Digital Commons Network^™

Co-Clinical Fdg-Pet Radiomic Signature In Predicting Response To Neoadjuvant Chemotherapy In Triple-Negative Breast Cancer, Sudipta Roy, Timothy D Whitehead, Shunqiang Li, Foluso O Ademuyiwa, Richard L Wahl, Farrokh Dehdashti, Kooresh I Shoghi

2020-Current year OA Pubs

PURPOSE: We sought to exploit the heterogeneity afforded by patient-derived tumor xenografts (PDX) to first, optimize and identify robust radiomic features to predict response to therapy in subtype-matched triple negative breast cancer (TNBC) PDX, and second, to implement PDX-optimized image features in a TNBC co-clinical study to predict response to therapy using machine learning (ML) algorithms.

METHODS: TNBC patients and subtype-matched PDX were recruited into a co-clinical FDG-PET imaging trial to predict response to therapy. One hundred thirty-one imaging features were extracted from PDX and human-segmented tumors. Robust image features were identified based on reproducibility, cross-correlation, and volume independence. A …

Genome-Wide Analysis Of Mitochondrial Dna Copy Number Reveals Loci Implicated In Nucleotide Metabolism, Platelet Activation, And Megakaryocyte Proliferation, R J Longchamps, Mary Feitosa, Mary Wojczynski, Aldi Kraja, Michael Province, Et Al.

2020-Current year OA Pubs

Mitochondrial DNA copy number (mtDNA-CN) measured from blood specimens is a minimally invasive marker of mitochondrial function that exhibits both inter-individual and intercellular variation. To identify genes involved in regulating mitochondrial function, we performed a genome-wide association study (GWAS) in 465,809 White individuals from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank (UKB). We identified 133 SNPs with statistically significant, independent effects associated with mtDNA-CN across 100 loci. A combination of fine-mapping, variant annotation, and co-localization analyses was used to prioritize genes within each of the 133 independent sites. Putative causal genes …

Checkpoint Blockade-Induced Cd8+ T Cell Differentiation In Head And Neck Cancer Responders, Liye Zhou, Paul Zolkind, Obi Griffith, Et Al

2020-Current year OA Pubs

BACKGROUND: Immune checkpoint blockade (ICB) response in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) is limited to 15%-20% of patients and underpinnings of resistance remain undefined.

METHODS: Starting with an anti-PD1 sensitive murine HNSCC cell line, we generated an isogenic anti-PD1 resistant model. Mass cytometry was used to delineate tumor microenvironments of both sensitive parental murine oral carcinoma (MOC1) and resistant MOC1esc1 tumors. To examine heterogeneity and clonal dynamics of tumor infiltrating lymphocytes (TILs), we applied paired single-cell RNA and TCR sequencing in three HNSCC models.

RESULTS: Anti-PD1 resistant MOC1esc1 line displayed a conserved cell intrinsic immune evasion signature. …

Phase I Clinical Trial Evaluating The Safety And Efficacy Of Adp-A2m10 Spear T Cells In Patients With Mage-A10+ Advanced Non-Small Cell Lung Cancer, George R Blumenschein, Siddhartha Devarakonda, Ramaswamy Govindan, Et Al

2020-Current year OA Pubs

BACKGROUND: ADP-A2M10 specific peptide enhanced affinity receptor (SPEAR) T cells (ADP-A2M10) are genetically engineered autologous T cells that express a high-affinity melanoma-associated antigen A10 (MAGE-A10)-specific T-cell receptor (TCR) targeting MAGE-A10

METHODS: Eligible patients were HLA-A*02 positive with advanced NSCLC expressing MAGE-A10. Patients underwent apheresis; T cells were isolated, transduced with a lentiviral vector containing the TCR targeting MAGE-A10, and expanded. Patients underwent lymphodepletion with varying doses/schedules of fludarabine and cyclophosphamide prior to receiving ADP-A2M10. ADP-A2M10 were administered at 0.08-0.12×10

RESULTS: Eleven patients (male, n=6; female, n=5) with NSCLC (adenocarcinoma, n=8; squamous cell carcinoma, n=3) were treated. Five, three, and three …

Left Ventricular Dysfunction In Outpatients With Frequent Ventricular Premature Complexes, Kyoung-Min Park, Sung Il Im, Sung Ho Lee, Hye Bin Gwag, Youngjun Park, Seung-Jung Park, June Soo Kim, Young Keun On

The Texas Heart Institute Journal

Frequent ventricular premature complexes (VPCs) and VPC QRS duration are risk factors for left ventricular (LV) dysfunction. To determine which clinical characteristics and electrocardiographic features are associated with LV dysfunction (ejection fraction,

We identified 412 consecutive outpatients (mean age, 54.7 ± 16.8 yr; 227 women [55.1%]) who were diagnosed with frequent VPCs and had no structural heart disease from January 2010 through December 2017. Available transthoracic echocardiograms and 24-hour Holter monitoring data were evaluated to correlate the occurrence of VPCs and symptoms.

