Digital Commons Network^™

Care4ad: A Technology-Driven Platform For Care Coordination And Management: Acceptability Study In Dementia, Ram Kinker Mishra, Catherine Park, Anmol Salim Momin, Nesreen El Rafaei, Mark Kunik, Michele K York, Bijan Najafi

Center on Aging Staff Publications

Introduction: The technology-driven solution can reduce the caregiving burden; however, the needs of dementia caregiving are unique, and attitudes towards adopting technology from the perspectives of all the stakeholders involved in dementia caregiving are unclear. This study aims to assess the acceptability and feasibility of a technology-driven platform to facilitate care coordination platform, Care4AD, from the end-user perspective.

Methods: Care4AD includes three components: (1) Care4AD app: the app is used by caregivers to coordinate care, monitor physical activity, and schedule reminders; (2) Care4AD tablet: a smart tablet is used by the care recipient to display scheduled reminders; and (3) Care4AD …

Optical Coherence Tomography For Dynamic Investigation Of Mammalian Reproductive Processes, Kohei Umezu, Irina V Larina

Faculty, Staff and Students Publications

The biological events associated with mammalian reproductive processes are highly dynamic and tightly regulated by molecular, genetic, and biomechanical factors. Implementation of live imaging in reproductive research is vital for the advancement of our understanding of normal reproductive physiology and for improving the management of reproductive disorders. Optical coherence tomography (OCT) is emerging as a promising tool for dynamic volumetric imaging of various reproductive processes in mice and other animal models. In this review, we summarize recent studies employing OCT-based approaches toward the investigation of reproductive processes in both, males and females. We describe how OCT can be applied to …

Supplementary Feeding And Infection Control In Pregnant Adolescents-A Secondary Analysis Of A Randomized Trial Among Malnourished Women In Sierra Leone, Aminata S Koroma, Mariama Ellie, Kadiatu Bangura, Per O Iversen, David T Hendrixson, Kevin Stephenson, Mark J Manary

2020-Current year OA Pubs

Undernutrition during pregnancy in adolescence confers a high risk of maternal morbidity and adverse birth outcomes, particularly in low-resource settings. In a secondary analysis, we hypothesized that younger undernourished pregnant adolescents (<18 years) would benefit more than undernourished pregnant adults (>20 years) from the intervention of supplementary food and anti-infective treatments. The original trial in Sierra Leone enrolled 236 younger adolescents (<18 years), 454 older adolescents (aged 18-19 years), and 741 adults (≥20 years), all with a mid-upper arm circumference ≤23 cm. Younger adolescents had lower final fundal height as well as smaller newborns (-0.3 kg; 95% confidence interval [CI], -0.3, -0.2; p < 0.001) and shorter newborns (-1.1 cm; 95% CI, -1.5, -0.7; p < 0.001) than adults. The intervention's effect varied significantly between maternal age groups: adults benefited more than younger adolescents with respect to newborn birth weight (difference in difference, 166 g; 95% CI, 26, 306; interaction p = 0.02), birth length (difference in difference, 7.4 mm; 95% CI, 0.1, 14.8; interaction p = 0.047), and risk for low birth weight (<2.5 kg) (interaction p = 0.019). The differences in response persisted despite adjustments for maternal anthropometry, the number of prior pregnancies, and human immunodeficiency virus status. Older adolescents similarly benefited more than younger adolescents, though differences did not reach statistical significance. In conclusion, newborns born to younger adolescent mothers had worse outcomes than those born to adult mothers, and adults and their newborns benefited more from the intervention than younger adolescents.

