American Physiological Society Research Articles

Renal Epithelial Mitochondria: Implications for Hypertensive Kidney Disease.

According to the Centers for Disease Control and Prevention, 1 in 2 U.S. adults have hypertension, and more than 1 in 7 chronic kidney disease. In fact, hypertension is the second leading cause of kidney failure in the United States; it is a complex disease characterized by, leading to, and caused by renal dysfunction. It is well-established that hypertensive renal damage is accompanied by mitochondrial damage and oxidative stress, which are differentially regulated and manifested along the nephron due to the diverse structure and functions of renal cells. This article provides a summary of the relevant knowledge of mitochondrial bioenergetics and metabolism, focuses on renal mitochondrial function, and discusses the evidence that has been accumulated regarding the role of epithelial mitochondrial bioenergetics in the development of renal tissue dysfunction in hypertension. © 2024 American Physiological Society. Compr Physiol 14:5225-5242, 2024.

Integrated Functions of Cardiac Energetics, Mechanics, and Purine Nucleotide Metabolism.

Purine nucleotides play central roles in energy metabolism in the heart. Most fundamentally, the free energy of hydrolysis of the adenine nucleotide adenosine triphosphate (ATP) provides the thermodynamic driving force for numerous cellular processes including the actin-myosin crossbridge cycle. Perturbations to ATP supply and/or demand in the myocardium lead to changes in the homeostatic balance between purine nucleotide synthesis, degradation, and salvage, potentially affecting myocardial energetics and, consequently, myocardial mechanics. Indeed, both acute myocardial ischemia and decompensatory remodeling of the myocardium in heart failure are associated with depletion of myocardial adenine nucleotides and with impaired myocardial mechanical function. Yet there remain gaps in the understanding of mechanistic links between adenine nucleotide degradation and contractile dysfunction in heart disease. The scope of this article is to: (i) review current knowledge of the pathways of purine nucleotide depletion and salvage in acute ischemia and in chronic heart disease; (ii) review hypothesized mechanisms linking myocardial mechanics and energetics with myocardial adenine nucleotide regulation; and (iii) highlight potential targets for treating myocardial metabolic and mechanical dysfunction associated with these pathways. It is hypothesized that an imbalance in the degradation, salvage, and synthesis of adenine nucleotides leads to a net loss of adenine nucleotides in both acute ischemia and under chronic high-demand conditions associated with the development of heart failure. This reduction in adenine nucleotide levels results in reduced myocardial ATP and increased myocardial inorganic phosphate. Both of these changes have the potential to directly impact tension development and mechanical work at the cellular level. © 2024 American Physiological Society. Compr Physiol 14:5345-5369, 2024.

Environmental Enrichment for Stroke and Traumatic Brain Injury: Mechanisms and Translational Implications.

Acquired brain injuries, such as ischemic stroke, intracerebral hemorrhage (ICH), and traumatic brain injury (TBI), can cause severe neurologic damage and even death. Unfortunately, currently, there are no effective and safe treatments to reduce the high disability and mortality rates associated with these brain injuries. However, environmental enrichment (EE) is an emerging approach to treating and rehabilitating acquired brain injuries by promoting motor, sensory, and social stimulation. Multiple preclinical studies have shown that EE benefits functional recovery, including improved motor and cognitive function and psychological benefits mediated by complex protective signaling pathways. This article provides an overview of the enriched environment protocols used in animal models of ischemic stroke, ICH, and TBI, as well as relevant clinical studies, with a particular focus on ischemic stroke. Additionally, we explored studies of animals with stroke and TBI exposed to EE alone or in combination with multiple drugs and other rehabilitation modalities. Finally, we discuss the potential clinical applications of EE in future brain rehabilitation therapy and the molecular and cellular changes caused by EE in rodents with stroke or TBI. This article aims to advance preclinical and clinical research on EE rehabilitation therapy for acquired brain injury. © 2024 American Physiological Society. Compr Physiol 14:5291-5323, 2024.

Behavioral Motor Performance.

