Stillbirth Associated With Anomalous Origin and Course of the Left Coronary Artery: A Report of 2 Cases.

Coronary artery anomalies and their potential sequelae are not well studied in association with stillbirth. Herein, we report the autopsy findings in two term stillborn fetuses with coronary artery anomalies. Both fetuses showed identical findings consisting of an abnormal origin of the left coronary artery from the right sinus of Valsalva and an interarterial course of the left coronary artery. Histologic vascular and myocardial changes were also present. These coronary artery findings are associated with sudden death in adults and neonates, and therefore, their potential to be a cause and/or contributor to fetal death is suspected.

Filling in the "GAPPS": an unusual presentation of a child with gastric adenocarcinoma and proximal polyposis of the stomach.

Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS) is a very rare gastric polyposis syndrome characterized by numerous polyps of the gastric fundus and body. We present the unusual case of a 10-year-old Polish-American male with history of eosinophilic esophagitis, who was found to have multiple fundic gland polyps (FGP) with low grade dysplasia on esophagogastroduodenoscopy. Subsequent evaluation including genetic testing confirmed the diagnosis of GAPPS, and after exhaustive multidisciplinary consultation the decision was made to proceed with prophylactic total gastrectomy given the markedly increased risk of gastric adenocarcinoma in GAPPS patients. To our knowledge, this represents the youngest patient diagnosed with GAPPS and the youngest patient who has undergone prophylactic gastrectomy for this disease at age 8 and 10 years, respectively. The pathophysiology, presentation, and treatment of GAPPS in a pediatric patient are discussed.

SARS-CoV-2 antibodies: IgA correlates with severity of disease in early COVID-19 infection.

Timing of detection of immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and their use to support the diagnosis are of increasing interest. We used the Gold Standard Diagnostics ELISA to evaluate the kinetics of SARS-CoV-2 IgG, IgA, and IgM antibodies in sera of 82 hospitalized patients with polymerase chain reaction (PCR)-confirmed coronavirus disease 2019 (COVID-19). Serum samples were collected 1-59 days post-onset of symptoms (PoS) and we examined the association of age, sex, disease severity, and symptoms' duration with antibody levels. We also tested sera of 100 ambulatory hospital employees with PCR-confirmed COVID-19 and samples collected during convalescence, 35-57 days PoS. All but four of the admitted patients (95.1%) developed antibodies to SARS-CoV-2. Antibodies were detected within 7 days PoS; IgA in 60.0%, IgM in 53.3%, and IgG in 46.7% of samples. IgG positivity increased to 100% on Day 21. We did not observe significant differences in the rate of antibody development in regard to age and sex. IgA levels were highest in patients with a severe and critical illness. In multiple regression analyses, only IgA levels were statistically significantly correlated with critical disease (p = .05) regardless of age, sex, and duration of symptoms. Among 100 ambulatory hospital employees who had antibody testing after 4 weeks PoS only 10% had positive IgA antibodies. The most frequently isolated isotype in sera of employees after 30 days PoS was IgG (88%). IgA was the predominant immunoglobulin in early disease and correlated independently with a critical illness. IgG antibodies remained detectable in almost 90% of samples collected up to two months after infection.

Investigating the spectrum of dermatologic manifestations in COVID-19 infection in severely ill patients: A series of four cases.

COVID-19, an infectious disease caused by the novel coronavirus, was initially identified in Wuhan, China, in December 2019. By March 2020, it was declared a pandemic by the World Health Organization. Although most findings have been reported in the lungs, primarily due to catastrophic respiratory decline, other organs, including the skin, are affected. Recent reports have been published describing the clinical spectrum of COVID-19-related lesions. In addition, recent case series have described a subset of these lesions having underlying thrombotic microangiopathy with increased complement activation characterized by increased C4d deposition within the blood vessel walls. Herein, we describe a series of COVID-19-related cutaneous manifestations found at autopsy examination and their underlying histopathologic findings. Although the clinical manifestations seen in these lesions vary widely, the underlying etiology of thrombotic microangiopathy remains consistent and reproducible.

Asymptomatic macrocephaly: to scan or not to scan.

