Medicine and Health Sciences Commons^™

Trajectory Of C-Reactive Protein And Incident Heart Failure In Black Adults: The Jackson Heart Study, Arsalan Hamid, Wondwosen K Yimer, Adebamike A Oshunbade, Muhammad Shahzeb Khan, Daisuke Kamimura, Rodney K Kipchumba, Ambarish Pandey, Donald Clark, Robert J Mentz, Ervin R Fox, Jarett D Berry, R Brandon Stacey, Amil Shah, Adolfo Correa, Salim S Virani, Javed Butler, Michael E Hall

Faculty, Staff and Students Publications

Background: Increased hsCRP (high-sensitivity C-reactive protein), a marker of inflammation, is associated with incident cardiovascular events. We aim to determine whether the baseline or trajectory of hsCRP levels over time predicts incident heart failure (HF) hospitalization.

Methods: JHS (Jackson Heart Study) participants' (n=3920 Black adults) hsCRP levels were measured over 3 visits (from 2000 to 2013). We assessed the association of hsCRP at baseline (visit 1) with incident HF hospitalization using Cox proportional hazards models. Furthermore, we assessed the association of the trajectory of hsCRP over repeated measurements (visits 1-3) with incident HF using joint models. Hazard ratios are reflective …

Adeno-Associated Virus Vector Delivery To The Brain: Technology Advancements And Clinical Applications, Dezhuang Ye, Chinwendu Chukwu, Yaoheng Yang, Zhongtao Hu, Hong Chen

2020-Current year OA Pubs

Adeno-associated virus (AAV) vectors have emerged as a promising tool in the development of gene therapies for various neurological diseases, including Alzheimer's disease and Parkinson's disease. However, the blood-brain barrier (BBB) poses a significant challenge to successfully delivering AAV vectors to the brain. Strategies that can overcome the BBB to improve the AAV delivery efficiency to the brain are essential to successful brain-targeted gene therapy. This review provides an overview of existing strategies employed for AAV delivery to the brain, including direct intraparenchymal injection, intra-cerebral spinal fluid injection, intranasal delivery, and intravenous injection of BBB-permeable AAVs. Focused ultrasound has emerged …

Crohn's Disease-Associated Granulomatous Pancreatitis With Exocrine Pancreatic Insufficiency, Anthony A Xu, Sara Vincent, Samuel Ma, Vanessa Catania, Neda Zarrin-Khameh

Faculty, Staff and Students Publications

Extraintestinal manifestations of inflammatory bowel disease occur commonly and can lead to considerable morbidity. Pancreatic manifestations of inflammatory bowel disease have been reported to be more common in Crohn's disease (CD) than ulcerative colitis. We report a case of granulomatous inflammation in the body of the pancreas with exocrine pancreatic insufficiency, which prompted a diagnosis switch from ulcerative colitis to CD. This is of interest to readers to remind them that pancreatic manifestations can occur and are more common in CD.

Derivation And Validation Of An Optimal Neutrophil Gelatinase-Associated Lipocalin Cutoff To Predict Stage 2/3 Acute Kidney Injury (Aki) In Critically Ill Children, Stuart L Goldstein, Ayse Akcan-Arikan, Natasha Afonso, David J Askenazi, Abby M Basalely, Rajit K Basu, Hostensia Beng, Julie C Fitzgerald, Katja Gist, Sarah Kizilbash, David Kwiatkowski, Christopher W Mastropietro, Shina Menon, Megan Soohoo, Avram Z Traum, Christopher A Bird

Faculty, Staff and Students Publications

INTRODUCTION: Acute kidney injury (AKI) defined by changes in serum creatinine (SCr), or oliguria is associated with increased morbidity and mortality in children who are critically ill. We derived and validated a clinical cutoff value for urine neutrophil gelatinase-associated lipocalin (NGAL), in a prospective multicenter study of children who were critically ill. We report the clinical performance of urine NGAL (uNGAL) to aid in pediatric AKI risk assessment.

METHODS: Eligible subjects were aged ≥ 90 days to < 22 years, admitted to an intensive care unit (ICU), and had 1 or more of the following: mechanical ventilation, vasoactive medication administration, solid organ or bone marrow transplantation, or hypotension within 24-hours of admission. uNGAL was assessed within 24-hours of admission. The primary outcome was SCr-based stage 2/3 AKI presence at 48- to 72-hours.

