Digital Commons Network^™

Pulse Oximetry Accuracy In Children With Dark Skin Tones: Relevance To Acute Lower Respiratory Infection Care In Low- And Middle-Income Countries, Shubhada Hooli, Tim Colbourn, Manish I Shah, Kristy Murray, Anna Mandalakas, Eric D Mccollum

Faculty, Staff and Students Publications

Acute lower respiratory infections (ALRI) are the leading post-neonatal cause of death in children under 5 years old. There is a high prevalence of pediatric ALRI-related hypoxemia in low- and middle-income countries. The WHO defines clinically meaningful hypoxemia in children as a SpO2 (peripheral oxygen saturation) < 90%. Multiple studies put this convention into question and found SpO2 of 90% to 92% to be associated with child ALRI mortality. An evolving body of evidence suggests that pulse oximeters systematically overestimate oxygen saturation in individuals with dark skin tones. We conducted a narrative review of pediatric studies evaluating pulse oximeter accuracy in children without COVID-19. Four studies, one prospective, examined pulse oximeter accuracy in children of varying ages with dark skin tones. All studies had limitations that affect their generalizability. There is evidence that certain pulse oximeters may overestimate oxygen saturation in children with dark skin tones. Further prospective research is urgently needed to identify affected populations and clinical implications. Despite recognized challenges, we strongly urge continued and expanded use of pulse oximetry as its use will save lives.

Assessment And Management Of Vitamin Status In Children With Ckd Stages 2-5, On Dialysis And Post-Transplantation: Clinical Practice Points From The Pediatric Renal Nutrition Taskforce., Caroline E. Anderson, Jetta Tuokkola, Leila Qizalbash, Matthew Harmer, Christina L. Nelms, Stella Stabouli, Barry Toole, Nonnie Polderman, An Desloovere, Jose Renken-Terhaerdt, Molly R Wong Vega, Evelien Snauwaert, Johan Vande Walle, Dieter Haffner, Fabio Paglialonga, Rukshana Shroff, Vanessa Shaw, Larry A. Greenbaum, Bradley A. Warady

Manuscripts, Articles, Book Chapters and Other Papers

Children with chronic kidney disease (CKD) are at risk for vitamin deficiency or excess. Vitamin status can be affected by diet, supplements, kidney function, medications, and dialysis. Little is known about vitamin requirements in CKD, leading to practice variation.The Pediatric Renal Nutrition Taskforce (PRNT), an international team of pediatric kidney dietitians and pediatric nephrologists, was established to develop evidence-based clinical practice points (CPPs) to address challenges and to serve as a resource for nutritional care. Questions were formulated using PICO (Patient, Intervention, Comparator, Outcomes), and literature searches undertaken to explore clinical practice from assessment to management of vitamin status in …

Acute Changes In Liver Function Tests During Initiation Of Ketogenic Diet, Akshat Katyayan, Anuranjita Nayak, Gloria Diaz-Medina, Maureen Handoko, James John Riviello

Faculty, Staff and Students Publications

BACKGROUND: Ketogenic diet is an effective therapy for patients with medically refractory epilepsy. It is generally well tolerated, with the most common side effects being gastrointestinal. Hepatic toxicity has been described as an uncommon side effect of ketogenic diet, usually with long-term use. However, there are limited data to implicate ketogenic diet in acute liver toxicity.

METHODS AND RESULTS: We analyzed all patients who underwent elective inpatient ketogenic diet initiation at our institution from June 2019 to June 2022. Of the 25 patients reviewed, we found 6 patients who showed acute, asymptomatic changes in liver function tests during initiation, in …

Viability Discrimination Of Bacterial Microbiomes In Home Kitchen Dish Sponges Using Propidium Monoazide Treatment, Christina K Carstens, Joelle K Salazar, Shreela Sharma, Wenyaw Chan, Charles Darkoh

Faculty, Staff and Student Publications

Dish sponges are known to support the proliferation of human bacterial pathogens, yet they are commonly used by consumers. Exposure to foodborne pathogens via sponge use may lead to illness, a serious concern among susceptible populations. The extent of exposure risks from sponge use has been limited by constraints associated with culture-independent or dependent methods for bacterial community characterization. Therefore, five used dish sponges were characterized to evaluate the presence of viable bacterial foodborne pathogens using the novel application of propidium monoazide (PMA) treatment and targeted 16S rRNA gene amplicon sequencing. Select pathogen viability was confirmed using targeted selective enrichment. …

Mechanisms By Which The Intratumoral Microbiome May Potentiate Immunotherapy Response, Dalissa Negrón-Figueroa, Lauren E Colbert

Faculty, Staff and Student Publications

No abstract provided.

