Medicine and Health Sciences Commons^™

International Society For Cell & Gene Therapy Position Paper: Key Considerations To Support Evidence-Based Cell And Gene Therapies And Oppose Marketing Of Unproven Products, Laertis Ikonomou, Natividad Cuende, Miguel Forte, Bambi J Grilley, Aaron D Levine, Megan Munsie, John E J Rasko, Leigh Turner, Hamid R Bidkhori, Rachele Ciccocioppo, Felix Grignon, Alok Srivastava, Daniel J Weiss, Patricia Zettler, Bruce L Levine

Center for Medical Ethics and Health Policy Staff Publications

The field of regenerative medicine, including cellular immunotherapies, is on a remarkable growth trajectory. Dozens of cell-, tissue- and gene-based products have received marketing authorization worldwide while hundreds-to-thousands are either in preclinical development or under clinical investigation in phased clinical trials. However, the promise of regenerative therapies has also given rise to a global industry of direct-to-consumer offerings of prematurely commercialized cell and cell-based products with unknown safety and efficacy profiles. Since its inception, the International Society for Cell & Gene Therapy Committee on the Ethics of Cell and Gene Therapy has opposed the premature commercialization of unproven cell- and …

Childhood Exposure To Parental Threatening Behaviors And Anxiety In Emerging Adulthood: Indirect Effects Of Perceived Stress, Erika S Trent, Andres G Viana, Elizabeth M Raines, Haley E Conroy Busch, Karina Silva, Eric A Storch, Michael J Zvolensky

Center for Medical Ethics and Health Policy Staff Publications

Background: Although childhood exposure to parental threatening behaviors is associated with elevated anxiety in emerging adulthood, the underlying mechanisms remain unexplored. Perceived stress-a subjective experience comprised of feelings of helplessness (being unable to cope or exert control) and poor self-efficacy (confidence in one's ability to manage stressors)-is one candidate mechanism. The present investigation examined the underlying role of perceived stress in the association between childhood exposure to parental threatening behaviors and anxiety symptom severity in a sample of emerging adults.

Methods: Participants (N = 855; Mage = 18.75 years, SD = 1.05, range 18-24; 70.8% female) were recruited from a …

Common Rituals In Obsessive-Compulsive Disorder And Implications For Treatment: A Mixed-Methods Study, Caitlin M Pinciotti, Nyssa Z Bulkes, Brenda E Bailey, Eric A Storch, Jonathan S Abramowitz, Leonardo F Fontenelle, Bradley C Riemann

Center for Medical Ethics and Health Policy Staff Publications

Obsessive-compulsive disorder (OCD) is characterized by engagement in rituals that serve to obtain certainty and prevent feared outcomes. Exposure and response prevention is most effective when rituals are resisted, yet existing self-report measures of OCD limit identification of the full range of possible rituals, and little is known about how rituals might cluster together and predict worsened severity and poorer treatment outcomes. In a retrospective sample of 641 adult patients who received intensive OCD treatment, the present study used a mixed-methods approach to (a) identify and validate treatment provider-identified rituals using the Yale-Brown Obsessive-Compulsive Scale, (b) identify clustering patterns of …

Integrating Social Determinants Of Health Into Ethical Digital Simulations, Kristin Kostick-Quenet, Vasiliki Rahimzadeh, Sharmila Anandasabapathy, Meghan Hurley, Anika Sonig, Amy Mcguire

Center for Medical Ethics and Health Policy Staff Publications

No abstract provided.

