Digital Commons Network^™

Goldenbraid20 E Coli: A Comprehensive And Characterized Toolkit For Enterics, Matthew B Cooke, Kobie T Welch, Laura D Ramirez, Alice X Wen, David C Marciano, Christophe Herman

Faculty, Staff and Students Publications

Modular cloning systems streamline laboratory workflows by consolidating genetic 'parts' into reusable and modular collections, enabling researchers to fast-track strain construction. The GoldenBraid 2.0 modular cloning system utilizes the cutting property of type IIS restriction enzymes to create defined genetic 'grammars', which facilitate the reuse of standardized genetic parts and assembly of genetic parts in the right order. Here, we present a GoldenBraid 2.0 toolkit of genetic parts designed to accelerate cloning in the model bacterium

Hypertriglyceridemia In New-Onset Type 1 Pediatric Diabetes, Colleen A Macke, Iman Al-Gadi, Nidhi Bansal, Sarah K Lyons, Aikaterini A Nella

Faculty, Staff and Students Publications

Hypertriglyceridemia (HTG) in the setting of newly diagnosed diabetes is common in both adult and pediatric populations, as insulin deficiency promotes lipolysis and impairs triglyceride (TG) clearance. Severe HTG (defined as TG levels above 1000 mg/dL) in pediatric patients with new-onset type 1 diabetes mellitus (T1D) is rare; the true incidence and sequela of this phenomenon have not been well characterized. We present a single-center experience on severe HTG in pediatric patients with new-onset T1D between 2013 and 2022 and summarize the cases previously reported in the literature. Our cases display variability in their presentation and in their association with …

Long-Term Mortality Following Sars-Cov-2 Infection In Rural Versus Urban Dwellers With Autoimmune Or Inflammatory Rheumatic Disease: A Retrospective Cohort Analysis From The National Covid Cohort Collaborative, A Jerrod Anzalone, Lesley E Jackson, Namrata Singh, Maria I Danila, Elizabeth Reisher, Rena C Patel, Jasvinder A Singh

Faculty, Staff and Students Publications

Objective: Autoimmune or inflammatory rheumatic diseases (AIRDs) increase the risk for poor COVID-19 outcomes. Although rurality is associated with higher post-COVID-19 mortality in the general population, whether rurality elevates this risk among people with AIRD is unknown. We assessed associations between rurality and post-COVID-19 all-cause mortality, up to two years post infection, among people with AIRD using a large nationally sampled US cohort.

Methods: This retrospective study used the National COVID Cohort Collaborative, a medical records repository containing COVID-19 patient data. We included adults with two or more AIRD diagnostic codes and a COVID-19 diagnosis documented between April 2020 and …

Altering The Intracellular Trafficking Of Necator Americanus Gst-1 Antigen Yields Novel Hookworm Mrna Vaccine Candidates, Athos Silva De Oliveira, Leroy Versteeg, Neima Briggs, Rakesh Adhikari, Maria Jose Villar, Jeanna R Redd, Peter Hotez, Maria Elena Bottazzi, Jeroen Pollet

Faculty, Staff and Students Publications

BACKGROUND: The antigen Na-GST-1, expressed by the hookworm Necator americanus, plays crucial biochemical roles in parasite survival. This study explores the development of mRNA vaccine candidates based on Na-GST-1, building on the success of recombinant Na-GST-1 (rNa-GST-1) protein, currently assessed as a subunit vaccine candidate, which has shown promise in preclinical and clinical studies.