Inhibition Of Hepatic Oxalate Overproduction Ameliorates Metabolic Dysfunction-Associated Steatohepatitis, Sandeep Das, Alexandra C Finney, Sumit Kumar Anand, Sumati Rohilla, Yuhao Liu, Nilesh Pandey, Alia Ghrayeb, Dhananjay Kumar, Kelley Nunez, Zhipeng Liu, Fabio Arias, Ying Zhao, Brenna H Pearson-Gallion, M Peyton Mckinney, Koral S E Richard, Jose A Gomez-Vidal, Chowdhury S Abdullah, Elizabeth D Cockerham, Joseph Eniafe, Andrew D Yurochko, Tarek Magdy, Christopher B Pattillo, Christopher G Kevil, Babak Razani, Md Shenuarin Bhuiyan, Erin H Seeley, Gretchen E Galliano, Bo Wei, Lin Tan, Iqbal Mahmud, Ida Surakka, Minerva T Garcia-Barrio, Philip L Lorenzi, Eyal Gottlieb, Eduardo Salido, Jifeng Zhang, A Wayne Orr, Wanqing Liu, Monica Diaz-Gavilan, Y Eugene Chen, Nirav Dhanesha, Paul T Thevenot, Ari J Cohen, Arif Yurdagul, Oren Rom

Faculty, Staff and Student Publications

The incidence of metabolic dysfunction-associated steatohepatitis (MASH) is on the rise, and with limited pharmacological therapy available, identification of new metabolic targets is urgently needed. Oxalate is a terminal metabolite produced from glyoxylate by hepatic lactate dehydrogenase (LDHA). The liver-specific alanine-glyoxylate aminotransferase (AGXT) detoxifies glyoxylate, preventing oxalate accumulation. Here we show that AGXT is suppressed and LDHA is activated in livers from patients and mice with MASH, leading to oxalate overproduction. In turn, oxalate promotes steatosis in hepatocytes by inhibiting peroxisome proliferator-activated receptor-α (PPARα) transcription and fatty acid β-oxidation and induces monocyte chemotaxis via C-C motif chemokine ligand 2. In …

Temporal Recording Of Mammalian Development And Precancer, Mirazul Islam, Yilin Yang, Alan J Simmons, Vishal M Shah, Krushna Pavan Musale, Yanwen Xu, Naila Tasneem, Zhengyi Chen, Linh T Trinh, Paola Molina, Marisol A Ramirez-Solano, Iannish D Sadien, Jinzhuang Dou, Andrea Rolong, Ken Chen, Mark A Magnuson, Jeffrey C Rathmell, Ian G Macara, Douglas J Winton, Qi Liu, Hamim Zafar, Reza Kalhor, George M Church, Martha J Shrubsole, Robert J Coffey, Ken S Lau

Faculty, Staff and Student Publications

Temporal ordering of cellular events offers fundamental insights into biological phenomena. Although this is traditionally achieved through continuous direct observations1,2, an alternative solution leverages irreversible genetic changes, such as naturally occurring mutations, to create indelible marks that enables retrospective temporal ordering3–5. Using a multipurpose, single-cell CRISPR platform, we developed a molecular clock approach to record the timing of cellular events and clonality in vivo, with incorporation of cell state and lineage information. Using this approach, we uncovered precise timing of tissue-specific cell expansion during mouse embryonic development, unconventional developmental relationships between cell …

Metagenomic Study Of The Mesa: Detection Of Gemella Morbillorum And Association With Coronary Heart Disease, Kent D Taylor, Alexis C Wood, Jerome I Rotter, Xiuqing Guo, David M Herrington, W Craig Johnson, Wendy S Post, Russell P Tracy, Stephen S Rich, Shaista Malik

Faculty, Staff and Students Publications

BACKGROUND: Inflammation is a feature of coronary heart disease (CHD), but the role of proinflammatory microbial infection in CHD remains understudied.

