Digital Commons Network^™

Leptin Receptor Neurons In The Dorsomedial Hypothalamus Require Distinct Neuronal Subsets For Thermogenesis And Weight Loss, Marie Francois, Laura Kaiser, Yanlin He, Yong Xu, J Michael Salbaum, Sangho Yu, Christopher D Morrison, Hans-Rudolf Berthoud, Heike Münzberg

Children’s Nutrition Research Center Staff Publications

The dorsomedial hypothalamus (DMH) receives inputs from the preoptic area (POA), where ambient temperature mediates physiological adaptations of energy expenditure and food intake. Warm-activated POA neurons suppress energy expenditure via brown adipose tissue (BAT) projecting neurons in the dorsomedial hypothalamus/dorsal hypothalamic area (dDMH/DHA). Our earlier work identified leptin receptor (Lepr)-expressing, BAT-projecting dDMH/DHA neurons that mediate metabolic leptin effects. Yet, the neurotransmitter (glutamate or GABA) used by dDMH/DHALepr neurons remains unexplored and was investigated in this study using mice. We report that dDMH/DHALepr neurons represent equally glutamatergic and GABAergic neurons. Surprisingly, chemogenetic activation of glutamatergic and/or GABAergic dDMH/DHA neurons were capable …

Beyond Traditional Body Composition Metrics: Load-Capacity Indices Emerge As Predictors Of Cardiometabolic Outcomes—A Systematic Review And Meta-Analysis, Zhongyang Guan, Marianna Minnetti, Steven B. Heymsfield, Eleonora Poggiogalle, Carla M. Prado, Marc Sim, Blossom C.M. Stephan, Jonathan C.K. Wells, Lorenzo M. Donini, Mario Siervo

Research outputs 2022 to 2026

The adaptive and independent interrelationships between different body composition components have been identified as crucial determinants of disease risk. On the basis of this concept, the load-capacity model of body composition, which utilizes measurements obtained through nonanthropometric techniques such as dual-energy X-ray absorptiometry, was proposed. This model is typically operationalized as the ratio of metabolic load (adipose mass) to metabolic capacity (lean mass). In recent years, a series of load-capacity indices (LCIs) have been utilized to identify abnormal body composition phenotypes such as sarcopenic obesity (SO) and to predict the risk of metabolic, cardiovascular, and cognitive disorders. In this review, …

Trajectories Of Supportive Care Needs For People Who Travel To Receive Cancer Treatment: A Longitudinal Study In Australia, Susannah K. Ayre, Elizabeth A. Johnston, Michael Ireland, Sonja March, Jeff Dunn, Suzanne Chambers, Belinda C. Goodwin

Research outputs 2022 to 2026

Objective: To describe trajectories of change in unmet supportive care needs over a two-year period among people diagnosed with cancer and assess whether these trajectories vary as a function of sociodemographic and clinical characteristics. Methods: This analysis used data from a longitudinal study of people in Queensland, Australia who travelled largely from regional and remote areas to metropolitan centres to receive cancer care (N = 784). Supportive care needs were measured at baseline, then at 3-, 12-, and 24-month post-baseline across five domains (‘psychological’, ‘physical and daily living’, ‘health systems and information’, ‘patient care and support’, ‘sexuality’) using the Supportive …

Relationship Between Gestational Weight Gain With Fetal Body Composition And Organ Volumes In The Eunice Kennedy Shriver National Institute Of Child Health And Human Development (Nichd) Fetal Dimensional Study: A Prospective Pregnancy Cohort, Kathryn A Wagner, Zhen Chen, Stefanie N Hinkle, Jessica L Gleason, Wesley Lee, William A Grobman, John Owen, Roger B Newman, Daniel W Skupski, Dian He, Seth Sherman, Robert E Gore-Langton, Cuilin Zhang, Jagteshwar Grewal, Katherine L Grantz

Faculty, Staff and Students Publications

Background: Inadequate and excessive gestational weight gain (GWG) are associated with increased risk of newborn small- and large-for-gestational-age, respectively, and future offspring adiposity. However, the relationship between GWG and three-dimensional (3D) measures of fetal body composition and organ volumes, which may provide greater insight into fetal growth via measurement of soft tissue, remains unknown.

Objectives: The objective of this study was to examine the relationship between trimester-specific GWG and 3D fetal body composition and organ volume measurements.

