Medicine and Health Sciences Commons^™

Analysis Of Insppire-2 Cohort: Risk Factors And Disease Burden In Children With Acute Recurrent Or Chronic Pancreatitis, Aliye Uc, Gretchen A Cress, Fuchenchu Wang, Maisam Abu-El-Haija, Kate M Ellery, Douglas S Fishman, Cheryl E Gariepy, Tanja Gonska, Tom K Lin, Quin Y Liu, Megha Mehta, Asim Maqbool, Brian A Mcferron, Veronique D Morinville, Chee Y Ooi, Emily R Perito, Sarah Jane Schwarzenberg, Zachary M Sellers, Jose Serrano, Uzma Shah, David M Troendle, Michael Wilschanski, Yuhua Zheng, Ying Yuan, Mark E Lowe, Consortium For The Study Of Chronic Pancreatitis, Diabetes And Pancreatic Cancer

Faculty, Staff and Students Publications

OBJECTIVES: The objective of this study is to investigate risk factors and disease burden in pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP).

METHODS: Data were obtained from INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2), the largest multi-center prospective cohort study in pediatric patients with ARP or CP.

RESULTS: Of 689 children, 365 had ARP (53%), 324 had CP (47%). CP was more commonly associated with female sex, younger age at first acute pancreatitis (AP) attack, Asian race, family history of CP, lower BMI%, genetic and obstructive factors, PRSS1 mutations and pancreas divisum. CFTR …

Temporal Trends In Lipoprotein(A) Concentrations: The Atherosclerosis Risk In Communities Study, Matthew R Deshotels, Caroline Sun, Vijay Nambi, Salim S Virani, Kunihiro Matsushita, Bing Yu, Christie M Ballantyne, Ron C Hoogeveen

Faculty, Staff and Students Publications

Background: Plasma lipoprotein(a) (Lp[a]) concentrations are primarily determined by genetic factors and are believed to remain stable throughout life. However, data are scarce on longitudinal trends in Lp(a) concentrations over time. Therefore, it is unclear whether measurement of Lp(a) once in a person's life is sufficient for cardiovascular risk assessment in all adults.

Methods and Results: Lp(a) concentrations, specifically apolipoprotein(a) concentrations, were measured at visits 4 and 5, ≈15 years apart, in 4734 adult participants of the ARIC (Atherosclerosis Risk in Communities) study (mean age at visits 4 and 5, 60.7±5.1 and 75.5±5.2 years, respectively). Participants were categorized by baseline …

Cardiac Size, Shape, And Ventricular Contractility In Fetuses At Sea Level With An Estimated Weight Less-Than 10th Centile, Wesley Lee, Lauren M Mack, Roxanna Miremadi, Betul Yilmaz Furtun, Haleh Sangi-Haghpeykar, Greggory R Devore

Faculty, Staff and Students Publications

OBJECTIVES: To investigate cardiac size, shape, and ventricular contractility in fetuses with estimated fetal weight (EFW)(Houston).

METHODS: A prospective ultrasound study examined 37 fetuses with EFWsize, shape, and contractility of both ventricles were analyzed with speckle tracking methods. Z scores were calculated using the mean ± standard deviation (SD) derived from normal controls. Measurements were abnormal if their Z score values were+1.65. The proportion of small fetuses with abnormal parameters was compared to normal reference ranges. Results were compared to a similar published study of small fetuses at higher altitude in Denver.

RESULTS: About one-third of Houston fetuses with EFW(RV) …

Stat6 Blockade Abrogates Aspergillus-Induced Eosinophilic Chronic Rhinosinusitis And Asthma, A Model Of Unified Airway Disease, Meng Lin, Amy T Ku, Jie Dong, Fei Yue, Weiyu Jiang, Ahmed Atef Ibrahim, Fanglue Peng, Chad J Creighton, Chandandeep Nagi, Carolina Gutierrez, Jeffrey M Rosen, Xiang H-F Zhang, Susan G Hilsenbeck, Xi Chen, Yi-Chieh Nancy Du, Shixia Huang, Aiping Shi, Zhimin Fan, Yi Li