Typical VPC-related symptoms (palpitations or dropped beats) were observed in 251 patients (61.1%). Electrocardiograms revealed VPCs with a …

Aging With Long-Term Physical Disability: Cohort Analysis Of Survey Sample In The U.S., Kerri A Morgan, Michelle Putnam, Sandra M Espin-Tello, Marian Keglovits, Margaret Campbell, Yan Yan, Aimee Wehmeier, Susan Stark

2020-Current year OA Pubs

BACKGROUND: Chronic health conditions, secondary conditions, and decreasing functional ability related to aging and/or changes in underlying impairment may influence participation for persons aging with long-term physical disability (AwD).

OBJECTIVE: To examine sample integrity and baseline findings through exploration of associations of sociodemographic, health, and disability factors with social participation for persons AwD.

METHODS: This is a longitudinal cohort study following persons AwD over three years, reporting baseline cohort study data. A convenience sample of 474 persons AwD aged 45-65 reporting physical disability of ≥5 years' duration was recruited through community organizations and social media. The cohort was majority female …

Reduced Expression In Preterm Birth Of Sflt-1 And Plgf With A High Sflt-1/Plgf Ratio In Extracellular Vesicles Suggests A Potential Biomarker, Sama Hussein, Weina Ju, Stephanie Pizzella, Michael Flory, Chu Chu, Yong Wang, Nanbert Zhong

2020-Current year OA Pubs

Preterm birth may have a pathological impact on intrauterine development of the fetal brain, resulting in developmental disabilities. In this study, we examine the expression of soluble Fms-like tyrosine kinase 1 (sFLT-1) and placental growth factor (PlGF), which is one of the vascular endothelial growth factors (VEGFs), as these play a key role in angiogenesis; in particular, we examine their effect on the sFLT-1/PlGF ratio in cases of preterm birth as compared to typical pregnancies. Enzyme-linked immunosorbent assay was performed on samples of maternal-derived plasma and extracellular vesicles-exosomes (EVs-EXs) isolated at the third trimester, consisting of 17 samples from cases …

Targeting The Pro-Survival Protein Bcl-2 To Prevent Breast Cancer, Adelaide Young, Wen Bu, Weiyu Jiang, Amy Ku, Jyoti Kapali, Sagar Dhamne, Lan Qin, Susan G Hilsenbeck, Yi-Chieh Nancy Du, Yi Li

Faculty, Staff and Students Publications

Current chemopreventive strategies require 3-5 years of continuous treatment and have the concerns of significant side effects; therefore, new chemopreventive agents that require shorter and safer treatments are urgently needed. In this study, we developed a new murine model of breast cancer that mimics human breast cancer initiation and is ideal for testing the efficacy of chemopreventive therapeutics. In this model, introduction of lentivirus carrying a PIK3CA gene mutant commonly found in breast cancers infects a small number of the mammary cells, leading to atypia first and then to ductal carcinomas that are positive for both estrogen receptor and progesterone …

Adrenomedullin And Its Receptors Are Expressed In Mouse Pancreatic Β-Cells And Suppresses Insulin Synthesis And Secretion, Yuanlin Dong, Simone Hernandez Ruano, Akansha Mishra, Kathleen A Pennington, Chandrasekhar Yallampalli

Faculty, Staff and Students Publications

Gestational diabetes mellitus (GDM) is associated with defective pancreatic β-cell adaptation in pregnancy, but the underlying mechanism remains obscure. Our previous studies demonstrated that GDM women display increased plasma adrenomedullin (ADM) levels, and non-obese GDM mice show decreased serum concentrations of insulin and the number of β-cells in pancreas islets. The aims of this study is to examine if ADM and its receptors are expressed in female mouse pancreas, and if so, whether insulin secretion is regulated by ADM in mouse β-cell line, NIT-1 cells and isolated mouse pancreatic islets. Present study shows that ADM and its receptor components CRLR, …