METHODS AND RESULTS: CHD was defined in the MESA (Multi-Ethnic Study of Atherosclerosis) as myocardial infarction (251 participants), resuscitated arrest (2 participants), and CHD death (80 participants). We analyzed sequencing reads from 4421 MESA participants in the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program using the PathSeq workflow of the Genome Analysis Tool Kit and a 65-gigabase microbial reference. Paired reads aligning to 840 microbes were detected in >1% of participants. The association of the …

Body Mass Index And Postacute Sequelae Of Sars-Cov-2 Infection In Children And Young Adults, Ting Zhou, Chongliang Luo, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Obesity is associated with increased severity of COVID-19. Whether obesity is associated with an increased risk of post-acute sequelae of SARS-CoV-2 infection (PASC) among pediatric populations, independent of its association with acute infection severity, is unclear.

OBJECTIVE: To quantify the association of body mass index (BMI) status before SARS-CoV-2 infection with pediatric PASC risk, controlling for acute infection severity.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study occurred at 26 US children's hospitals from March 2020 to May 2023 with a minimum follow-up of 179 days. Eligible participants included children and young adults aged 5 to 20 years with …

Accessibility Of And Barriers To Long-Term Follow-Up Care For Childhood Cancer Survivors, Jiaoyang Cai, Sara Malone, Nickhill Bhakta, Ching-Hon Pui, Jing Chen, Shaoyan Hu, Hui Jiang, Xiuli Ju, Fen Zhou, Melissa M Hudson, Yin Ting Cheung

2020-Current year OA Pubs

IMPORTANCE: Childhood cancer survivorship programs and long-term follow-up (LTFU) practices are inadequate in most regions of China.

OBJECTIVE: To understand the clinician and caregiver perceptions of LTFU care and to identify barriers to adherence to LTFU care in mainland China.

DESIGN, SETTING, AND PARTICIPANTS: This survey study had a 2-phase sequential mixed-methods approach, consisting of a cross-sectional survey followed by semistructured interviews. Participants included oncology clinicians recruited through an educational seminar on LTFU and caregivers recruited through convenience sampling. Data were collected from November 2022 to September 2023.

MAIN OUTCOMES AND MEASURES: The clinician survey and interview focused on the …

Discordance Between Aptt And Anti-Xa In Monitoring Heparin Anticoagulation In Mechanical Circulatory Support, Song Li, Ang Li, Jennifer A Beckman, Christopher Kim, Marian A Granich, John Mondin, Daniel E Sabath, David A Garcia, Claudius Mahr

Faculty, Staff and Students Publications

AIMS: It is unclear whether activated partial thromboplastin time (aPTT) or anti-Xa is more accurate for monitoring heparin anticoagulation in mechanical circulatory support (MCS) patients. This study investigates the relationship between aPTT and anti-Xa in MCS patients and identifies predictors of discordance.

METHODS AND RESULTS: aPTT and anti-Xa were simultaneously measured in a prospective cohort of MCS patients receiving unfractionated heparin at a tertiary academic medical centre. Therapeutic aPTT and anti-Xa levels were 60-100 s and 0.3-0.7 IU/mL, respectively, and concordance was defined as both levels being subtherapeutic, therapeutic, or supratherapeutic. To identify predictors of discordance, both a machine learning …

Perineuronal Nets’ Role In Metabolism, Nan Zhang, Beite Song, Peng Bai, Li Du, Lulu Chen, Yong Xu, Tianshu Zeng

Faculty, Staff and Students Publications

Perineuronal nets (PNNs), specialized extracellular matrix (ECM) structures that envelop neurons, have recently been recognized as key players in the regulation of metabolism. This review explores the growing body of knowledge concerning PNNs and their role in metabolic control, drawing insights from recent research and relevant studies. The pivotal role of PNNs in the context of energy balance and whole body blood glucose is examined. This review also highlights novel findings, including the effects of astroglia, microglia, sex and gonadal hormones, nutritional regulation, circadian rhythms, and age on PNNs dynamics. These findings illuminate the complex and multifaceted role of PNNs …

Pancreatic Enzyme Use Reduces Pancreatitis Frequency In Children With Acute Recurrent Or Chronic Pancreatitis: A Report From Insppire, Alvin Jay Freeman, Kenneth Ng, Fuchenchu Wang, Maisam A Abu-El-Haija, Ankur Chugh, Gretchen A Cress, Douglas S Fishman, Cheryl E Gariepy, Matthew J Giefer, Praveen Goday, Tanja Y Gonska, Amit S Grover, Douglas Lindblad, Quin Y Liu, Asim Maqbool, Jacob A Mark, Brian A Mcferron, Megha S Mehta, Veronique D Morinville, Robert A Noel, Chee Y Ooi, Emily R Perito, Sarah Jane Schwarzenberg, Zachary M Sellers, Michael Wilschanski, Yuhua Zheng, Ying Yuan, Dana K Andersen, Mark E Lowe, Aliye Uc, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Students Publications