Novel Lss Variants In Alopecia And Intellectual Disability Syndrome: New Case Report And Clinical Spectrum Of Lss-Related Rare Disease Traits, Hasnaa M Elbendary, Dana Marafi, Ahmed K Saad, Rasha Elhossini, Ruizhi Duan, Karima Rafat, Shalini N Jhangiani, Richard A Gibbs, Davut Pehlivan, Daniel G Calame, Jennifer E Posey, James R Lupski, Maha S Zaki

Faculty, Staff and Students Publications

Pathogenic biallelic variants in LSS are associated with three Mendelian rare disease traits including congenital cataract type 44, autosomal recessive hypotrichosis type 14, and alopecia-intellectual disability syndrome type 4 (APMR4). We performed trio research exome sequencing on a family with a four-year-old male with global developmental delay, epilepsy and striking alopecia, and identified novel compound heterozygous LSS splice site (c.14+2T>C) and missense (c.1357 G>A; p.V453L) variant alleles. Rare features associated with APMR4 such as cryptorchidism, micropenis, mild cortical brain atrophy and thin corpus callosum were detected. Previously unreported APMR4 findings including cerebellar involvement in the form of unsteady …

Early Initiation Of B-Vitamin Supplementation May Reduce Symptoms And Explain Intrafamilial Variability: Insights From Two Sibling Pairs From The Tango2 Natural History Study, Christina Y Miyake, Saad A Ehsan, Lilei Zhang, Samuel J Mackenzie, Mahshid S Azamian, Daryl A Scott, Andres Hernandez-Garcia, Seema R Lalani

Faculty, Staff and Students Publications

TANGO2-deficiency disorder (TDD) is an autosomal recessive condition arising from pathogenic biallelic variants in the TANGO2 gene. TDD is characterized by symptoms typically beginning in late infancy including delayed developmental milestones, cognitive impairment, dysarthria, expressive language deficits, and gait abnormalities. There is wide phenotypic variability where some are severely affected while others have mild symptoms. This variability has been documented even among sibling pairs who share the same genotype, but reasons for this variability have not been well understood. Emerging data suggest a potential link between B-complex or multivitamin supplementation and decreased metabolic crises in TDD. In this report, we …

A Qualitative Exploration Of Patient Perspectives On Psychosocial Burdens And Positive Factors In Adults With Osteogenesis Imperfecta, W Conor Rork, Alyssa G Hertz, Andrew D Wiese, Kristin M Kostick, Dianne Nguyen, Sophie C Schneider, Whitney S Shepherd, Hannah Cho, Members Of The Bbdc, Chaya N Murali, Brendan Lee, V Reid Sutton, Eric A Storch

Faculty, Staff and Students Publications

Osteogenesis imperfecta (OI) is a pleiotropic, heritable connective tissue disorder associated with a wide range of health implications, including frequent bone fracture. While progress has been made to understand the spectrum of these physical health implications, the impact of OI on psychosocial well-being, as well as protective factors that buffer against adverse psychosocial outcomes, remain understudied. This present study relies on a qualitative approach to assess patient perspectives on both protective and adverse psychosocial factors specific to OI in 15 adults with varying disease status. Semi-structured interviews were conducted, subsequently coded, and themes extracted. Themes concerning psychosocial burdens (i.e., negative …

Phenoscore Quantifies Phenotypic Variation For Rare Genetic Diseases By Combining Facial Analysis With Other Clinical Features Using A Machine-Learning Framework, Alexander J M Dingemans, Max Hinne, Kim M G Truijen, Lia Goltstein, Jeroen Van Reeuwijk, Nicole De Leeuw, Janneke Schuurs-Hoeijmakers, Rolph Pfundt, Illja J Diets, Joery Den Hoed, Elke De Boer, Jet Coenen-Van Der Spek, Sandra Jansen, Bregje W Van Bon, Noraly Jonis, Charlotte W Ockeloen, Anneke T Vulto-Van Silfhout, Tjitske Kleefstra, David A Koolen, Philippe M Campeau, Elizabeth E Palmer, Hilde Van Esch, Gholson J Lyon, Fowzan S Alkuraya, Anita Rauch, Ronit Marom, Diana Baralle, Pleuntje J Van Der Sluijs, Gijs W E Santen, R Frank Kooy, Marcel A J Van Gerven, Lisenka E L M Vissers, Bert B A De Vries