Female Athlete Health Domains: A Supplement To The International Olympic Committee Consensus Statement On Methods For Recording And Reporting Epidemiological Data On Injury And Illness In Sport, Isabel S. Moore, Kay M. Crossley, Kari Bo, Margo Mountjoy, Kathryn E. Ackerman, Juliana D. S. Antero, Jorunn S. Borgen, Wendy J. Brown, Caroline S. Bolling, Benjamin Clarsen, Wayne Derman, Paul Dijkstra, Amber Donaldson, Kirsty J. Elliott-Sale, Carolyn A. Emery, Lene Haakstad, Astrid Junge, Nonhlanhla S. Mkumbuzi, Sophia Nimphius, Debbie Palmer, Mireille Van Poppel, Jane S. Thornton, Rita Tomás, Phathokuhle C. Zondi, Evert Verhagen

Research outputs 2022 to 2026

The IOC made recommendations for recording and reporting epidemiological data on injuries and illness in sports in 2020, but with little, if any, focus on female athletes. Therefore, the aims of this supplement to the IOC consensus statement are to (i) propose a taxonomy for categorisation of female athlete health problems across the lifespan; (ii) make recommendations for data capture to inform consistent recording and reporting of symptoms, injuries, illnesses and other health outcomes in sports injury epidemiology and (iii) make recommendations for specifications when applying the Strengthening the Reporting of Observational Studies in Epidemiology-Sport Injury and Illness Surveillance (STROBE-SIIS) …

Milder Loss Of Insulin-Containing Islets In Individuals With Type 1 Diabetes And Type 2 Diabetes-Associated Tcf7l2 Genetic Variants, Maria J Redondo, Sarah J Richardson, Daniel Perry, Charles G Minard, Alice L J Carr, Todd Brusko, Irina Kusmartseva, Alberto Pugliese, Mark A Atkinson

Faculty, Staff and Students Publications

AIMS/HYPOTHESIS: TCF7L2 variants are the strongest genetic risk factor for type 2 diabetes. In individuals with type 1 diabetes, these variants are associated with a higher C-peptide AUC, a lower glucose AUC during an OGTT, single autoantibody positivity near diagnosis, particularly in individuals older than 12 years of age, and a lower frequency of type 1 diabetes-associated HLA genotypes. Based on initial observations from clinical cohorts, we tested the hypothesis that type 2 diabetes-predisposing TCF7L2 genetic variants are associated with a higher percentage of residual insulin-containing cells (ICI%) in pancreases of donors with type 1 diabetes, by examining genomic data …

Effects Of Aging On Urinary Tract Epithelial Homeostasis And Immunity, Marianne M Ligon, Chetanchandra S Joshi, Bisiayo E Fashemi, Arnold M Salazar, Indira U Mysorekar

Faculty, Staff and Students Publications

A global increase in older individuals creates an increasing demand to understand numerous healthcare challenges related to aging. This population is subject to changes in tissue physiology and the immune response network. Older individuals are particularly susceptible to infectious diseases, with one of the most common being urinary tract infections (UTIs). Postmenopausal and older women have the highest risk of recurrent UTIs (rUTIs); however, why rUTIs become more frequent after menopause and during old age is incompletely understood. This increased susceptibility and severity among older individuals may involve functional changes to the immune system with age. Aging also has substantial …

Transferrin Receptor In Primary And Metastatic Breast Cancer: Evaluation Of Expression And Experimental Modulation To Improve Molecular Targeting, Francesca Fontana, Alison K. Esser, Christopher Egbulefu, Partha Karmakar, Xinming Su, John S. Allen, Yalin Xu, Jennifer L. Davis, Ariel Gabay, Jingyu Xiang, Kristin A. Kwakwa, Brad Manion, Suzanne Bakewell, Shunqiang Li, Haeseong Park, Gregory M. Lanza, Samuel Achilefu, Katherine N. Weilbaecher

2020-Current year OA Pubs

BACKGROUND: Conjugation of transferrin (Tf) to imaging or nanotherapeutic agents is a promising strategy to target breast cancer. Since the efficacy of these biomaterials often depends on the overexpression of the targeted receptor, we set out to survey expression of transferrin receptor (TfR) in primary and metastatic breast cancer samples, including metastases and relapse, and investigate its modulation in experimental models.