Faculty, Staff and Student Publications

Signal transducer and activator of transcription 5 (STAT5) promotes cell survival and instigates breast tumor formation, and in the normal breast it also drives alveolar differentiation and lactogenesis. However, whether STAT5 drives a differentiated phenotype in breast tumorigenesis and therefore impacts cancer spread and metastasis is unclear. We found in two genetically engineered mouse models of breast cancer that constitutively activated Stat5a (Stat5aca) caused precancerous mammary epithelial cells to become lactogenic and evolve into tumors with diminished potential to metastasize. We also showed that STAT5aca reduced the migratory and invasive ability of human breast cancer cell lines in …

Cardiac Size, Shape, And Ventricular Contractility In Fetuses At Sea Level With An Estimated Weight Less-Than 10th Centile, Wesley Lee, Lauren M Mack, Roxanna Miremadi, Betul Yilmaz Furtun, Haleh Sangi-Haghpeykar, Greggory R Devore

Faculty, Staff and Students Publications

OBJECTIVES: To investigate cardiac size, shape, and ventricular contractility in fetuses with estimated fetal weight (EFW)(Houston).

METHODS: A prospective ultrasound study examined 37 fetuses with EFWsize, shape, and contractility of both ventricles were analyzed with speckle tracking methods. Z scores were calculated using the mean ± standard deviation (SD) derived from normal controls. Measurements were abnormal if their Z score values were+1.65. The proportion of small fetuses with abnormal parameters was compared to normal reference ranges. Results were compared to a similar published study of small fetuses at higher altitude in Denver.

RESULTS: About one-third of Houston fetuses with EFW(RV) …

Accounting For The Growth Of Observation Stays In The Assessment Of Medicare's Hospital Readmissions Reduction Program, Amber K Sabbatini, Karen E Joynt-Maddox, Joshua M Liao, Anirban Basu, Canada Parrish, William Kreuter, Brad Wright

2020-Current year OA Pubs

IMPORTANCE: Decreases in 30-day readmissions following the implementation of the Medicare Hospital Readmissions Reduction Program (HRRP) have occurred against the backdrop of increasing hospital observation stay use, yet observation stays are not captured in readmission measures.

OBJECTIVE: To examine whether the HRRP was associated with decreases in 30-day readmissions after accounting for observation stays.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included a 20% sample of inpatient admissions and observation stays among Medicare fee-for-service beneficiaries from January 1, 2009, to December 31, 2015. Data analysis was performed from November 2021 to June 2022. A differences-in-differences analysis assessed changes in …

A Comparison Of Methods To Harmonize Cortical Thickness Measurements Across Scanners And Sites, Delin Sun, Evan Gordon, Et Al.

2020-Current year OA Pubs

Results of neuroimaging datasets aggregated from multiple sites may be biased by site-specific profiles in participants' demographic and clinical characteristics, as well as MRI acquisition protocols and scanning platforms. We compared the impact of four different harmonization methods on results obtained from analyses of cortical thickness data: (1) linear mixed-effects model (LME) that models site-specific random intercepts (LME

Quantification Of Sulcal Emergence Timing And Its Variability In Early Fetal Life: Hemispheric Asymmetry And Sex Difference, Hyuk Jin Yun, Hyun Ju Lee, Joo Young Lee, Tomo Tarui, Caitlin K. Rollins, Cynthia M. Ortinau, Henry A. Feldman, P. Ellen Grant, Kiho Im

2020-Current year OA Pubs

Human fetal brains show regionally different temporal patterns of sulcal emergence following a regular timeline, which may be associated with spatiotemporal patterns of gene expression among cortical regions. This study aims to quantify the timing of sulcal emergence and its temporal variability across typically developing fetuses by fitting a logistic curve to presence or absence of sulcus. We found that the sulcal emergence started from the central to the temporo-parieto-occipital lobes and frontal lobe, and the temporal variability of emergence in most of the sulci was similar between 1 and 2 weeks. Small variability (< 1 week) was found in the left central and postcentral sulci and larger variability (>2 weeks) was shown in …

The Serotonin Receptor 3e Variant Is A Risk Factor For Female Ibs-D, Nikola Fritz, Gregory Sayuk, Et Al.