RESULTS: Twenty-five (12.3%) derivation study patients had stage 2/3 AKI at 48- to 72-hours. uNGAL concentration of 125 ng/ml was the optimal cutoff. …

Parkinson’S Disease Variant Detection And Disclosure: Pd Generation, A North American Study, Lola Cook, Jennifer Verbrugge, Tae-Hwi Schwantes-An, Jeanine Schulze, Tatiana Foroud, Anne Hall, Karen S Marder, Ignacio F Mata, Niccolò E Mencacci, Martha A Nance, Michael A Schwarzschild, Tanya Simuni, Susan Bressman, Anne-Marie Wills, Hubert H Fernandez, Irene Litvan, Kelly E Lyons, Holly A Shill, Carlos Singer, Thomas F Tropea, Nora Vanegas Arroyave, Janfreisy Carbonell, Rossy Cruz Vicioso, Linn Katus, Joseph F Quinn, Priscila D Hodges, Yan Meng, Samuel P Strom, Cornelis Blauwendraat, Katja Lohmann, Cynthia Casaceli, Shilpa C Rao, Kamalini Ghosh Galvelis, Anna Naito, James C Beck, Roy N Alcalay

Faculty, Staff and Students Publications

Variants in seven genes (LRRK2, GBA1, PRKN, SNCA, PINK1, PARK7 and VPS35) have been formally adjudicated as causal contributors to Parkinson's disease; however, individuals with Parkinson's disease are often unaware of their genetic status since clinical testing is infrequently offered. As a result, genetic information is not incorporated into clinical care, and variant-targeted precision medicine trials struggle to enrol people with Parkinson's disease. Understanding the yield of genetic testing using an established gene panel in a large, geographically diverse North American population would help patients, clinicians, clinical researchers, laboratories and insurers better understand the importance of genetics in approaching Parkinson's …

Pediatric Mental Health Emergency Department Visits From 2017 To 2022: A Multicenter Study, Jennifer A Hoffmann, Camille P Carter, Cody S Olsen, David Ashby, Kamali L Bouvay, Susan J Duffy, James M Chamberlain, Sofia S Chaudhary, Nicolaus W Glomb, Jacqueline Grupp-Phelan, Maya Haasz, Erin P O'Donnell, Mohsen Saidinejad, Bashar S Shihabuddin, Leah Tzimenatos, Neil G Uspal, Joseph J Zorc, Lawrence J Cook, Elizabeth R Alpern

Faculty, Staff and Students Publications

Background: The COVID-19 pandemic adversely affected children's mental health (MH) and changed patterns of MH emergency department (ED) utilization. Our objective was to assess how pediatric MH ED visits during the COVID-19 pandemic differed from expected prepandemic trends.

Methods: We retrospectively studied MH ED visits by children 5 to < 18 years old at nine U.S. hospitals participating in the Pediatric Emergency Care Applied Research Network Registry from 2017 to 2022. We described visit length by time period: prepandemic (January 2017-February 2020), early pandemic (March 2020-December 2020), midpandemic (2021), and late pandemic (2022). We estimated expected visit rates from prepandemic data using multivariable Poisson regression models. We calculated rate ratios (RRs) of observed to expected visits per 30 days during each pandemic time period, overall and by sociodemographic and clinical characteristics.

Results: We identified 175,979 pediatric MH ED visits. Visit length exceeded 12 h for 7.3% prepandemic, 8.4% early pandemic, 15.0% midpandemic, and 19.2% late pandemic visits. During the early pandemic, observed visits per 30 days decreased relative to expected rates (RR 0.80, 95% confidence interval [CI] 0.78-0.84), were similar to expected …

A Content Analysis Of Self-Report Child Anxiety Measures, Minjee Kook, Jane W Clinger, Eric Lee, Sophie C Schneider, Eric A Storch, Andrew G Guzick

Faculty, Staff and Students Publications

A clear understanding of the item content of psychological assessments is critical but often overlooked. This study describes the content overlap of seven commonly used and psychometrically validated measures of anxiety among children and adolescents. Symptom codes were created for all items across measures and items were sorted by these codes, which all fell into specific symptom categories. We conducted two analyses of all items: a "bottom-up" content categorization approach, which used symptom categories that were developed during this study, and a "top-down" DSM-5 categorization which mapped items onto symptoms of anxiety disorders in the DSM-5. Findings reveal a weak …