The human sensorimotor control system has exceptional abilities to perform skillful actions. We easily switch between strenuous tasks that involve brute force, such as lifting a heavy sewing machine, and delicate movements such as threading a needle in the same machine. Using a structure with different control architectures, the motor system is capable of updating its ability to perform through our daily interaction with the fluctuating environment. However, there are issues that make this a difficult computational problem for the brain to solve. The brain needs to control a nonlinear, nonstationary neuromuscular system, with redundant and occasionally undesired degrees of freedom, in an uncertain environment using a body in which information transmission is subject to delays and noise. To gain insight into the mechanisms of motor control, here we survey movement laws and invariances that shape our everyday motion. We then examine the major solutions to each of these problems in the three parts of the sensorimotor control system, sensing, planning, and acting. We focus on how the sensory system, the control architectures, and the structure and operation of the muscles serve as complementary mechanisms to overcome deviations and disturbances to motor behavior and give rise to skillful motor performance. We conclude with possible future research directions based on suggested links between the operation of the sensorimotor system across the movement stages. © 2024 American Physiological Society. Compr Physiol 14:5179-5224, 2024.

Advanced Imaging Techniques for the Characterization of Subcellular Organelle Structure in Pancreatic Islet β Cells.

Type 2 diabetes (T2D) affects more than 32.3 million individuals in the United States, creating an economic burden of nearly $966 billion in 2021. T2D results from a combination of insulin resistance and inadequate insulin secretion from the pancreatic β cell. However, genetic and physiologic data indicate that defects in β cell function are the chief determinant of whether an individual with insulin resistance will progress to a diagnosis of T2D. The subcellular organelles of the insulin secretory pathway, including the endoplasmic reticulum, Golgi apparatus, and secretory granules, play a critical role in maintaining the heavy biosynthetic burden of insulin production, processing, and secretion. In addition, the mitochondria enable the process of insulin release by integrating the metabolism of nutrients into energy output. Advanced imaging techniques are needed to determine how changes in the structure and composition of these organelles contribute to the loss of insulin secretory capacity in the β cell during T2D. Several microscopy techniques, including electron microscopy, fluorescence microscopy, and soft X-ray tomography, have been utilized to investigate the structure-function relationship within the β cell. In this overview article, we will detail the methodology, strengths, and weaknesses of each approach. © 2024 American Physiological Society. Compr Physiol 14:5243-5267, 2024.

Poor statistical reporting, inadequate data presentation and spin persist despite Journal awareness and updated Information for Authors.

Sound reporting of research results is fundamental to good science. Unfortunately, poor reporting is common and does not improve with editorial educational strategies. We investigated whether publicly highlighting poor reporting at a journal can lead to improved reporting practices. We also investigated whether reporting practices that are required or strongly encouraged in journal Information for Authors are enforced by journal editors and staff. A 2016 audit highlighted poor reporting practices in the Journal of Neurophysiology. In August 2016 and 2018, the American Physiological Society updated the Information for Authors, which included the introduction of several required or strongly encouraged reporting practices. We audited Journal of Neurophysiology papers published in 2019 and 2020 (downloaded through the library of the University of New South Wales) on reporting items selected from the 2016 audit, the newly introduced reporting practices, and items from previous audits. Summary statistics (means, counts) were used to summarize audit results. In total, 580 papers were audited. Compared to results from the 2016 audit, several reporting practices remained unchanged or worsened. For example, 60% of papers erroneously reported standard errors of the mean, 23% of papers included undefined measures of variability, 40% of papers failed to define a statistical threshold for their tests, and when present, 64% of papers with p-values between 0.05 and 0.1 misinterpreted them as statistical trends. As for the newly introduced reporting practices, required practices were consistently adhered to by 34 to 37% of papers, while strongly encouraged practices were consistently adhered to by 9 to 26% of papers. Adherence to the other audited reporting practices was comparable to our previous audits. Publicly highlighting poor reporting practices did little to improve research reporting. Similarly, requiring or strongly encouraging reporting practices was only partly effective. Although the present audit focused on a single journal, this is likely not an isolated case. Stronger, more strategic measures are required to improve poor research reporting.

Impact of Aging and Cellular Senescence in the Pathophysiology of Preeclampsia.

The incidence of hypertensive disorders of pregnancy is increasing, which may be due to several factors, including an increased age at pregnancy and more comorbid health conditions during reproductive years. Preeclampsia, the most severe hypertensive disorder of pregnancy, has been associated with an increased risk of future disease, including cardiovascular and kidney diseases. Cellular senescence, the process of cell cycle arrest in response to many physiologic and maladaptive stimuli, may play an important role in the pathogenesis of preeclampsia and provide a mechanistic link to future disease. In this article, we will discuss the pathophysiology of preeclampsia, the many mechanisms of cellular senescence, evidence for the involvement of senescence in the development of preeclampsia, as well as evidence that cellular senescence may link preeclampsia to the risk of future disease. Lastly, we will explore how a better understanding of the role of cellular senescence in preeclampsia may lead to therapeutic trials. © 2023 American Physiological Society. Compr Physiol 13:5077-5114, 2023.