METHODS: Gene expression was investigated by datamining in twelve publicly-available datasets. Dedicated Tissue microarrays (TMAs) were generated to evaluate matched primary and bone metastases as well as and pre and post chemotherapy tumors from the same patient. TMA were …

Inhibition Of Mirna Associated With A Disease-Specific Signature And Secreted Via Extracellular Vesicles Of Systemic Lupus Erythematosus Patients Suppresses Target Organ Inflammation In A Humanized Mouse Model, Nicholas A Young, Emily Schwarz, Braden M Zeno, Shane Bruckner, Rosana A Mesa, Kyle Jablonski, Lai-Chu Wu, Elisha D O Roberson, Wael N Jarjour

2020-Current year OA Pubs

INTRODUCTION: Distinct, disease-associated intracellular miRNA (miR) expression profiles have been observed in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematous (SLE) patients. Additionally, we have identified novel estrogenic responses in PBMCs from SLE patients and demonstrated that estrogen upregulates toll-like receptor (TLR)7 and TLR8 expression. TLR7 and TLR8 bind viral-derived single-stranded RNA to stimulate innate inflammatory responses, but recent studies have shown that miR-21, mir-29a, and miR-29b can also bind and activate these receptors when packaged and secreted in extracellular vesicles (EVs). The objective of this study was to evaluate the association of EV-encapsulated small RNA species in SLE …

Clinical Characterization Of Data-Driven Diabetes Clusters Of Pediatric Type 2 Diabetes, Mahsan Abbasi, Mustafa Tosur, Marcela Astudillo, Ahmad Refaey, Ashutosh Sabharwal, Maria J Redondo

Faculty, Staff and Students Publications

BACKGROUND: Pediatric Type 2 diabetes (T2D) is highly heterogeneous. Previous reports on adult-onset diabetes demonstrated the existence of diabetes clusters. Therefore, we set out to identify unique diabetes subgroups with distinct characteristics among youth with T2D using commonly available demographic, clinical, and biochemical data.

METHODS: We performed data-driven cluster analysis (K-prototypes clustering) to characterize diabetes subtypes in pediatrics using a dataset with 722 children and adolescents with autoantibody-negative T2D. The six variables included in our analysis were sex, race/ethnicity, age, BMI

RESULTS: We identified five distinct clusters of pediatric T2D, with different features, treatment regimens and risk of diabetes complications: …

Factors Associated With Nonsyndromic Anotia And Microtia, Texas, 1999–2014, Jeremy M Schraw, J P Woodhouse, Renata H Benjamin, Charles J Shumate, Joanne Nguyen, Mark A Canfield, A J Agopian, Philip J Lupo

Faculty, Staff and Students Publications

BACKGROUND: Few risk factors have been identified for nonsyndromic anotia/microtia (A/M).

METHODS: We obtained data on cases and a reference population of all livebirths in Texas for 1999-2014 from the Texas Birth Defects Registry (TBDR) and Texas vital records. We estimated prevalence ratios (PRs) and 95% confidence intervals (CIs) for A/M (any, isolated, nonisolated, unilateral, and bilateral) using Poisson regression. We evaluated trends in prevalence rates using Joinpoint regression.

RESULTS: We identified 1,322 cases, of whom 982 (74.3%) had isolated and 1,175 (88.9%) had unilateral A/M. Prevalence was increased among males (PR: 1.3, 95% CI: 1.2-1.4), offspring of women with …

Editorial: Molecular Mechanisms In Ocular Development And Disease, Rajalekshmy Shyam, Daisy Y Shu, Elizabeth Zuniga-Sanchez, Deepika Vasudevan

Faculty, Staff and Students Publications

No abstract provided.

Transcriptomic Analyses Of Ovarian Clear-Cell Carcinoma With Concurrent Endometriosis, Kaitlyn E Collins, Xiyin Wang, Yuliya Klymenko, Noah B Davis, Maria C Martinez, Chi Zhang, Kaman So, Aaron Buechlein, Douglas B Rusch, Chad J Creighton, Shannon M Hawkins

Faculty, Staff and Students Publications

INTRODUCTION: Endometriosis, a benign inflammatory disease whereby endometrial-like tissue grows outside the uterus, is a risk factor for endometriosis-associated ovarian cancers. In particular, ovarian endometriomas, cystic lesions of deeply invasive endometriosis, are considered the precursor lesion for ovarian clear-cell carcinoma (OCCC).