2020-Current year OA Pubs

Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT

Association Of Noncontrast Computed Tomography And Perfusion Modalities With Outcomes In Patients Undergoing Late-Window Stroke Thrombectomy, Guilherme B F Porto, Joshua Osbun, Et Al.

2020-Current year OA Pubs

IMPORTANCE: There is substantial controversy with regards to the adequacy and use of noncontrast head computed tomography (NCCT) for late-window acute ischemic stroke in selecting candidates for mechanical thrombectomy.

OBJECTIVE: To assess clinical outcomes of patients with acute ischemic stroke presenting in the late window who underwent mechanical thrombectomy stratified by NCCT admission in comparison with selection by CT perfusion (CTP) and diffusion-weighted imaging (DWI).

DESIGN, SETTING, AND PARTICIPANTS: In this multicenter retrospective cohort study, prospectively maintained Stroke Thrombectomy and Aneurysm (STAR) database was used by selecting patients within the late window of acute ischemic stroke and emergent large vessel …

Sars-Cov-2 Mrna Vaccination Causes Prolonged Increased Cortical Thickening And Vascularity In Ipsilateral Axillary Lymph Nodes, Sharlene A Teefey, William D Middleton, Jackson S Turner, Ali H Ellebedy, Teresa Suessen, Michael Wallendorf, Jane A O'Halloran, Rachel Presti

2020-Current year OA Pubs

OBJECTIVES: To describe the serial grey-scale and color Doppler appearance of ipsilateral axillary lymphadenopathy in response to the Pfizer-BioNTech Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) messenger RNA (mRNA) vaccine over 24 to 28 weeks.

METHODS: The data for this study were collected during an observational study to determine whether mRNA vaccination induced a germinal center B cell reaction in blood and draining axillary lymph nodes. The current study evaluated the serial color Doppler and grey-scale sonographic appearance of these lymph nodes. Ten participants who each underwent 6 sonograms and FNAs over 24 to 28 weeks were included in the study. …

Chemotherapy-Induced Toxicities And Their Associations With Clinical And Non-Clinical Factors Among Breast Cancer Patients In Vietnam, Sang M Nguyen, Anh T Pham, Lan M Nguyen, Hui Cai, Thuan V Tran, Xiao-Ou Shu, Huong T T Tran

Faculty, Staff and Student Publications

Understanding the burden and factors related to chemotherapy-induced toxicity is important in treatment planning for breast cancer patients. We conducted a prospective study among 396 newly diagnosed and chemotherapy-treated breast cancer patients recruited in two major cancer hospitals in northern Vietnam. Toxicities were captured through medical chart reviews and patient self-reports and graded using NCI CTCAE classification. Associations for sociodemographic and clinical factors with chemotherapy-induced toxicities during first-line chemotherapy were evaluated via multivariable logistic regression. Severe (i.e., grade ≥ 3) hematological (38.6%), and gastrointestinal (12.9%) toxicities were common. A pre-existing nephrological condition was significantly associated with the risk of severe …