Mechanosensitive Channels in Lung Health and Disease.

The lung is an inherently mechanosensitive organ, where cells of the airway and parenchyma experience a range of mechanical forces throughout life including shear, stretch, and compression, in both health and disease. In this regard, pediatric and adult lung diseases such as wheezing and asthma, bronchopulmonary dysplasia (BPD), chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis (PF) all involve macroscopic and cellular changes to the mechanical properties of the bronchial airways and/or parenchyma to varying extents. Accordingly, understanding how mechanical forces are sensed in the lung, and the responses of cells and tissues in the context of normal development and health versus disease conditions becomes highly relevant. There is increasing recognition that transduction of mechanical forces into cellular responses involves a number of channels, some of which are inherently mechanosensitive. Such channels trigger mechanotransduction pathways that may further mediate cellular remodeling, inflammation, and other pathophysiologic mechanisms in response to stretch, stiffness, and inflammatory cascades. Two particularly important channel families have emerged in pulmonary pathophysiology: the transient receptor potential vanilloid family with focus on member TRPV4 and the recently identified Piezo (PZ) channels. Here, we explore current understanding of the contributions of TRPV4 and PZ channels in lung health and disease states, focusing on the interactions between these mechanosensitive channels and their local environment including immune cells, the extracellular matrix, and cellular cytoskeletal elements. We further discuss potential areas for future research to better understand the impact of mechanical channels on pulmonary health and disease. © 2023 American Physiological Society. Compr Physiol 13:5157-5178, 2023.

Links between Exercise Capacity, Exercise Training, and Metabolism.

Exercise capacity of an individual describes the ability to perform physical activity. This exercise capacity is influenced by intrinsic factors such as genetic constitution and extrinsic factors such as exercise training. On the metabolic level exercise and metabolism are linked. As an important site of metabolism and the main source for ATP needed for muscle contraction, mitochondrial function can determine exercise capacity, and exercise inversely influences mitochondrial function. It has been suggested that exercise mediates many of its effects due to such metabolic changes. Although extrinsic factors affect exercise capacity, a major part of an individual's exercise capacity is genetically determined, and extrinsic factors can only improve on this baseline. Looking at the effect of exercise capacity on and with disease, the two go hand in hand. On one hand, disease is negatively affecting an individual's exercise capacity; on the other hand, exercise offers an effective treatment option. Combining these factors, exercise capacity is an often-ignored prognostic variable for life expectancy as well as morbidity and mortality. In this review, we aim to provide the current knowledge on the links between inherited and acquired exercise capacity, as well as the mechanisms in which metabolism interacts with exercise capacity. © 2023 American Physiological Society. Compr Physiol 13:5115-5155, 2023.

Insulin Resistance and Insulin Handling in Chronic Kidney Disease.

Insulin regulates energy metabolism involving multiple organ systems. Insulin resistance (IR) occurs when organs exhibit reduced insulin sensitivity, leading to difficulties in maintaining glucose homeostasis. IR ensures decades prior to development of overt diabetes and can cause silent metabolic derangements. IR is typically seen very early in the course of chronic kidney disease (CKD) and is evident even when the estimated glomerular filtration rate (eGFR) is within the normal range and IR persists at various stages of kidney disease. In this article, we will discuss insulin handling by the kidneys, mechanisms responsible for IR in CKD, measurements and management of IR in patients with CKD, and recent type 2 diabetic trials with implications for improved cardiovascular outcomes in CKD. © 2023 American Physiological Society. Compr Physiol 13:5069-5076, 2023.

A review of the historical use of sex as a biological variable in the American Journal of Physiology-Heart and Circulatory Physiology.