Predicting Post-Surgical Functional Status In High-Grade Glioma With Resting State Fmri And Machine Learning, Patrick H Luckett, Michael O Olufawo, Ki Yun Park, Bidhan Lamichhane, Donna Dierker, Gabriel Trevino Verastegui, John J Lee, Peter Yang, Albert Kim, Omar H Butt, Milan G Chheda, Abraham Z Snyder, Joshua S Shimony, Eric C Leuthardt

2020-Current year OA Pubs

PURPOSE: High-grade glioma (HGG) is the most common and deadly malignant glioma of the central nervous system. The current standard of care includes surgical resection of the tumor, which can lead to functional and cognitive deficits. The aim of this study is to develop models capable of predicting functional outcomes in HGG patients before surgery, facilitating improved disease management and informed patient care.

METHODS: Adult HGG patients (N = 102) from the neurosurgery brain tumor service at Washington University Medical Center were retrospectively recruited. All patients completed structural neuroimaging and resting state functional MRI prior to surgery. Demographics, measures of …

Accumulation Of Alkyl-Lysophosphatidylcholines In Niemann-Pick Disease Type C1, Sonali Mishra, Pamela Kell, David Scherrer, Dennis J Dietzen, Charles H Vite, Elizabeth Berry-Kravis, Cristin Davidson, Stephanie M Cologna, Forbes D Porter, Daniel S Ory, Xuntian Jiang

2020-Current year OA Pubs

Lysosomal function is impaired in Niemann-Pick disease type C1 (NPC1), a rare and inherited neurodegenerative disorder, resulting in late endosomal/lysosomal accumulation of unesterified cholesterol. The precise pathogenic mechanism of NPC1 remains incompletely understood. In this study, we employed metabolomics to uncover secondary accumulated substances in NPC1. Our findings unveiled a substantial elevation in the levels of three alkyl-lysophosphatidylcholine [alkyl-LPC, also known as lyso-platelet activating factor (PAF)] species in NPC1 compared to controls across various tissues, including brain tissue from individuals with NPC1, liver, spleen, cerebrum, cerebellum, and brain stem from NPC1 mice, as well as in both brain and liver …

Potential Clinical Applications Of Advanced Genomic Analysis In Cerebral Palsy, Sara A Lewis, Andrew Ruttenberg, Tuğçe Iyiyol, Nahyun Kong, Sheng Chih Jin, Michael C Kruer

2020-Current year OA Pubs

Cerebral palsy (CP) has historically been attributed to acquired insults, but emerging research suggests that genetic variations are also important causes of CP. While microarray and whole-exome sequencing based studies have been the primary methods for establishing new CP-gene relationships and providing a genetic etiology for individual patients, the cause of their condition remains unknown for many patients with CP. Recent advancements in genomic technologies offer additional opportunities to uncover variations in human genomes, transcriptomes, and epigenomes that have previously escaped detection. In this review, we outline the use of these state-of-the-art technologies to address the molecular diagnostic challenges experienced …

Activated Sputum Eosinophils Associated With Exacerbations In Children On Mepolizumab, Gabriella E Wilson, Michelle Gill, Et Al.

2020-Current year OA Pubs

BACKGROUND: MUPPITS-2 was a randomized, placebo-controlled clinical trial that demonstrated mepolizumab (anti-IL-5) reduced exacerbations and blood and airway eosinophils in urban children with severe eosinophilic asthma. Despite this reduction in eosinophilia, exacerbation risk persisted in certain patients treated with mepolizumab. This raises the possibility that subpopulations of airway eosinophils exist that contribute to breakthrough exacerbations.

OBJECTIVE: We aimed to determine the effect of mepolizumab on airway eosinophils in childhood asthma.

METHODS: Sputum samples were obtained from 53 MUPPITS-2 participants. Airway eosinophils were characterized using mass cytometry and grouped into subpopulations using unsupervised clustering analyses of 38 surface and intracellular markers. …

Medicare Utilization And Cost Trends For Car T Cell Therapies Across Settings Of Care In The Treatment Of Diffuse Large B-Cell Lymphoma, James Wu, Armin Ghobadi, Richard Maziarz, Krish Patel, Hil Hsu, Zihao Liu, Caitlin Sheetz, Peter Kardel, Christine Fu

2020-Current year OA Pubs

INTRODUCTION: Chimeric antigen receptor T-cell (CAR T) therapies have transformed diffuse large B-cell lymphoma (DLBCL) treatment. It is important to better understand their use in Medicare Fee-for-Service (FFS) patients, who often differ from commercially insured populations in important ways.