Methods: In a diverse, US prospective pregnancy cohort, trimester-specific GWG was calculated as difference between maternal weight at beginning and end of each …

Testosterone Modulation Of Muscle Transcriptomic Profile During Lifestyle Therapy In Older Men With Obesity And Hypogonadism, Viola Viola, Tagari Samanta, Maria Liza Duremdes Nava, Alessandra Celli, Reina Armamento-Villareal, Ngoc Ho Lam Nguyen, Georgia Colleluori, Yoann Barnouin, Nicola Napoli, Clifford Qualls, Benny Abraham Kaipparettu, Dennis T Villareal

Faculty, Staff and Students Publications

Background: Testosterone replacement therapy (TRT) added to lifestyle therapy can mitigate weight-loss-induced reduction of muscle mass and bone mineral density (BMD) in older men with obesity and hypogonadism.

Objective: To investigate the molecular mechanisms underlying the attenuation of muscle and BMD loss in response to TRT during intensive lifestyle intervention in this high-risk older population.

Methods: Among 83 older (≥ 65 years) men with obesity (BMI ≥ 30 kg/m2) and hypogonadism (early AM testosterone persistently < 300 ng/dL) associated with frailty (Modified Physical Performance Test score ≤ 31) randomized into 26-week lifestyle therapy plus testosterone (LT+TRT) or placebo (LT+Pbo) in the LITROS trial, 38 underwent serial muscle biopsies for the muscle transcriptomics substudy.

Results: Despite similar ~10% weight loss, lean body mass and thigh muscle volume decreased less in LT+TRT than LT+Pbo (-2% vs. -4%, respectively; p = …

Prospective Analysis Of Liver Stiffness Measurement By Vibration Controlled Transient Elastography As A Predictor Of Outcomes In Biliary Atresia, Jean P Molleston, Nathan P Goodrich, Wen Ye, Daniel H Leung, Ronald J Sokol, Benjamin L Shneider, Children Force Outcomes Working Group

Faculty, Staff and Students Publications

No abstract provided.

Pediatric Participation In Biobanking Related To Inflammatory Bowel Diseases, Jennifer Saccente Thompson, Sahna Reddy, Alison Shaw, Antone R Opekun, Richard Kellermayer

Faculty, Staff and Students Publications

No abstract provided.

Effectiveness Of The Primary Bacillus Calmette-Guérin Vaccine Against The Risk Of Mycobacterium Tuberculosis Infection And Tuberculosis Disease: A Meta-Analysis Of Individual Participant Data, Puck T Pelzer, Logan Stuck, Leonardo Martinez, Alexandra S Richards, Carlos Acuña-Villaorduña, Naomi E Aronson, Maryline Bonnet, Anna C Carvalho, Pei-Chun Chan, Li-Min Huang, Chi-Tai Fang, Gavin Churchyard, Helena Del Corral-Londoño, Manjula Datta, Marcos A Espinal, Katherine Fielding, Andrew J Fiore-Gartland, Alberto Garcia-Basteiro, Willem Hanekom, Mark Hatherill, Phillip C Hill, Helena Huerga, Edward C Jones-López, Afranio Kritski, Anna M Mandalakas, Punam Mangtani, Eduardo Martins Netto, Harriet Mayanja, Rufaida Mazahir, Megan Murray, Molebogeng Rangaka, Thomas Scriba, Jitendra Singh, Sarman Singh, Catherine M Stein, Johan Vekemans, Lilly M Verhagen, Julian A Villalba, Anne Wajja, Basilea Watson, Richard G White, Frank G J Cobelens

Faculty, Staff and Students Publications

Background: Tuberculosis vaccine trials using disease as the primary endpoint are large, time consuming, and expensive. An earlier immunological measure of the protection against disease would accelerate tuberculosis vaccine development. We aimed to assess whether the effectiveness of the Bacillus Calmette-Guérin (BCG) vaccine for prevention of Mycobacterium tuberculosis infection was consistent with that for prevention of tuberculosis disease.