METHODOLOGY/FINDINGS: By leveraging the flexible design of RNA vaccines and protein intracellular trafficking signal sequences, we developed three variants of Na-GST-1 as native (cytosolic), secretory, and plasma membrane-anchored (PM) antigens. After one immunization in mice, mRNA vaccines induced an earlier onset of antigen-specific antibodies compared to …

Tobacco Exposure Linked To Warthin’S Tumor Being The Most Common Benign Parotid Neoplasm In Veterans: A Retrospective Cohort Study, Louis Abarca, Linda K Green, Ray Y Wang, Vlad C Sandulache, David J Hernandez

Faculty, Staff and Students Publications

Objective: Parotid gland neoplasms account for a large proportion of benign salivary gland tumors, with pleomorphic adenomas (PA) being the most common in the civilian population, followed by Warthin's tumor (WT). However, the distinct risk profiles of Veterans significantly influence the incidence and prevalence of salivary gland neoplasms. We investigated the diagnostic and management algorithms for benign parotid gland neoplasms in Veterans.

< >Methods: Retrospective cohort study. Descriptive statistics were calculated using Microsoft Excel. Categorical variables were compared using chi square tests, and were reported with 95% confidence intervals, with statistical significance set at P <  .05.

Results: The study included 158 patients …

Interleukin-15-Armoured Gpc3 Car T Cells For Patients With Solid Cancers, David Steffin, Nisha Ghatwai, Antonino Montalbano, Purva Rathi, Amy N Courtney, Azlann B Arnett, Julien Fleurence, Ramy Sweidan, Tao Wang, Huimin Zhang, Prakash Masand, John M Maris, Daniel Martinez, Jennifer Pogoriler, Navin Varadarajan, Sachin G Thakkar, Deborah Lyon, Natalia Lapteva, Mei Zhuyong, Kalyani Patel, Dolores Lopez-Terrada, Carlos A Ramos, Premal Lulla, Tannaz Armaghany, Bambi J Grilley, Stephen Gottschalk, Gianpietro Dotti, Leonid S Metelitsa, Helen E Heslop, Malcolm K Brenner, Pavel Sumazin, Andras Heczey

Faculty, Staff and Students Publications

Interleukin-15 (IL15) promotes the survival of T lymphocytes and enhances the antitumor properties of CAR T cells in preclinical models of solid neoplasms in which CAR T cells have limited efficacy1-4. Glypican-3 (GPC3) is expressed in a group of solid cancers5-10, and here we report the first evaluation in humans of the effects of IL15 co-expression on GPC3-CAR T cells. Cohort 1 patients (NCT02905188/NCT02932956) received GPC3-CAR T cells, which were safe but produced no objective antitumor responses and reached peak expansion at two weeks. Cohort 2 patients ( …

Recessive Loss-Of-Function Variants In Dph1 Identified As The Molecular Cause In A Sibling Pair Previously Diagnosed With Fine-Lubinsky Syndrome, Emily R Waskow, Lisa T Emrick, Jill A Rosenfeld, Shamika Ketkar, Lindsay C Burrage, Daryl A Scott

Faculty, Staff and Students Publications

Fine-Lubinsky syndrome is a rare clinically defined syndrome sometimes referred to as brachycephaly, deafness, cataract, microstomia, and impaired intellectual development syndrome. Here we provide a clinical and molecular update for a sibling pair diagnosed with Fine-Lubinsky syndrome. An extensive genetic work-up, including chromosomal microarray analysis and quad exome sequencing, was nondiagnostic. However, a research reanalysis of their exome sequencing data revealed that both were homozygous for an intronic c.749+39G>A [NM_001383.6] variant in DPH1. RNAseq analysis performed on RNA from fibroblasts revealed significantly reduced expression of DPH1 transcripts suggestive of abnormal splicing followed by nonsense mediated mRNA decay. Since the …

Atherogenic Lipoproteins Associate With Loss Of Glycemic Control In Youth-Onset Type 2 Diabetes: Results From The Today Study, Lorraine E Levitt Katz, Samuel S Gidding, James D Otvos, Kimberly L Drews, Fida Bacha, Steven Willi, Santica Marcovina, Siripoom Mckay, Ruth S Weinstock, Today Study Group

Faculty, Staff and Students Publications

Background: Type 2 diabetes (T2D) in adolescents is associated with an unfavorable lipid profile, but lipoprotein particle subspecies and branched-chain amino acid (BCAA) data are scarce.