Introduction: Among children who suffer from acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP), acute pancreatitis (AP) episodes are painful, often require hospitalization, and contribute to disease complications and progression. Despite this recognition, there are currently no interventions to prevent AP episodes. In this retrospective cohort study, we assessed the impact of pancreatic enzyme therapy (PERT) use on clinical outcomes among children with pancreatic-sufficient ARP or CP.

Methods: Children with pancreatic-sufficient ARP or CP in the INSPPIRE-2 cohort were included. Clinical outcomes were compared for those receiving vs not receiving PERT, as well as frequency of AP before and after …

What Would Happen In The United States If There Were No Cow Milk-Based Preterm Infant Nutritional Products: Historical Perspective And Evaluation Of Nutrient-Related Challenges, Steven A Abrams, Robert J Shulman

Faculty, Staff and Students Publications

Recent litigation has led to a situation where preterm cow milk-based infant nutritional products (PCMBPs) may soon have limited or no availability in the United States. Given their limited availability, similar products based only on human milk are unlikely to meet the needs of most preterm infants requiring such products, especially those born >1500 g or very preterm infants born at < 1500 g after they reach 34-35 wk postmenstrual age. Alternative nutritional strategies, used before the introduction of specialized preterm products, would require modular nutrient additions to a formula designed for full-term infants and donor or maternal milk. The addition of modular products would require careful calibration to provide needed macro and micronutrients which would expose infants to risks of contamination, poor growth, and limited bioavailability of some of these modulars. Substantial risks of metabolic derangements, and ultimately, poor outcomes would occur. In the long-term greater availability and support for the use of human milk-based products is needed. However, policymakers cannot assume that PCMBPs will not be critically needed and should identify strategies for their continued marketplace availability.

Interpregnancy Maternal Weight Change Is Not Associated With Offspring Weight And Obesity At Age 2 Years, Kate Maslin, Lieveke Ameye, Diederik Vancoppenolle, Anne Rochtus, Hanne Van Uytsel, Jill Shawe, Roland Devlieger, Annick Bogaerts

School of Nursing and Midwifery

Background: Weight retention between pregnancies is associated with increased risk of perinatal complications, but it is unclear whether there is an association with offspring weight status. This study aimed to determine whether maternal interpregnancy weight change is associated with offspring overweight/obesity, controlling for confounding variables. Subjects/methods: Routinely collected linked data from perinatal and child datasets, in Flanders, Belgium were used. Women having their first and second live births between 2009–2018 were included. The association between maternal interpregnancy weight change and overweight/obesity in the second child at 2 years was examined by logistical regression models. Results: A total of 33,172 women …

Rehabilitation Transition Program To Improve Community Participation Among Stroke Survivors: A Randomized Clinical Trial, Rebecca M Bollinger, Melissa J Krauss, Emily K Somerville, Brianna M Holden, Gabrielle Blenden, Holly Hollingsworth, Audrey A Keleman, Alexandre Carter, Timothy D Mcbride, Abigail R Barker, Yan Yan, Susan L Stark

2020-Current year OA Pubs

IMPORTANCE: Interventions are needed to support the long-term needs of stroke survivors when they transition from inpatient rehabilitation to home, where they face new home and community environmental barriers.

OBJECTIVE: To compare the efficacy of a novel, enhanced rehabilitation transition program with attentional control to improve community participation and activity of daily living (ADL) performance and to reduce environmental barriers in the home and community after stroke.

DESIGN, SETTING, AND PARTICIPANTS: This phase 2b, parallel randomized clinical trial assessed patients 50 years or older who had experienced an acute ischemic stroke or intracerebral hemorrhage, were independent in ADLs before stroke, …

Digital Education On Hospital Nutrition Diets: What Do Patients Want To Know?, Neha Gutta, Som Singh, Dharti Patel, Aleena Jamal, Fawad Qureshi

SKMC Student Presentations and Publications

INTRODUCTION: Therapeutic nutrition plays an imperative role during a patient's hospital course. There is a tremendous body of literature that emphasizes the systematic delivery of information regarding hospital nutrition diets. A major component of delivering healthcare information is the principle of providing quality healthcare information, but this has not yet been investigated on hospital nutrition diets. This study aimed to evaluate the comprehension and readability of patient education materials regarding therapeutic hospital diets.

