Can ChatGPT Replace an Otolaryngologist in Guiding Parents on Tonsillectomy?

Background: ChatGPT is an artificial intelligence tool, which utilizes machine learning to analyze and generate human-like text. The user-friendly accessibility of this tool enables patients conveniently access medical information without intricate terminology challenges. The objective of this study was to assess the accuracy of ChatGPT in providing insights into indications and management of complications after tonsillectomy, a common pediatric otolaryngology procedure. Methods: The responses generated by ChatGPT were compared to the "Clinical practice guidelines: tonsillectomy in children-executive summary" developed by the American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF). An assessment was carried out by presenting predetermined questions regarding indications and complications post tonsillectomy to ChatGPT, followed by a comparison of its responses with the established guideline by 2 otolaryngology experts. The responses of both parties were reviewed by the senior author. Results: A total of 16 responses generated by ChatGPT were assessed. After a comprehensive review, it was concluded that 15 out of 16 (93.8%) responses demonstrated a high degree of reliability and accuracy, closely adhering to the standard established by the AAO-HNSF guideline. Conclusion: The results validate the potential of using ChatGPT to enhance healthcare delivery making guidelines more accessible to patients while also emphasizing the importance of ensuring the provision of accurate and reliable medical advice to patients.

Can ChatGPT Guide Parents on Tympanostomy Tube Insertion?

BACKGROUND: The emergence of ChatGPT, a state-of-the-art language model developed by OpenAI, has introduced a novel avenue for patients to seek medically related information. This technology holds significant promise in terms of accessibility and convenience. However, the use of ChatGPT as a source of accurate information enhancing patient education and engagement requires careful consideration. The objective of this study was to assess the accuracy and reliability of ChatGPT in providing information on the indications and management of complications post-tympanostomy, the most common pediatric procedure in otolaryngology. METHODS: We prompted ChatGPT-3.5 with questions and compared its generated responses with the recommendations provided by the latest American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF) "Clinical Practice Guideline: Tympanostomy Tubes in Children (Update)". RESULTS: A total of 23 responses were generated by ChatGPT against the AAO-HNSF guidelines. Following a thorough review, it was determined that 22/23 (95.7%) responses exhibited a high level of reliability and accuracy, closely aligning with the gold standard. CONCLUSION: Our research study indicates that ChatGPT may be of assistance to parents in search of information regarding tympanostomy tube insertion and its clinical implications.

Exploring trust development in families of children towards surgical and emergency care providers: A scoping review of the literature.

BACKGROUND: Trust is central to the therapeutic relationship between patients and their providers, yet little is known about how it is developed in the unique context of children facing surgical emergencies. We sought to identify factors fostering trust development, gaps, and areas for improvement. METHODS: We searched eight databases from inception to June 2021 to identify studies focusing on trust in pediatric surgical and urgent care settings. PRISMA-ScR protocols were followed, and screening carried out by two independent reviewers. Data collection included study characteristics, outcomes, and results. RESULTS: Out of 5578 articles screened, 12 fulfilled the inclusion criteria. Four major trust constructs were identified: competence, communication, dependability, and caring. Despite various instruments used, all studies reported a high level of parental trust. Nearly all studies (11/12) noted trust depending on parents' sociodemographic background, with ethnicity (3/12) and level of education and language barriers (2/12) limiting parents' confidence in physicians. High trust levels significantly correlated with effective communication and perceived quality of care. Most effective interventions enhancing trust included communication and caring trust constructs (10/12) rather than competence and dependability (5/12). Parents' individual experiences, development of compassionate interactions, and practice of family-centered care appeared important in developing trust. CONCLUSIONS: Improving communication and providing compassionate care, as well as encouraging a patient-centered approach, appear to be most effective in promoting trust in pediatric surgical and urgent settings. Our findings can guide future educational interventions towards strengthening parental trust and promoting child- and family-centered care in pediatric surgical settings.

Expression and biochemical analyses of proteins involved in the transport of carotenoids and retinoids.