METHODS: To explore this transcriptomic landscape, OCCC from women with pathology-proven concurrent endometriosis (n = 4) were compared to benign endometriomas (n = 4) by bulk RNA and small-RNA sequencing.

RESULTS: Analysis of protein-coding genes identified 2449 upregulated and 3131 downregulated protein-coding genes (DESeq2, P< 0.05, log2 fold-change > |1|) in OCCC with concurrent endometriosis compared to endometriomas. Gene set enrichment …

The Neurotoxin Dsp-4 Dysregulates The Locus Coeruleus-Norepinephrine System And Recapitulates Molecular And Behavioral Aspects Of Prodromal Neurodegenerative Disease, Alexa F. Iannitelli, Michael A. Kelberman, Daniel J. Lustberg, Anu Korukonda, Katharine E. Mccann, Bernard Mulvey, Arielle Segal, L Cameron Liles, Steven A. Sloan, Joseph D. Dougherty, David Weinshenker

2020-Current year OA Pubs

The noradrenergic locus coeruleus (LC) is among the earliest sites of tau and α-synuclein pathology in Alzheimer's disease (AD) and Parkinson's disease (PD), respectively. The onset of these pathologies coincides with loss of noradrenergic fibers in LC target regions and the emergence of prodromal symptoms including sleep disturbances and anxiety. Paradoxically, these prodromal symptoms are indicative of a noradrenergic hyperactivity phenotype, rather than the predicted loss of norepinephrine (NE) transmission following LC damage, suggesting the engagement of complex compensatory mechanisms. Because current therapeutic efforts are targeting early disease, interest in the LC has grown, and it is critical to identify …

Gene-Environment Interactions Underlying The Etiology Of Neural Tube Defects, Carlo Donato Caiaffa, Cristiane Sá Roriz Fonteles, Lei Yunping, Richard H Finnell

Faculty, Staff and Students Publications

Neural tube defects (NTDs) consist of severe structural malformations of the brain and spinal cord and are the second most common structural birth defect in humans, accounting for approximately 2700 affected pregnancies every year in the United States. These numbers are highly significant, considering that birth defects remain a leading cause of infant mortality in the United States, affecting approximately 120,000 babies born annually. Survivors of these congenital malformations face long-term disability and lifelong challenges imposed by severe physical burdens compromising the afflicted individual's overall quality of life. Clearly, birth defects, and especially NTDs remain a global public health challenge, …

Editorial: Health Effects And Pathophysiological Mechanisms Of One-Carbon Metabolism Nutrients Intake Throughout The Life Cycle, Jufen Liu, Yunping Lei, Lei Wang, Chao Guo

Faculty, Staff and Students Publications

No abstract provided.

Renewed Calls For Abortion-Related Research In The Post-Roe Era, Sophie L Schott, April Adams, Ryan J Dougherty, Taylor Montgomery, Folasade C Lapite, Faith E Fletcher

Center for Medical Ethics and Health Policy Staff Publications

Nearly 50 years after Roe versus Wade, the United States Supreme Court's decision in Dobbs versus Jackson Women's Health Organization unraveled the constitutional right to abortion, allowing individual states to severely restrict or ban the procedure. In response, leading medical, public health, and community organizations have renewed calls for research to elucidate and address the burgeoning social and medical consequences of new abortion restrictions. Abortion research not only includes studies that establish the safety, quality, and efficacy of evidence-based abortion care protocols, but also encompasses studies on the availability of abortion care, the consequences of being denied an abortion, and …

Vigorous-Intensity Exercise As A Modulator Of Cardiac Adipose Tissue In Women With Obesity: A Cross-Sectional And Randomized Pilot Study, Sumsen Thapa, Bharath S Selvaraj, Paige N Davis, Bryan Smith, Amy H Givan, Jose A Perez-Rivera, Pamela K Woodard, Jon D Klingensmith, Maria Fernandez-Del-Valle