METHODOLOGY: The methodology employed the use of publicly available questions regarding hospital nutrition diets and categorized them per Rothwell's Classification of Questions. Additionally, the questions were extracted …

Nongenetic And Genetic Factors Associated With White Matter Brain Aging: Exposome-Wide And Genome-Wide Association Study, Li Feng, Halley S Milleson, Zhenyao Ye, Travis Canida, Hongjie Ke, Menglu Liang, Si Gao, Shuo Chen, L Elliot Hong, Peter Kochunov, David K Y Lei, Tianzhou Ma

Faculty, Staff and Student Publications

BACKGROUND/OBJECTIVES: Human brain aging is a complex process that affects various aspects of brain function and structure, increasing susceptibility to neurological and psychiatric disorders. A number of nongenetic (e.g., environmental and lifestyle) and genetic risk factors are found to contribute to the varying rates at which the brain ages among individuals.

METHODS: In this paper, we conducted both an exposome-wide association study (XWAS) and a genome-wide association study (GWAS) on white matter brain aging in the UK Biobank, revealing the multifactorial nature of brain aging. We applied a machine learning algorithm and leveraged fractional anisotropy tract measurements from diffusion tensor …

Barriers And Facilitators To Dental Care Services Utilization Among Children With Disabilities: A Systematic Review And Thematic Synthesis, Shiamaa Al-Mashhadani, Mona Nasser, Anas Alsalami, Lorna Burns, Martha Paisi

Peninsula Dental School

BACKGROUND: This systematic review investigates barriers and enablers to dental care utilization by disabled children. Given the high global prevalence of disabilities in children, coupled with poor oral hygiene and a 45% rate of dental caries in this group, developing inclusive oral health strategies is critical. The review aims to synthesize literature on factors affecting oral healthcare improvement for disabled children, identifying barriers, facilitators and knowledge gaps.

METHODS: The review was conducted following the Joanna Briggs Institute's methods and reported according to PRISMA guidelines. A comprehensive search spanned multiple databases, considering perspectives from carers, parents, dentists and health professionals. The …

Untargeted Metabolomic Biomarker Discovery For The Detection Of Ectopic Pregnancy, Onur Turkoglu, Ayse Citil, Ceren Katar, Ismail Mert, Robert A Quinn, Ray O Bahado-Singh, Stewart F Graham

Faculty, Staff and Students Publications

Ectopic pregnancy (EP) is the leading cause of maternal morbidity and mortality in the first trimester. Using an untargeted metabolomic approach, we sought to identify putative plasma biomarkers using tandem liquid chromatography-mass spectrometry for the detection of tubal EP. This case-control study included the prospective recruitment of 50 tubal EP cases and 50 early intrauterine pregnancy controls. To avoid over-fitting, logistic regression models were developed in a randomly selected discovery group (30 cases vs. 30 controls) and validated in the test group (20 cases vs. 20 controls). In total, 585 mass spectral features were detected, of which 221 molecular features …

Treatment Outcomes Among Patients With A Positive Candida Culture Close To Randomization Receiving Rezafungin Or Caspofungin In The Restore Study, Alex Soriano, Marin Kollef, Et Al.

2020-Current year OA Pubs

BACKGROUND: Rezafungin, a novel, once-weekly echinocandin for the treatment of candidemia and/or invasive candidiasis (IC) was noninferior to caspofungin for day 30 all-cause mortality (ACM) and day 14 global cure in the phase 3 ReSTORE trial (NCT03667690). We conducted preplanned subgroup analyses for patients with a positive culture close to randomization in ReSTORE.

METHODS: ReSTORE was a multicenter, double-blind, double-dummy, randomized trial in patients aged ≥18 years with candidemia and/or IC treated with once-weekly intravenous rezafungin (400 mg/200 mg) or once-daily intravenous caspofungin (70 mg/50 mg). This analysis comprised patients with a positive blood culture drawn between 12 hours before …

Nutrition Management In Children Less Than 5 Years Of Age With Glycogen Storage Disease Type I: Survey Results, Mary Sowa, Monica Boyer, Jessica Green, Surekha Pendyal, Heather Saavedra

Faculty, Staff and Student Publications

Background: Nutrition management for GSD Type I (GSDI; OMIM #232200, 232220) is complex, with the goal being to maintain euglycemia while minimizing metabolic derangements. Management guidelines were published in 2002 and 2014. However, there is limited information on the nuances of nutrition management and the unique feeding challenges of children.