BACKGROUND: Macrocephaly is a common finding in infants and is often idiopathic or familial. In the absence of clinical signs and symptoms, it can be difficult to determine when concern for underlying pathology is justified. OBJECTIVES: The objectives of this study were to determine the utility of screening head ultrasound (US) in asymptomatic infants with macrocephaly and to identify clinical factors associated with significant US findings. MATERIALS AND METHODS: A 20-year retrospective review was performed of infants undergoing head US for macrocephaly or rapidly increasing head circumference. Data collected included age, gender, head circumference at birth and at the time of US, specialty of the ordering physician, US findings, computed tomography (CT) or magnetic resonance imaging (MRI) findings, and clinical course including interventions. RESULTS: Four hundred and forty infants met inclusion criteria. Two hundred and eighty studies (64%) were found to be normal, 137 (31%) had incidental findings, 17 (3.8%) had indeterminate but potentially significant findings, and 6 (1.4%) had significant findings. Twenty of the 23 infants with indeterminate or significant findings had subsequent CT or MRI. This confirmed significant findings in eight infants (1.8%): three subdural hematomas, two intracranial tumors, two aqueductal stenoses, and one middle fossa cyst. Five of the eight infants required surgical procedures. The only statistically significant association found with having a significant finding on head US was head circumference at birth. CONCLUSION: Ultrasound is a useful initial study to evaluate infantile macrocephaly, identifying several treatable causes in our study and, when negative, effectively excluding significant pathology.

Procedure for optimal implementation of automatic tube potential selection in pediatric CT to reduce radiation dose and improve workflow.

It is important to employ radiation dose reduction techniques in pediatric computed tomography (CT) to reduce potential risks of radiation-induced malignancy. Automatic tube potential (kV) selection tools have been developed and become available on many CT scanners, which select the optimum kV based on the patient size and clinical task to improve the radiation dose efficiency. However, its use in pediatric CT has been mostly empirical, following manufacturer's default recommendation without solid demonstration for quality improvement. This study aimed to implement an automatic tube potential tool (CAREkV, Siemens Healthcare) into routine pediatric CT practice, using the "Plan-Do-Study-Act" quality improvement process, in place of an existing kV/mAs technique chart. The design of this quality improvement project involved Plan-Do-Study-Act stages. Plan and Do stages identified the criteria for optimal automatic kV selection; a range of phantoms representing typical pediatric groups were scanned on a dual-source 128-slice scanner using a fast-pitch scanning mode. The identified CAREkV settings were implemented into the CT protocol and evaluated after a 6-month period. In the Study stage, an objective evaluation of the image metrics and radiation dose for two similar patient cohorts using CAREkV and the technique-chart, respectively, were compared. The kV selected, image quality and radiation dose determined by CAREkV were comparable to those obtained while using the technique-chart. The CAREkV was successfully implemented into our pediatric abdominopelvic CT practice. By utilizing the "PDSA" process optimal image quality and radiation dose reduction were achieved with an automatic kV selection tool to improve CT workflow.

Reproducibility of Lung and Liver Volume Measurements on Fetal Magnetic Resonance Imaging in Left-Sided Congenital Diaphragmatic Hernia.

INTRODUCTION: Congenital diaphragmatic hernia (CDH) affects 1 in 3,000 live births and is associated with significant morbidity and mortality. METHODS: A review of fetal magnetic resonance imaging (MRI) examinations was performed for fetuses with left CDH and normal lung controls. Image review and manual tracings were performed by 4 pediatric radiologists; right and left lung volumes in the coronal and axial planes as well as liver volume above and below the diaphragm in the coronal plane were measured. Intra- and interreviewer reproducibility was assessed using intraclass correlation coefficient (ICC) and Bland-Altman analysis. RESULTS: Excellent intra- and interreviewer reproducibility of the right and left lung volume measurements was observed in both axial planes (interreviewer ICC: right lung: 0.97, 95% CI: 0.95-0.99; left lung: 0.97, 95% CI: 0.95-0.98) and coronal planes (interreviewer ICC: right lung: 0.97, 95% CI: 0.95-0.98; left lung: 0.96, 95% CI: 0.93-0.98). Moderate-to-good interreviewer reproducibility was observed for liver volume above the diaphragm (ICC 0.7, 95% CI: 0.59-0.81). Liver volume below the diaphragm had a good-to-excellent interreviewer reproducibility (ICC 0.88, 95% CI: 9.82-0.93). CONCLUSIONS: The present study demonstrated an excellent intra- and interreviewer reproducibility of MRI lung volume measurements and good-to-moderate inter- and intrareviewer reproducibility of liver volume measurements after standardization of the methods at our fetal center.

Increased Incidence of Barotrauma in Patients with COVID-19 on Invasive Mechanical Ventilation.

