Medical Specialties Commons^™

Gut Microbiota From Sjögren Syndrome Patients Causes Decreased T Regulatory Cells In The Lymphoid Organs And Desiccation-Induced Corneal Barrier Disruption In Mice, Laura Schaefer, Claudia M Trujillo-Vargas, Firas S Midani, Stephen C Pflugfelder, Robert A Britton, Cintia S De Paiva

Faculty, Staff and Students Publications

Sjögren syndrome (SS) is an autoimmune inflammatory disorder characterized by secretory dysfunction in the eye and mouth; in the eye, this results in tear film instability, reduced tear production, and corneal barrier disruption. A growing number of studies show that homeostasis of the ocular surface is impacted by the intestinal microbiome, and several 16S sequencing studies have demonstrated dysbiosis of the intestinal microbiota in SS patients. In this study, we utilized metagenomic sequencing to perform a deeper analysis of the intestinal microbiome using stools collected from sex- and age-matched healthy (n = 20), dry eye (n = 4) …

Clonal Hematopoiesis Analyses In Clinical, Epidemiologic, And Genetic Aging Studies To Unravel Underlying Mechanisms Of Age-Related Dysfunction In Humans, Kenneth Walsh, Nalini Raghavachari, Candace Kerr, Alexander G Bick, Steven R Cummings, Todd Druley, Cynthia E Dunbar, Giulio Genovese, Margaret A Goodell, Siddhartha Jaiswal, Jaroslaw Maciejewski, Pradeep Natarajan, Anastasia V Shindyapina, Alan R Shuldiner, Erik B Van Den Akker, Jan Vijg

Faculty, Staff and Students Publications

Aging is characterized by increased mortality, functional decline, and exponential increases in the incidence of diseases such as cancer, stroke, cardiovascular disease, neurological disease, respiratory disease, etc. Though the role of aging in these diseases is widely accepted and considered to be a common denominator, the underlying mechanisms are largely unknown. A significant age-related feature observed in many population cohorts is somatic mosaicism, the detectable accumulation of somatic mutations in multiple cell types and tissues, particularly those with high rates of cell turnover (e.g., skin, liver, and hematopoietic cells). Somatic mosaicism can lead to the development of cellular clones that …

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. …

Endometriosis-Associated Angiogenesis And Anti-Angiogenic Therapy For Endometriosis, Monica S Chung, Sang Jun Han

Faculty, Staff and Students Publications

Endometriosis is a known estrogen-dependent inflammatory disease affecting reproductive-aged women. Common symptoms include pelvic pain, dysmenorrhea, dyspareunia, heavy menstrual bleeding, and infertility. The exact etiology of endometriosis is largely unknown, and, thus, the diagnosis and treatment of endometriosis are challenging. A complex interplay of many molecular mechanisms is thought to aid in the progression of endometriosis, most notably angiogenesis. This mini-review examines our current knowledge of the molecular etiology of endometriosis-associated angiogenesis and discusses anti-angiogenic therapy, in the blockade of endometriosis-associated angiogenesis, as potential non-hormonal therapy for the treatment of endometriosis.

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. …

An Exploratory Assessment Of The Management Of Pediatric Traumatic Brain Injury In Three Centers In Africa, Madiha Raees, Shubhada Hooli, Amélie O Von Saint André-Von Arnim, Tsegazeab Laeke, Easmon Otupiri, Anthony Fabio, Kristina E Rudd, Rashmi Kumar, Patrick T Wilson, Abenezer Tirsit Aklilu, Lisine Tuyisenge, Chunyan Wang, Robert C Tasker, Derek C Angus, Patrick M Kochanek, Ericka L Fink, Tigist Bacha

Faculty, Staff and Students Publications

PURPOSE: Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in low- and middle-income countries (LMICs). Hospital care practices of pediatric TBI patients in LMICs are unknown. Our objective was to report on hospital management and outcomes of children with TBI in three centers in LMICs.