Methods: We conducted an individual participant data (IPD) meta-analysis on experimental and observational longitudinal studies before April 6, 2018, identified through systematic reviews, known to us through expert knowledge in the field, reporting on BCG vaccination status, M tuberculosis infection test (QuantiFERON …

Establishing A Student-Run Mobile Clinic In Appalachian Kentucky: A Community-Based Pilot Program To Address Health Inequities, Bradley A. Firchow, John C. Cornelius

Journal of Appalachian Health

The establishment of a student-run mobile clinic in Morehead, Kentucky, led by students from the University of Kentucky College of Medicine’s (UKCOM) Rural Physician Leadership Program (RPLP), aims to address health inequities in rural Appalachian communities. This pilot program is designed to serve vulnerable populations, including the unhoused, by delivering free, accessible healthcare services directly to underserved populations. This program serves as a model for expanding access to healthcare in rural regions while promoting a collaborative, community-based approach to addressing social determinants of health.

The Adiponectin-Pparγ Axis In Hepatic Stellate Cells Regulates Liver Fibrosis, Shangang Zhao, Qingzhang Zhu, Wang-Hsin Lee, Jan-Bernd Funcke, Zhuzhen Zhang, May-Yun Wang, Qian Lin, Bianca Field, Xue-Nan Sun, Guannan Li, Mbolle Ekane, Toshiharu Onodera, Na Li, Yi Zhu, Christine M Kusminski, Terry D Hinds, Philipp E Scherer

Faculty, Staff and Students Publications

Hepatic stellate cells (HSCs) are key drivers of local fibrosis. Adiponectin, conventionally thought of as an adipokine, is also expressed in quiescent HSCs. However, the impact of its local expression on the progression of liver fibrosis remains unclear. We recently generated a transgenic mouse line (Lrat-rtTA) that expresses the doxycycline-responsive transcriptional activator rtTA under the control of the HSC-specific lecithin retinol acyltransferase (Lrat) promoter, which enables us to specifically and inducibly overexpress or eliminate genes in these cells. The inducible elimination of HSCs protects mice from methionine/choline-deficient (MCD) diet-induced liver fibrosis, confirming their causal involvement in fibrosis development. We generated …

Sex-Specific Astrocyte Regulation Of Spinal Motor Circuits By Nkx61, Navish A Bosquez Huerta, Zhung-Fu Lee, Eun-Ah Christine Song, Junsung Woo, Yi-Ting Cheng, Debosmita Sardar, Ozlem Sert, Ehson Maleki, Kwanha Yu, Ekin Su Akdemir, Kaitlyn Sanchez, Juyeon Jo, Matthew N Rasband, Hyun Kyoung Lee, Akdes Serin Harmanci, Benjamin Deneen

Faculty, Staff and Students Publications

Astrocytes exhibit diverse cellular and molecular properties across the central nervous system (CNS). Recent studies identified region-specific transcription factors (TF) that oversee these diverse properties; how sex differences intersect with region-specific transcriptional programs to regulate astrocyte function is unknown. Here, we show that the TF Nkx6.1 is specifically expressed in ventral astrocytes of the spinal cord and that its deletion results in sex-specific effects on astrocyte morphology. Astrocytes from males exhibit enhanced morphological complexity, accompanied by increased motor function and cholinergic synapses. In contrast, female astrocytes exhibit reduced complexity and no changes in motor function. Mechanistically, we found that Nkx6.1 …

Correlates Of Inaccuracy In Reporting Of Energy Intake Among Persons With Multiple Sclerosis, Stephanie L Silveira, Brenda Jeng, Barbara A Gower, Gary R Cutter, Robert W Motl

Faculty, Staff and Student Publications

BACKGROUND/OBJECTIVES: Persons with multiple sclerosis (MS) are interested in diet as a second-line approach for disease management. This study examined potential variables that correlate with inaccuracy of self-reported energy intake (EI) in adults with MS.

METHODS: Twenty-eight participants completed two assessment appointments within a 14-day period that included a standard doubly labeled water (DLW) protocol for estimating total energy expenditure (TEE). The participants reported their EI using the Automated Self-Administered 24 h (ASA24) Dietary Assessment Tool. The primary variables of interest for explaining the discrepancy between TEE and ASA24 EI (i.e., inaccuracy) included cognition (processing speed, visuospatial memory, and verbal …

Social, Racial, And Economic Disparities Affecting Outcomes Of Hypertensive Adolescents, Kanya Singhapakdi, Amelia Haydel, Marla Johnston, Shengping Yang, Tamara Bradford, Dedrick Moulton, Thomas R. Kimball