METHODS: We analyzed Medicare FFS claims data, focusing on the utilization patterns across three CAR T products-lisocabtagene maraleucel (liso-cel), tisagenlecleucel (tisa-cel), and axicabtagene autoleucel (axi-cel)-which are indicated for the treatment of DLBCL. Our investigation covered the period from 2021 through 2022. This analysis spanned a 180-day period prior to CAR T procedure and extended to a 90-day post-CAR T. Utilization of …

Estimation Of Differential Pathlength Factor From Nirs Measurement In Skeletal Muscle, B Koirala, A Concas, A Cincotti, Yi Sun, A Hernández, M L Goodwin, L B Gladden, N Lai

2020-Current year OA Pubs

The utilization of continuous wave (CW) near-infrared spectroscopy (NIRS) device to measure non-invasively muscle oxygenation in healthy and disease states is limited by the uncertainties related to the differential path length factor (DPF). DPF value is required to quantify oxygenated and deoxygenated heme groups' concentration changes from measurement of optical densities by NIRS. An integrated approach that combines animal and computational models of oxygen transport and utilization was used to estimate the DPF value in situ. The canine model of muscle oxidative metabolism allowed measurement of both venous oxygen content and tissue oxygenation by CW NIRS under different oxygen delivery …

Heroin Or Fentanyl: Prevalence Of Confirmed Fentanyl In Ed Patients With Suspected Heroin Overdose, Siri Shastry, Evan Schwarz, Et Al.

2020-Current year OA Pubs

BACKGROUND: United States drug overdose deaths are being driven by the increasing prevalence of fentanyl, but whether patients are knowingly using fentanyl is unclear. We examined the analytical confirmation of fentanyl in emergency department (ED) patients with documented heroin overdose.

HYPOTHESIS: We hypothesized that the proportion of fentanyl and fentanyl analogs would be higher than that of confirmed heroin.

METHODS: This is a subgroup analysis from a prospective multicenter consecutive cohort of ED patients age 18+ with opioid overdose presenting to 10 US sites within the Toxicology Investigators Consortium from 2020 to 2021. Toxicology analysis was performed using liquid chromatography …

Vaccines At The Intersection Of Religion And Politics, Charles Downey

Master's Theses

Vaccine hesitancy – a delay in acceptance or refusal of vaccines despite their availability – is a rising threat to global health and has increased in recent years in higher income countries. This is a complex phenomenon with the potential to undo decades of progress toward eradicating communicable diseases. The recent COVID-19 pandemic introduced a new wave of vaccine hesitancy, with evangelical Christians as leading actors in the movement away from vaccines in the United States. The present study investigated factors related to vaccine hesitancy and sources of health-related information among members of evangelical Christian churches in and around Hattiesburg, …

Genomic Sequencing Research In Pediatric Cancer Care: Decision Making, Attitudes, And Perceived Utility Among Adolescents And Young Adults And Their Parents, Amanda M Gutierrez, Jill O Robinson, Hadley S Smith, Lauren R Desrosiers-Battu, Sarah R Scollon, Isabel Canfield, Rebecca L Hsu, Nicole M Schneider, D Williams Parsons, Sharon E Plon, Wendy Allen-Rhoades, Mary A Majumder, Janet Malek, Amy L Mcguire

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Professional guidelines recommend engaging adolescents and young adults (AYAs) in medical decision making (DM), including whether to undergo genomic sequencing (GS). We explored DM around GS and attitudes after return of GS results among a diverse group of AYAs with cancer and their parents.