METHODS: We completed a secondary analysis of a prospective observational study in children (<18 >years) over a 4-week period. Outcome was determined by Pediatric Cerebral Performance Category (PCPC) score; an unfavorable score was defined as PCPC > 2 or an increase of two points from baseline. Data were compared using Chi-square and …

The Autophagic Protein P62 Is A Target Of Reactive Aldehydes In Human And Murine Cholestatic Liver Disease, Colin T Shearn, Aimee L Anderson, Michael W Devereux, David J Orlicky, Cole Michel, Dennis R Petersen, Colin G Miller, Sanjiv Harpavat, Edward E Schmidt, Ronald J Sokol

Faculty, Staff and Students Publications

Inflammatory cholestatic liver diseases, including Primary Sclerosing Cholangitis (PSC), are characterized by periportal inflammation with progression to cirrhosis. The objective of this study was to examine interactions between oxidative stress and autophagy in cholestasis. Using hepatic tissue from male acute cholestatic (bile duct ligated) as well as chronic cholestatic (Mdr2KO) mice, localization of oxidative stress, the antioxidant response and induction of autophagy were analyzed and compared to human PSC liver. Concurrently, the ability of reactive aldehydes to post-translationally modify the autophagosome marker p62 was assessed in PSC liver tissue and in cell culture. Expression of autophagy markers was upregulated in …

Hepatic Pparα Is Destabilized By Sirt1 Deacetylase In Undernourished Male Mice, Ji Ho Suh, Kang Ho Kim, Margaret E Conner, David D Moore, Geoffrey A Preidis

Faculty, Staff and Students Publications

The nutrient sensing nuclear receptor peroxisome proliferator-activated receptor-α (PPARα) regulates the host response to short-term fasting by inducing hepatic transcriptional programming of ketogenesis, fatty acid oxidation and transport, and autophagy. This adaptation is ineffective in chronically undernourished individuals, among whom dyslipidemia and hepatic steatosis are common. We recently reported that hepatic PPARα protein is profoundly depleted in male mice undernourished by a low-protein, low-fat diet. Here, we identify PPARα as a deacetylation target of the NAD-dependent deacetylase sirtuin-1 (SIRT1) and link this to the decrease in PPARα protein levels in undernourished liver. Livers from undernourished male mice expressed high levels …

De Novo Glycine Synthesis Is Reduced In Adults With Morbid Obesity And Increases Following Bariatric Surgery, Hong Chang Tan, Jean W Hsu, E Shyong Tai, Shaji Chacko, Vieon Wu, Chun Fan Lee, Jean-Paul Kovalik, Farook Jahoor

Faculty, Staff and Students Publications

BACKGROUND: Glycine is a dietary non-essential amino acid that is low in obesity and increases following bariatric surgery. However, the exact mechanism responsible remains unclear and it is unknown whether hypoglycinemia is a cause or consequence of insulin resistance.

OBJECTIVE: Using multiple isotopically labeled tracers, we aimed to determine the underlying kinetic changes responsible for hypoglycinemia in obesity by: 1) Comparing glycine kinetics between participants with morbid obesity (BMI ≥ 32.5 kg/m

METHODS: [1,2-

RESULTS: Compared to controls, participants with morbid obesity had significantly lower plasma glycine concentrations at 163 (153-171) vs. 201 (172-227) µmol/L and significantly reduced

CONCLUSION: Hypoglycinemia …

Adult Food Protein-Induced Enterocolitis Syndrome, Sara Anvari, Melanie A Ruffner

Faculty, Staff and Students Publications

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE, cell-mediated food allergy, commonly diagnosed in infants and young children. In recent years, new-onset adult FPIES has been recognized. The underlying pathogenic mechanism of FPIES has yet to be elucidated, thus disease-specific diagnostic biomarkers have yet to be determined and an oral food challenge (OFC) remains the gold-standard for the diagnosis. Pediatric patients with FPIES classically present with symptoms of delayed, repetitive vomiting approximately 1 to 4 hours following ingestion of a food allergen. However, adults with FPIES have been reported to have a different symptom profile and different food triggers compared …

Features Of Burnout Amongst Pathologists: A Reassessment, Michael B Cohen, Marisa Saint Martin, David J Gross, Kristen Johnson, Stanley J Robboy, Thomas M Wheeler, Rebecca L Johnson, W Stephen Black-Schaffer