Faculty, Staff and Students Publications

Several molecular and phenotypic algorithms exist that establish genotype-phenotype correlations, including facial recognition tools. However, no unified framework that investigates both facial data and other phenotypic data directly from individuals exists. We developed PhenoScore: an open-source, artificial intelligence-based phenomics framework, combining facial recognition technology with Human Phenotype Ontology data analysis to quantify phenotypic similarity. Here we show PhenoScore's ability to recognize distinct phenotypic entities by establishing recognizable phenotypes for 37 of 40 investigated syndromes against clinical features observed in individuals with other neurodevelopmental disorders and show it is an improvement on existing approaches. PhenoScore provides predictions for individuals with variants …

The Complete Sequence Of A Human Y Chromosome, Arang Rhie, Sergey Nurk, Monika Cechova, Savannah J Hoyt, Dylan J Taylor, Nicolas Altemose, Paul W Hook, Sergey Koren, Mikko Rautiainen, Ivan A Alexandrov, Jamie Allen, Mobin Asri, Andrey V Bzikadze, Nae-Chyun Chen, Chen-Shan Chin, Mark Diekhans, Paul Flicek, Giulio Formenti, Arkarachai Fungtammasan, Carlos Garcia Giron, Erik Garrison, Ariel Gershman, Jennifer L Gerton, Patrick G S Grady, Andrea Guarracino, Leanne Haggerty, Reza Halabian, Nancy F Hansen, Robert Harris, Gabrielle A Hartley, William T Harvey, Marina Haukness, Jakob Heinz, Thibaut Hourlier, Robert M Hubley, Sarah E Hunt, Stephen Hwang, Miten Jain, Rupesh K Kesharwani, Alexandra P Lewis, Heng Li, Glennis A Logsdon, Julian K Lucas, Wojciech Makalowski, Christopher Markovic, Fergal J Martin, Ann M Mc Cartney, Rajiv C Mccoy, Jennifer Mcdaniel, Brandy M Mcnulty, Paul Medvedev, Alla Mikheenko, Katherine M Munson, Terence D Murphy, Hugh E Olsen, Nathan D Olson, Luis F Paulin, David Porubsky, Tamara Potapova, Fedor Ryabov, Steven L Salzberg, Michael E G Sauria, Fritz J Sedlazeck, Kishwar Shafin, Valery A Shepelev, Alaina Shumate, Jessica M Storer, Likhitha Surapaneni, Angela M Taravella Oill, Françoise Thibaud-Nissen, Winston Timp, Marta Tomaszkiewicz, Mitchell R Vollger, Brian P Walenz, Allison C Watwood, Matthias H Weissensteiner, Aaron M Wenger, Melissa A Wilson, Samantha Zarate, Yiming Zhu, Justin M Zook, Evan E Eichler, Rachel J O'Neill, Michael C Schatz, Karen H Miga, Kateryna D Makova, Adam M Phillippy

Faculty, Staff and Students Publications

The human Y chromosome has been notoriously difficult to sequence and assemble because of its complex repeat structure including long palindromes, tandem repeats, and segmental duplications1–3. As a result, more than half of the Y chromosome is missing from the GRCh38 reference sequence and it remains the last human chromosome to be finished4,5. Here, the Telomere-to-Telomere (T2T) consortium presents the complete 62,460,029 base pair sequence of a human Y chromosome from the HG002 genome (T2T-Y) that corrects multiple errors in GRCh38-Y and adds over 30 million base pairs of sequence to the …

Children’S Oncology Group’S 2023 Blueprint For Research: Epidemiology, Philip J Lupo, Erin L Marcotte, Michael E Scheurer, Jenny N Poynter, Logan G Spector