Animals acquire carotenoids from the diet and convert them to retinoids. These lipids must be distributed in the body to support retinoid signaling in peripheral tissues and photoreceptor function in the eyes. However, the hydrophobicity of carotenoids and retinoids limit their diffusion in the aqueous environment of the body. Therefore, membrane proteins and cellular binding proteins transport these lipids between extra- and intracellular compartments and facilitate their metabolism. Mutations in genes encoding these transport proteins are associated with a wide spectrum of blinding disorders. Here, we describe approaches used by our laboratories that have proven successful in expressing these proteins and examining their biochemical properties in the test tube and in cell-based assays. These assays can be utilized for screening of small molecule modulators of their activities to correct pathologies associated with retinoid metabolism.

Carotenoid modifying enzymes in metazoans.

Carotenoids constitute an essential dietary component of animals and other non-carotenogenic species which use these pigments in both their modified and unmodified forms. Animals utilize uncleaved carotenoids to mitigate light damage and oxidative stress and to signal fitness and health. Carotenoids also serve as precursors of apocarotenoids including retinol, and its retinoid metabolites, which carry out essential functions in animals by forming the visual chromophore 11-cis-retinaldehyde. Retinoids, such as all-trans-retinoic acid, can also act as ligands of nuclear hormone receptors. The fact that enzymes and biochemical pathways responsible for the metabolism of carotenoids in animals bear resemblance to the ones in plants and other carotenogenic species suggests an evolutionary relationship. We will explore some of the modes of transmission of carotenoid genes from carotenogenic species to metazoans. This apparent relationship has been successfully exploited in the past to identify and characterize new carotenoid and retinoid modifying enzymes. We will review approaches used to identify putative animal carotenoid enzymes, and we will describe methods used to functionally validate and analyze the biochemistry of carotenoid modifying enzymes encoded by animals.

Regenerating Skeletal Muscle Compensates for the Impaired Macrophage Functions Leading to Normal Muscle Repair in Retinol Saturase Null Mice.

Skeletal muscle repair is initiated by local inflammation and involves the engulfment of dead cells (efferocytosis) by infiltrating macrophages at the injury site. Macrophages orchestrate the whole repair program, and efferocytosis is a key event not only for cell clearance but also for triggering the timed polarization of the inflammatory phenotype of macrophages into the healing one. While pro-inflammatory cytokines produced by the inflammatory macrophages induce satellite cell proliferation and differentiation into myoblasts, healing macrophages initiate the resolution of inflammation, angiogenesis, and extracellular matrix formation and drive myoblast fusion and myotube growth. Therefore, improper efferocytosis results in impaired muscle repair. Retinol saturase (RetSat) initiates the formation of various dihydroretinoids, a group of vitamin A derivatives that regulate transcription by activating retinoid receptors. Previous studies from our laboratory have shown that RetSat-null macrophages produce less milk fat globule-epidermal growth factor-factor-8 (MFG-E8), lack neuropeptide Y expression, and are characterized by impaired efferocytosis. Here, we investigated skeletal muscle repair in the tibialis anterior muscle of RetSat-null mice following cardiotoxin injury. Our data presented here demonstrate that, unexpectedly, several cell types participating in skeletal muscle regeneration compensate for the impaired macrophage functions, resulting in normal muscle repair in the RetSat-null mice.

Mechanisms of Feedback Regulation of Vitamin A Metabolism.

Vitamin A is an essential nutrient required throughout life. Through its various metabolites, vitamin A sustains fetal development, immunity, vision, and the maintenance, regulation, and repair of adult tissues. Abnormal tissue levels of the vitamin A metabolite, retinoic acid, can result in detrimental effects which can include congenital defects, immune deficiencies, proliferative defects, and toxicity. For this reason, intricate feedback mechanisms have evolved to allow tissues to generate appropriate levels of active retinoid metabolites despite variations in the level and format, or in the absorption and conversion efficiency of dietary vitamin A precursors. Here, we review basic mechanisms that govern vitamin A signaling and metabolism, and we focus on retinoic acid-controlled feedback mechanisms that contribute to vitamin A homeostasis. Several approaches to investigate mechanistic details of the vitamin A homeostatic regulation using genomic, gene editing, and chromatin capture technologies are also discussed.