Lipid Dysfunction And Adrenomedullin Expression In Omental Versus Subcutaneous Adipose Tissues In Diabetic Pregnancies, Yuanlin Dong, Ancizar Betancourt, Michael A Belfort, Chandrasekhar Yallampalli

Faculty, Staff and Students Publications

Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy but the underlying mechanism remains obscure. The aims of this study are to examine if omental adipose tissue (OMAT) and subcutaneous AT (SCAT) differentially express proinflammatory and lipid metabolic adipokines, and if so, whether their regional differences have implications on lipid metabolism in GDM. Paired samples of OMAT and SCAT were excised from pregnant women in scheduled Cesarean sections with non-obese (NOBS), obese (OBS) and GDM. The results showed that the mRNA of monocyte chemoattractant protein (MCP)-1, macrophage marker CD68, and cytokines IL-6, IL-8, and TNF-α are …

Selectively Targeting Disease-Restricted Secretogranin Iii To Alleviate Choroidal Neovascularization, Liyang Ji, Prabuddha Waduge, Lili Hao, Avinash Kaur, Wencui Wan, Yan Wu, Hong Tian, Jinsong Zhang, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

Choroidal neovascularization (CNV), a leading cause of blindness in the elderly, is routinely treated with vascular endothelial growth factor (VEGF) inhibitors that have limited efficacy and potentially adverse side effects. An unmet clinical need is to develop novel therapies against other angiogenic factors for alternative or combination treatment to improve efficacy and safety. We recently described secretogranin III (Scg3) as a disease-selective angiogenic factor, causally linked to diabetic retinopathy and acting independently of the VEGF pathway. An important question is whether such a disease-selective Scg3 pathway contributes to other states of pathological angiogenesis beyond diabetic retinopathy. By applying a novel …

Screening For Balance In Children And Adults In A Community Science Education Setting: Normative Data, Influence Of Age, Sex, And Body Mass Index, And Feasibility, Phyllis Friello, Nathan Silver, Haleh Sangi-Haghpeykar, Helen S Cohen

Faculty, Staff and Students Publications

BACKGROUND: Screening standing and walking balance is useful for people suspected of having vestibular disorders, a variety of neurologic and musculoskeletal disorders, and for screening astronauts returning after exposure to microgravity. Visitors to a community science education center children and adults, aged 4 to 85, were tested on tandem walking with eyes closed and the modified Romberg test on compliant foam. They were then asked about their experience participating in research, many people for the first time.

METHODS: Subjects performed 10 steps of tandem walking with eyes closed, and three trials of the modified Romberg, or Clinical Test of Sensory …

Subjective Versus Objective Tests Of Dizziness And Vestibular Function In Epidemiologic Screening Research, Helen S Cohen, Haleh Sangi-Haghpeykar, Michael W Plankey

Faculty, Staff and Students Publications

BACKGROUND: Many epidemiologic studies of vestibular disorders are based on responses to questionnaires which have not been tested against objective tests of the vestibular system.

OBJECTIVE: The goal was to determine if the dizziness and balance questions used in the National Health Interview Survey (NHIS) are valid and predict performance on objective tests of the vestibular system (VNG).

METHODS: Data from 367 participants recruited from the community, aged 21.4 to 87.6 years, were collected in the Otolaryngology department at a tertiary care center. They were asked the eight NHIS questions twice, at least 30 minutes apart and were tested on …

An Asian Case Of Combined 17Α-Hydroxylase/17,20-Lyase Deficiency Due To Homozygous Pr96q Mutation: A Case Report And Review Of The Literature, Qian Liao, Rufei Shen, Mingyu Liao, Chenxi Ran, Ling Zhou, Yuling Zhang, Guiliang Peng, Zheng Sun, Hongting Zheng, Min Long

Center on Aging Staff Publications

Background: Combined 17α-hydroxylase/17,20-lyase deficiency (17-OHD) is a very rare form of congenital adrenal hyperplasia (CAH) caused by mutations in the CYP17A1 gene. Almost 100 different mutations of the CYP17A1 gene have been reported, including p.R96Q mutation, but no case of p.R96Q mutation has been described in Asian populations.