Faculty, Staff and Students Publications

The Children's Oncology Group (COG) Epidemiology Committee has a primary focus on better understanding the etiologies of childhood cancers. Over the past 10 years, the committee has leveraged the Childhood Cancer Research Network, and now more recently Project:EveryChild (PEC), to conduct epidemiologic assessments of various childhood cancers, including osteosarcoma, neuroblastoma, germ cell tumors, Ewing sarcoma, rhabdomyosarcoma, and Langerhans cell histiocytosis. More recent studies have utilized questionnaire data collected as part of PEC to focus on specific characteristics and/or features, including the presence of congenital disorders and the availability of stored cord blood. Members of the COG Epidemiology Committee have also …

Equine Bronchial Epithelial Cells Are Susceptible To Cell Entry With A Sars-Cov-2 Pseudovirus But Reveal Low Replication Efficiency, Rebecca M Legere, Angelica R Allegro, Yvonne Affram, Bibiana Petri Da Silveira, Jennifer L Fridley, Kelsey M Wells, Numan Oezguen, Robert C Burghardt, Gus A Wright, Jeroen Pollet, Angela I Bordin, Paul De Figueiredo, Julian L Leibowitz, Noah D Cohen

Faculty, Staff and Students Publications

Objective: To examine the susceptibility of cultured primary equine bronchial epithelial cells (EBECs) to a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus relative to human bronchial epithelial cells (HBECs).

Sample: Primary EBEC cultures established from healthy adult horses and commercially sourced human bronchial epithelial cells (HBECs) were used as a positive control.

Methods: Angiotensin-converting enzyme 2 (ACE2) expression by EBECs was demonstrated using immunofluorescence, western immunoblot, and flow cytometry. EBECs were transduced with a lentivirus pseudotyped with the SARS-CoV-2 spike protein that binds to ACE2 and expresses the enhanced green fluorescent protein (eGFP) as a reporter. Cells were transduced …

Fetal Echocardiographic Z Score Pilot Project: Study Design And Impact Of Gestational Age And Variable Type On Reproducibility Of Measurements Within And Across Investigators, Anita J Moon-Grady, Hyejung Lee, Leo Lopez, Oluwatosin Fatusin, Lindsay R Freud, Whitnee Hogan, Anita Krishnan, Carol Mcfarland, L Luann Minich, Shaine A Morris, Nelangi Pinto, Angela P Presson, Theresa A Tacy, Mary T Donofrio

Faculty, Staff and Students Publications

Background: Fetal echocardiography is widely available, but normative data are not robust. In this pilot study, the authors evaluated (1) the feasibility of prespecified measurements in a normal fetal echocardiogram to inform study design and (2) measurement variability to assign thresholds of clinical significance and guide analyses in larger fetal echocardiographic Z score initiatives.

Methods: Images from predefined gestational age groups (16-20, >20-24, >24-28, and >28-32 weeks) were retrospectively analyzed. Fetal echocardiography expert raters attended online group training and then independently analyzed 73 fetal studies (18 per age group) in a fully crossed design of 53 variables; each observer repeated …

Genomic Medicine To Reduce Tobacco And Related Disorders: Translation To Precision Prevention And Treatment, Li-Shiun Chen, Timothy B Baker, Alex Ramsey, Christopher I Amos, Laura J Bierut

Faculty, Staff and Students Publications

Genomic medicine can enhance prevention and treatment. First, we propose that advances in genomics have the potential to enhance assessment of disease risk, improve prognostic predictions, and guide treatment development and application. Clinical implementation of polygenic risk scores (PRSs) has emerged as an area of active research. The pathway from genomic discovery to implementation is an iterative process. Second, we provide examples on how genomic medicine has the potential to solve problems in prevention and treatment using two examples: Lung cancer screening and evidence-based tobacco treatment are both under-utilized and great opportunities for genomic interventions. Third, we discuss the translational …

From Pre-Copd To Copd: A Simple, Low Cost And Easy To Implement (Slim) Risk Calculator, Miguel J Divo, Congjian Liu, Francesca Polverino, Peter J Castaldi, Bartolome R Celli, Yohannes Tesfaigzi

Faculty, Staff and Students Publications

BACKGROUND: The lifetime risk of developing clinical COPD among smokers ranges from 13% to 22%. Identifying at-risk individuals who will develop overt disease in a reasonable timeframe may allow for early intervention. We hypothesised that readily available clinical and physiological variables could help identify ever-smokers at higher risk of developing chronic airflow limitation (CAL).