Objective: To evaluate lipoprotein particle distributions, lipoprotein insulin resistance index (LP-IR), and BCAA levels longitudinally and their relationships with sex, race/ethnicity, treatment, and loss of glycemic control in adolescents with youth-onset T2D.

Methods: Participants from the TODAY study (n = 348) had samples analyzed yearly for glycated hemoglobin and nuclear magnetic resonance lipoprotein and BCAA assessments.

Results: At baseline, participants with T2D were 13.7 years old with T2D, obesity, and from racial and ethnic …

Nitrate And Nitrite Bioavailability In Plasma And Saliva: Their Association With Blood Pressure - A Systematic Review And Meta-Analysis, Raul Bescos, Laura Gallardo-Alfaro, Ammar Ashor, Lucia Rizzolo-Brime, Mario Siervo, Patricia Casas-Agustench

School of Health Professions

In this study, we conducted a systematic review and meta-analysis to determine plasma and salivary nitrate (NO ₃ ⁻) and nitrite (NO ₂ ⁻) concentrations under resting and fasting conditions in different type of individuals and their association with blood pressure levels. A total of 77 studies, involving 1918 individuals aged 19–74 years (males = 906; females = 1012), which measured plasma and/or salivary NO ₃ ⁻ and NO ₂ ⁻ using the chemiluminescence technique, were included. Mean plasma NO ₃ ⁻ and NO ₂ ⁻ concentrations were 33.9 μmol/L and 158.3 nmol/L, respectively. Subgroup analyses revealed lower …

Association Of Insulin Resistance With Radiographic Lung Abnormalities And Incident Lung Disease: The Framingham Offspring Study, Sarath Raju, Paula Sierra, Vickram Tejwani, Kristen A Staggers, Meredith Mccormack, Dennis T Villareal, Ivan O Rosas, Nicola A Hanania, Tianshi David Wu

Faculty, Staff and Students Publications

Objective: Insulin resistance (IR) may be a risk factor for lung disease, but objective evidence is limited. We sought to define the relationship of longitudinal IR with radiographic imaging outcomes and examiner-identified incident lung disease in the Framingham Offspring Study.

Research design and methods: Participants without baseline lung disease underwent repeated measurements of fasting insulin and glucose levels over an average period of 13.6 years, from which time-weighted average HOMA-IR was calculated. Each participant then underwent a cardiac gated whole-lung computed tomography scan, which was analyzed for the presence of emphysema, interstitial lung abnormalities (ILAs), and quantitative airway features. Incident …

The Association Of Human Milk Intake And Outcomes In Biliary Atresia, Mary Elizabeth M Tessier, Jeremy M Schraw, Stacey Beer, Sanjiv Harpavat, M Kyle Jensen, John C Magee, Vicky Ng, Michael E Scheurer, Sarah A Taylor, Benjamin L Shneider

Faculty, Staff and Students Publications

Objectives: Human milk intake has many benefits which could influence outcomes in biliary atresia (BA). However, the role of human milk in BA has not been examined. We hypothesized that human milk intake would be associated with improved outcomes in BA.

Methods: We assessed the impact of any human milk (AHM) as compared to formula only (FO) intake before Kasai portoenterostomy (KP) on outcomes in 447 infants with BA using the PROBE database (NCT00061828) post hoc. The primary outcome was clearance of jaundice (COJ = total bilirubin (TB) < 2 mg/dL by 3 months post-KP). Secondary outcomes included 2-year survival with native liver (SNL), bilirubin levels, cholangitis, ascites, and growth. We assessed the fecal microbiome (n = 8) comparing AHM versus FO.