Role of cellular retinol-binding protein, type 1 and retinoid homeostasis in the adult mouse heart: A multi-omic approach.

The main active metabolite of Vitamin A, all-trans retinoic acid (RA), is required for proper cellular function and tissue organization. Heart development has a well-defined requirement for RA, but there is limited research on the role of RA in the adult heart. Homeostasis of RA includes regulation of membrane receptors, chaperones, enzymes, and nuclear receptors. Cellular retinol-binding protein, type 1 (CRBP1), encoded by retinol-binding protein, type 1 (Rbp1), regulates RA homeostasis by delivering vitamin A to enzymes for RA synthesis and protecting it from non-specific oxidation. In this work, a multi-omics approach was used to characterize the effect of CRBP1 loss using the Rbp1-/- mouse. Retinoid homeostasis was disrupted in Rbp1-/- mouse heart tissue, as seen by a 33% and 24% decrease in RA levels in the left and right ventricles, respectively, compared to wild-type mice (WT). To further inform on the effect of disrupted RA homeostasis, we conducted high-throughput targeted metabolomics. A total of 222 metabolite and metabolite combinations were analyzed, with 33 having differential abundance between Rbp1-/- and WT hearts. Additionally, we performed global proteome profiling to further characterize the impact of CRBP1 loss in adult mouse hearts. More than 2606 unique proteins were identified, with 340 proteins having differential expression between Rbp1-/- and WT hearts. Pathway analysis performed on metabolomic and proteomic data revealed pathways related to cellular metabolism and cardiac metabolism were the most disrupted in Rbp1-/- mice. Together, these studies characterize the effect of CRBP1 loss and reduced RA in the adult heart.

Multi-omic Analysis of Non-human Primate Heart after Partial-body Radiation with Minimal Bone Marrow Sparing.

ABSTRACT: High-dose radiation exposure results in hematopoietic and gastrointestinal acute radiation syndromes followed by delayed effects of acute radiation exposure, which encompasses multiple organs, including heart, kidney, and lung. Here we sought to further characterize the natural history of radiation-induced heart injury via determination of differential protein and metabolite expression in the heart. We quantitatively profiled the proteome and metabolome of left and right ventricle from non-human primates following 12 Gy partial body irradiation with 2.5% bone marrow sparing over a time period of 3 wk. Global proteome profiling identified more than 2,200 unique proteins, with 220 and 286 in the left and right ventricles, respectively, showing significant responses across at least three time points compared to baseline levels. High-throughput targeted metabolomics analyzed a total of 229 metabolites and metabolite combinations, with 18 and 22 in the left and right ventricles, respectively, showing significant responses compared to baseline levels. Bioinformatic analysis performed on metabolomic and proteomic data revealed pathways related to inflammation, energy metabolism, and myocardial remodeling were dysregulated. Additionally, we observed dysregulation of the retinoid homeostasis pathway, including significant post-radiation decreases in retinoic acid, an active metabolite of vitamin A. Significant differences between left and right ventricles in the pathology of radiation-induced injury were identified. This multi-omic study characterizes the natural history and molecular mechanisms of radiation-induced heart injury in NHP exposed to PBI with minimal bone marrow sparing.

Identifying vitamin A signaling by visualizing gene and protein activity, and by quantification of vitamin A metabolites.

Vitamin A (retinol) is an essential nutrient for embryonic development and adult homeostasis. Signaling by vitamin A is carried out by its active metabolite, retinoic acid (RA), following a two-step conversion. RA is a small, lipophilic molecule that can diffuse from its site of synthesis to neighboring RA-responsive cells where it binds retinoic acid receptors within RA response elements of target genes. It is critical that both vitamin A and RA are maintained within a tight physiological range to protect against developmental disorders and disease. Therefore, a series of compensatory mechanisms exist to ensure appropriate levels of each. This strict regulation is provided by a number synthesizing and metabolizing enzymes that facilitate the precise spatiotemporal control of vitamin A metabolism, and RA synthesis and signaling. In this chapter we describe protocols that (1) biochemically isolate and quantify vitamin A and its metabolites and (2) visualize the spatiotemporal activity of genes and proteins involved in the signaling pathway.