2020-Current year OA Pubs

Cardiac adipose tissue (CAT) has become an important target for the reduction of disease risk. Supervised exercise programs have shown potential to "significantly" reduce CAT; however, the impact of different exercise modalities is not clear, and the relationships between CAT, physical activity (PA) levels and fitness (PFit) remain unknown. Therefore, the purpose of this study was to analyze the relationships between CAT, PA and PFit, and to explore the effects of different exercise modalities in a group of women with obesity. A total of 26 women (age: 23.41 ± 5.78 years-old) were enrolled in the cross-sectional study. PA, cardiorespiratory fitness, …

Gene Expression Profiles In Cancers And Their Therapeutic Implications, Chad J Creighton

Faculty, Staff and Students Publications

The vast amount of gene expression profiling data of bulk tumors and cell lines available in the public domain represents a tremendous resource. For any major cancer type, expression data can identify molecular subtypes, predict patient outcome, identify markers of therapeutic response, determine the functional consequences of somatic mutation, and elucidate the biology of metastatic and advanced cancers. This review provides a broad overview of gene expression profiling in cancer (which may include transcriptome and proteome levels) and the types of findings made using these data. This review also provides specific examples of accessing public cancer gene expression data sets …

Oocyte-Specific Wee1-Like Protein Kinase 2 Is Dispensable For Fertility In Mice, Kaori Nozawa, Zian Liao, Yuhkoh Satouh, Ting Geng, Masahito Ikawa, Diana Monsivais, Martin M Matzuk

Faculty, Staff and Students Publications

Wee1-like protein kinase 2 (WEE2) is an oocyte-specific protein tyrosine kinase involved in the regulation of oocyte meiotic arrest in humans. As such, it has been proposed as a candidate for non-hormonal female contraception although pre-clinical models have not been reported. Therefore, we developed two novel knockout mouse models using CRISPR/Cas9 to test loss-of-function of Wee2 on female fertility. A frameshift mutation at the Wee2 translation start codon in exon 2 had no effect on litter size, litter production, or the ability of oocytes to maintain prophase I arrest. Because of the lack of a reproductive phenotype, we additionally generated …

Growth And Differentiation Factor 15 (Gdf15) Levels Predict Adverse Respiratory Outcomes In Premature Neonates, Faeq Almudares, Joseph Hagan, Xinpu Chen, Sridevi Devaraj, Bhagavatula Moorthy, Krithika Lingappan

Faculty, Staff and Students Publications

Growth and differentiation factor 15 (GDF15) is a stress-responsive cytokine, and its expression increases during inflammation, hyperoxia, and senescence. Significantly, GDF15 is secreted by the placenta, and maternal levels increase throughout pregnancy. Serum GDF15 level is a promising biomarker for many lung diseases like pulmonary hypertension and pulmonary fibrosis. However, circulating GDF15 levels in preterm infants and their role as a predictor of respiratory outcomes have not been studied. We hypothesized that GDF15 levels would increase with gestational age at birth, and that postnatal GDF15 will be correlated with adverse respiratory outcomes in preterm infants. Scavenged blood samples were retrieved …

The Nr2f2-Hand2 Signaling Axis Regulates Progesterone Actions In The Uterus At Early Pregnancy, Yeongseok Oh, Elvis Quiroz, Tianyuan Wang, Yassmin Medina-Laver, Skylar Montague Redecke, Francisco Dominguez, John P Lydon, Francesco J Demayo, San-Pin Wu

Faculty, Staff and Students Publications

Endometrial function is dependent on a tight crosstalk between the epithelial and stromal cells of the endometrium. This communication is critical to ensure a fertile uterus and relies on progesterone and estrogen signaling to prepare a receptive uterus for embryo implantation in early pregnancy. One of the key mediators of this crosstalk is the orphan nuclear receptor NR2F2, which regulates uterine epithelial receptivity and stromal cell differentiation. In order to determine the molecular mechanism regulated by NR2F2, RNAseq analysis was conducted on the uterus of

The Fgfr1 Signaling Pathway Upregulates The Oncogenic Transcription Factor Foxq1 To Promote Breast Cancer Cell Growth, Yan Lin, Fengkang Lin, Zhuoran Zhang, Lijia Peng, Wenli Yang, Mao Yang, Bo Luo, Ting Wu, Dabing Li, Xuesen Li, Bing Ran, Songyot Anuchapreeda, Rujirek Chaiwongsa, Pinyaphat Khamphikham, Suwit Duangmano, Jianming Xu, Tao He, Sakorn Pornprasert