Faculty, Staff and Students Publications

There has been little rigorous assessment of burnout among pathologists and pathology trainees. Given this relative dearth of relevant literature on pathologist burnout, this report aims to raise awareness of the issue among those working in and around this specialty. Our results are based on a survey given in conjunction with the American Board of Pathology's (ABPath) biennial Continuing Certification (CC) reporting of activities required of diplomates to maintain certification. The survey was voluntary, open to all diplomates participating in CC, and conducted over two consecutive years (2019 and 2020), with alternate years comprising different sets of diplomates. The data …

Urine Alcam, Pf4 And Vcam-1 Surpass Conventional Metrics In Identifying Nephritis Disease Activity In Childhood-Onset Systemic Lupus Erythematosus, Samar A Soliman, Anam Haque, Kamala Vanarsa, Ting Zhang, Faten Ismail, Kyung Hyun Lee, Claudia Pedroza, Larry A Greenbaum, Sherene Mason, M John Hicks, Scott E Wenderfer, Chandra Mohan

Faculty, Staff and Students Publications

OBJECTIVES: Serial kidney biopsy for repeat evaluation and monitoring of lupus nephritis (LN) in childhood-onset Systemic Lupus Erythematosus (cSLE) remains challenging, thus non-invasive biomarkers are needed. Here, we evaluate the performance of ten urine protein markers of diverse nature including cytokines, chemokines, and adhesion molecules in distinguishing disease activity in cSLE.

METHODS: Eighty-four pediatric patients meeting ≥4 ACR criteria for SLE were prospectively enrolled for urine assay of 10 protein markers normalized to urine creatinine, namely ALCAM, cystatin-C, hemopexin, KIM-1, MCP-1, NGAL, PF-4, Timp-1, TWEAK, and VCAM-1 by ELISA. Samples from active renal (LN) and active non-renal SLE patients were …

Loss Of H2r Signaling Disrupts Neutrophil Homeostasis And Promotes Inflammation-Associated Colonic Tumorigenesis In Mice, Zhongcheng Shi, Yuko Mori-Akiyama, Wa Du, Robert Fultz, Yanling Zhao, Wenly Ruan, Susan Venable, Melinda A Engevik, James Versalovic

Faculty, Staff and Students Publications

BACKGROUND & AIMS: We previously showed that histamine suppressed inflammation-associated colonic tumorigenesis through histamine type 2 receptor (H2R) signaling in mice. This study aimed to precisely elucidate the downstream effects of H2R activation in innate immune cells.

METHODS: Analyses using online databases of single-cell RNA sequencing of intestinal epithelial cells in mice and RNA sequencing of mouse immune cells were performed to determine the relative abundances of 4 histamine receptors among different cell types. Mouse neutrophils, which expressed greater amounts of H2R, were collected from the peritoneum of wild-type and H2R-deficient mice, of which low-density and high-density neutrophils were extracted …

Comprehensive Improvement Of Cardiology Inpatient Transfers: A Bed-Availability Triggered Approach, Judson A Moore, Lindsay F Eilers, Amanda J Willis, Michael D Chance, Julie A La Salle, Ellen H Delgado, Katie M Bien, Jordana R Goldman, Shreya S Sheth

Faculty, Staff and Students Publications

INTRODUCTION: Patient transfers pose a potential risk during hospitalizations. Structured communication practices are necessary to ensure effective handoffs, but occur amidst competing priorities and constraints. We sought to design and implement a multidisciplinary process to enhance communication between pediatric cardiovascular intensive care unit and cardiology floor teams with a comprehensive approach evaluating efficiency, safety, and culture.

METHODS: We conducted a prospective quality improvement study to enact a bed-availability triggered bedside handoff process. The primary aim was to reduce the time between handoff and unit transfer. Secondary metrics captured the impact on safety (reported safety events, overnight transfers, bounce backs, and …

Evaluation Of Cervical Spine Pathology In Children With Loeys-Dietz Syndrome, Marc Andrew Prablek, Melissa Lopresti, Brandon Bertot, Shaine Alaine Morris, David Bauer, Sandi Lam, Vijay Ravindra

Faculty, Staff and Students Publications

BACKGROUND: Loeys-Dietz syndrome (LDS) is a genetic connective tissue disorder associated with multiple musculoskeletal anomalies, including cervical spine instability. We sought to examine the nature of imaging for cervical spine instability in children with LDS due to likely pathogenic or pathogenic variants in

METHODS: A retrospective chart review was conducted, examining relevant data for all children with LDS screened at our institution from 2004 through 2021. Cervical spine X-rays were used to assess cervical instability, cervical lordosis, and basilar impression.