School of Medicine Faculty Publications

Essential hypertension is one of the most common conditions managed in pediatric cardiology and can result in lasting deleterious effects on the cardiovascular system. Pediatric hypertension is so prevalent in the United States that it is often referred to as a public health challenge. Social determinants of health (SDH) are the cultural, economic, educational, healthcare accessibility, and political influences in the environment in which an individual is born or lives, all of which can affect that individual's overall health. This study investigated the impact of social determinants such as rurality, food insecurity, transportation challenges, minority status, income, and race on …

Ethnic Disparities In Hba1c And Hypoglycemia Among Youth With Type 1 Diabetes: Beyond Access To Technology, Social Deprivation And Mean Blood Glucose, J. Pemberton, Zhide Fang, Stuart Chalew, S. Uday

School of Public Health Faculty Publications

Introduction The UK national pediatric diabetes audit reports higher HbA1c for children and young people (CYP) with type 1 diabetes (T1D) of Black ethnicity compared with White counterparts. This is presumably related to higher mean blood glucose (MBG) due to lower socioeconomic status (SES) and less access to technology. We aimed to determine if HbA1c ethnic disparity persists after accounting for the above variables. Research design and methods A retrospective analysis of participants who received structured education in continuous glucose monitoring (CGM) use was conducted at a tertiary center. HbA1c was paired with glucose metrics from 90-day CGM data. The …

Are Maternal Adverse Childhood Experiences (Aces) And Resilience Associated With Breastfeeding Rates And Neonatal Growth?, Lily Zheng, Krystal Hunter, Hsiao-Wei M. Banks, Leslie Abraham, Alla Kushnir

Cooper Rowan Medical Journal

Background: Adverse childhood experiences (ACEs) have shown to have a negative impact on health outcomes. There is evidence of how negative childhood events adversely affect self-esteem in adulthood. Not only do ACEs have an impact on one's own life, but maternal ACEs have shown to have consequences on infants’ development as well, indicating a negative intergenerational impact.

Objectives: To analyze the relationship between maternal ACEs on infant outcomes, breastfeeding adherence, and maternal self-perception

Design/Methods: Between 2020 and 2023, 120 mother-infant pairs from a New Jersey urban hospital were approached between their 2nd trimester and the 2-month well …

The Association Between Thyroid Differentiation Score And Survival Outcomes In Papillary Thyroid Carcinoma, Jennifer R Wang, Mark E Zafereo, Maria E Cabanillas, Chia Chin Wu, Li Xu, Yaoyi Dai, Wenyi Wang, Stephen Y Lai, Ying Henderson, Lauren Erasmus, Michelle D Williams, Corinne Joshu, Debashree Ray

Faculty, Staff and Student Publications

Context: Thyroid differentiation score (TDS), calculated based on mRNA expression levels of 16 genes controlling thyroid metabolism and function, has been proposed as a measure to quantify differentiation in papillary thyroid carcinoma (PTC).

Objective: The objective of this study is to determine whether TDS is associated with survival outcomes across patient cohorts.

Methods: Two independent cohorts of patients with PTC were used: (1) The Cancer Genome Atlas (TCGA) thyroid cancer study (N = 372), (2) MD Anderson Cancer Center (MDACC) cohort (N = 111). The primary survival outcome of interest was progression-free interval (PFI). Association with overall survival (OS) was …

Geographic Disparities Impacting Oral Vaccine Performance: Observations And Future Directions, Rachel M Burke, Sasirekha Ramani, Julia Lynch, Laura V Cooper, Haeun Cho, Ananda S Bandyopadhyay, Carl D Kirkwood, A Duncan Steele, Gagandeep Kang