Results: At baseline, 211 infants received AHM and 215 received …

Learning-Associated Astrocyte Ensembles Regulate Memory Recall, Michael R Williamson, Wookbong Kwon, Junsung Woo, Yeunjung Ko, Ehson Maleki, Kwanha Yu, Sanjana Murali, Debosmita Sardar, Benjamin Deneen

Faculty, Staff and Students Publications

The physical manifestations of memory formation and recall are fundamental questions that remain unresolved1. At the cellular level, ensembles of neurons called engrams are activated by learning events and control memory recall1-5. Astrocytes are in close proximity to neurons and engage in a range of activities that support neurotransmission and circuit plasticity6-10. Moreover, astrocytes exhibit experience-dependent plasticity11-13; however whether specific ensembles of astrocytes participate in memory recall remains obscure. Here we show that learning events induce c-Fos expression in a subset of hippocampal astrocytes, which subsequently …

Placentas From Sars-Cov-2 Infection During Pregnancy Exhibit Foci Of Oxidative Stress And Dna Damage, Guilherme M Nobrega, Eliza R Mccoll, Arthur Antolini-Tavares, Renato T Souza, José Guilherme Cecatti, Maria Laura Costa, Indira U Mysorekar

Faculty, Staff and Students Publications

Problem: COVID-19 during pregnancy is linked to increased maternal morbidity and a higher incidence of preterm births (PTBs), yet the underlying mechanisms remain unclear. Cellular senescence, characterized by the irreversible cessation of cell division, is a critical process in placental function, and its dysregulation has been implicated in pregnancy complications like PTB. Senescence can be induced by various stressors, including oxidative stress, DNA damage, and viral infections.

Method of study: In this study, we determined whether COVID-19 had an impact on placental senescence. We examined placentas from women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n = 10 …

Mutations In Retinal Cyclic Nucleotide-Gated Channels Identified In Familial Cases Of Inherited Retinal Dystrophies From Pakistan, Zainab Akhtar, Kiran Afshan, Yumei Li, Sumaira Altaf, Aleesha Asghar, Ume Sughra, Wajid Ali Khan, Haiba Kaul, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

Purpose: Cyclic nucleotide-gated (CNG) channels are ligand-gated ion channels that transduce light signals into electrical signals in the retinal photoreceptors. Pathogenic variants in CNG channel genes are reported to cause inherited retinal dystrophies (IRDs). The current study used targeted panel sequencing to describe the mutational spectrum of CNG channel genes in familial cases of IRDs from eight consanguineous Pakistani families.

Methods: The current study included consanguineous Pakistani families with at least two affected members. DNA was extracted from whole blood samples by the phenol-chloroform method. Two affected members from each family were initially analyzed using targeted panel sequencing of 344 …

Microbiota Dynamics During Ascaris Suum Larval Migration: Implications For Host Microbial Communities In A Murine Model, Sergio Castañeda, Cristina Poveda, Charlie Suarez-Reyes, Yifan Wu, Noah Haugen, Luz H Patiño, Jill E Weatherhead, Juan David Ramírez

Faculty, Staff and Students Publications

The complex interactions between parasites, their hosts, and associated microbiota hold significant implications for host health and disease outcomes. Helminths like Ascaris lumbricoides and Ascaris suum can significantly alter the host's intestinal microbiota, affecting both parasite biology and host pathology. Despite extensive research on host-microbiota changes due to helminth infections, the study of helminth-associated microbiota remains limited. This study aims to characterize the microbiota associated with Ascaris larvae and surrounding host tissues at distinct developmental stages (day 4, day 8, day 14), during larval migration through the liver, lungs, and intestine, and its impact on the host's microbiota in a …

Detection Of Viral Rna And Dna And Immune Response Following Administration Of Live Attenuated Measles And Varicella Vaccines In Children With Chronic Liver Disease, Sarah Kemme, Jennifer D Canniff, Krystle M Garth, Shaobing Li, Krupa Mysore, Adriana Weinberg, Amy G Feldman

Faculty, Staff and Students Publications

Infections preventable by live virus vaccines are surging in the setting of decreased herd immunity. Many children with chronic liver diseases (CLDs) are unimmunized and at increased risk for infection due to guidelines recommending against live vaccines within 4 weeks pretransplant. This prospective study of 21 children with CLD and 13 healthy controls defined the timing of measles virus and varicella-zoster virus (VZV) RNA- and DNA-emia following vaccination and compared immune responses to measles and varicella vaccines in both groups. Measles virus RNA and VZV DNA real-time PCR were measured weekly following vaccination; measles virus RNA was undetectable in all …