RESULTS: A total of 39 patients were identified; 16 underwent cervical spine screening (56.25% male). Median age at initial screening …

Flow Dynamics In Anomalous Aortic Origin Of A Coronary Artery In Children: Importance Of The Intramural Segment, Hoda Hatoum, Rajesh Krishnamurthy, Jayanthi Parthasarathy, Dorma C Flemister, Carly M Krull, Benjamin A Walter, Carlos M Mery, Silvana Molossi, Lakshmi Prasad Dasi

Faculty, Staff and Students Publications

This study aims to assess the differences in pressure, fractional flow reserve (FFR) and coronary flow (with increasing pressure) of the proximal coronary artery in patients with anomalous aortic origin of a coronary artery with a confirmed ischemic event, without ischemic events, and before and after unroofing surgery, and compare to a patient with normal coronary arteries. Patient-specific flow models were 3D printed for 3 subjects with anomalous right coronary arteries with intramural course, 2 of them had documented ischemia, and compared with a patient with normal coronaries. The models were placed in the aortic position of a pulse duplicator …

Optimal Fenestration Of The Fontan Circulation, Zan Ahmad, Lynn H Jin, Daniel J Penny, Craig G Rusin, Charles S Peskin, Charles Puelz

Faculty, Staff and Students Publications

In this paper, we develop a pulsatile compartmental model of the Fontan circulation and use it to explore the effects of a fenestration added to this physiology. A fenestration is a shunt between the systemic and pulmonary veins that is added either at the time of Fontan conversion or at a later time for the treatment of complications. This shunt increases cardiac output and decreases systemic venous pressure. However, these hemodynamic benefits are achieved at the expense of a decrease in the arterial oxygen saturation. The model developed in this paper incorporates fenestration size as a parameter and describes both …

Common Genomic Aberrations In Mouse And Human Breast Cancers With Concurrent P53 Deficiency And Activated Pten-Pi3k-Akt Pathway, Jarrod D Martinez, Qianxing Mo, Yixiang Xu, Li Qin, Yi Li, Jianming Xu

Faculty, Staff and Students Publications

Simultaneous P53 loss and activation of the PTEN-restricted PI3K-AKT pathway frequently occur in aggressive breast cancers. P53 loss causes genome instability, while PTEN loss and/or activating mutations of PIK3CA and AKT promote cancer cell proliferation that also increases incidences of genomic aberrations. However, the genomic alterations associated with P53 loss and activated PTEN-PI3K-AKT signaling in breast cancer have not been defined. Spatiotemporally controlled breast cancer models with inactivation of both P53 and Pten in adult mice have not been established for studying genomic alterations. Herein, we deleted both floxed Pten and Tp53 genes in the mammary gland epithelial cells in …

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 …

Factors Impacting Vaccine Uptake During Pregnancy: A Retrospective Analysis, Maame Aba Coleman, Deepa Dongarwar, Jessica Ramirez, Mei-Li Laracuente, Chelsea Livingston, Julliet Ogu, Racquel Lyn, Arabella Hall, Sylvia Adu-Gyamfi, Hamisu M Salihu

Faculty, Staff and Students Publications

BACKGROUND AND OBJECTIVE: Vaccine uptake rates during pregnancy remain below target goals due to a convergence of factors. In particular, women of lower socioeconomic means and racial minorities typically have reduced rates of vaccine acceptance. This study aims to identify additional factors contributing to vaccine acceptance within a sample population of women receiving prenatal care in Houston, Texas, United States of America.