A retrospective cohort study evaluating correlates of deep tissue infections among patients enrolled in opioid agonist treatment using administrative data in Ontario, Canada.

OBJECTIVE: The objective of this study was to evaluate the relationship between individual characteristics and deep tissue infections in patients enrolled in opioid agonist treatment in Ontario, Canada. METHODS: A retrospective cohort study was conducted on patients in opioid agonist treatment between January 1, 2011, and December 31, 2015 in Ontario, Canada. Patients were identified using data from the Ontario Health Insurance Plan Database, and the Ontario Drug Benefit Plan Database. We identified other study variables including all-cause mortality using data from the Registered Persons Database. Encrypted patient identifiers were used to link across databases. Logistic regression models were used to measure potential correlates of deep tissue infections. RESULTS: An increase in the incidence of deep tissue infections was observed between 2011 and 2016 for patients on opioid agonist treatment. Additionally, age, sex, positive HIV diagnosis, and all-cause mortality was correlated with deep tissue infection in our study population. CONCLUSION: The study indicates factors that are associated with deep tissue infections in the opioid use disorder population and can be used to identify opportunities to reduce the incidence of new infections.

Role of carotenoids and retinoids during heart development.

The nutritional requirements of the developing embryo are complex. In the case of dietary vitamin A (retinol, retinyl esters and provitamin A carotenoids), maternal derived nutrients serve as precursors to signaling molecules such as retinoic acid, which is required for embryonic patterning and organogenesis. Despite variations in the composition and levels of maternal vitamin A, embryonic tissues need to generate a precise amount of retinoic acid to avoid congenital malformations. Here, we summarize recent findings regarding the role and metabolism of vitamin A during heart development and we survey the association of genes known to affect retinoid metabolism or signaling with various inherited disorders. A better understanding of the roles of vitamin A in the heart and of the factors that affect retinoid metabolism and signaling can help design strategies to meet nutritional needs and to prevent birth defects and disorders associated with altered retinoid metabolism. This article is part of a Special Issue entitled Carotenoids recent advances in cell and molecular biology edited by Johannes von Lintig and Loredana Quadro.

Modulation of retinoid signaling: therapeutic opportunities in organ fibrosis and repair.

The vitamin A metabolite, retinoic acid, is an important signaling molecule during embryonic development serving critical roles in morphogenesis, organ patterning and skeletal and neural development. Retinoic acid is also important in postnatal life in the maintenance of tissue homeostasis, while retinoid-based therapies have long been used in the treatment of a variety of cancers and skin disorders. As the number of people living with chronic disorders continues to increase, there is great interest in extending the use of retinoid therapies in promoting the maintenance and repair of adult tissues. However, there are still many conflicting results as we struggle to understand the role of retinoic acid in the multitude of processes that contribute to tissue injury and repair. This review will assess our current knowledge of the role retinoic acid signaling in the development of fibroblasts, and their transformation to myofibroblasts, and of the potential use of retinoid therapies in the treatment of organ fibrosis.

Retinol Saturase Knock-Out Mice are Characterized by Impaired Clearance of Apoptotic Cells and Develop Mild Autoimmunity.

Apoptosis and the proper clearance of apoptotic cells play a central role in maintaining tissue homeostasis. Previous work in our laboratory has shown that when a high number of cells enters apoptosis in a tissue, the macrophages that engulf them produce retinoids to enhance their own phagocytic capacity by upregulating several phagocytic genes. Our data indicated that these retinoids might be dihydroretinoids, which are products of the retinol saturase (RetSat) pathway. In the present study, the efferocytosis of RetSat-null mice was investigated. We show that among the retinoid-sensitive phagocytic genes, only transglutaminase 2 responded in macrophages and in differentiating monocytes to dihydroretinol. Administration of dihydroretinol did not affect the expression of the tested genes differently between differentiating wild type and RetSat-null monocytes, despite the fact that the expression of RetSat was induced. However, in the absence of RetSat, the expression of numerous differentiation-related genes was altered. Among these, impaired production of MFG-E8, a protein that bridges apoptotic cells to the αvß3/ß5 integrin receptors of macrophages, resulted in impaired efferocytosis, very likely causing the development of mild autoimmunity in aged female mice. Our data indicate that RetSat affects monocyte/macrophage differentiation independently of its capability to produce dihydroretinol at this stage.