Interval Advanced Adenomas And Neoplasia In Patients With Negative Colonoscopy Following Positive Stool-Based Colorectal Cancer Screening Test, Kyle S Liu, Rollin George, Caleb Shin, Jia Q Xiong, Taher Jamali, Yan Liu, Priya Roy, Sonia Singh, Samuel Ma, Hashem B El-Serag, Mimi C Tan

Faculty, Staff and Students Publications

BACKGROUND/AIMS: Fecal occult blood test (FOBT) and fecal immunohistochemical test (FIT) are used for colorectal cancer (CRC) screening. However, when no adenomas are found following a positive FOBT/FIT, the future risk of advanced adenomas or colorectal cancer (CRC) is unclear. We determined the incidence and determinants of advanced adenomas or CRC after a negative index colonoscopy following a positive FOBT/FIT.

METHODS: We identified patients in the Harris Health System (Houston, Texas) who underwent a colonoscopy following a positive FOBT/FIT from 01/2010 to 01/2013. We compared the incidence rates of advanced adenomas (≥ 1 cm, villous histopathology, or high-grade dysplasia) or …

Resilience Of The Gut Microbiome To Short Proton Pump Inhibitor Therapy With Or Without High-Dosage L Reuteri In H Pylori-Infected Adults, Stefano Bibbò, Gustav Ahlström, Giovanni Mario Pes, David Y Graham, Lars Engstrand, Elettra Merola, Maria Pina Dore

Faculty, Staff and Students Publications

Background: Helicobacter pylori eradication therapy typically consists of a combination of antibiotics and an antisecretory drug. Probiotics may be added to reduce side effects and possibly improve outcomes.

Materials and methods: We conducted a double-blind, randomized trial of pantoprazole plus either Lactobacillus reuteri (Gastrus) (high dose) or a matching placebo to assess the impact on the gut microbiota of H. pylori-positive adults. Fecal samples were collected at baseline and after one and 2 months for shotgun metagenomic sequencing.

Results: A total of 26 patients were recruited and completed therapy. L. reuteri was only detected in the group that received supplemental …

Deletions In The Cdkl5 5′ Untranslated Region Lead To Cdkl5 Deficiency Disorder, Isabel Haviland, Ralph D Hector, Lindsay C Swanson, Aubrie Soucy Verran, Emma Sherrill, Zoë Frazier, Annemarie M Denny, Jenna Lucash, Bo Zhang, Holly A Dubbs, Eric D Marsh, Judith L Weisenberg, Helen Leonard, Milena Crippa, Francesca Cogliati, Silvia Russo, Bernhard Suter, Rajsekar Rajaraman, Alan K Percy, John M Schreiber, Scott Demarest, Timothy A Benke, Maya Chopra, Timothy W Yu, Heather E Olson

Faculty, Staff and Students Publications

Pathogenic variants in the cyclin-dependent kinase-like 5 (CDKL5) gene are associated with CDKL5 deficiency disorder (CDD), a severe X-linked developmental and epileptic encephalopathy. Deletions affecting the 5' untranslated region (UTR) of CDKL5, which involve the noncoding exon 1 and/or alternatively spliced first exons (exons 1a-e), are uncommonly reported. We describe genetic and phenotypic characteristics for 15 individuals with CDKL5 partial gene deletions affecting the 5' UTR. All individuals presented characteristic features of CDD, including medically refractory infantile-onset epilepsy, global developmental delay, and visual impairment. We performed RNA sequencing on fibroblast samples from three individuals with small deletions involving exons 1 …