Case presentation: We describe a 22-year-old female patient of 46,XY karyotype, who presented with pseudohermaphrodism, primary amenorrhea, underdeveloped secondary sexual characteristics, delayed epiphyseal healing, hypertension, and hypokalemia. The diagnosis of 17-OHD was reached by measurement of steroid hormones and abdominal CT scan and confirmed by genetic sequencing, which revealed a homozygous p.R96Q …

Surgical Intervention For Phlegmasia Cerulea Dolens In A 61-Year-Old Cancer Patient, Christopher Ruben-Castillo, Cesar Cuen-Ojeda, Gabriel Lopez-Peña, Javier E Anaya-Ayala, Carlos A Hinojosa

The Texas Heart Institute Journal

Phlegmasia cerulea dolens, a rare and potentially fatal complication of acute deep vein thrombosis, is characterized by substantial edema, intense pain, and cyanosis. Phlegmasia cerulea dolens may compromise limb perfusion and lead to acute ischemia, gangrene, amputation, and death. We present the case of a 61-year-old woman with a history of breast cancer who had signs and symptoms of phlegmasia cerulea dolens in her left leg. She was treated promptly with open surgical thrombectomy and sequential distal compression with use of an Esmarch bandage to ensure complete thrombus extraction. These techniques restored venous flow and saved her leg. Open surgical …

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. …

The Barriers And Facilitators Of Hiv-Exposed Infant Testing As Perceived By Hiv-Positive Mothers In Botswana: A Qualitative Study, Grace Karugaba, Jennifer Simpson, Bathusi Mathuba, Onkemetse Phoi, Thato Regonamanye, Keofentse Mathuba, Eldah Dintwa, Bornapate Nkomo, Dinah Ramaabya, Mathabo Relebohile Pule, Mogomotsi Matshaba

Faculty, Staff and Students Publications

BACKGROUND: Despite high rates of HIV testing and enrolment of HIV-positive pregnant women on antiretroviral therapy in Botswana, coverage for HIV-exposed infant (HEI) testing remains suboptimal. Many factors can contribute to suboptimal HEI testing rates, but they have seldom been thoroughly investigated in Botswana. Therefore, the aim of this study was to explore the experiences and perspectives of HIV-positive mothers on the barriers and facilitators of HEI testing to inform interventions to promote HEI testing in Botswana.

METHODS: We conducted focus group discussions (FGDs) with HIV-positive mothers who gave birth in 2016 at the three largest public hospitals in Botswana. …

Characterization And Outcomes Of Hospitalized Children With Coronavirus Disease 2019: A Report From A Multicenter, Viral Infection And Respiratory Illness Universal Study (Coronavirus Disease 2019) Registry, Utpal S Bhalala, Katja M Gist, Sandeep Tripathi, Karen Boman, Vishakha K Kumar, Lynn Retford, Kathleen Chiotos, Allison M Blatz, Heda Dapul, Sourabh Verma, Imran A Sayed, Varsha P Gharpure, Erica Bjornstad, Nancy Tofil, Katherine Irby, Ronald C Sanders, Julia A Heneghan, Melissa Thomas, Manoj K Gupta, Franscene E Oulds, Grace M Arteaga, Emily R Levy, Neha Gupta, Margit Kaufman, Amr Abdelaty, Mark Shlomovich, Shivanand S Medar, A M Iqbal O'Meara, Joshua Kuehne, Shina Menon, Paras B Khandhar, Aaron S Miller, Suzanne M Barry, Valerie C Danesh, Ashish K Khanna, Kimberly Zammit, Casey Stulce, Patrick W Mcgonagill, Asher Bercow, Ioana G Amzuta, Sandeep Gupta, Mohammed A Almazyad, Louisdon Pierre, Prithvi Sendi, Sidra Ishaque, Harry L Anderson, Pooja Nawathe, Murtaza Akhter, Patrick G Lyons, Catherine Chen, Allan J Walkey, Azra Bihorac, Imam Wada Bello, Judith Ben Ari, Tanja Kovacevic, Vikas Bansal, John T Brinton, Jerry J Zimmerman, Rahul Kashyap

Faculty, Staff and Students Publications

OBJECTIVES: Multicenter data on the characteristics and outcomes of children hospitalized with coronavirus disease 2019 are limited. Our objective was to describe the characteristics, ICU admissions, and outcomes among children hospitalized with coronavirus disease 2019 using Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study: Coronavirus Disease 2019 registry.