METHODS: We performed a retrospective cross-sectional analysis of 11,500 pregnant women covered by Medicaid or ChipPerinate who received prenatal care during 2013-2021, assessing influenza (flu) and combined Tetanus, Diphtheria, Acellular Pertussis (TDAP) vaccine acceptance in the patient population. …

Clinical And Sociodemographic Characteristics Associated With Emergency Peripartum Hysterectomy Due To Puerperal Sepsis In Malawi, Mary Stokes, Amber Olson, Clare Algeo, Bakari Rajab, Carolyn Mwalwanda, Deepa Dongarwar, Rachel Pope

Faculty, Staff and Students Publications

BACKGROUND AND OBJECTIVE: In Malawi, emergency peripartum hysterectomy continues to be routine for the management of puerperal sepsis. While the hysterectomy may be life-saving for the mother, it carries with it life-altering permanent sterility. The surgeon is left with a difficult dilemma: remove the infection source (uterus) to preserve the life of the patient at the cost of her fertility, or preserve the uterus and fertility but risk worsening infection and possible death for the patient. The objective of this study was to (1) identify characteristics associated with mortality post-laparotomy due to puerperal sepsis and (2) identify characteristics associated with …

Evaluation Of The Clinical Effectiveness Of Modified Sacrospinous Ligament Fixation, Yuanyuan Lyu, Huafeng Ding, Ying Zhang, Suhua Shi, Jin Ding, Chengcheng Zhu, Xiaoming Guan, Guantai Ni, Yonghong Luo

Faculty, Staff and Students Publications

OBJECTIVE: To describe the surgical techniques and short-term outcomes for 50 cases of modified sacrospinous ligament fixation

METHODS: 100 patients with pelvic organ prolapse (stage III or stage IV based on POP-Q staging) from January 2018 to January 2020 were retrospectively analyzed. Among them, 50 patients received modified sacrospinous ligament fixation via the anterior vaginal wall path for pelvic organ prolapse (mSSLF group), while the other 50 patients received pelvic reconstruction using T4 mesh (T4 group). Operative time, blood loss, postoperative POP-Q score, length of the hospital stay, complications, and postoperative pain were compared between the two groups.

RESULTS: The …

"It Just Kind Of Feels Like A Different World Now:" Stress And Resilience For Adolescents With Type 1 Diabetes In The Era Of Covid-19, Maeve B O'Donnell, Marisa E Hilliard, Viena T Cao, Miranda C Bradford, Krysta S Barton, Samantha Hurtado, Brenda Duran, Samantha Garcia Perez, Kiswa S Rahman, Samantha Scott, Faisal S Malik, Daniel J Desalvo, Catherine Pihoker, Chuan Zhou, Abby R Rosenberg, Joyce P Yi-Frazier

Faculty, Staff and Students Publications

PURPOSE: The COVID-19 pandemic has been a major stressor for adolescents. Given the unique implications of the pandemic for youth with type 1 diabetes (T1D), who already navigate multiple stressors as a function of their chronic condition, we aimed to describe the impact of the pandemic on adolescents with T1D and describe their coping strategies and resilience resources.

RESEARCH METHOD: In a 2-site (Seattle WA, Houston TX) clinical trial of a psychosocial intervention targeting stress/resilience, adolescents 13-18 years old with T1D ≥ 1 year and elevated diabetes distress were enrolled August 2020 - June 2021. Participants completed a baseline survey …

The Third International Hackathon For Applying Insights Into Large-Scale Genomic Composition To Use Cases In A Wide Range Of Organisms, Kimberly Walker, Divya Kalra, Rebecca Lowdon, Guangyi Chen, David Molik, Daniela C Soto, Fawaz Dabbaghie, Ahmad Al Khleifat, Medhat Mahmoud, Luis F Paulin, Muhammad Sohail Raza, Susanne P Pfeifer, Daniel Paiva Agustinho, Elbay Aliyev, Pavel Avdeyev, Enrico R Barrozo, Sairam Behera, Kimberley Billingsley, Li Chuin Chong, Deepak Choubey, Wouter De Coster, Yilei Fu, Alejandro R Gener, Timothy Hefferon, David Morgan Henke, Wolfram Höps, Anastasia Illarionova, Michael D Jochum, Maria Jose, Rupesh K Kesharwani, Sree Rohit Raj Kolora, Jędrzej Kubica, Priya Lakra, Damaris Lattimer, Chia-Sin Liew, Bai-Wei Lo, Chunhsuan Lo, Anneri Lötter, Sina Majidian, Suresh Kumar Mendem, Rajarshi Mondal, Hiroko Ohmiya, Nasrin Parvin, Carolina Peralta, Chi-Lam Poon, Ramanandan Prabhakaran, Marie Saitou, Aditi Sammi, Philippe Sanio, Nicolae Sapoval, Najeeb Syed, Todd Treangen, Gaojianyong Wang, Tiancheng Xu, Jianzhi Yang, Shangzhe Zhang, Weiyu Zhou, Fritz J Sedlazeck, Ben Busby

