Camp

Medicine Faculty Publications

Leclercia adecarboxylata is a rarely described motile, aerobic, gram-negative bacillus reported to cause clinically significant solitary infections in immunocompromised patients and polymicrobial wound infections in immunocompetent patients [1-5]. We present a case of a polymicrobial infection including L. adecarboxylata in a healthy female patient with a subungual splinter, to increase awareness and aid in the diagnosis and treatment of cutaneous L. adecarboxylata infections. To our knowledge, this is the first reported case of trauma-related subungual L. adecarboxylata infection reported in the dermatology literature.

Dyspnea Associated With Silicone Breast Implant Rupture, Katherine Rider, Hatice Kaya, Guillermo Gutierrez

Medicine Faculty Publications

We present a case of a 48-year-old woman with a significant history of atopy. She presented with a 1-month history of dyspnea on exertion. Pulmonary function testing was normal, with no obstruction or reversibility post-bronchodilation. Bilateral breast implant rupture was detected on further investigation for a left upper lobe nodule, and the patient underwent bilateral implant removal. There was an improvement in her respiratory symptoms. Systemic symptoms, labeled as “Autoimmune/Inflammatory Syndrome Induced by Adjuvants,” are known to be associated with breast implants, with 14% of women in a cohort developing autoimmune disease secondary to their implants. An improvement in symptoms …

May Circulating Micrornas Be Gastric Cancer Diagnostic Biomarkers?, Xiaoling Wu, Xiaohui (Jane) Tan, Sidney W. Fu

Medicine Faculty Publications

Gastric cancer (GC) is the third leading cause of cancer-related deaths. More than 80% of the diagnosis was made at the advanced stages of the disease, highlighting the urgent demand for novel biomarkers that can be used for early detection. Recently, a number of studies suggest that circulating microRNAs (miRNAs) could be potential biomarkers for GC diagnosis. Cancer-related circulating miRNAs, as well as tissue miRNAs, provide a hopeful prospect of detecting GC at early stages, and the prospective participation of miRNAs in biomarker development will enhance the sensitivity and specificity of diagnostic tests for GC. As miRNAs in blood are …