Methods: A REDCap survey focusing on staffing and current practices in the nutrition management of children with GSD I who were < 5 years of age was sent to the metabolic dietitian's listserv and GMDI membership in 8/2023.

Results: There were 21 North American respondents. In 17/21 clinics (81%), Prosobee® was the primary choice for infant formula. Dietitians used different methods to determine hourly glucose needs. Fasting …

A Bayesian Semi-Parametric Scalar-On-Function Regression With Measurement Error Using Instrumental Variables, Roger S Zoh, Yuanyuan Luan, Lan Xue, David B Allison, Carmen D Tekwe

Children’s Nutrition Research Center Staff Publications

Wearable devices such as the ActiGraph are now commonly used in research to monitor or track physical activity. This trend corresponds with the growing need to assess the relationships between physical activity and health outcomes, such as obesity, accurately. Device-based physical activity measures are best treated as functions when assessing their associations with scalar-valued outcomes such as body mass index. Scalar-on-function regression (SoFR) is a suitable regression model in this setting. Most estimation approaches in SoFR assume that the measurement error in functional covariates is white noise. Violating this assumption can lead to underestimating model parameters. There are limited approaches …

Fueling The Heart: What Are The Optimal Dietary Strategies In Heart Failure?, Anahita Ataran, Alexander Pompian, Hamidreza Hajirezaei, Rehman Lodhi, Ali Javaheri

2020-Current year OA Pubs

OBJECTIVES: Heart failure (HF) is a global health concern with rising incidence and poor prognosis. While the essential role of nutritional and dietary strategies in HF patients is acknowledged in the existing scientific guidelines and clinical practice, there are no comprehensive nutritional recommendations for optimal dietary management of HF.

METHODS: In this review, we discuss results from recent studies on the obesity paradox and the effects of calorie restriction and weight loss, intermittent fasting, the Western diet, the Mediterranean diet, the ketogenic diet, and the DASH diet on HF progression.

RESULTS: Many of these strategies remain under clinical and basic …

14-Month-Old Female With Anti-Mda5 Juvenile Dermatomyositis Complicated By Liver Disease: A Case Report., Mitch Kinkor, Sameena Hameed, Alexander Kats, Voytek Slowik, Emily Fox, Maria Ibarra

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Juvenile Dermatomyositis (JDM) is a rare disorder with subtypes associated with different myositis-specific antibodies (MSAs) including anti-MDA5. Hepatic involvement in JDM is rare and has not previously been documented in anti-MDA5 JDM. There is a lack of formal research on treatment protocols for anti-MDA5 JDM, though tofacitinib is a highly regarded emerging therapy.

CASE PRESENTATION: A previously healthy 14-month-old Hispanic female presented to a pediatric rheumatology clinic with eight months of worsening rash, weakness, periorbital edema, intermittent fevers, and weight loss. Her physical exam was notable for fever, thinning of hair, heliotrope rash, periorbital edema, violaceous macules on her …

Prenatal Environment Is Associated With The Pace Of Cortical Network Development Over The First Three Years Of Life, Ursula A Tooley, Aidan Latham, Jeanette K Kenley, Dimitrios Alexopoulos, Tara A Smyser, Ashley N Nielsen, Lisa Gorham, Barbara B Warner, Joshua S Shimony, Jeffrey J Neil, Joan L Luby, Deanna M Barch, Cynthia E Rogers, Christopher D Smyser

2020-Current year OA Pubs

Environmental influences on brain structure and function during early development have been well-characterized, but whether early environments are associated with the pace of brain development is not clear. In pre-registered analyses, we use flexible non-linear models to test the theory that prenatal disadvantage is associated with differences in trajectories of intrinsic brain network development from birth to three years (n = 261). Prenatal disadvantage was assessed using a latent factor of socioeconomic disadvantage that included measures of mother's income-to-needs ratio, educational attainment, area deprivation index, insurance status, and nutrition. We find that prenatal disadvantage is associated with developmental increases in …