Despite National Institute of Health (NIH) mandates requiring sex as a biological variable (SABV), female underrepresentation persists in research, driving the American Journal of Physiology-Heart and Circulatory Physiology (Am J Physiol-Heart Circ) to publish SABV expectations in 2021. To determine progress within the Am J Physiol-Heart Circ, this mini-review evaluated SABV during the first 6 mo of each decade from 1980 to 2020, and 2019, to mitigate pandemic influence. Of the 1,205 articles published, 1,087 articles were included in this review (articles without original research subjects were excluded), of which 72.9% identified subjects. There were consistently fewer female human participants than males, except within 2019 (1980: females n = 3, males n = 5; 1990: females n = 70, males n = 199; 2000: females n = 305, males n = 355; 2010: females n = 186, males n = 472; 2019: females n = 1,695, males n = 1,550; 2020: females n = 1,157, males n = 1,222) and fewer female animals than males (1980: females n = 58, males n = 1,291; 1990: females n = 447, males n = 2,628; 2000: females n = 590, males n = 3,083; 2010: females n = 663, males n = 4,517; 2019: females n = 338, males n = 1,340; 2020: females n = 1,372, males n = 1,973). Only 16 (12.3%) articles including humans discussed SABV from 1980 to 2020. There are persistent SABV disparities within Am J Physiol-Heart Circ with some improvements in recent years. It is imperative that organizations such as the American Physiological Society and NIH foster an expectation of SABV as the norm, not the exception.

Gallstone and Gallbladder Disease: Biliary Tract and Cholangiopathies.

Cholestatic liver diseases are named primarily due to the blockage of bile flow and buildup of bile acids in the liver. Cholestasis can occur in cholangiopathies, fatty liver diseases, and during COVID-19 infection. Most literature evaluates damage occurring to the intrahepatic biliary tree during cholestasis; however, there may be associations between liver damage and gallbladder damage. Gallbladder damage can manifest as acute or chronic inflammation, perforation, polyps, cancer, and most commonly gallstones. Considering the gallbladder is an extension of the intrahepatic biliary network, and both tissues are lined by biliary epithelial cells that share common mechanisms and properties, it is worth further evaluation to understand the association between bile duct and gallbladder damage. In this comprehensive article, we discuss background information of the biliary tree and gallbladder, from function, damage, and therapeutic approaches. We then discuss published findings that identify gallbladder disorders in various liver diseases. Lastly, we provide the clinical aspect of gallbladder disorders in liver diseases and ways to enhance diagnostic and therapeutic approaches for congruent diagnosis. © 2023 American Physiological Society. Compr Physiol 13:4909-4943, 2023.

Spatial Single-Cell Technologies for Exploring Gastrointestinal Tissue Transcriptome.

In the gastrointestinal (GI) system, like in other organ systems, the histological structure is a key determinant of physiological function. Tissues form multiple layers in the GI tract to perform their specialized functions in secretion, absorption, and motility. Even at the single layer, the heterogeneous cell population performs a diverse range of digestive or regulatory functions. Although many details of such functions at the histological and cell biological levels were revealed by traditional methods such as cell sorting, isolation, and culture, as well as histological methods such as immunostaining and RNA in situ hybridization, recent advances in spatial single-cell technologies could further contribute to our understanding of the molecular makeup of GI histological structures by providing a genome-wide overview of how different genes are expressed across individual cells and tissue layers. The current minireview summarizes recent advances in the spatial transcriptomics field and discusses how such technologies can promote our understanding of GI physiology. © 2023 American Physiological Society. Compr Physiol 13:4709-4718, 2023.

Serotonergic Control of Gastrointestinal Development, Motility, and Inflammation.

Although it is most well-known for its roles in central nervous system (CNS) function, the vast majority of serotonin, or 5-hydroxytryptamine (5-HT), is produced in the gastrointestinal (GI) tract. 5-HT is synthesized mostly by enterochromaffin (EC) cells of the GI epithelium and, in small part, by neurons of the enteric nervous system (ENS). The GI tract contains an array of broadly distributed 5-HT receptors, which participate in functions such as motility, sensation, inflammation, and neurogenesis. The roles of 5-HT in these functions are reviewed, as well as its role in the pathophysiology of disorders of gut-brain interaction (DGBIs) and inflammatory bowel diseases (IBD). © 2023 American Physiological Society. Compr Physiol 13:4851-4868, 2023.