Faculty, Staff and Students Publications

Oral vaccines have several advantages compared with parenteral administration: they can be relatively cheap to produce in high quantities, easier to administer, and induce intestinal mucosal immunity that can protect against infection. These characteristics have led to successful use of oral vaccines against rotavirus, polio, and cholera. Unfortunately, oral vaccines for all three diseases have demonstrated lower performance in the highest-burden settings where they are most needed. Rotavirus vaccines are estimated to have >85% effectiveness against hospitalization in children < 12 months in countries with low child mortality, but only ~65% effectiveness in countries with high child mortality. Similarly, oral polio vaccines have lower immunogenicity in developing country settings compared with high-resource settings. Data are more limited for oral cholera vaccines, but suggest lower titers among children compared with adults, and, for some vaccines, lower efficacy in endemic settings compared with non-endemic settings. These disparities are likely multifactorial, and available evidence suggests a role for maternal factors (e.g. transplacental antibodies, breastmilk), host factors (e.g. genetic polymorphisms-with the best evidence for rotavirus-or previous infection), and environmental factors (e.g. gut microbiome, co-infections). Overall, these data highlight the rather ambiguous and often contradictory nature of evidence on factors affecting oral vaccine response, cautioning against broad extrapolation of outcomes based on one population or one vaccine type. Meaningful impact on performance of oral vaccines will likely only be possible with a suite of interventions, given the complex and multifactorial nature of the problem, and the degree to which contributing factors are intertwined.

Using Community Engagement To Create A Telecoaching Intervention To Improve Self-Management In Adolescents And Young Adults With Cystic Fibrosis: Qualitative Study., Christina L. Duncan, Emily F. Muther, Jennifer J. Lindwall, Kristine Durkin, Elizabeth Ruvalcaba, Eliza Williamson, Corrine Ahrabi-Nejad, Evelyn Bord, Angela Green, Megan L. Harrison, Deepika Polineni

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Adolescents and young adults (AYA) with cystic fibrosis (CF) are at risk for deviating from their daily treatment regimen due to significant time burden, complicated daily therapies, and life stressors. Developing patient-centric, effective, engaging, and practical behavioral interventions is vital to help sustain therapeutically meaningful self-management.

OBJECTIVE: This study aimed to devise and refine a patient-centered telecoaching intervention to foster self-management in AYA with CF using a combination of intervention development approaches, including an evidence- and theory-based approach (ie, applying existing theories and research evidence for behavior change) and a target population-centered approach (ie, intervention refinement based on the …

Research Progress And Clinical Translation Potential Of Coronary Atherosclerosis Diagnostic Markers From A Genomic Perspective, Hanxiang Liu, Yuchen Zhang, Yueyan Zhao, Yuzhen Li, Xiaofeng Zhang, Lingyu Bao, Rongkai Yan, Yixin Yang, Huixian Zhou, Jinming Zhang, Siyuan Song

Children’s Nutrition Research Center Staff Publications

Objective: Coronary atherosclerosis (CAD) is characterized by arterial intima lipid deposition, chronic inflammation, and fibrous tissue proliferation, leading to arterial wall thickening and lumen narrowing. As the primary cause of coronary heart disease and acute coronary syndrome, CAD significantly impacts global health. Recent genetic studies have demonstrated CAD's polygenic and multifactorial nature, providing molecular insights for early diagnosis and risk assessment. This review analyzes recent advances in CAD-related genetic markers and evaluates their diagnostic potential, focusing on their applications in diagnosis and risk stratification within precision medicine.

Methods: We conducted a systematic review of CAD genomic studies from PubMed and …

Examining The Impact Of An Education Intervention On Parents' Perceptions Of Sport Specialization, Lauren Schlacht Butler, Justin S. Disanti, Joseph J. Janosky, Jane S. Chung, James F. Russomano, Amanda M. Black, Shelly Fetchen Dicesaro, Eric Post, Jonathan A. Santana, Troy M. Smurawa, Tamara Valovich Mcleod

Internet Journal of Allied Health Sciences and Practice

PURPOSE: Several organizations have developed educational materials to provide stakeholders with information about the health risks of early sport specialization (ESS), though the impact of these efforts is not yet known. Therefore, the purpose of this study was to describe and assess the effect of an educational intervention on parental knowledge and perceptions of ESS. We hypothesized that a video-based educational intervention would increase parental knowledge and change perceptions of ESS. METHODS: Eighty-three parents of youth athletes completed a web-based survey. Participants were randomized into an intervention (ESS video) or control (concussion video) group. Each group completed a pre-and post-intervention …

Strategies For Optimizing Female Athlete Health: A Multidisciplinary Approach To Mitigate Stress Fractures And Minimize Missed Participation In Collegiate Sports, Natalie B. Allen, Melissa R. Penkalski, Shannon M. Hauschildt, Kristin A. Paloncy-Patel

Internet Journal of Allied Health Sciences and Practice

Background: If not recognized early, low energy availability, along with overtraining, may result in stress fractures and significant time lost from sports participation for athletes at any level. Objective/Aim: The multidisciplinary collegiate medical team plays a key role in early identification of Female Athlete Triad (Triad) and Relative Energy Density in Sport (RED-S). To help with early identification, which may in turn lead to fewer stress fractures and less time missed from sports participation, this study’s objective was to implement the use of the 2014 Female Athlete Triad Cumulative Risk Assessment (FACTRA) and test early identification. The first …

Congenital Rickets, Melissa Intriago

Mako: NSU Undergraduate Student Journal

No abstract provided.