DESIGN: Retrospective study.

SETTING: Society of Critical Care Medicine Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) registry.

PATIENTS: Children (< 18 yr) hospitalized with coronavirus disease 2019 at participating hospitals from February 2020 to January 2021.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: The primary outcome was ICU admission. Secondary outcomes included hospital and ICU duration of stay and ICU, hospital, …

Identification Of Serum Mirna Signature And Establishment Of A Nomogram For Risk Stratification In Patients With Pancreatic Ductal Adenocarcinoma, Raju Kandimalla, Tadanobu Shimura, Saurav Mallik, Fuminori Sonohara, Susan Tsai, Douglas B Evans, Song Cheol Kim, Hideo Baba, Yasuhiro Kodera, Daniel Von Hoff, Xi Chen, Ajay Goel

Faculty, Staff and Students Publications

OBJECTIVE: The aim of the study was to perform mRNA-miRNA regulatory network analyses to identify a miRNA panel for molecular subtype identification and stratification of high-risk patients with pancreatic ductal adenocarcinoma (PDAC).

BACKGROUND: Recent transcriptional profiling effort in PDAC has led to the identification of molecular subtypes that associate with poor survival; however, their clinical significance for risk stratification in patients with PDAC has been challenging.

METHODS: By performing a systematic analysis in The Cancer Genome Atlas and International Cancer Genome Consortium cohorts, we discovered a panel of miRNAs that associated with squamous and other poor molecular subtypes in PDAC. …

Paraventricular Vitamin D Receptors Are Required For Glucose Tolerance In Males But Not Females, Jessie Beck, Silvania Da Silva Teixeira, Keisha Harrison, Gabrielle Phillips, Yanlin He, Stephanie Sisley

Faculty, Staff and Students Publications

When delivered directly into the brain, vitamin D, can improve glucose levels in male mice. Additionally, the loss of the vitamin D receptor (VDR) in male mice's paraventricular hypothalamus (PVH) results in impaired glucose tolerance. Data in humans shows that low vitamin D levels are detrimental to glucose homeostasis, an effect that may be more prominent in men. However, it is unknown if vitamin D action in the brain is required for normal glucose regulation in female mice. This study shows that in both viral and genetic models, male mice with obesity and PVH VDR loss have impaired glucose tolerance …

Nuclear Progesterone Receptor Expressed By The Cortical Thymic Epithelial Cells Dictates Thymus Involution In Murine Pregnancy, Soo Hyun Ahn, Sean L Nguyen, Tae Hoon Kim, Jae-Wook Jeong, Ripla Arora, John P Lydon, Margaret G Petroff

Faculty, Staff and Students Publications

Progesterone is a gonadal pro-gestational hormone that is absolutely necessary for the success of pregnancy. Most notable actions of progesterone are observed in the female reproductive organs, the uterus and the ovary. Acting through the nuclear progesterone receptor (PGR), progesterone prepares the endometrium for implantation of the embryo. Interestingly, the maternal thymus also is a known expressor of Pgr; its absence is associated with murine pregnancy complications. However, the localization of its expression and its functional importance were not known. Here, we used a transgenic dual fluorescent reporter mouse model and genetic deletion of Pgr in Foxn1+ thymic epithelial …

Biomarkers Of Response And Resistance To Palbociclib Plus Letrozole In Patients With Er+/Her2- Breast Cancer, Mitch Dowsett, Lucy Kilburn, Mothaffar F Rimawi, C Kent Osborne, Katherine Pogue-Geile, Yuan Liu, Samuel A Jacobs, Melanie Finnigan, Shannon Puhalla, Andrew Dodson, Vera Martins, Maggie Cheang, Sophie Perry, Chris Holcombe, Nick Turner, Claire Swift, Judith M Bliss, Stephen Johnston

Faculty, Staff and Students Publications

PURPOSE: To determine (i) the relationship between candidate biomarkers of the antiproliferative (Ki67) response to letrozole and palbociclib alone and combined in ER

EXPERIMENTAL DESIGN: 307 postmenopausal women with ER+/HER2− primary breast cancer were randomly assigned to neoadjuvant treatment with letrozole for 14 weeks; letrozole for 2 weeks, then letrozole+palbociclib to 14 weeks; palbociclib for 2 weeks, then letrozole+palbociclib to 14 weeks; or letrozole+palbociclib for 14 weeks. Biopsies were taken at baseline, 2 and 14 weeks and surgery at varying times after stopping palbociclib. Immunohistochemical analyses were conducted for Ki67, c-PARP, ER, PgR, RB1, CCNE1, and CCND1.