Recent insights on the role and regulation of retinoic acid signaling during epicardial development.

The vitamin A metabolite, retinoic acid, carries out essential and conserved roles in vertebrate heart development. Retinoic acid signals via retinoic acid receptors (RAR)/retinoid X receptors (RXRs) heterodimers to induce the expression of genes that control cell fate specification, proliferation, and differentiation. Alterations in retinoic acid levels are often associated with congenital heart defects. Therefore, embryonic levels of retinoic acid need to be carefully regulated through the activity of enzymes, binding proteins and transporters involved in vitamin A metabolism. Here, we review evidence of the complex mechanisms that control the fetal uptake and synthesis of retinoic acid from vitamin A precursors. Next, we highlight recent evidence of the role of retinoic acid in orchestrating myocardial compact zone growth and coronary vascular development.

Alterations in retinoic acid signaling affect the development of the mouse coronary vasculature.

BACKGROUND: During the final stages of heart development the myocardium grows and becomes vascularized by means of paracrine factors and cell progenitors derived from the epicardium. There is evidence to suggest that retinoic acid (RA), a metabolite of vitamin A, plays an important role in epicardial-based developmental programming. However, the consequences of altered RA-signaling in coronary development have not been systematically investigated. RESULTS: We explored the developmental consequences of altered RA-signaling in late cardiogenic events that involve the epicardium. For this, we used a model of embryonic RA excess based on mouse embryos deficient in the retinaldehyde reductase DHRS3, and a complementary model of embryonic RA deficiency based on pharmacological inhibition of RA synthesis. We found that alterations in embryonic RA signaling led to a thin myocardium and aberrant coronary vessel formation and remodeling. Both excess, and deficient RA-signaling are associated with reductions in ventricular coverage and density of coronary vessels, altered vessel morphology, and impaired recruitment of epicardial-derived mural cells. Using a combined transcriptome and proteome profiling approach, we found that RA treatment of epicardial cells influenced key signaling pathways relevant for cardiac development. CONCLUSIONS: Epicardial RA-signaling plays critical roles in the development of the coronary vasculature needed to support myocardial growth. Developmental Dynamics 247:976-991, 2018. © 2018 Wiley Periodicals, Inc.

Hippo Signaling Plays an Essential Role in Cell State Transitions during Cardiac Fibroblast Development.

During development, progenitors progress through transition states. The cardiac epicardium contains progenitors of essential non-cardiomyocytes. The Hippo pathway, a kinase cascade that inhibits the Yap transcriptional co-factor, controls organ size in developing hearts. Here, we investigated Hippo kinases Lats1 and Lats2 in epicardial diversification. Epicardial-specific deletion of Lats1/2 was embryonic lethal, and mutant embryos had defective coronary vasculature remodeling. Single-cell RNA sequencing revealed that Lats1/2 mutant cells failed to activate fibroblast differentiation but remained in an intermediate cell state with both epicardial and fibroblast characteristics. Lats1/2 mutant cells displayed an arrested developmental trajectory with persistence of epicardial markers and expanded expression of Yap targets Dhrs3, an inhibitor of retinoic acid synthesis, and Dpp4, a protease that modulates extracellular matrix (ECM) composition. Genetic and pharmacologic manipulation revealed that Yap inhibits fibroblast differentiation, prolonging a subepicardial-like cell state, and promotes expression of matricellular factors, such as Dpp4, that define ECM characteristics.

Retinoic acid signaling promotes the cytoskeletal rearrangement of embryonic epicardial cells.