How Did Covid-19 Impact Physiology Research Globally? – Lessons Learned And Future Recommendations, Jeet Patel, Santanu De

Mako: NSU Undergraduate Student Journal

The Coronavirus Infectious Disease 2019 (COVID-19) pandemic caused massive changes in the medical field across the globe. As the whole world moved from in-person to remote activities, students found themselves in a predicament where they were compelled towards schooling and work online from home. This would mean that all projects, research, tests, and meetings were conducted over Zoom or other online meeting platforms. Laboratories were shut down or only a limited number of people were allowed to enter to conduct the necessary research. This paper discusses how the COVID-19 pandemic affected research process and experiments within various aspects of the …

Dysregulated Klf4 Expression Plays A Pivotal Role In The Pathogenesis Of Pancreatic Intraductal Papillary Mucinous Neoplasms, Xiangsheng Zuo, Liang Wang, Yi Liu, Huamin Wang, Margarete Hafley, Mihai Gagea, Ru Chen, Yun Xiong, Sheng Pan, Imad Shureiqi, Robert S Bresalier, Daoyan Wei

Faculty, Staff and Student Publications

No abstract provided.

Light-Dark Shift Promotes Colon Carcinogenesis Through Accelerated Colon Aging, Deepak Sharma, Phillip A Engen, Abu Osman, Darbaz Adnan, Maliha Shaikh, Mostafa K Abdel-Reheem, Ankur Naqib, Stefan J Green, Bruce Hamaker, Christopher B Forsyth, Lin Cheng, Ali Keshavarzian, Khashayarsha Khazaie, Faraz Bishehsari

Faculty, Staff and Student Publications

Colorectal cancer (CRC) is the third most common cancer worldwide, with rising prevalence among younger adults. Several lifestyle factors, particularly disruptions in circadian rhythms by light-dark (LD) shifts, are known to increase CRC risk. Epidemiological studies previously showed LD-shifts are associated with increased risk of CRC. To explore the mechanisms and interactions between LD-shift and intestinal aging, we investigated how the combination of LD-shifts and aging impacts colon carcinogenesis development. Our data showed that LD-shifts and aging increased colon tumorigenesis. Notably, LD-shift accelerated intestinal aging by altering aging-related pathways, such as intestinal barrier damage, accompanied by dysbiotic changes in the …

Associations Between Deficit Accumulation Frailty And Baseline Markers Of Lifestyle In The Us Pointer Trial, Mark A Espeland, Yitbarek N Demesie, Kayloni Olson, Samuel N Lockhart, Sarah E Tomaszewski Farias, Maryjo L Cleveland, Christy C Tangney, Lucia Crivelli, Heather M Snyder, Michele K York, Laura D Baker, Rachel A Whitmer, Rena R Wing, Katelyn R Garcia, Kathryn E Callahan

Faculty, Staff and Students Publications

BACKGROUND: Multidomain lifestyle interventions may have the potential to slow biological aging as captured by deficit accumulation frailty indices. We describe the distribution and composition of the 49-component frailty index developed by the U.S. POINTER clinical trial team of investigators and assess its cross-sectional associations with sociodemographic factors and markers chosen to be representative of behaviors targeted by the trial's multidomain interventions.