Genetic Testing To Inform Epilepsy Treatment Management From An International Study Of Clinical Practice, Dianalee Mcknight, Ana Morales, Kathryn E. Hatchell, Sara L. Bristow, Joshua L. Bonkowsky, Michael Scott Perry, Anne T. Berg, Felippe Borlot, Edward D. Esplin, Chad Moretz, Katie Angione, Loreto Ríos-Pohl, Robert L. Nussbaum, Swaroop Aradhya, Chad R. Haldeman-Englert, Rebecca J. Levy, Venu G. Parachuri, Guillermo Lay-Son, David J. Dávila-Ortiz De Montellano, Miguel Angel Ramirez-Garcia, Edmar O. Benítez Alonso, Julie Ziobro, Adela Chirita-Emandi, Temis M. Felix, Dianne Kulasa-Luke, Andre Megarbane, Shefali Karkare, Sarah L. Chagnon, Jennifer B. Humberson, Melissa J. Assaf, Sebastian Silva, Katherine Zarroli, Oksana Boyarchuk, Gary R. Nelson, Rachel Palmquist, Katherine C. Hammond, Sean T. Hwang, Susan B. Boutlier, Melinda Nolan, Kaitlin Y. Batley, Devraj Chavda, Carlos Alberto Reyes-Silva, Oleksandr Miroshnikov, Britton Zuccarelli, Louise Amlie-Wolf, James W. Wheless, Syndi Seinfeld, Manoj Kanhangad, Jeremy L. Freeman, Susana Monroy-Santoyo, Natalia Rodriguez-Vazquez, Monique M. Ryan, Michelle Machie, Patricio Guerra, Muhammad Jawad Hassan, Meghan S. Candee, Caleb P. Bupp, Kristen L. Park, Eric Muller, Pamela Lupo, Robert C. Pedersen, Amir M. Arain, Andrea Murphy, Krista Schatz, Weiyi Mu, Paige M. Kalika, Lautaro Plaza, Marissa A. Kellogg, Evelyn G. Lora, Robert P. Carson, Victoria Svystilnyk, Viviana Venegas, Rebecca R. Luke, Huiyuan Jiang, Tetiana Stetsenko, Milagros M. Dueñas-Roque, Joseph Trasmonte, Rebecca J. Burke, Anna C. E. Hurst, Douglas M. Smith, Lauren J. Massingham, Laura Pisani, Carrie E. Costin, Betsy Ostrander, Francis M. Filloux, Amitha L. Ananth, Ismail S. Mohamed, Alla Nechai, Jasmin M. Dao, Michael C. Fahey, Ermal Aliu, Stephen Falchek, Craig A. Press, Lauren Treat, Krista Eschbach, Angela Starks, Ryan Kammeyer, Joshua J. Bear, Mona Jacobson, Veronika Chernuha, Bailey Meibos, Kristen Wong, Matthew T. Sweney, A. Chris Espinoza, Colin B. Van Orman, Arie Weinstock, Ashutosh Kumar, Claudia Soler-Alfonso, Danielle A. Nolan, Muhammad Raza, Miguel David Rojas Carrion, Geetha Chari, Eric D. Marsh, Yael Shiloh-Malawsky, Sumit Parikh, Ernesto Gonzalez-Giraldo, Stephen Fulton, Yoshimi Sogawa, Kaitlyn Burns, Myroslava Malets, Johnny David Montiel Blanco, Christa W. Habela, Carey A. Wilson, Guillermo G. Guzmán, Mariia Pavliuk

Department of Pediatrics Faculty Papers

IMPORTANCE: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes.

OBJECTIVE: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a …

The Risks Of Birth Defects And Childhood Cancer With Conception By Assisted Reproductive Technology, Barbara Luke, Morton B Brown, Ethan Wantman, Maria J Schymura, Marilyn L Browne, Sarah C Fisher, Nina E Forestieri, Chandrika Rao, Hazel B Nichols, Mahsa M Yazdy, Susan T Gershman, Caitlin R Sacha, Melanie Williams, Mary K Ethen, Mark A Canfield, Kevin J Doody, Michael L Eisenberg, Valerie L Baker, Carrie Williams, Alastair G Sutcliffe, Melissa A Richard, Philip J Lupo

Center for Medical Ethics and Health Policy Staff Publications

Study question: Is there an association between fertility status, method of conception and the risks of birth defects and childhood cancer?

Summary answer: The risk of childhood cancer had two independent components: (i) method of conception and (ii) presence, type and number of birth defects.