Hypoxia in the Pathophysiology of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is an idiopathic disease of disordered chronic inflammation in the intestines that affects many people across the world. While the disease is still being better characterized, greater progress has been made in understanding the many components that intersect in the disease. Among these components are the many pieces that compose the intestinal epithelial barrier, the various cytokines and immune cells, and the population of microbes that reside in the intestinal lumen. Since their discovery, the hypoxia-inducible factors (HIFs) have been found to play an expansive role in physiology as well as diseases such as inflammation due to their role in oxygen sensing-related gene transcription, and metabolic control. Making use of existing and developing paradigms in the immuno-gastroenterology of IBD, we summarized that hypoxic signaling plays as another component in the status and progression of IBD, which may include possible functions at the origins of inflammatory dysregulation. © 2023 American Physiological Society. Compr Physiol 13:4767-4783, 2023.

Energetic Stress-Induced Metabolic Regulation by Extracellular Vesicles.

Recent studies have demonstrated that extracellular vesicles (EVs) serve powerful and complex functions in metabolic regulation and metabolic-associated disease, although this field of research is still in its infancy. EVs are released into the extracellular space from all cells and carry a wide range of cargo including miRNAs, mRNA, DNA, proteins, and metabolites that have robust signaling effects in receiving cells. EV production is stimulated by all major stress pathways and, as such, has a role in both restoring homeostasis during stress and perpetuating disease. In metabolic regulation, the dominant stress signal is a lack of energy due to either nutrient deficits or damaged mitochondria from nutrient excess. This stress signal is termed "energetic stress," which triggers a robust and evolutionarily conserved response that engages major cellular stress pathways, the ER unfolded protein response, the hypoxia response, the antioxidant response, and autophagy. This article proposes the model that energetic stress is the dominant stimulator of EV release with a focus on metabolically important cells such as hepatocytes, adipocytes, myocytes, and pancreatic β-cells. Furthermore, this article will discuss how the cargo in stress-stimulated EVs regulates metabolism in receiving cells in both beneficial and detrimental ways. © 2023 American Physiological Society. Compr Physiol 13:5051-5068, 2023.

Research journey into multiple-sensor theory.

In 1998, I was asked by the American Physiological Society to review a book written by Dr. Michael de Burgh Daly, Peripheral Arterial Chemoreceptors and Respiratory-Cardiovascular Integration. Inspired by this work, I came to appreciate how researchers in the later stages of their careers and who provide a detailed review of their experimental approach might effectively contribute to science, especially to the benefit of young scientists (Yu J. The Physiologist 41: 231, 1998.). This article is written in that vein. Over several decades of intensive investigation of cardiopulmonary reflexes, focused on the sensory receptors, my colleagues and I advanced a novel multiple-sensor theory (MST) to explain the role of the vagal mechanosensory system. Described here is our research journey through various stages of developing MST and the process of how the problem was identified, approached, and tackled. MST redefines conventional mechanosensor doctrines and is supported by new studies that clarify a century of research data. It entails reinterpretation of many established findings. Hopefully, this article will benefit young scientists, such as graduate and postdoctoral students in the cardiopulmonary sensory research field.

Editorial introductions.