METHODS: We draw baseline data from the 2 111 volunteers enrolled in U.S. POINTER who were ages 60-79 years and at increased risk for cognitive decline. Frailty components were grouped into 9 domains. Associations that frailty index scores …

Sex Differences In Response To Diet Enriched With Glutathione Precursors In The Aging Heart, Aude Angelini, Grecia Garcia Marquez, Anna Malovannaya, Marta L Fiorotto, Alexander Saltzman, Antrix Jain, Joann Trial, George E Taffet, Katarzyna A Cieslik

Faculty, Staff and Students Publications

Common features of the aging heart are dysregulated metabolism, inflammation, and fibrosis. Elevated oxidative stress is another hallmark of cardiac aging that can exacerbate each of these conditions. We hypothesize that by increasing natural antioxidant levels (glutathione), we will improve cardiac function. Twenty-one-month-old mice were fed glycine and N-acetyl cysteine (GlyNAC; glutathione precursors)-supplemented or control diets for 12 weeks. Heart function was monitored longitudinally, and the exercise performance was determined at the end of the study. We found that the GlyNAC diet was beneficial for old male but not old female mice, leading to an increase of Ndufb8 expression (a …

Synesis As A Framework To Enable Safety Interventions In Complex Healthcare Environments, Aarti Bavare, Tiffany Wrenn, Anne Lam, Jamie Cargill, Lauren Salinas, Itode Idowu, Asma Razavi, Venessa Lynn Pinto, Eric Williams

Faculty, Staff and Students Publications

BACKGROUND: Despite wide adoption in the healthcare of safety event report (SER) systems, there is a paucity of unified structures for prompt analysis and action while retaining reporter confidentiality. We used a synesis framework to change siloed reviews of safety reports to a comprehensive appraisal of quality, safety, productivity and reliability to facilitate interventions.

METHODS: After a needs assessment survey, we launched serial plan-do-study-act cycles to (1) enhance teams' ability to access SERs, (2) facilitate regular multidisciplinary review of SERs to identify actionable opportunities, (3) allocate action priority using failure mode and effects analysis, and (4) launch actions and summarise …

Neoadjuvant Or Concurrent Atezolizumab With Chemoradiation For Locally Advanced Cervical Cancer: A Randomized Phase I Trial, Jyoti Mayadev, Dmitriy Zamarin, Wei Deng, Heather A. Lankes, Giulio Pesci, Hayeon Kim, Junzo P. Chino, Barbara Banbury, Ned Sherry, Elad Sharon, Sharad A. Ghamande, Catherine Ferguson, Loren Mell, Laura Holman, Cara Mathews, David O'Malley, Alexander Olawaiye, Elizabeth Hopp, Charles Leath, Larry Copeland, Robert Mannel, Roisin O'Cearbhaill, Carol Aghajanian, Russell J. Schilder

Department of Medical Oncology Faculty Papers

Combined immune checkpoint blockade (ICB) and chemoradiation (CRT) is approved in patients with locally advanced cervical cancer (LACC) but optimal sequencing of CRT and ICB is unknown. NRG-GY017 (NCT03738228) was a randomized phase I trial of atezolizumab (anti-PD-L1) neoadjuvant and concurrent with CRT (Arm A) vs. concurrent with CRT (Arm B) in patients with high-risk node-positive LACC. The primary endpoint was the fraction of expanded tumor-associated T-cell receptor (TCR) clones in blood at day 21 as a surrogate measure of anti-tumor immune response. Secondary objectives were safety and feasibility, 2-year disease-free survival (DFS), and predictive value of PD-L1 expression. Forty …

Alleviation Of Liver Fibrosis By Inhibiting A Non-Canonical Atf4-Regulated Enhancer Program In Hepatic Stellate Cells, Li-Xian Yang, Chuangye Qi, Si Lu, Xiang-Shi Ye, Parnaz Merikhian, Du-Yu Zhang, Tao Yao, Jiang-Sha Zhao, Ying Wu, Yongshi Jia, Bo Shan, Jinghai Chen, Xiaozhou Mou, Jia You, Wenbo Li, Yu-Xiong Feng

Faculty, Staff and Student Publications

Liver fibrosis is a critical liver disease that can progress to more severe manifestations, such as cirrhosis, yet no effective targeted therapies are available. Here, we identify that ATF4, a master transcription factor in ER stress response, promotes liver fibrosis by facilitating a stress response-independent epigenetic program in hepatic stellate cells (HSCs). Unlike its canonical role in regulating UPR genes during ER stress, ATF4 activates epithelial-mesenchymal transition (EMT) gene transcription under fibrogenic conditions. HSC-specific depletion of ATF4 suppresses liver fibrosis in vivo. Mechanistically, TGFβ resets ATF4 to orchestrate a unique enhancer program for the transcriptional activation of pro-fibrotic EMT genes. …