Heterologous Prime-Pull Mucosal Vaccination With An Adjuvanted Rbd Vaccine Elicits Robust Iga Production And Protects Against Sars-Cov-2, Allyson H Hirsch, Calder R Ellsworth, William A Lewis, Ryan Craig, Amy E Meyer, Jonatan Maldonado, Frania Ramirez Lopez, Syamala Rani Thimmiraju, James B Mclachlan, Xuebin Qin, Nicholas J Maness, Jeroen Pollet, Ulrich Strych, Maria Elena Bottazzi, Peter J Hotez, Lisa A Morici

Faculty, Staff and Students Publications

Despite the efficacy of approved severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in preventing severe disease and death, breakthrough infections continue to occur in vaccinated individuals, contributing to further viral mutation and spread. These limitations may be attributable to the poor induction of mucosal immunity by parenteral vaccination. Mucosal adjuvants, such as T-vant, can enhance vaccine-induced immune responses through the generation of antigen-specific antibodies and T cells in the respiratory tract. In this study, we evaluated the protective efficacy of adjuvanted SARS-CoV-2 receptor binding domain (RBD) subunit vaccines administered by homologous and heterologous routes. Immunized mice were challenged with …

Mutations In Retinal Cyclic Nucleotide-Gated Channels Identified In Familial Cases Of Inherited Retinal Dystrophies From Pakistan, Zainab Akhtar, Kiran Afshan, Yumei Li, Sumaira Altaf, Aleesha Asghar, Ume Sughra, Wajid Ali Khan, Haiba Kaul, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

Purpose: Cyclic nucleotide-gated (CNG) channels are ligand-gated ion channels that transduce light signals into electrical signals in the retinal photoreceptors. Pathogenic variants in CNG channel genes are reported to cause inherited retinal dystrophies (IRDs). The current study used targeted panel sequencing to describe the mutational spectrum of CNG channel genes in familial cases of IRDs from eight consanguineous Pakistani families.

Methods: The current study included consanguineous Pakistani families with at least two affected members. DNA was extracted from whole blood samples by the phenol-chloroform method. Two affected members from each family were initially analyzed using targeted panel sequencing of 344 …

Dissemination And Implementation Of Injury Prevention Interventions: A Scoping Review For The Female, Woman And Girl Athlete Injury Prevention (Fair) Consensus, Brooke E. Patterson, Carly D. Mckay, Meghan L. Critchley, Destiny Lutz, Sallie M. Cowan, Nicholas Kolesky, Vanda White, Allison M. Ezzat, Andrew G. Ross, William M. Adams, Eva Ageberg, Clare L. Ardern, Marelise Badenhorst, Molly Coventry, Marc Olivier Dubé, Stacey Emmonds, Libby J. Gracias, K. Alix Hayden, Hanna Lindblom, Merete Møller, Christine Holm Moseid, Nancy Harrington, Dai Sugimoto, Evert Verhagen, Kate K. Yung, Phathokuhle C. Zondi

Research outputs 2022 to 2026

Objective: To synthesise evidence related to the dissemination and implementation (D&I) of injury prevention interventions for female, woman and/or girl (female/woman/girl) athletes. Design Scoping review. Data sources MEDLINE, APA PsycInfo, Cochrane Databases for Systematic Review, Cochrane Central Register for Controlled Trials Registry, EMBASE, CINAHL, SPORTDiscus, ERIC, ProQuest Dissertation and Theses Global. Eligibility Primary research including ≥25% female/woman/girl athletes of any age or people working with them (eg, coaches), participating in sports competition and/or performance, were eligible. Papers reporting D&I outcomes (eg, coach knowledge, adoption and maintenance) related to an injury prevention intervention and/or a factor (eg, coach beliefs) associated with …

Cancer-Targeted Pro-Theranostic Bi-Metallic Organo-Coordination Nanoparticles, Hengbo Huang, Lei Fang, Janaka Wansapura, Julie L Prior, Brad Manion, Baogang Xu, Cody Hongsermeier, Nisha Gamadia, Nicole Blasi, Rui Tang, Christopher Egbulefu, Monica Shokeen, James D Quirk, Samuel Achilefu

2020-Current year OA Pubs

No abstract provided.