Methods: We surveyed AYAs with cancer (n = 75) and their parents (n = 52) 6 months after receiving GS results through the Texas KidsCanSeq study. We analyzed AYAs' DM role in GS research enrollment and their satisfaction with that role. We compared AYAs' and parents' self-reported understanding of, attitudes toward, and perceived utility of …

Protocol For The Development And Initial Validation Of The Cog-Impact Tool: A Purpose-Built Unmet Needs Assessment For Cancer-Related Cognitive Impairment, Darren Haywood, Moira O’Connor, Frank D. Baughman, Alexandre Chan, Raymond J. Chan, Evan Dauer, Haryana M. Dhillon, Ashley M. Henneghan, Blake J. Lawrence, Maryam Lustberg, Janette L. Vardy, Susan L. Rossell, Nicolas H. Hart

Research outputs 2022 to 2026

(1) Background: A significant proportion of cancer survivors report experiencing a cognitive ‘fog’ that affects their ability to think coherently and quickly, and reason with clarity. This has been referred to as cancer-related cognitive impairment (CRCI). CRCI has extensive impacts on the daily lives of people living with or beyond cancer, including occupational, social, and psychological functioning. Oncology health professionals report feeling under-resourced to effectively assess the needs of an individual with CRCI and then provide optimal care and referral. (2) Methods: The objective of this project is to develop and provide an initial validation of the first purpose-built unmet …

Sex-Dependent Differences In Vulnerability To Early Risk Factors For Posttraumatic Stress Disorder: Results From The Aurora Study, Stephanie Haering, Stacey L House, Et Al.

2020-Current year OA Pubs

BACKGROUND: Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD.

METHODS: As part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with …

Impact Of Clinical Factors On 18f-Flotufolastat Detection Rates In Men With Recurrent Prostate Cancer: Exploratory Analysis Of The Phase 3 Spotlight Study, Benjamin H Lowentritt, Ashesh B Jani, Brian T Helfand, Edward M Uchio, Michael A Morris, Jeff M Michalski, Albert Chau, Phillip Davis, Brian F Chapin, David M Schuster, Spotlight Study Group

2020-Current year OA Pubs

PURPOSE:

METHODS AND MATERIALS: The impact of baseline prostate-specific antigen (PSA), PSA doubling time (PSAdt), and International Society of Urologic Pathology Grade Group (GG) on

RESULTS: In total, 389 men (median PSA: 1.10 ng/mL) were evaluable. By majority read,

CONCLUSIONS:

The Role Of The Cerebellum In Learning To Predict Reward: Evidence From Cerebellar Ataxia, Jonathan Nicholas, Christian Amlang, Chi-Ying R Lin, Leila Montaser-Kouhsari, Natasha Desai, Ming-Kai Pan, Sheng-Han Kuo, Daphna Shohamy

Faculty, Staff and Students Publications

Recent findings in animals have challenged the traditional view of the cerebellum solely as the site of motor control, suggesting that the cerebellum may also be important for learning to predict reward from trial-and-error feedback. Yet, evidence for the role of the cerebellum in reward learning in humans is lacking. Moreover, open questions remain about which specific aspects of reward learning the cerebellum may contribute to. Here we address this gap through an investigation of multiple forms of reward learning in individuals with cerebellum dysfunction, represented by cerebellar ataxia cases. Nineteen participants with cerebellar ataxia and 57 age- and sex-matched …

Predicting Wait Time For Pediatric Kidney Transplant: A Novel Index, Alexandra Alvarez, Ashley Montgomery, Nhu Thao Nguyen Galván, Eileen D Brewer, Abbas Rana

Faculty, Staff and Students Publications

BACKGROUND: Over one thousand pediatric kidney transplant candidates are added to the waitlist annually, yet the prospective time spent waiting is unknown for many. Our study fills this gap by identifying variables that impact waitlist time and by creating an index to predict the likelihood of a pediatric candidate receiving a transplant within 1 year of listing. This index could be used to guide patient management by giving clinicians a potential timeline for each candidate's listing based on a unique combination of risk factors.

METHODS: A retrospective analysis of 3757 pediatric kidney transplant candidates from the 2014 to 2020 OPTN/UNOS …

Amplitude-Integrated Electroencephalography: A Readily Available Tool For Neonatologists, Michelle H Lucena, Palanikumar Balasundaram, Shu-Wei Hsu, Diosely C Silveira, Orna Rosen