RESULTS: Higher baselines …

“I Have Nothing More To Give”: Disparities In Burnout And The Protective Role Of Immigrant Status During The Covid-19 Pandemic, Gene Chibuchim Otuonye, Nancy Shenoi, Tianshi David Wu, Kalpalatha Guntupalli, Nidal Moukaddam

Faculty, Staff and Students Publications

Burnout is an epidemic, with deleterious effects on individuals, patient care, and healthcare systems. The Coronavirus Disease 2019 (COVID-19) pandemic may be exacerbating this problem. We aimed to explore socio-cultural and gender norms that modulate burnout development in physicians during the pandemic and analyze any disparities associated with gender, marital and immigration status and work-life balance. We conducted an online cross-sectional survey of physicians (August-November, 2021): The Maslach Burnout Inventory-Human Services Survey (MBI-HSS) was used to measure burnout, combined with a validated survey assessing work-life balance. Demographic data was obtained for each participant. MBI-HSS subscales were measured, along with work …

Racial/Ethnic Variations In Alcohol And Cigarette Use By Pregnancy Status Among 20- To 44-Year-Old Women, Nhanes 2001–2018, Jacqueline M Hirth, Catherine Valadez, Sandra Gonzalez, Alicia Kowalchuk, Judith A Gutierrez, Roger Zoorob

Faculty, Staff and Students Publications

OBJECTIVES: This study examines alcohol consumption and smoking behaviors by pregnancy status and race/ethnicity in order to inform improved interventions designed to assist women of all races to avoid alcohol and tobacco use during pregnancy for their health and to prevent potential fetal exposure.

METHODS: This retrospective secondary data analysis utilized nationally representative National Health and Nutrition Examination Survey data between 2001 and 2018. Smoking and alcohol use were evaluated by race/ethnicity and pregnancy risk. Sexual behavior, reproductive health, and prescription drug use determined pregnancy risk, categorized as low pregnancy risk, at risk of becoming pregnant, and pregnant. Binary and …

A Novel Model Of Gestational Diabetes: Acute High Fat High Sugar Diet Results In Insulin Resistance And Beta Cell Dysfunction During Pregnancy In Mice, Akansha Mishra, Simone Hernandez Ruano, Pradip K Saha, Kathleen A Pennington

Faculty, Staff and Students Publications

Gestational diabetes mellitus (GDM) affects 7–18% of all pregnancies. Despite its high prevalence, there is no widely accepted animal model. To address this, we recently developed a mouse model of GDM. The goal of this work was to further characterize this animal model by assessing insulin resistance and beta cell function. Mice were randomly assigned to either control (CD) or high fat, high sugar (HFHS) diet and mated 1 week later. At day 0 (day of mating) mice were fasted and intraperitoneal insulin tolerance tests (ipITT) were performed. Mice were then euthanized and pancreata were collected for histological analysis. Euglycemic …

The Human Male Liver Is Predisposed To Inflammation Via Enhanced Myeloid Responses To Inflammatory Triggers, Adrian Kuipery, Deeqa Mahamed, Shirin Nkongolo, June Ann D'Angelo, Alexandra Johnson Valiente, Aman Mehrotra, William C Chapman, Peter Horton, Ian Mcgilvray, Harry L A Janssen, Adam J Gehring

2020-Current year OA Pubs

BACKGROUND & AIM: Men have a higher prevalence of liver disease. Liver myeloid cells can regulate tissue inflammation, which drives progression of liver disease. We hypothesized that sex alters the responsiveness of liver myeloid cells, predisposing men to severe liver inflammation.