Novel Loci For Triglyceride/Hdl-C Ratio Longitudinal Change Among Subjects Without T2d, Lihua Wang, Siyu Wang, Jason A Anema, Vaha A Moghaddam, Yanli Lu, Shiow Lin, E Warwick Daw, Allison L Kuipers, Iva Miljkovic, Michael Brent, Gary J Patti, Bharat Thygarajan, Joseph M Zmuda, Michael A Province, Ping An

2020-Current year OA Pubs

Triglyceride (TG)/HDL-C ratio (THR) is a surrogate predictor of hyperinsulinemia. To identify novel genetic loci for THR change over time (ΔTHR), we conducted genome-wide association study (GWAS) and genome-wide linkage scan (GWLS) among nondiabetic Europeans from the Long Life Family Study (n = 1,384). Subjects with diabetes or on dyslipidemia medications were excluded. ΔTHR was derived using growth curve modeling and adjusted for age, sex, field centers, and principal components. GWAS used a linear mixed model accounting for familial relatedness. GWLS employed haplotype-based identity-by-descent estimation with 0.5 cM average spacing. Heritability of ΔTHR was moderate (46%). Our GWAS identified a …

The Dna Demethylase Tet1 Modifies The Impact Of Maternal Folic Acid Status On Embryonic Brain Development, Lehua Chen, Bernard K Van Der Veer, Qiuying Chen, Spyridon Champeris Tsaniras, Wannes Brangers, Harm H M Kwak, Rita Khoueiry, Yunping Lei, Robert Cabrera, Steven S Gross, Richard H Finnell, Kian Peng Koh

Faculty, Staff and Students Publications

Folic acid (FA) is well known to prevent neural tube defects (NTDs), but we do not know why many human NTD cases still remain refractory to FA supplementation. Here, we investigate how the DNA demethylase TET1 interacts with maternal FA status to regulate mouse embryonic brain development. We determined that cranial NTDs display higher penetrance in non-inbred than in inbred Tet1−/− embryos and are resistant to FA supplementation across strains. Maternal diets that are either too rich or deficient in FA are linked to an increased incidence of cranial deformities in wild type and Tet1+/− offspring and to …

Longitudinal Host Transcriptional Responses To Sars-Cov-2 Infection In Adults With Extremely High Viral Load, Vasanthi Avadhanula, Chad J Creighton, Laura Ferlic-Stark, Divya Nagaraj, Yiqun Zhang, Richard Sucgang, Erin G Nicholson, Anubama Rajan, Vipin Kumar Menon, Harshavardhan Doddapaneni, Donna Marie Muzny, Ginger A Metcalf, Sara Joan Javornik Cregeen, Kristi Louise Hoffman, Richard A Gibbs, Joseph F Petrosino, Pedro A Piedra

Faculty, Staff and Students Publications

Current understanding of viral dynamics of SARS-CoV-2 and host responses driving the pathogenic mechanisms in COVID-19 is rapidly evolving. Here, we conducted a longitudinal study to investigate gene expression patterns during acute SARS-CoV-2 illness. Cases included SARS-CoV-2 infected individuals with extremely high viral loads early in their illness, individuals having low SARS-CoV-2 viral loads early in their infection, and individuals testing negative for SARS-CoV-2. We could identify widespread transcriptional host responses to SARS-CoV-2 infection that were initially most strongly manifested in patients with extremely high initial viral loads, then attenuating within the patient over time as viral loads decreased. Genes …

Maternal Rest Improves Growth In Small-For-Gestational-Age Fetuses (<10th Percentile), Greggory R Devore, Bardo Polanco, Wesley Lee, Jeffrey Brian Fowlkes, Emma E Peek, Manesha Putra, John C Hobbins

Faculty, Staff and Students Publications

BACKGROUND: Optimal management of fetuses diagnosed as small for gestational age based on an estimated fetal weight ofHowever, maternal bed rest has not been recommended based on the results of a randomized clinical trial that showed that maternal rest does not improve fetal growth in small-for-gestational-age fetuses. This study was conducted to revisit this question.