Faculty, Staff and Students Publications

Hypoxic-ischemic encephalopathy (HIE) is a common condition occurring at birth, impairing central nervous system function. Therapeutic hypothermia is beneficial for suspected HIE as it reduces mortality and disability in survivors but not for other types of encephalopathy (e.g., metabolic). Amplitude-integrated electroencephalography (aEEG) complements limited resource Neonatal Intensive Care Units as a screening tool that can provide information regarding the degree of encephalopathy and electrographic seizures. Patients with HIE are at increased risk for seizures, which are subclinical in half of the cases. The aEEG emphasizes electroencephalographic amplitude differences, whereas continuous video electroencephalography (cEEG) provides a high-resolution picture of cerebral electrical …

Food Allergy Thresholds, Context, And Balance In 2025, Marcus S Shaker, Jason Sanders, Aikaterini Anagnostou

Faculty, Staff and Students Publications

Food allergy impacts are far-reaching, across individuals, families, and societies, and affect both nutrition and psychological health. Understanding risk in context as well as thresholds of reactivity can help to improve food allergy management. These strategies can provide empowerment and improve quality of life. Food allergy thresholds and reaction severity can vary but both tend toward stability, at least in the short-term. An understanding of food allergen thresholds may better leverage active food allergy management as well as better tailor the most appropriate avoidance in selected individuals. Shared decision-making is central to operationalizing food allergen thresholds.

Selecting Patients For Food Allergy Therapy, Aikaterini Anagnostou

Faculty, Staff and Students Publications

Background: Food allergies pose a significant burden on the daily life of individuals with food allergy, including dietary, psychosocial, and economic impact. The management of food allergy has shifted recently from previous passive avoidance approaches to current active therapeutic interventions.

Objective: This article aims to discuss selection of patients with food allergies for different therapies.

Methods: Published literature on risks and benefits of various therapies as well as articles on shared decision-making were reviewed for this article. Key papers are included.

Results and conclusion: In addition to the two U.S. Food and Drug Administration approved therapies currently available (for oral …

Bigh3 Mediates Apoptosis And Gap Junction Failure In Osteocytes During Renal Cell Carcinoma Bone Metastasis Progression, Tianhong Pan, Fengshuo Liu, Xiaoxin Hao, Shubo Wang, Murtaza Wasi, Jian H Song, Valerae O Lewis, Patrick P Lin, Bryan Moon, Justin E Bird, Theocharis Panaretakis, Sue-Hwa Lin, Danielle Wu, Mary C Farach-Carson, Liyun Wang, Ningyan Zhang, Zhiqiang An, Xiang H-F Zhang, Robert L Satcher

Faculty, Staff and Student Publications

Renal cell carcinoma (RCC) bone metastatis progression is driven by crosstalk between tumor cells and the bone microenvironment, which includes osteoblasts, osteoclasts, and osteocytes. RCC bone metastases (RCCBM) are predominantly osteolytic and resistant to antiresorptive therapy. The molecular mechanisms underlying pathologic osteolysis and disruption of bone homeostasis remain incompletely understood. We previously reported that BIGH3/TGFBI (transforming growth factor-beta-induced protein ig-h3, shortened to BIGH3 henceforth) secreted by colonizing RCC cells drives osteolysis by inhibiting osteoblast differentiation, impairing healing of osteolytic lesions, which is reversible with osteoanabolic agents. Here, we report that BIGH3 induces osteocyte apoptosis in both human RCCBM tissue specimens …

Impact Of Pretreatment Body Mass Index On The Survival Of Head And Neck Cancer Patients, Zheng Yang, Jobran Mansour, Peng Sun, Peng Wei, Kristina R Dahlstrom, Mark Zafereo, Guojun Li, Neil D Gross

Faculty, Staff and Student Publications

Background: Differences in pretreatment body mass index (BMI) have been associated with survival in squamous cell carcinoma of head and neck (SCCHN). We examined effects of BMI on survival in SCCHN patients after stratifying patients by tumor human papillomavirus (HPV) status and subsite.

Methods: Totally 2204 SCCHN patients in a prospective study were included in this secondary analysis. Multivariable Cox models were used to evaluate associations between pretreatment BMI and overall survival, disease-specific survival, and disease-free survival.