What is known already: The rarity of the co-occurrence of birth defects, cancer and ART makes studying their association challenging. Prior studies have indicated that infertility and ART are associated with an increased risk of birth defects or cancer but have been limited by small sample size and inadequate statistical power, failure to adjust for …

Steroid Receptor Coactivator-3 Inhibition Generates Breast Cancer Antitumor Immune Microenvironment, Sang Jun Han, Nuri Sung, Jin Wang, Bert W O'Malley, David M Lonard

Faculty, Staff and Students Publications

BACKGROUND: The tumor immune microenvironment (TIME) generated by cancer-infiltrating immune cells has a crucial role in promoting or suppressing breast cancer progression. However, whether the steroid receptor coactivator-3 (SRC-3) modulates TIME to progress breast cancer is unclear. Therefore, the present study evaluates whether SRC-3 generates a tumor-promoting TIME in breast tumors using a syngeneic immune-intact mouse model of breast cancer.

METHODS: We employed E0771 and 4T1 breast cancer in immune-intact syngeneic female C57BL/6 and BALB/c mice, respectively. SI-2, a specific small-molecule inhibitor of SRC-3, was administered daily (2.5 mg/kg) to E0771 and 4T1 breast tumor-bearing immune-intact mice. In addition, SRC-3 …

Loneliness And Alcohol-Related Problems Among College Students Who Report Binge Drinking Behavior: The Moderating Role Of Food And Alcohol Disturbance, Luke Herchenroeder, Stacy M Post, Michelle L Stock, Ellen W Yeung

Faculty, Staff and Student Publications

Loneliness and alcohol misuse are common among college students and pose a threat to public health. To better understand the longitudinal association between these public health concerns we examined food and alcohol disturbance (FAD; i.e., restricting one's caloric intake prior to drinking) as a moderator in the association between loneliness and alcohol-related problems. Participants were 456 college students from a mid-sized university who engaged in past 30-day binge drinking. The majority of participants identified as being White (67.1%), female (78.1%), and reported a mean age of 19.61 (SD = 1.54) years. Participants completed two surveys (3 weeks apart) over the …

Comparison Of Metagenomic Sequencing And The Nanostring Ncounter Analysis System For The Characterization Of Bacterial And Viral Communities In Vaginal Samples, Todd N Wylie, Jane Schrimpf, Haley Gula, Brandi N Herter, Kristine M Wylie

2020-Current year OA Pubs

DNA sequencing assays have been used to characterize the vaginal microbiome and to identify associations with clinical outcomes. The purpose of this study was to evaluate the utility of the NanoString nCounter platform, a more efficient assay compared to sequencing, for the characterization of vaginal microbial communities. A panel of NanoString nCounter probes was designed to detect common vaginal bacteria and viruses with relevance to reproductive health. A defined synthetic community of microbes and 43 clinical samples were interrogated with NanoString nCounter assays and compared to known compositions or metagenomic shotgun sequencing (MSS) results. The NanoString nCounter platform and MSS …

Successful Buprenorphine Transition While Overlapping With A Full Opioid Agonist To Treat Chronic Pain: A Case Report, Kishan V. Patel, Sidharth Sahni, Lanvin F. Taylor

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Buprenorphine is a partial mu opioid agonist that has been increasingly utilized to treat patients with chronic pain and opioid use disorder (OUD). The drug has proven to provide significant chronic pain relief at low doses ranging from 75 to 1800 mcg. The conventional buprenorphine transitional process delays its introduction until patients begin withdrawal. However, this process can pose a barrier to both patients and providers due to some patients' inability to tolerate traditional prerequisite withdrawal. To our knowledge, this is a rare reported case to describe a transitional process utilizing buccal buprenorphine in which a patient with chronic pain …

Biomarkers Beyond Brca: Promising Combinatorial Treatment Strategies In Overcoming Resistance To Parp Inhibitors, Yu-Yi Chu, Clinton Yam, Hirohito Yamaguchi, Mien-Chie Hung

Faculty, Staff and Student Publications

Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) exploit the concept of synthetic lethality and offer great promise in the treatment of tumors with deficiencies in homologous recombination (HR) repair. PARPi exert antitumor activity by blocking Poly(ADP-ribosyl)ation (PARylation) and trapping PARP1 on damaged DNA. To date, the U.S. Food and Drug Administration (FDA) has approved four PARPi for the treatment of several cancer types including ovarian, breast, pancreatic and prostate cancer. Although patients with HR-deficient tumors benefit from PARPi, majority of tumors ultimately develop acquired resistance to PARPi. Furthermore, even though BRCA1/2 mutations are commonly used as markers of PARPi sensitivity in …