Neuroinflammation And Brain Health Risks In Veterans Exposed To Burn Pit Toxins, Athena Brooks, Brian Sandri, Joshua Nixon, Timothy Nurkiewicz, Paul Barach, Janeen Trembley, Tammy Butterick

College of Population Health Faculty Papers

Military burn pits, used for waste disposal in combat zones, involve the open-air burning of waste materials, including plastics, metals, chemicals, and medical waste. The pits release a complex mixture of occupational toxic substances, including particulate matter (PM), volatile organic compounds (VOCs), heavy metals, dioxins, and polycyclic aromatic hydrocarbons (PAHs). Air pollution significantly impacts brain health through mechanisms involving neuroinflammation. Pollutants penetrate the respiratory system, enter the bloodstream, and cross the blood-brain barrier (BBB), triggering inflammatory responses in the central nervous system (CNS). Chronic environmental exposures result in sustained inflammation, oxidative stress, and neuronal damage, contributing to neurodegenerative diseases and …

Parp-1 Selectively Impairs Kras-Driven Phenotypic And Molecular Features In Intrahepatic Cholangiocarcinoma, Friederike L Keggenhoff, Darko Castven, Diana Becker, Stojan Stojkovic, Jovana Castven, Carolin Zimpel, Beate K Straub, Tiemo Gerber, Harald Langer, Patricia Hähnel, Thomas Kindler, Jörg Fahrer, Colm J O'Rourke, Ursula Ehmer, Anna Saborowski, Lichun Ma, Xin Wei Wang, Timo Gaiser, Matthias S Matter, Christian Sina, Stefanie Derer, Ju-Seog Lee, Stephanie Roessler, Bernd Kaina, Jesper B Andersen, Peter R Galle, Jens U Marquardt

Faculty, Staff and Student Publications

Objective: Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer with limited therapeutic options. KRAS mutations are among the most abundant genetic alterations in iCCA associated with poor clinical outcome and treatment response. Recent findings indicate that Poly(ADP-ribose)polymerase1 (PARP-1) is implicated in KRAS-driven cancers, but its exact role in cholangiocarcinogenesis remains undefined.

Design: PARP-1 inhibition was performed in patient-derived and established iCCA cells using RNAi, CRISPR/Cas9 and pharmacological inhibition in KRAS-mutant, non-mutant cells. In addition, Parp-1 knockout mice were combined with iCCA induction by hydrodynamic tail vein injection to evaluate an impact on phenotypic and molecular …

Early Identification Of Hepatocellular Carcinoma Patients At High-Risk Of Recurrence Using The Adv Score: A Multicenter Retrospective Study, Shuya Cao, Zheyu Zhou, Chaobo Chen, Wenwen Li, Jinsong Liu, Jiawei Xu, Chunlong Zhao, Yihang Yuan, Zhenggang Xu, Huaiyu Wu, Guwei Ji, Xiaoliang Xu, Ke Wang

Faculty, Staff and Student Publications

BACKGROUND: Postoperative recurrence is a vital reason for poor 5-year overall survival in hepatocellular carcinoma (HCC) patients. The ADV score is considered a parameter that can quantify HCC aggressiveness. This study aimed to identify HCC patients at high-risk of recurrence early using the ADV score.

METHODS: The medical data of consecutive HCC patients undergoing hepatectomy from The First Affiliated Hospital of Nanjing Medical University (TFAHNJMU) and Nanjing Drum Tower Hospital (NJDTH) were retrospectively reviewed. Based on the status of microvascular invasion and the Edmondson-Steiner grade, HCC patients were divided into three groups: low-risk group (group 1: no risk factor exists), …

Menopausal Hormone Therapy Use Among Postmenopausal Women, Lin Yang, Adetunji T Toriola

2020-Current year OA Pubs

IMPORTANCE: Menopausal hormone therapy (MHT) is the treatment of choice for symptoms of menopause. However, its adoption is hindered by the risk-benefit trade-off in relation to acute and chronic diseases.

OBJECTIVE: To evaluate trends in and correlates of MHT use among postmenopausal women in the US from 1999 to March 2020.

DESIGN, SETTING, AND PARTICIPANTS: This serial cross-sectional analysis of MHT use used data from the nationally representative National Health and Nutrition Examination Survey (NHANES). Participants included noninstitutionalized US postmenopausal women from 10 NHANES study cycles (1999-2000 to 2017-March 2020 [pre-COVID-19 pandemic]). Data were analyzed from December 2023 to April …