Background A high number of patients with coronavirus disease 2019 (COVID-19) pneumonia who had barotrauma related to invasive mechanical ventilation at the authors' institution were observed. Purpose To determine if the rate of barotrauma in patients with COVID-19 infection was greater than in other patients requiring invasive mechanical ventilation at the authors' institution. Materials and Methods In this retrospective study, clinical and imaging data of patients seen between March 1, 2020, and April 6, 2020, who tested positive for COVID-19 and experienced barotrauma associated with invasive mechanical ventilation, were compared with patients without COVID-19 infection during the same period. Historical comparison was made to barotrauma rates of patients with acute respiratory distress syndrome from February 1, 2016, to February 1, 2020, at the authors' institution. Comparison of patient groups was performed using categoric or continuous statistical testing as appropriate, with multivariable regression analysis. Patient survival was assessed using Kaplan-Meier curves analysis. Results A total of 601 patients with COVID-19 infection underwent invasive mechanical ventilation (mean age, 63 years ± 15 [standard deviation]; 71% men). Of the total, there were 89 (15%) patients with one or more barotrauma events for a total of 145 barotrauma events (24% overall events) (95% confidence interval [CI]: 21%, 28%). During the same period, 196 patients without COVID-19 infection (mean age, 64 years ± 19; 52% men) with invasive mechanical ventilation had one barotrauma event (0.5%; 95% CI: 0%, 3%; P < .001 vs the group with COVID-19 infection). Of 285 patients with acute respiratory distress syndrome on invasive mechanical ventilation during the previous 4 years (mean age, 68 years ± 17; 60% men), 28 patients (10%) had 31 barotrauma events, with an overall barotrauma rate of 11% (95% CI: 8%, 15%; P < .001 vs the group with COVID-19 infection). Barotrauma is an independent risk factor for death in COVID-19 (odds ratio = 2.2; P = .03) and is associated with a longer hospital stay (odds ratio = 0.92; P < .001). Conclusion Patients with coronavirus disease 2019 (COVID-19) infection and invasive mechanical ventilation had a higher rate of barotrauma than patients with acute respiratory distress syndrome and patients without COVID-19 infection. © RSNA, 2020 Online supplemental material is available for this article.

The Reemergence of Ketamine for Treatment in Critically Ill Adults.

OBJECTIVES: To assess the evidence and discuss the risks and clinical relevance of ketamine for the treatment of various disease states impacting the adult critically ill population. DATA SOURCES: A literature review was performed using PubMed evaluating primary literature published until August 2018. STUDY SELECTION: Case reports, observational studies (cohort, case-control), and randomized controlled trials involving patients 18 years and older in a nonperioperative setting using either IV or intramuscular ketamine were included for analysis. Uses of ketamine discussed focused on critically ill patients in the ICU and emergency department settings. DATA EXTRACTION: Included studies were evaluated for dosing, outcomes, and adverse effects of ketamine. For each study, the design, population, intervention, investigated outcomes, and results were assessed. DATA SYNTHESIS: The evidence was organized according to use of ketamine, which included pain, sedation, status asthmaticus, alcohol withdrawal syndrome, status epilepticus, and acute behavioral psychologic disturbances. Evaluation of the evidence was based on the included primary literature along with any related guideline recommendations. CONCLUSIONS: Ketamine has suggested potential benefit in several disease states impacting critically ill patients including pain, alcohol withdrawal syndrome, status epilepticus, and acute agitation. Further supporting evidence is needed to validate its use in the setting of critical illness.

Persistent organic pollutant exposure and celiac disease: A pilot study.

Celiac disease affects approximately 1% of the population worldwide. Little is known about environmental factors that may modulate risk in genetically susceptible populations. Persistent organic pollutants (POPs) are known endocrine disruptors and, given the interplay between the endocrine and immune systems, are plausible contributors to celiac disease. The current study aims to elucidate the association between POPs and celiac disease. We conducted a single-site pilot study of 88 patients recruited from NYU Langone's Hassenfeld Children's Hospital outpatient clinic, 30 of which were subsequently diagnosed with celiac disease using standard serology and duodenal biopsy examination. Polybrominated diphenyl ether (PBDEs), perfluoroalkyl substances (PFASs), and p,p'-dichlorodiphenyldichloroethylene (DDE) and HLA-DQ genotype category were measured in blood serum and whole blood, respectively. Multivariable logistic regressions were used to obtain odds ratios for celiac disease associated with serum POP concentrations. Controlling for sex, race, age, BMI, and genetic susceptibility score, patients with higher serum DDE concentrations had 2-fold higher odds of celiac disease (95% CI: 1.08, 3.84). After stratifying by sex, we found higher odds of celiac disease in females with serum concentrations of DDE (OR = 13.0, 95% CI = 1.54, 110), PFOS (OR = 12.8, 95% CI = 1.17, 141), perfluorooctanoic acid (OR = 20.6, 95% CI = 1.13, 375) and in males with serum BDE153, a PBDE congener (OR = 2.28, 95% CI = 1.01, 5.18). This is the first study to report on celiac disease with POP exposure in children. These findings raise further questions of how environmental chemicals may affect autoimmunity in genetically susceptible individuals.