14-3-3Τ Drives Estrogen Receptor Loss Via Erα36 Induction And Gata3 Inhibition In Breast Cancer, Lidija A Wilhelms Garan, Yang Xiao, Weei-Chin Lin

Faculty, Staff and Students Publications

About one-fourth of recurrent estrogen receptor-positive (ER+) breast cancers lose ER expression, leading to endocrine therapy failure. However, the mechanisms underlying ER loss remain to be fully explored. We now show that 14-3-3τ, up-regulated in ∼60% of breast cancer, drives the conversion of ER+ to ER- and epithelial-to-mesenchymal transition (EMT). We identify ERα36, an isoform of ERα66, as a downstream effector of 14-3-3τ. Overexpression of 14-3-3τ induces ERα36 in xenografts and tumor spheroids. The regulation is further supported by a positive correlation between ERα36 and 14-3-3τ expression in human breast cancers. ERα36 can antagonize ERα66 and inhibit ERα66 expression. Isoform-specific …

Interferon Signaling In The Endometrium And In Endometriosis, Yuri Park, Sang Jun Han

Faculty, Staff and Students Publications

Endometriosis is an estrogen-dependent inflammatory disease that develops in reproductive-aged women who experience pelvic pain and infertility. Even though endometriosis is not a new disease, its molecular etiology has not been clearly elucidated. Defects in the immune system might be one of the factors that promote endometriosis progression. For example, elevated levels of proinflammatory cytokines are associated with endometriosis. Interferon is one of the cytokines that is elevated in endometriotic tissues compared with normal endometrium. Therefore, high interferon levels play a crucial role in endometriosis progression. In addition to endometriosis, however, interferon has a critical role in endometrial function, particularly …

The Impact Of Tsc-1 And -2 Mutations On Response To Therapy In Malignant Pecoma: A Multicenter Retrospective Analysis, Lawrence Liu, Nikhil Grandhi, Yang Lyu, Xiao Zhang, Jingqin Luo, Mia Weiss, Brian Van Tine, Angela C Hirbe, Et Al.

2020-Current year OA Pubs

BACKGROUND: Perivascular epithelioid cell neoplasms (PEComas) are a diverse family of mesenchymal tumors with myomelanocytic differentiation that disproportionately affect women and can be associated with tuberous sclerosis (TS). Although mTOR inhibition is widely used as first-line treatment, it is unclear what genomic alterations exist in these tumors and how they influence the response to therapy.

METHODS: This was a multicenter study conducted at five sites within the US. The data were collected from 1 January 2004 to 31 January 2021. We conducted a retrospective analysis to identify PEComa patients with next-generation sequencing (NGS) data and compared outcomes based on mutations. …

Prevalence Of Prediabetes And Diabetes Vary By Ethnicity Among Us Asian Adults At Healthy Weight, Overweight, And Obesity Ranges: An Electronic Health Record Study, William S Vicks, Joan C Lo, Lynn Guo, Jamal S Rana, Sherry Zhang, Nirmala D Ramalingam, Nancy P Gordon

Faculty, Staff and Student Publications

BACKGROUND: Asian adults develop Type 2 diabetes at a lower body mass index (BMI) compared to other racial/ethnic groups. We examined the variation in prevalence of prediabetes and diabetes among Asian ethnic groups within weight strata by comparing middle-aged Chinese, Filipino, South Asian, and White adults receiving care in the same integrated healthcare delivery system.