METHODS: Among 2273 Lovelace Smokers' Cohort (LSC) participants, we included 677 (mean age 54 years) with normal spirometry at baseline and a minimum of three spirometries, each 1 year apart. Repeated spirometric measurements were used to determine incident CAL. Using logistic regression, demographics, anthropometrics, smoking history, …

Maternal Metabolism Influences Neural Tube Closure, Rachel A Keuls, Richard H Finnell, Ronald J Parchem

Faculty, Staff and Students Publications

Changes in maternal nutrient availability due to diet or disease significantly increase the risk of neural tube defects (NTDs). Because the incidence of metabolic disease continues to rise, it is urgent that we better understand how altered maternal nutrient levels can influence embryonic neural tube development. Furthermore, primary neurulation occurs before placental function during a period of histiotrophic nutrient exchange. In this review we detail how maternal metabolites are transported by the yolk sac to the developing embryo. We discuss recent advances in understanding how altered maternal levels of essential nutrients disrupt development of the neuroepithelium, and identify points of …

Myths And Methodologies: Cardiopulmonary Exercise Testing For Surgical Risk Stratification In Patients With An Abdominal Aortic Aneurysm; Balancing Risk Over Benefit, Damian M Bailey, Richard G Davies, George A Rose, Michael H Lewis, Ahmed Abd Aldayem, Chistopher P Twine, Wael Awad, Matti Jubouri, Idhrees Mohammed, Carlos A Mestres, Edward P Chen, Joseph S Coselli, Ian M Williams, Mohamad Bashir, International Academic Surgical Consortium (Thalamus)

Faculty, Staff and Students Publications

The extent to which patients with an abdominal aortic aneurysm (AAA) should exercise remains unclear, given theoretical concerns over the perceived risk of blood pressure-induced rupture, which is often catastrophic. This is especially pertinent during cardiopulmonary exercise testing, when patients are required to perform incremental exercise to symptom-limited exhaustion for the determination of cardiorespiratory fitness. This multimodal metric is being used increasingly as a complementary diagnostic tool to inform risk stratification and subsequent management of patients undergoing AAA surgery. In this review, we bring together a multidisciplinary group of physiologists, exercise scientists, anaesthetists, radiologists and surgeons to challenge the enduring …

Approach To Non-Type 2 Asthma, Muhammad Adrish, Praveen Akuthota

Faculty, Staff and Students Publications

No abstract provided.

Information-Seeking Preferences In Diverse Patients Receiving A Genetic Testing Result In The Clinical Sequencing Evidence-Generating Research (Cser) Study, Anne Slavotinek, Hannah Prasad, Simon Outram, Sarah Scollon, Shannon Rego, Tiffany Yip, Hannah Hoban, Kate M Foreman, Whitley Kelley, Candice Finnila, Jonathan Berg, Priyanka Murali, Katherine E Bonini, Lisa J Martin, Adam Hott

Faculty, Staff and Students Publications

Purpose: Accurate and understandable information after genetic testing is critical for patients, family members, and professionals alike.

Methods: As part of a cross-site study from the Clinical Sequencing Evidence-Generating Research consortium, we investigated the information-seeking practices among patients and family members at 5 to 7 months after genetic testing results disclosure, assessing the perceived utility of a variety of information sources, such as family and friends, health care providers, support groups, and the internet.