Current Opinion in Pediatrics was launched in 1989. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The fields of pediatrics are divided into 18 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Editor in Chief and Section Editors for this issue. SECTION EDITORS Clifford W BogueClifford W BogueClifford W. Bogue, MD, a pediatric critical care specialist, is the Waldemar Von Zedtwitz Professor and Chairman of Pediatrics at Yale School of Medicine, USA, where he has been on the faculty since 1993. In 2014, he was named the inaugural Chief Medical Officer of Yale-New Haven Children's Hospital, USA. Dr Bogue was named Chairman of the Department of Pediatrics in August 2017. He received his undergraduate and medical degrees from the University of Virginia (UVA), USA and was a resident and chief resident in pediatrics at Vanderbilt University before completing a fellowship in pediatric critical care medicine at Yale. During his career at Yale, Dr Bogue has held several medical school and hospital leadership positions. He has been actively involved in training students, residents and fellows and is committed to the development of pediatric physician-scientists. His academic career at Yale also included establishing and directing an NIH-funded research program in the developmental biology of the lung, liver and cardiovascular system for over 20 years. Dr Bogue has served on several national and international boards in academic pediatrics. Jean KligJean KligJean E. Klig, MD is the Director for Undergraduate Education in the Division of Pediatric Emergency Medicine, Department of Emergency Medicine at the Massachusetts General Hospital, USA and an Assistant Professor of Pediatrics and Emergency Medicine at Harvard Medical School, USA. She earned her medical degree at the Albert Einstein College of Medicine, USA in 1988, and completed her internship and residency in pediatrics at Children's Hospital Boston, USA. Following residency, she completed her fellowship in pediatric emergency medicine at Children's Hospital Oakland, USA. Dr Klig then joined the Department of Pediatrics at Yale University School of Medicine, USA, as faculty in the Pediatric Emergency Department of the Children's Hospital at Yale-New Haven from its opening in 1993 until 2004. During this time, she contributed to the development of a pediatric emergency medicine clinical service and held an array of roles in medical education, including early simulation-based teaching, at the graduate and undergraduate levels. Dr Klig returned to Boston and continued her work in medical education focusing on clinical skills development and simulation-based teaching at the undergraduate and graduate levels. She joined the Harvard-Macy International educator course faculty in 2008, where she continues to serve on the strategic planning committee, lead the microteaching program, and co-lead the faculty development team. Dr Klig served as the Associate Chief of Pediatric Emergency Services (2008 - 2018), followed by expansion of her role in undergraduate education at Harvard Medical School, where she now serves as senior Core Clinical Skills Assessment Faculty and lead faculty for the Harvard Medical School Course Directors Leadership Institute. On a national level, Dr Klig recently co-chaired the Pediatric Emergency Medicine Education Research and Scholarship Consensus session and report for the Society of Academic Emergency Medicine. Dr Klig lectures nationally and internationally on pediatric emergency medicine and medical education. David N CornfieldDavid N CornfieldDavid N. Cornfield earned a medical degree from the University of Wisconsin School of Medicine (1986) and completed residency at Children's Mercy Hospital in Kansas City, Missouri, USA where he was recognized as the Most Outstanding House Officer and Chief Resident (1989). He later completed his fellowship in both pediatric pulmonology and critical care medicine at the University of Colorado Health Sciences Center, USA Denver Children's and National Jewish Hospital, Denver, USA (1993). Cornfield was appointed the first holder of the Anne T. and Robert M. Bass Professorship in Pediatric Pulmonary Medicine at Stanford University School of Medicine in December 2005. He is director of the Center for Excellence in Pulmonary Biology, and chief of the division of pediatric pulmonary, asthma, and sleep medicine at Stanford University, USA. Prior to joining the faculty of Stanford University, David served as professor of pediatrics, physiology, and surgery at the University of Minnesota Medical School, USA and Division Director of Pediatric Pulmonary and Critical Care Medicine, interim head of the Department of Pediatrics, and as the Associate Dean for Research. At Stanford University, Dr Cornfield led the Division of Pediatric Critical Care Medicine from 2006 through 2015. Dr Cornfield's basic science research focuses on pulmonary vascular development, alveolarization, and the molecular mechanisms underlying oxygen sensing. His research has provided insight into the fundamental biology of the transition of pulmonary circulation at birth, determinants of pulmonary vascular tone, and lung development. Ongoing research includes the transcriptomics of the developing lung using single cell RNA sequencing, uterine contractility in term and preterm labour, and lung barrier function. His laboratory has been NIH funded for the past 25 years. Clinical and translational research has included work on inhaled nitric oxide, acute lung injury in infants and children, non-invasive approaches to detect organ rejection, the lung microbiome in cystic fibrosis, remote monitoring of asthma, design and creation of low-cost mechanical