From Favorable Histology to Relapse: The Clonal Evolution of a Wilms Tumor.

Favorable histology (FH) Wilms tumor (WT) is one of the most curable of all human cancers, yet a small minority of patients fail treatment. The underlying biological pathways that lead to therapy resistance are unknown. We report a case of initially unresectable, FH WT which revealed limited necrosis and persistent blastemal predominant histology following neoadjuvant chemotherapy. Despite intensification of therapy and whole abdominal radiation, the patient relapsed and succumbed to her disease. In an effort to discover candidate drivers of drug resistance, whole exome sequencing and copy number analysis were performed on samples from all 3 tumor specimens. Sequencing results revealed outgrowth of clones with a dramatically different genetic landscape including dominant mutations that could explain therapy evasion, some of which have not been previously reported in WT. Our results implicate PPM1D, previously shown to be associated with drug resistance in other tumors, as the major driver of treatment failure.

Mitochondrial oxidative stress causes insulin resistance without disrupting oxidative phosphorylation.

Mitochondrial oxidative stress, mitochondrial dysfunction, or both have been implicated in insulin resistance. However, disentangling the individual roles of these processes in insulin resistance has been difficult because they often occur in tandem, and tools that selectively increase oxidant production without impairing mitochondrial respiration have been lacking. Using the dimer/monomer status of peroxiredoxin isoforms as an indicator of compartmental hydrogen peroxide burden, we provide evidence that oxidative stress is localized to mitochondria in insulin-resistant 3T3-L1 adipocytes and adipose tissue from mice. To dissociate oxidative stress from impaired oxidative phosphorylation and study whether mitochondrial oxidative stress per se can cause insulin resistance, we used mitochondria-targeted paraquat (MitoPQ) to generate superoxide within mitochondria without directly disrupting the respiratory chain. At ≤10 µm, MitoPQ specifically increased mitochondrial superoxide and hydrogen peroxide without altering mitochondrial respiration in intact cells. Under these conditions, MitoPQ impaired insulin-stimulated glucose uptake and glucose transporter 4 (GLUT4) translocation to the plasma membrane in both adipocytes and myotubes. MitoPQ recapitulated many features of insulin resistance found in other experimental models, including increased oxidants in mitochondria but not cytosol; a more profound effect on glucose transport than on other insulin-regulated processes, such as protein synthesis and lipolysis; an absence of overt defects in insulin signaling; and defective insulin- but not AMP-activated protein kinase (AMPK)-regulated GLUT4 translocation. We conclude that elevated mitochondrial oxidants rapidly impair insulin-regulated GLUT4 translocation and significantly contribute to insulin resistance and that MitoPQ is an ideal tool for studying the link between mitochondrial oxidative stress and regulated GLUT4 trafficking.

High dietary fat and sucrose results in an extensive and time-dependent deterioration in health of multiple physiological systems in mice.

Obesity is associated with metabolic dysfunction, including insulin resistance and hyperinsulinemia, and with disorders such as cardiovascular disease, osteoporosis, and neurodegeneration. Typically, these pathologies are examined in discrete model systems and with limited temporal resolution, and whether these disorders co-occur is therefore unclear. To address this question, here we examined multiple physiological systems in male C57BL/6J mice following prolonged exposure to a high-fat/high-sucrose diet (HFHSD). HFHSD-fed mice rapidly exhibited metabolic alterations, including obesity, hyperleptinemia, physical inactivity, glucose intolerance, peripheral insulin resistance, fasting hyperglycemia, ectopic lipid deposition, and bone deterioration. Prolonged exposure to HFHSD resulted in morbid obesity, ectopic triglyceride deposition in liver and muscle, extensive bone loss, sarcopenia, hyperinsulinemia, and impaired short-term memory. Although many of these defects are typically associated with aging, HFHSD did not alter telomere length in white blood cells, indicating that this diet did not generally promote all aspects of aging. Strikingly, glucose homeostasis was highly dynamic. Glucose intolerance was evident in HFHSD-fed mice after 1 week and was maintained for 24 weeks. Beyond 24 weeks, however, glucose tolerance improved in HFHSD-fed mice, and by 60 weeks, it was indistinguishable from that of chow-fed mice. This improvement coincided with adaptive ß-cell hyperplasia and hyperinsulinemia, without changes in insulin sensitivity in muscle or adipose tissue. Assessment of insulin secretion in isolated islets revealed that leptin, which inhibited insulin secretion in the chow-fed mice, potentiated glucose-stimulated insulin secretion in the HFHSD-fed mice after 60 weeks. Overall, the excessive calorie intake was accompanied by deteriorating function of numerous physiological systems.