Faculty, Staff and Students Publications

FGFR1 is a receptor tyrosine kinase deregulated in certain breast cancers (BCs) with a poor prognosis. Although FGFR1-activated phosphorylation cascades have been mapped, the key genes regulated by FGFR1 in BC are largely unclear. FOXQ1 is an oncogenic transcription factor. Although we found that activation of FGFR1 robustly upregulated FOXQ1 mRNA, how FGFR1 regulates FOXQ1 gene expression and whether FOXQ1 is essential for FGFR1-stimulated cell proliferation are unknown. Herein, we confirmed that activation of FGFR1 robustly upregulated FOXQ1 mRNA and protein in BC cells. Knockdown of FOXQ1 blocked the FGFR1 signaling-stimulated BC cell proliferation, colony formation, and xenograft tumor growth. …

Proceedings Of The 2023 Santa Fe Bone Symposium: Progress And Controversies In The Management Of Patients With Skeletal Diseases, E Michael Lewiecki, Teresita Bellido, John P Bilezikian, Jacques P Brown, Azeez Farooki, Christopher S Kovacs, Brendan Lee, William D Leslie, Michael R Mcclung, Mark L Prasarn, Deborah E Sellmeyer

Faculty, Staff and Students Publications

The Santa Fe Bone Symposium (SFBS) held its 23rd annual event on August 5-6, 2023, in Santa Fe, New Mexico, USA. Attendees participated in-person and remotely, representing many states and countries. The program included plenary presentations, panel discussions, satellite symposia, a Project ECHO workshop, and a session on healthcare policy and reimbursement for fracture liaison programs. A broad range of topics were addressed, including transitions of osteoporosis treatments over a lifetime; controversies in vitamin D; update on Official Positions of the International Society for Clinical Densitometry; spine surgery and bone health; clinical applications of bone turnover markers; basic bone biology …

A Novel Biosignature Identifies Patients With Dcis With High Risk Of Local Recurrence After Breast Conserving Surgery And Radiation Therapy, Frank A Vicini, G Bruce Mann, Chirag Shah, Sheila Weinmann, Michael C Leo, Pat Whitworth, Rachel Rabinovitch, Mylin A Torres, Julie A Margenthaler, David Dabbs, Jess Savala, Steven C Shivers, Karuna Mittal, Fredrik Wärnberg, Troy Bremer

2020-Current year OA Pubs

PURPOSE: There is an unmet need to identify women diagnosed with ductal carcinoma in situ (DCIS) with a low risk of in-breast recurrence (IBR) after breast conserving surgery (BCS), which could omit radiation therapy (RT), and also to identify those with elevated IBR risk remaining after BCS plus RT. We evaluated a novel biosignature for a residual risk subtype (RRt) to help identify patients with elevated IBR risk after BCS plus RT.

METHODS AND MATERIALS: Women with DCIS treated with BCS with or without RT at centers in the US, Australia, and Sweden (n = 926) were evaluated. Patients were …

Apolipoprotein E Genetic Variation, Atherogenic Index And Cardiovascular Disease Risk Assessment In An African Population: An Analysis Of Hiv And Malaria Patients In Ghana, Nicholas Ekow Thomford, Akwasi Anyanful, Richmond Owusu Ateko, Dee Blackhurst, Robert Peter Biney, Dennis Boadi, Samuel Badu Nyarko, Martins Ekor, George Boateng Kyei

2020-Current year OA Pubs

BACKGROUND: Apolipoprotein E is involved in lipid transport and clearance of lipoprotein through low-density lipoprotein receptors (LDLR). ApoE variation has been linked to cardiovascular disease (CVD) risk. There are 3 isoforms of ApoE which originate from two non-synonymous single nucleotide polymorphisms denoted as ε2, ε3 and ε4. The ε2 isoform is implicated in higher levels of atherogenic lipoprotein with the ε4 isoform causing LDLR downregulation. This leads to variable effects and differential CVD risk. Malaria and HIV are life-threatening diseases affecting several countries globally especially in sub-Saharan Africa. Parasite and viral activities have been implicated in lipid dysregulation leading to …