Faculty, Staff and Students Publications

In October 2021, 59 scientists from 14 countries and 13 U.S. states collaborated virtually in the Third Annual Baylor College of Medicine & DNANexus Structural Variation hackathon. The goal of the hackathon was to advance research on structural variants (SVs) by prototyping and iterating on open-source software. This led to nine hackathon projects focused on diverse genomics research interests, including various SV discovery and genotyping methods, SV sequence reconstruction, and clinically relevant structural variation, including SARS-CoV-2 variants. Repositories for the projects that participated in the hackathon are available at https://github.com/collaborativebioinformatics.

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 …

Selective Vulnerability Of The Intermediate Retinal Capillary Plexus Precedes Retinal Ganglion Cell Loss In Ocular Hypertension, Priyamvada M Pitale, Guofu Shen, Rohini R Sigireddi, Maria Polo-Prieto, Yong H Park, Solomon E Gibson, Peter D Westenskow, Roomasa Channa, Benjamin J Frankfort

Faculty, Staff and Students Publications

Introduction: Glaucoma, a disease of retinal ganglion cell (RGC) injury and potentially devastating vision loss, is associated with both ocular hypertension (OHT) and reduced ocular blood flow. However, the relationship between OHT and retinal capillary architecture is not well understood. In this project, we studied microvasculature damage in mice exposed to mild levels of induced OHT.

Methods: Mild OHT was induced with the microbead model for 2 weeks. At this time point, some retinas were immunostained with CD31 (endothelium), Collagen IV (basement membrane), and RBPMS (RGCs) for z-stack confocal microscopy. We processed these confocal images to distinguish the three retinal …

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 …

New, Potent, Small Molecule Agonists Of Tyrosine Kinase Receptors Attenuate Dry Eye Disease, Zhiyuan Yu, Shaon Joy, Tianxiong Mi, Ghasem Yazdanpanah, Kevin Burgess, Cintia S De Paiva

Faculty, Staff and Students Publications

Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin3 (NT-3) bind to tyrosine kinase (Trk) receptors, TrkA, TrkB, and TrkC, respectively. This study investigated the efficacy of novel molecule agonists of Trk receptors in an in vivo model of dry eye disease (DED). Small molecule TrkC agonist (C1) and a pan-Trk agonist (pan) were synthesized for this. C57BL/6J mice were subjected to desiccating stress (DS) and received bilateral eye drops of C1, pan, or vehicle (2x/day). Dry eye signs, inflammation and expression of corneal barrier function, and conjunctival goblet cell (GC) densities were measured as part of the DED …

Cathepsin S Is A Novel Target For Age-Related Dry Eye, Zhiyuan Yu, Jinmiao Li, Gowthaman Govindarajan, Sarah F Hamm-Alvarez, Jehan Alam, De-Quan Li, Cintia S De Paiva

Faculty, Staff and Students Publications

Cathepsin S (CTSS) is a protease that is proinflammatory on epithelial cells. The purpose of this study was to investigate the role of CTSS in age-related dry eye disease. Ctss−/− mice [in a C57BL/6 (B6) background] of different ages were compared to B6 mice. CTSS activity in tears and lacrimal gland (LG) lysates was measured. The corneal barrier function was investigated in naïve mice or after topical administration of CTSS eye drops 5X/day for two days. Eyes were collected, and conjunctival goblet cell density was measured in PAS-stained sections. Immunoreactivity of the tight junction proteins, ZO-1 and occludin, was …

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, …