Results: We found that individuals placed a high value on information obtained from genetics professionals and health care workers, independent of genetic testing result case classifications …

Loss Of The Maternal Effect Gene Nlrp2 Alters The Transcriptome Of Ovulated Mouse Oocytes And Impacts Expression Of Histone Demethylase Kdm1b, Zahra Anvar, Imen Chakchouk, Momal Sharif, Sangeetha Mahadevan, Eleni Theodora Nasiotis, Li Su, Zhandong Liu, Ying-Wooi Wan, Ignatia B Van Den Veyver

Faculty, Staff and Students Publications

The subcortical maternal complex (SCMC) is a multiprotein complex in oocytes and preimplantation embryos that is encoded by maternal effect genes. The SCMC is essential for zygote-to-embryo transition, early embryogenesis, and critical zygotic cellular processes, including spindle positioning and symmetric division. Maternal deletion of Nlrp2, which encodes an SCMC protein, results in increased early embryonic loss and abnormal DNA methylation in embryos. We performed RNA sequencing on pools of meiosis II (MII) oocytes from wild-type and Nlrp2-null female mice that were isolated from cumulus-oocyte complexes (COCs) after ovarian stimulation. Using a mouse reference genome-based analysis, we found 231 …

Polygenic Genetic Variation Affecting Antibody Formation Underlies Hypertensive Renal Injury In The Stroke-Prone Spontaneously Hypertensive Rat, Isha S Dhande, Yaming Zhu, Aniket S Joshi, M John Hicks, Michael C Braun, Peter A Doris

Faculty, Staff and Students Publications

During development of the spontaneously hypertensive rat (SHR), several distinct but closely related lines were generated. Most lines are resistant to hypertensive renal disease. However, the SHR-A3 line (stroke-prone SHR) experiences end-organ injury (EOI) and provides a model of injury susceptibility that can be used to uncover genetic causation. In the present study, we generated a congenic line in which three distinct disease loci in SHR-A3 are concurrently replaced with homologous loci from an injury-resistant SHR line (SHR-B2). Verification that all three loci were homozygously replaced in this triple congenic line [SHR-A3(Trip B2)] while the genetic background of SHR-A3 was …

Unexpected Drug-Induced Liver Injury Associated With Menofit: A Synbiotic Menopause Supplement, Apaar Dadlani, Azubuogu Anudu, E Celia Marginean

Faculty, Staff and Students Publications

MenoFit is a widely available over-the-counter synbiotic supplement, which is marketed for use in relieving menopausal symptoms. So far, there is no published data on liver injury because of its use. We present the first reported case of MenoFit-induced liver injury in a patient who presented with 1 week of jaundice and abnormal liver biochemical tests in the absence of other risk factors and negative comprehensive workup for known etiologies of liver disease.

Automated Prediction Of Cardiorespiratory Deterioration In Patients With Single-Ventricle Parallel Circulation: A Multicenter Validation Study, Craig G Rusin, Sebastian I Acosta, Kennith M Brady, Eric Vu, Carly Scahill, Brian Fonseca, Cindy Barrett, Janet Simsic, Andrew R Yates, Brenna Klepczynski, William J Gaynor, Daniel J Penny

Faculty, Staff and Students Publications

OBJECTIVES: Patients with single-ventricle physiology have a significant risk of cardiorespiratory deterioration between their first- and second-stage palliation surgeries. Detection of deterioration episodes may allow for early intervention and improved outcomes.

METHODS: A prospective study was executed at Nationwide Children's Hospital, Children's Hospital of Philadelphia, and Children's Hospital Colorado to collect physiologic data of subjects with single ventricle physiology during all hospitalizations between neonatal palliation and II surgeries using the Sickbay software platform (Medical Informatics Corp). Timing of cardiorespiratory deterioration events was captured via chart review. The predictive algorithm previously developed and validated at Texas Children's Hospital was applied to …

Risk And Accuracy Of Outpatient-Identified Hypoxaemia For Death Among Suspected Child Pneumonia Cases In Rural Bangladesh: A Multifacility Prospective Cohort Study, Eric D Mccollum, Salahuddin Ahmed, Arunangshu D Roy, Asmd Ashraful Islam, Holly B Schuh, Carina King, Shubhada Hooli, Mohammad Abdul Quaiyum, Amy Sarah Ginsburg, William Checkley, Abdullah H Baqui, Tim Colbourn

Faculty, Staff and Students Publications

BACKGROUND: Hypoxaemic pneumonia mortality risk in low-income and middle-income countries is high in children who have been hospitalised, but unknown among outpatient children. We sought to establish the outpatient burden, mortality risk, and prognostic accuracy of death from hypoxaemia in children with suspected pneumonia in Bangladesh.