Pregnancy-Induced Differential Expression Of Sars-Cov-2 And Influenza A Viral Entry Factors In The Lower Respiratory Tract, Tusar Giri, Santosh Panda, Arvind Palanisamy

2020-Current year OA Pubs

Despite differences in the clinical presentation of coronavirus disease-19 and pandemic influenza in pregnancy, fundamental mechanistic insights are currently lacking because of the difficulty in recruiting critically ill pregnant subjects for research studies. Therefore, to better understand host-pathogen interaction during pregnancy, we performed a series of foundational experiments in pregnant rats at term gestation to assess the expression of host entry factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV) and genes associated with innate immune response in the lower respiratory tract. We report that pregnancy is characterized by a decrease in host factors mediating …

Versican Provides The Provisional Matrix For Uterine Spiral Artery Dilation And Fetal Growth, Yusuke Sagae, Akihito Horie, Akihiro Yanai, Tsutomu Ohara, Baku Nakakita, Yoshimi Kitawaki, Asuka Okunomiya, Hirohiko Tani, Ken Yamaguchi, Junzo Hamanishi, John P Lydon, Takiko Daikoku, Hideto Watanabe, Masaki Mandai

Faculty, Staff and Students Publications

The extracellular matrix (ECM) in the endometrium plays a crucial role in mammalian pregnancy. We have shown that versican secreted from the endometrial epithelium promotes embryo implantation. Versican is a proteoglycan, a major player in the provisional matrix, and versikine, its N-terminal fragment cleaved by ADAMTS proteinases, serves as a bioactive molecule. Here, since versican expression in the placenta was dynamically altered in humans and mice, we investigated the role of versican in pregnancy using uterine-specific Vcan deletion mice (uKO mice) and ADAMTS-resistant versican expressing mice (V1R mice). uKO mice exhibited insufficient spiral artery dilation, followed by fetal growth restriction …

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

Faculty, Staff and Students Publications

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 risk of cerebral injury.

Spatial Analysis Of Nanoparticle Distribution In Human Breast Xenografts Reveals Nanoparticles Targeted To Cancer Cells Localized With Tumor-Associated Stromal Cells, Sean Healy, Elizabeth T Henderson, Suqi Ke, Jacqueline Kelly, Brian W Simons, Chen Hu, Robert Ivkov, Preethi Korangath

Faculty, Staff and Students Publications

The biological influence of physicochemical parameters of “targeted” nanoparticles on their delivery to cancer tumors remains poorly understood. A comparative analysis of nanoparticle distributions in tumors following systemic delivery across several models can provide valuable insights.

Methods: Bionized nanoferrite nanoparticles (iron oxide core coated with starch), either conjugated with a targeted anti-HER2 antibody (BH), or unconjugated (BP), were intravenously injected into athymic nude or NOD-scid gamma (NSG) female mice bearing one of five human breast cancer tumor xenografts growing in a mammary fat pad. Tumors were harvested 24 hours after nanoparticle injection, fixed, mounted, and stained. We performed detailed histopathology …

Sex-Specific Associations Between Urinary Bisphenols Concentrations During Pregnancy And Problematic Child Behaviors At Age 2 Years, Sarah Dee Geiger, Salma Musaad, Jennifer Hill, Andréa Aguiar, Susan Schantz

Faculty, Staff and Students Publications

Effects of prenatal bisphenol A (BPA) exposure on child behavior are mixed with some reports suggesting increased problematic behaviors in girls (e.g., aggression and emotional reactivity) and in boys (i.e., externalizing behaviors), while other reports suggest decreased problematic behaviors in girls. Little is known about the potential impact of pregnancy bisphenol S (BPS) exposure on child behavior. In a prospective cohort study (n=68), five maternal spot urine samples collected across pregnancy were pooled and analyzed for BPA and BPS. Child behavior at 2 years was assessed using the Child Behavior Checklist (CBCL). Linear regression models were used to assess associations …