METHODS: Our retrospective cross-sectional U.S. study examined data from 283,110 (non-Hispanic) White, 33,263 Chinese, 38,766 Filipino, and 17,959 South Asian adults aged 45-64 years who were members of a Northern California health plan in 2016 and had measured height and weight. Prediabetes and diabetes were …

Sex Difference Leads To Differential Gene Expression Patterns And Therapeutic Efficacy In Mucopolysaccharidosis Iva Murine Model Receiving Aav8 Gene Therapy, Matthew Matthew Piechnik, Paige C. Amendum, Kazuki Sawamoto, Molly Stapleton, Shaukat Khan, Nidhi Fnu, Victor Álvarez, Angelica Maria Herreño Pachon, Olivier Danos, Joseph T. Bruder, Subha Karumuthil-Melethil, Shunji Tomatsu

Student Papers, Posters & Projects

Adeno-associated virus (AAV) vector-based therapies can effectively correct some disease pathology in murine models with mucopolysaccharidoses. However, immunogenicity can limit therapeutic effect as immune responses target capsid proteins, transduced cells, and gene therapy products, ultimately resulting in loss of enzyme activity. Inherent differences in male versus female immune response can significantly impact AAV gene transfer. We aim to investigate sex differences in the immune response to AAV gene therapies in mice with mucopolysaccharidosis IVA (MPS IVA). MPS IVA mice, treated with different AAV vectors expressing human N-acetylgalactosamine 6-sulfate sulfatase (GALNS), demonstrated a more robust antibody response in female mice resulting …

A Randomized Feasibility Pilot-Study Of Intravenous And Subcutaneous Administration Of Ketamine To Prevent Postpartum Depression After Planned Cesarean Delivery Under Neuraxial Anesthesia, David Thomas Monks, Arvind Palanisamy, Danish Jaffer, Preet Mohinder Singh, Ebony Carter, Shannon Lenze

2020-Current year OA Pubs

BACKGROUND: Evidence suggests ketamine may prevent postpartum depression (PPD) after cesarean delivery (CD) although intolerability and inconvenience of administration are problematic. We assessed the feasibility of studying ketamine (0.5 mg/kg, via subcutaneous injection or 40-min intravenous infusion) to prevent PPD after CD.

METHODS: Twenty-three women scheduled for cesarean delivery under neuraxial anesthesia were randomized to one of three groups: subcutaneous ketamine (SC Group, n = 8), intravenous ketamine (IV Group, n = 8) or placebo (n = 7). We measured depression (Edinburgh Postpartum Depression Scale [EPDS]) scores pre-operatively and at 1, 2, 21 and 42 days postoperatively. Anxiety, adverse effects, …

A Comparison Of Bioimpedance Analysis Vs. Dual X-Ray Absorptiometry For Body Composition Assessment In Postpartum Women And Non-Postpartum Controls, Valene Garr Barry, Samantha L Martin, Paula Chandler-Laney, Ebony B Carter, Camille S Worthington

2020-Current year OA Pubs

Postpartum fat mass (FM) and fat-free mass (FFM) may be informative predictors of future disease risk among women; hence, there is growing use of bioelectrical impedance analysis (BIA) to quantify FFM and FM among postpartum women due to the quick, non-invasive, and inexpensive nature of BIA. Despite this, very few studies have examined BIA's performance, and it remains unclear as to whether specific BIA equations are needed for postpartum women. To explore these questions, we measured total body FFM and FM with a multi-frequency, segmental BIA, and dual-X-ray absorptiometry (DXA) in (1) women at one and four months postpartum (

Hdac6 Inhibition Reverses Cisplatin-Induced Mechanical Hypersensitivity Via Tonic Delta Opioid Receptor Signaling, Jixiang Zhang, Jazzmine M Junigan, Ronnie Trinh, Annemieke Kavelaars, Cobi J Heijnen, Peter M Grace

Faculty, Staff and Student Publications

Peripheral neuropathic pain induced by the chemotherapeutic cisplatin can persist for months to years after treatment. Histone deacetylase 6 (HDAC6) inhibitors have therapeutic potential for cisplatin-induced neuropathic pain since they persistently reverse mechanical hypersensitivity and spontaneous pain in rodent models. Here, we investigated the mechanisms underlying reversal of mechanical hypersensitivity in male and female mice by a 2 week treatment with an HDAC6 inhibitor, administered 3 d after the last dose of cisplatin. Mechanical hypersensitivity in animals of both sexes treated with the HDAC6 inhibitor was temporarily reinstated by a single injection of the neutral opioid receptor antagonist 6β-naltrexol or …