ventilator, bronchopulmonary dysplasia (BPD), violence prevention in developing countries, microlending in Africa, and training and retaining physician-scientists in pediatrics. Dr Cornfield has been the PI of an NIH training grant in pulmonary biology since 2014. Dr Cornfield is an active member of the American Pediatric Society (APS), American Thoracic Society, Society for Pediatric Research (SPR), American Academy of Pediatrics (AAP), and American Physiological Society, and served previously as President of the SPR. He serves on the editorial boards of the American Journal of Physiology, Pediatrics, and Pulmonary Circulation. He served as a regular member of study sections of the NIH (NHLBI, NICHD), the March of Dimes, and the American Heart Association (AHA) and as a member of the AAP pediatric education committee, Pediatric Academic Societies (PAS) advocacy committee, and the Federation of Pediatric Organizations task force on training and scholarship. Dr Cornfield is committed to training the next generation of physician-scientists and is a founding co-Director of the Chan Zuckerberg Biohub Physician-Scientist Training Program and Director of the Wu Tsai Human Performance Alliance Physician-Scientist Fellowship Program. Dr Cornfield is the recipient of numerous professional honors including the Daniel C. Darrow Award from Children's Mercy Hospital, the Richard B. Rowe Award for outstanding achievements in perinatal cardiology from the SPR, the Established-Investigator and Clinician-Scientist Awards from the AHA, and Clinician of the Year Award from the University of Minnesota Medical School and has been recognized annually as an Outstanding Faculty Educator, “Top Pediatrician” and “Best Doctor.” Henry H BernsteinHenry H BernsteinDr Bernstein is a Professor of Pediatrics at Zucker School of Medicine at Hofstra/Northwell in New York, USA. He taps into his extensive 38–year experience as a general pediatrician in private practice, the National Health Service Corps, and as Chief of General Academic Pediatrics at urban, suburban, and rural children's hospitals to promote the health and well-being of children, their families, and their communities. His private, community-based primary care (generalist) experiences in combination with academic leadership responsibilities have provided him with a value-added, translational science perspective, unique from many others in academia. This tacit knowledge enables him to fulfil a lifelong passion of communicating, educating, and translating science into clinical settings, educational venues, policymaking, and media interactions to advance the health of children. Research is consistently woven into the fabric of Dr Bernstein's clinical practice, which has served as a “laboratory” for his active studies. His research and quality improvement initiatives focus on issues important to Academic General Pediatrics and community-based practice, including immunizations, infectious diseases, postpartum newborn discharge, childhood obesity, breastfeeding, health promotion, preventive health screening in primary care, technology and medical education. His commitment, innovative spirit, and enthusiasm also encompass many facets of medical education along the continuum from training and mentoring future physicians to fostering lifelong learning and supporting the continuous professional development of practicing pediatricians. Dr Bernstein is a voting member of the US Food and Drug Administration's (FDA) Vaccines and Related Biological Products Advisory Committee (VRBPAC) and a former voting member of the Centers for Disease Control and Prevention's (CDC) Advisory Committee on Immunization Practice (ACIP). He serves as a consultant on the ACIP COVID-19, Influenza, and Immunization Schedules for Adults and Children workgroups. He also is an ex-officio member of the American Academy of Pediatrics’ (AAP) Committee on Infectious Diseases (Red Book Committee) and was Associate Editor of the AAP's Red Book Online for 12 years. In addition, he is Editor-in-Chief Emeritus of PediaLink, the AAP's online home for lifelong learning, and past Chair of the interdisciplinary Bright Futures Health Promotion Workgroup, which created a distinctive health promotion curriculum, videos, and a companion educational website (www.pediatricsinpractice.org). Dr Bernstein has been Editor of the Office Pediatrics Series in Current Opinion in Pediatrics since 1995 and was Senior Editor of Pediatrics on the public website of Harvard Medical School's Health Publications Division for 17 years. He regularly shares his knowledge and expertise by educating the public, writing for health information websites and often participating in media interviews on a variety of pediatric health care issues including immunizations, diagnosis and treatment of common childhood infectious diseases and conditions, and practical information for parents, teachers and caregivers. In the spirit of lifelong learning, Dr Bernstein earned a masters in healthcare management (MHCM) at Harvard T. H. Chan School of Public Health, USA in 2013 and has been a faculty member in this Executive Education Masters degree program since. He actively maintains his certification by the American Board of Pediatrics. He completed his residency training in pediatrics at St. Christopher's Hospital for Children in Philadelphia, USA after earning his medical degree from the University of Medicine and Dentistry of New Jersey - School of Osteopathic Medicine, USA. Hank and his wife, Sophie, have been married for 43 years, are extremely proud of their 38-year-old daughter, Lauren, and 32-year-old son, David, and are “over the moon” with their 2 granddaughters, Eva and Vienne.