Results: BMI was significantly higher among patients with HPV-positive tumors than HPV-negative tumors. BMI >25 kg/m2 was associated with improved survival, while BMI …

Hypoxaemia And Risk Of Death Among Children: Rethinking Oxygen Saturation, Risk-Stratification, And The Role Of Pulse Oximetry In Primary Care, Hamish R Graham, Carina King, Trevor Duke, Salahuddin Ahmed, Abdullah H Baqui, Tim Colbourn, Adegoke G Falade, Helena Hildenwall, Shubhada Hooli, Yewande Kamuntu, Rami Subhi, Eric D Mccollum

Faculty, Staff and Students Publications

Pulse oximeters are essential for assessing blood oxygen levels in emergency departments, operating theatres, and hospital wards. However, although the role of pulse oximeters in detecting hypoxaemia and guiding oxygen therapy is widely recognised, their role in primary care settings is less clear. In this Viewpoint, we argue that pulse oximeters have a crucial role in risk-stratification in both hospital and primary care or outpatient settings. Our reanalysis of hospital and primary care data from diverse low-income and middle-income settings shows elevated risk of death for children with moderate hypoxaemia (ie, peripheral oxygen saturations [SpO2] 90–93%) and severe hypoxaemia (ie, …

Histone H3k18 & H3k23 Acetylation Directs Establishment Of Mll-Mediated H3k4 Methylation, Geoffrey C Fox, Karl F Poncha, B Rutledge Smith, Lara N Van Der Maas, Nathaniel N Robbins, Bria Graham, Jill M Dowen, Brian D Strahl, Nicolas L Young, Kanishk Jain

Faculty, Staff and Students Publications

In an unmodified state, positively charged histone N-terminal tails engage nucleosomal DNA in a manner which restricts access to not only the underlying DNA but also key tail residues subject to binding and/or modification. Charge-neutralizing modifications, such as histone acetylation, serve to disrupt this DNA-tail interaction, facilitating access to such residues. We previously showed that a polyacetylation-mediated chromatin "switch" governs the read-write capability of H3K4me3 by the MLL1 methyltransferase complex. Here, we discern the relative contributions of site-specific acetylation states along the H3 tail and extend our interrogation to other chromatin modifiers. We show that the contributions of H3 tail …

Associations Of Mid-To-Late-Life Inflammation With Late-Life Mobility And The Influences Of Chronic Comorbidities, Race, And Social Determinants Of Health: The Atherosclerosis Risk In Communities Study, Kirby G Parker, B Gwen Windham, Chad Blackshear, Keenan A Walker, Sara B Parker, Ron C Hoogeveen, Christie M Ballantyne, Anna Kucharska-Newton, Priya Palta, Elizabeth Selvin, Maria Vassilaki, Thomas H Mosley, Michael E Griswold

Faculty, Staff and Students Publications

Background: Relationships of midlife inflammation with late-life mobility and influences of chronic health conditions, race, and social determinants of health (SDoH) on these relationships are poorly understood.

Methods: Among 4758 community-dwelling participants (41% men, 20% Black), high-sensitivity C-reactive protein (hsCRP) was measured over 20+ years: in midlife at study visit 2 (V2: 1990-1992, 47-68 years); at V4 (1996-1998, 53-74 years); and with concurrent late-life 4-m gait speed at V5 (2011-2013, 67-88 years, mean 75 years). SDoH measures included race, the national-rank area deprivation index, education, and income. We examined associations of late-life gait speed with midlife hsCRP (V2 continuous and …

Low Vitamin D Levels In Patients With Symptoms Of Gastroparesis: Relationships With Nausea And Vomiting, Gastric Emptying And Gastric Myoelectrical Activity, Kenneth L Koch, Henry P Parkman, Katherine P Yates, Mark L Van Natta, Madhusudan Grover, Gianrico Farrugia, Thomas L Abell, Richard W Mccallum, Irene Sarosiek, Braden Kuo, Robert J Shulman, Laura Miriel, James Tonascia, Pankaj J Pasricha

Faculty, Staff and Students Publications

Patients with gastroparesis (Gp) often have diets deficient in calories, electrolytes, and vitamins. Vitamin D levels have been reported to be low in some patients with Gp but has not been systematically studied.

AIMS: To determine vitamin D levels and relationships among symptoms, gastric emptying and gastric myoelectrical activity (GMA) in patients with symptoms of Gp.

METHODS: 25-hydroxy-vitamin D was measured in patients at enrollment in the Gastroparesis Clinical Consortium Registry. Gastroparesis Cardinal Symptoms Index (GCSI), gastric emptying, and GMA before and after water load satiety test (WLST) were measured. GMA, expressed as percentage distribution of activity in normal and …