OBJECTIVE: This study aimed to determine whether maternal bed rest was associated with an increase in the fetal biometric parameters that reflect growth after the diagnosis of a small-for-gestational-age fetus.

STUDY DESIGN: A retrospective study was conducted on fetuses who were diagnosed as small for …

Relationships Of Personality Traits With The Taxonomic Composition Of The Gut Microbiome Among Psychiatric Inpatients, William Orme, Sandra L Grimm, Divya S N Vella, J Christopher Fowler, B Christopher Frueh, Benjamin L Weinstein, Joseph Petrosino, Cristian Coarfa, Alok Madan

Faculty, Staff and Students Publications

Objective: Through the brain-gut-microbiome axis, myriad psychological functions that affect behavior share a dynamic, bidirectional relationship with the intestinal microbiome. Little is known about the relationship between personality-a stable construct that influences social- and health-related behaviors-and the bacterial ecosystem. The authors of this exploratory study examined the relationship between general and maladaptive personality traits and the composition of the gut microbiome.

Methods: In total, 105 psychiatric inpatients provided clinical data and fecal samples. Personality traits were measured with the five-factor model of personality, the Structured Clinical Interview for DSM-IV Axis II Personality Disorders, and the Personality Inventory for DSM-5; 16S …

Monoallelic Expression Can Govern Penetrance Of Inborn Errors Of Immunity, O'Jay Stewart, Conor Gruber, Haley E Randolph, Roosheel Patel, Meredith Ramba, Enrica Calzoni, Lei Haley Huang, Jay Levy, Sofija Buta, Angelica Lee, Christos Sazeides, Zoe Prue, David P Hoytema Van Konijnenburg, Ivan K Chinn, Luis A Pedroza, James R Lupski, Erica G Schmitt, Megan A Cooper, Anne Puel, Xiao Peng, Stéphanie Boisson-Dupuis, Jacinta Bustamante, Satoshi Okada, Marta Martin-Fernandez, Jordan S Orange, Jean-Laurent Casanova, Joshua D Milner, Dusan Bogunovic

Faculty, Staff and Students Publications

Inborn errors of immunity (IEIs) are genetic disorders that underlie susceptibility to infection, autoimmunity, autoinflammation, allergy and/or malignancy1. Incomplete penetrance is common among IEIs despite their monogenic basis2. Here we investigate the contribution of autosomal random monoallelic expression (aRMAE), a somatic commitment to the expression of one allele3,4, to phenotypic variability observed in families with IEIs. Using a clonal primary T cell system to assess aRMAE status of genes in healthy individuals, we find that 4.30% of IEI genes and 5.20% of all genes undergo aRMAE. Perturbing H3K27me3 and DNA methylation alters …

Mixed-Methods Evaluation And Behavior Change Interventions To Improve Hand Hygiene Resources And Practices Among Healthcare Workers In Polyclinics And Health Centers In Belize, 2023, Anh N Ly, Kelsey Mcdavid, Christina Craig, Rosalva Blanco, Vickie Romero, Melissa Diaz-Musa, Francis Morey, Russell Manzanero, Gerhaldine Morazan, Makenzie Towery, Anna Impellitteri, Matthew Lozier, Kristy O Murray

Faculty, Staff and Students Publications

Background: Hand hygiene (HH) is an effective public health measure to prevent the spread of infections in healthcare settings. A previous study in Belize showed gaps in HH practices in hospitals and large polyclinics; however, there are limited national data assessing access to and use of HH resources in smaller outpatient primary care facilities, especially in rural areas.

Methods: In February 2023, facility assessments were conducted at 26 health centers and polyclinics in Belize to assess the availability of HH resources. Of these, 12 pilot healthcare facilities (HCF) were selected for additional evaluation, which included observation of HH practices, hand …