Dietary-induced changes in the hindgut microbiome and metabolism of a marine herbivorous fish

To advance our understanding of the factors that influence gut physiology and function, we are examining how the gut microbiome changes under varying environments and diets. We integrated the gut transcriptome and microbiome to understand how dietary changes impact Cebidichthys violaceus, an herbivorous fish native to the California coast that is known to have an active microbial community in its hindgut. Wild-caught fish from San Simeon, California were fed either herbivore, omnivore, or carnivore diets in the laboratory for six months. We expected the microbiome, as well as the hindgut and liver transcriptome, to change with dietary perturbations, with wild herbivorous fish being most similar to lab-herbivore fish. Wild fish microbial communities were indeed different from laboratory-fed fish (P<0.001, Bray-Curtis distances), but the laboratory-omnivore diet fish were the most similar to wild fish, sharing a high abundance of taxa in the Bacteroidota and Bacillota (Families Ruminococcaceae and Rikenellaceae), whereas the laboratory-herbivore and laboratory-carnivore fish shared a high abundance of taxa from the Pseudomonodota (Families Burkholderiaceae and Oxalobacteraceae). The microbial diversity patterns in multivariate space among the fish on the different diets directly resembled that of host distal intestine gene expression in multivariate space (i.e., wild and lab-omnivore diet fish were the most similar). The hindgut had 519 differentially expressed genes, and wild fish highly express genes involved in ion transport and lipid and glucose metabolism. The liver, on the other hand, presented 4650 differentially expressed genes, and wild fish highly express genes for fatty acid synthesis and proteolysis. These data show how the gut microbiome and transcriptome varies as a function of different diets in an herbivorous marine fish. Our project provides insight into what it takes for fish to deal with shifting resources, which is important for marine resource management and new potential aquaculture species development. NSF Grant IOS-1355224 and William Townsend Porter Pre-doctoral Fellowship from the American Physiological Society. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Blood Brain Barrier is functional 24 hours following Pregnancy related Acute Kidney Renal Injury

From 1999 to 2011, incidences of pregnancy related acute kidney injury (PR-AKI) increased from 2.4 to 6.3 per every 10,0000 deliveries in the U.S. Acute Kidney Injury (AKI) is associated with increased circulating uremic toxins such as indoxyl sulfate (I.S) and p cresyl sulfate (PCS), cognitive dysfunction and blood brain barrier (BBB) disruption. The purpose of these experiments was to determine if 24 hours following AKI there is evidence of BBB dysfunction in a model of PR-AKI. We hypothesized that AKI would lead to BBB disruption while the treatment of I.S alone does not as our overall hypothesis is that accumulation of uremic toxins following renal injury leads to cognitive dysfunction. Time-pregnant Sprague Dawley rats arrived on gestational day (GD)10 and were randomized into the following groups: normal pregnant (NP; n=5-9), AKI (n=5-8), 100 I.S (n=5-10), and 200 I.S (n=5-9). Beginning on GD11, a subset of rats received either 100 mg/kg body weight (BW) or 200 mg/kg BW dose of I.S via drinking water daily. On GD18, AKI rats received a 45-min bilateral renal ischemic reperfusion surgery. On GD19, blood pressure was taken via CODA tail cuff followed by organ and blood collection. Five animals per group were injected with 4% Evan’s Blue (EB) for 30 mins and flushed with saline. Residual EB was measured in the frontal and posterior cortices, brain stem, and cerebellum. Serum was used to measure I.S and PCS via mass spectrometry. Creatinine was measured in both urine and serum via assay (BioAssay Systems). Data was analyzed via one-way ANOVA followed by multiple comparisons via GraphPad Prism. Statistical significance was determined as p<0.05. AKI animals had a higher kidney weight/BW ratio to NP (p=0.04), 100 I.S (p=0.003), and 200 I.S (p=0.04) while 200 I.S had a larger kidney to BW ratio to NP rats (p=0.02). AKI had smaller spleen weight/BW(p=0.02) ratios compared to NP rats. Pups born to AKI dams were significantly smaller than NP (p=0.001), 100 I.S (p=0.01), and 200 I.S (p <0.0001) dams. 200 I.S (p=0.02) had an increase in placental efficiency (placenta weight/ pup weight) compared to NP rats. Circulating I.S is significantly decreased in 100 I.S rats compared to NP (p=0.04) and AKI (p=0.04). PCS was significantly increased in AKI rats compared to NP (p=0.02), 100 I.S (p=0.03), and 200 I.S (p=0.03). When EB was measured, 200 I.S had significantly more EB in the brain stem region (p=0.01) compared to AKI rats. A one-way ANOVA showed differences in creatinine levels between groups (p=0.04), but multiple comparisons showed no differences between specific groups. PR-AKI led to changes in kidney and spleen weight without differences in BW which could be contributed by the immune response of the injury. We have preliminary data showing increases in circulating I.S 4 months post-partum which suggests increases occur later in postpartum. The brain stem is an interest of study as it has been shown to be implicated in chronic renal failure. Funding to AG (William Townsend Porter Predoctoral Fellowship from American Physiological Society), to KW (Chan Zuckerberg Initiative Science Diversity Leadership Award) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.