METHODS: We conducted a prospective community-based cohort study encompassing three upazila (subdistrict) health complex catchment areas in Sylhet, Bangladesh. Children aged 3-35 months participating in a community surveillance programme and presenting to one of three upazila health complex Integrated Management of Childhood Illness (IMCI) outpatient clinics with an acute illness and signs of difficult …

Exome Sequencing Implicates Dgkz , Esrra , And Gxylt1 For Modulating Granuloma Formation In Crohn Disease, R Alan Harris, Allyson H Bush, Todd N Eagar, Justin Qian, Michael P Greenwood, Antone R Opekun, Robert Baldassano, Stephen L Guthery, Joshua D Noe, Anthony Otley, Joel R Rosh, Subra Kugathasan, Richard Kellermayer

Faculty, Staff and Students Publications

Non-caseating granulomas may indicate a more aggressive phenotype of Crohn disease (CD). Genetic associations of granulomatous CD (GCD) may help elucidate disease pathogenesis. Whole-exome sequencing was performed on peripheral blood-derived DNA from 17 pediatric patients with GCD and 19 with non-GCD (NGCD), and from an independent validation cohort of 44 GCD and 19 NGCD cases. PLINK (a tool set for whole-genome association and population-based linkage analyses) analysis was used to identify single nucleotide polymorphisms (SNPs) differentiating between groups, and subgroup allele frequencies were also compared to a public genomic database (gnomAD). The Combined Annotation Dependent Depletion scoring tool was used …

Age Differences In Core Symptoms And Symptom Relationships In Patients With Irritable Bowel Syndrome: A Network Analysis, Pei-Lin Yang, Kendra J Kamp, Robert L Burr, Hsin-Yi Jean Tang, Adrian Dobra, Robert J Shulman, Margaret M Heitkemper

Faculty, Staff and Students Publications

INTRODUCTION: Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction, characterized by symptoms of abdominal pain and changes in bowel habits. It often co-occurs with extraintestinal somatic and psychological symptoms. However, the nature of the interrelationships among these symptoms is unclear. Although previous studies have noted age differences in IBS prevalence and specific symptom severity, it remains unknown whether specific symptoms and symptom relationships may differ by age.

METHODS: Symptom data were collected in 355 adults with IBS (mean age 41.4 years, 86.2% female). Network analysis was used to examine the interrelationships among 28 symptoms and to identify …

Loss Of Growth Differentiation Factor 15 Exacerbates Lung Injury In Neonatal Mice, Faeq Al-Mudares, Manuel Cantu Gutierrez, Abiud Cantu, Weiwu Jiang, Lihua Wang, Xiaoyu Dong, Bhagavatula Moorthy, Eniko Sajti, Krithika Lingappan

Faculty, Staff and Students Publications

Growth differentiation factor 15 (GDF15) is a divergent member of the transforming growth factor-β (TGF-β) superfamily, and its expression increases under various stress conditions, including inflammation, hyperoxia, and senescence. GDF15 expression is increased in neonatal murine bronchopulmonary dysplasia (BPD) models, and GDF15 loss exacerbates oxidative stress and decreases cellular viability in vitro. Our overall hypothesis is that the loss of GDF15 will exacerbate hyperoxic lung injury in the neonatal lung in vivo. We exposed neonatal

A Recorder/Time Coach Decreases Time Errors During Neonatal Resuscitation: A Randomized, Simulation-Based Clinical Trial, Nicole K Neveln, Mona Khattab, Joseph L Hagan, Regine M Fortunov, Nathan C Sundgren

Faculty, Staff and Students Publications

AIM: To evaluate the effects of a hands-off recorder/time coach versus an additional hands-on healthcare provider on Neonatal Resuscitation Program (NRP) algorithm compliance and team member workload in neonatal resuscitations.