METHODS: Luminex was done on plasma from Hepatitis B Virus infected patients undergoing nucleoside analogue cessation in 45 male and female patients. We collected immune cells from the sinusoids of uninfected livers of 53 male and female donors. Multiparametric flow cytometry was used to phenotype and characterize immune composition. Isolated monocytes were stimulated with TLR ligands to measure the …

Barriers And Facilitators To Diabetes Screening And Prevention After A Pregnancy Complicated By Gestational Diabetes, Drishti D. Sinha, Roxann C. Williams, Laura N. Hollar, Hannah R. Lucas, Bethany Johnson-Javois, Heidi B. Miller, Amanda Stoermer, Graham A. Colditz, Aimee S. James, Cynthia J. Herrick

2020-Current year OA Pubs

OBJECTIVE: Gestational diabetes mellitus (GDM) is increasing in the United States, with higher rates among minoritized racial and ethnic populations and lower income populations. GDM increases risk for type 2 diabetes (T2DM), and postpartum diabetes screening and prevention are imperative. This qualitative study examines barriers and facilitators to postpartum T2DM screening and prevention among non-privately insured individuals with a history of GDM in a state prior to Medicaid expansion.

METHODS: Thirty-six non-privately insured women with a history of GDM completed semi-structured interviews. Four focus groups and seven interviews were conducted with 30 nurse practitioners, physicians, physician assistants, nurses and registered …

Law School News: Rwu Law Remembers Sarah Weddington 12/30/2021, Michael M. Bowden

Life of the Law School (1993- )

No abstract provided.

Epigenome-Wide Association Study Of Mitochondrial Genome Copy Number, Penglong Wang, Christina A Castellani, Jie Yao, Tianxiao Huan, Lawrence F Bielak, Wei Zhao, Jeffrey Haessler, Roby Joehanes, Xianbang Sun, Xiuqing Guo, Ryan J Longchamps, Joann E Manson, Megan L Grove, Jan Bressler, Kent D Taylor, Tuuli Lappalainen, Silva Kasela, David J Van Den Berg, Lifang Hou, Alexander Reiner, Yongmei Liu, Eric Boerwinkle, Jennifer A Smith, Patricia A Peyser, Myriam Fornage, Stephen S Rich, Jerome I Rotter, Charles Kooperberg, Dan E Arking, Daniel Levy, Chunyu Liu

Faculty, Staff and Student Publications

We conducted cohort- and race-specific epigenome-wide association analyses of mitochondrial deoxyribonucleic acid (mtDNA) copy number (mtDNA CN) measured in whole blood from participants of African and European origins in five cohorts (n = 6182, mean age = 57-67 years, 65% women). In the meta-analysis of all the participants, we discovered 21 mtDNA CN-associated DNA methylation sites (CpG) (P < 1 × 10-7), with a 0.7-3.0 standard deviation increase (3 CpGs) or decrease (18 CpGs) in mtDNA CN corresponding to a 1% increase in DNA methylation. Several significant CpGs have been reported to be associated with at least two risk factors (e.g. chronological age or smoking) for cardiovascular disease (CVD). Five genes [PR/SET domain 16, nuclear receptor subfamily 1 group H member 3 (NR1H3), DNA repair protein, DNA polymerase kappa and decaprenyl-diphosphate synthase subunit 2], which harbor nine significant CpGs, are known to be involved in mitochondrial biosynthesis and functions. For example, NR1H3 encodes a transcription factor that is differentially expressed during an adipose tissue transition. The methylation level of cg09548275 in NR1H3 was negatively associated with mtDNA CN (effect size = -1.71, P = 4 × 10-8) and was positively associated with the NR1H3 expression level (effect size = 0.43, P = 0.0003), which indicates that the methylation level in NR1H3 may underlie the relationship between mtDNA CN, the NR1H3 transcription factor and energy expenditure. In summary, the study results suggest that mtDNA CN variation in whole blood is associated with DNA methylation levels in genes that are involved in a wide range of mitochondrial activities. These findings will help reveal molecular mechanisms between mtDNA CN and CVD.

Women And Ethnoracial Minorities With Poor Cardiovascular Health Measures Associated With A Higher Risk Of Developing Mood Disorder, Aixia Guo, Kari A Stephens, Yosef M Khan, James R Langabeer, Randi E Foraker

2020-Current year OA Pubs

BACKGROUND: Mood disorders (MDS) are a type of mental health illness that effects millions of people in the United States. Early prediction of MDS can give providers greater opportunity to treat these disorders. We hypothesized that longitudinal cardiovascular health (CVH) measurements would be informative for MDS prediction.

METHODS: To test this hypothesis, the American Heart Association's Guideline Advantage (TGA) dataset was used, which contained longitudinal EHR from 70 outpatient clinics. The statistical analysis and machine learning models were employed to identify the associations of the MDS and the longitudinal CVH metrics and other confounding factors.

RESULTS: Patients diagnosed with MDS …