Loss Of Activity-Induced Mitochondrial Atp Production Underlies The Synaptic Defects In A Drosophila Model Of Als, Nicholas E Karagas, Richa Gupta, Elham Rastegari, Kai Li Tan, Ho Hang Leung, Hugo J Bellen, Kartik Venkatachalam, Ching-On Wong

Faculty, Staff and Students Publications

Mutations in the gene encoding vesicle-associated membrane protein B (VAPB) cause a familial form of amyotrophic lateral sclerosis (ALS). Expression of an ALS-related variant of vapb (vapb^P58S) in Drosophila motor neurons results in morphologic changes at the larval neuromuscular junction (NMJ) characterized by the appearance of fewer, but larger, presynaptic boutons. Although diminished microtubule stability is known to underlie these morphologic changes, a mechanism for the loss of presynaptic microtubules has been lacking. By studying flies of both sexes, we demonstrate the suppression of vapb^P58S-induced changes in NMJ morphology by either a loss of endoplasmic …

Can The "Female Protective Effect" Liability Threshold Model Explain Sex Differences In Autism Spectrum Disorder?, Joseph D Dougherty, Natasha Marrus, Susan E Maloney, Benjamin Yip, Sven Sandin, Tychele N Turner, Din Selmanovic, Kristen L Kroll, David H Gutmann, John N Constantino, Lauren A Weiss

2020-Current year OA Pubs

Male sex is a strong risk factor for autism spectrum disorder (ASD). The leading theory for a "female protective effect" (FPE) envisions males and females have "differing thresholds" under a "liability threshold model" (DT-LTM). Specifically, this model posits that females require either a greater number or larger magnitude of risk factors (i.e., greater liability) to manifest ASD, which is supported by the finding that a greater proportion of females with ASD have highly penetrant genetic mutations. Herein, we derive testable hypotheses from the DT-LTM for ASD, investigating heritability, familial recurrence, correlation between ASD penetrance and sex ratio, population traits, clinical …

Association Of Mrna Vaccination With Clinical And Virologic Features Of Covid-19 Among Us Essential And Frontline Workers, The Heroes-Recover Network, Mark G Thompson, Sarang K Yoon, Allison L Naleway, Jennifer Meece, Thomas P Fabrizio, Alberto J Caban-Martinez, Jefferey L Burgess, Manjusha Gaglani, Lauren E W Olsho, Allen Bateman, Jessica Lundgren, Lauren Grant, Andrew L Phillips, Holly C Groom, Elisha Stefanski, Natasha Schaefer Solle, Katherine Ellingson, Karen Lutrick, Kayan Dunnigan, Meredith G Wesley, Kyley Guenther, Angela Hunt, Josephine Mak, Kurt T Hegmann, Jennifer L Kuntz, Adam Bissonnette, James Hollister, Spencer Rose, Tyler C Morrill, Karley Respet, Ashley L Fowlkes, Matthew S Thiese, Patrick Rivers, Meghan K Herring, Marilyn J Odean, Young M Yoo, Matthew Brunner, Edward J Bedrick, Deanna E Fleary, John T Jones, Jenna Praggastis, James Romine, Monica Dickerson, Sana M Khan, Julie Mayo Lamberte, Shawn Beitel, Richard J Webby, Harmony L Tyner

Faculty, Staff and Student Publications

IMPORTANCE: Data on the epidemiology of mild to moderately severe COVID-19 are needed to inform public health guidance.

OBJECTIVE: To evaluate associations between 2 or 3 doses of mRNA COVID-19 vaccine and attenuation of symptoms and viral RNA load across SARS-CoV-2 viral lineages.

DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of essential and frontline workers in Arizona, Florida, Minnesota, Oregon, Texas, and Utah with COVID-19 infection confirmed by reverse transcriptase-polymerase chain reaction testing and lineage classified by whole genome sequencing of specimens self-collected weekly and at COVID-19 illness symptom onset. This analysis was conducted among 1199 participants with SARS-CoV-2 …