METHODS: Two interventions were studied using a 2 × 2 factorial design: an additional hands-on team member and the presence of a designated, hands-off recorder/time coach. The recorder/time coach documented interventions and delivered pre-specified prompts at defined points during the resuscitation. The primary outcome was cumulative time error. Secondary outcomes were time to first dose of IV epinephrine, overall team performance as assessed by the Neonatal Resuscitation Performance Evaluation (NRPE) …

Distribution Of Hand Function By Age In Individuals With Rett Syndrome, Jeffrey L Neul, Tim A Benke, Eric D Marsh, Jane B Lane, David N Lieberman, Steven A Skinner, Daniel G Glaze, Bernhard Suter, Peter T Heydemann, Arthur A Beisang, Shannon M Standridge, Robin C C Ryther, Richard H Haas, Lloyd J Edwards, Amitha Ananth, Alan K Percy

Faculty, Staff and Students Publications

OBJECTIVE: To determine the longitudinal distribution of hand function skills in individuals with classic Rett Syndrome (RTT), an X-linked dominant neurodevelopmental disorder, and correlate with

METHOD: We conducted a longitudinal study of 946 girls and young women with typical RTT seen between 2006 and 2021 in the US Natural History Study (NHS) featuring a structured clinical evaluation to assess the level of hand function skills. The specific focus in this study was to assess longitudinal variation of hand skills from age 2 through age 18 years in relation to specific

RESULTS: Following the initial regression period, hand function continues to …

New Records Of Ornithodoros Turicata (Ixodida: Argasidae) In Rural And Urban Sites In The Mexican States Of Aguascalientes And Zacatecas Indicate The Potential For Tick-Borne Relapsing Fever, Edwin Vázquez-Guerrero, José Luis González-Quiroz, María Lilia Domínguez-López, Alexander R Kneubehl, Aparna Krishnavajhala, Michael W Curtis, Alejandro Ponce-Mendoza, Paulina Estrada-De Los Santos, Job E Lopez, J Antonio Ibarra

Faculty, Staff and Students Publications

Soft ticks from the Ornithodoros genus are vectors of relapsing fever (RF) spirochetes around the world. In Mexico, they were originally described in the 19th century. However, few recent surveillance studies have been conducted in Mexico, and regions where RF spirochetes circulate remain vague. Here, the presence of soft ticks in populated areas was assessed in two sites from the Mexican states of Aguascalientes and Zacatecas. Argasidae ticks were collected, identified by morphology and mitochondrial 16S rDNA gene sequencing, and tested for RF borreliae. The specimens in both sites were identified as Ornithodoros turicata but no RF spirochetes were detected. …

Assessing The Severity Of Cervical Dystonia: Ask The Doctor Or Ask The Patient?, Adam C Cotton, Laura Scorr, William Mcdonald, Cynthia Comella, Joel S Perlmutter, Christopher G Goetz, Joseph Jankovic, Laura Marsh, Stewart Factor, H A Jinnah

Faculty, Staff and Students Publications

BACKGROUND: Assessing disease severity can be performed using either clinician-rated scales (CRS) or patient-rated outcome (PRO) tools. These two measures frequently demonstrate poor correlations.

OBJECTIVES: To determine if the correlation between a CRS and PRO for motor features of cervical dystonia (CD) improves by accounting for non-motor features.

METHODS: Subjects with CD (N = 209) were evaluated using a CRS (Toronto Western Spasmodic Torticollis Rating Scale, TWSTRS) and a PRO (Cervical Dystonia Impact Profile, CDIP-58).

RESULTS: Linear regression revealed a weak correlation between the two measures, even when considering only the motor subscales of each. The strength of this relationship …