All- trans-retinoic acid (RA), a vitamin A metabolite, is an important signaling molecule required for the proper development of the heart. The epicardium is the main source of RA in the embryonic heart, yet the cardiogenic functions of epicardial-produced RA are not fully understood. Here, we investigated the roles of RA signaling in the embryonic epicardium using in vivo and in vitro models of excess or deficiency of RA. Our results suggested that RA signaling facilitates the cytoskeletal rearrangement required for the epicardial-to-mesenchymal transition of epicardial cells. In vivo treatment with an inhibitor of RA synthesis delayed the migration of epicardial-derived precursor cells (EPDCs) into the myocardium; the opposite was seen in the case of dehydrogenase/reductase superfamily (DHRS)3-deficient embryos, a mouse model of RA excess. Analysis of the behavior of epicardial cells exposed to RA receptor agonists or inhibitors of RA synthesis in vitro revealed that appropriate levels of RA are important in orchestrating the platelet-derived growth factor-induced loss of epithelial character, cytoskeletal remodeling, and migration, necessary for the infiltration of the myocardium by EPDCs. To understand the molecular mechanisms by which RA regulates epicardial cytoskeletal rearrangement, we used a whole transcriptome profiling approach, which in combination with pull-down and inhibition assays, demonstrated that the Ras homolog gene family, member A (RhoA) pathway is required for the morphologic changes induced by RA in epicardial cells. Collectively, these data demonstrate that RA regulates the cytoskeletal rearrangement of epicardial cells via a signaling cascade that involves the RhoA pathway.-Wang, S., Yu, J., Jones, J. W., Pierzchalski, K., Kane, M. A., Trainor, P. A., Xavier-Neto, J., Moise, A. R. Retinoic acid signaling promotes the cytoskeletal rearrangement of embryonic epicardial cells.

Retinol saturase modulates lipid metabolism and the production of reactive oxygen species.

Retinol saturase (RetSat) catalyzes the saturation of double bonds of all-trans-retinol leading to the production of dihydroretinoid metabolites. Beside its role in retinoid metabolism, there is evidence that RetSat modulates the cellular response to oxidative stress and plays critical roles in adipogenesis and the accumulation of lipids. Here, we explore the relationship between RetSat, lipid metabolism and oxidative stress using in vitro and in vivo models with altered expression of RetSat. Our results reveal that RetSat is a potent modulator of the cellular response to oxidative stress and the generation of reactive oxygen species (ROS). The levels of reactive aldehydes products of lipid peroxidation, as measured based on thiobarbituric acid reactivity, are increased in RetSat overexpressing cells and, conversely, reduced in cells and tissues with reduced or absent expression of RetSat compared to controls. Despite increased weight gain, neutral lipid accumulation and alterations in hepatic lipid composition, RetSat-/- mice exhibit normal responses to insulin. In conclusion, our findings further expand upon the role of RetSat in oxidative stress and lipid metabolism and could provide insight in the significance of alterations of RetSat expression as observed in metabolic disorders.

New insights and changing paradigms in the regulation of vitamin A metabolism in development.

Vitamin A and its active metabolite retinoic acid are essential for embryonic development and adult homeostasis. Surprisingly, excess or deficiency of vitamin A and retinoic acid can cause similar developmental defects. Therefore, strict feedback and other mechanisms exist to regulate the levels of retinoic acid within a narrow physiological range. The oxidation of vitamin A to retinal has recently been established as a critical nodal point in the synthesis of retinoic acid, and over the past decade, RDH10 and DHRS3 have emerged as the predominant enzymes that regulate this reversible reaction. Together they form a codependent complex that facilitates negative feedback maintenance of retinoic acid levels and thus guard against the effects of dysregulated vitamin A metabolism and retinoic acid synthesis. This review focuses on advances in our understanding of the roles of Rdh10 and Dhrs3 and their impact on development and disease. WIREs Dev Biol 2017, 6:e264. doi: 10.1002/wdev.264 For further resources related to this article, please visit the WIREs website.