Diagnostic accuracy of the McGill thyroid nodule score in paediatric patients.

INTRODUCTION: Thyroid cancer is the most common paediatric endocrine cancer; accurate diagnosis and prompt management of paediatric thyroid nodules is critical. The McGill Thyroid Nodule Score (MTNS), based upon clinical, ultrasound (US) and cytology criteria, has recently been modified and studied in a pilot paediatric group with good results. We aim to describe the diagnostic accuracy of the paediatric modified MTNS (PMTNS) in a large paediatric cohort. METHODS: We utilized an established retrospective cohort between 1996 and 2015 of 99 patients ≤21 years old with 131 thyroid nodules. Two experienced paediatric radiologists, blinded to pathology and radiology reports, reviewed US features. We abstracted cytology, histology and laboratory results, assigning each nodule a PMTNS. PMTNS performance was compared to FNA and histology. RESULTS: Approximately 33% of nodules were malignant. The cohort was predominantly adolescent (mean age 15.4 ± 3.8 years). The average PMTNS for malignant and benign nodules, based on final histology, was 12.7 ± 4.3 and 1.7 ± 2.9, respectively. A PMTNS ≥8 resulted in a 93.2% sensitivity and 93.1% specificity for detecting malignancy, while a PMTNS ≥9 resulted in a 90.9% sensitivity and 96.6% specificity. However, Bethesda cytology category ≥4 independently had a 97.7% sensitivity and 94.0% specificity for detecting malignancy. The PMTNS had diminishing diagnostic accuracy in younger children compared with older children. CONCLUSION: Paediatric modified McGill Thyroid Nodule Score predicts malignancy, perhaps due to the score's emphasis on cytology results; however, the score is less accurate in younger patients. While cytology results remain reliable, further work is needed to develop a non-invasive scoring system to predict malignancy in children.

Changes in factors influencing fellowship choices among radiology residents from 2008 to 2018 and methods that may increase interest in the pediatric radiology subspecialty.

BACKGROUND: Fewer residents are choosing a career in pediatric radiology, which is contributing to an ongoing shortage of pediatric radiologists. OBJECTIVE: To identify potential causes of reduced interest in pediatric radiology as a career given a projected worsening of a nationwide shortage of pediatric radiologists. MATERIALS AND METHODS: An online questionnaire using previously published questions was approved and distributed by the Program Directors in Diagnostic Radiology to diagnostic radiology residents on behalf of the Society for Pediatric Radiology (SPR). Descriptive statistics including means with standard error and independent t-tests were used to compare mean scores between survey years. RESULTS: Nearly all of the 353 respondents (90.9%) planned on pursuing a fellowship. The majority (57.7%) identified their fellowship subspecialty before the 3rd year of residency with only 5.7% selecting pediatric radiology. Overall, 18.2% of survey respondents favored academic practice compared to 40% in the pediatric radiology subgroup. Fellowship choices were most strongly based on area of strong personal interest, marketability and area of strong personal knowledge, while the pediatric radiology subgroup emphasized area of strong personal interest, increased interaction with other physicians and enjoyable residency rotations. The pediatric radiology subgroup believed their impact on patient care was more significant than other subspecialties. Pediatric radiology job opportunities were thought to be more limited, geographically confining, and to have lower salaries than other subspecialties. More flexible job opportunities and higher demand were identified as factors needing to change before a resident would consider a pediatric radiology career. CONCLUSION: The influence on fellowship selection is multifactorial. By emphasizing the favorable job market and marketability of pediatric radiology in all practice types/geographic locations, correcting perceived salary gaps and stressing the impact on patient care as early as medical school, the number of residents choosing a career in pediatric radiology may grow.

Metabolomic analysis of insulin resistance across different mouse strains and diets.

Insulin resistance is a major risk factor for many diseases. However, its underlying mechanism remains unclear in part because it is triggered by a complex relationship between multiple factors, including genes and the environment. Here, we used metabolomics combined with computational methods to identify factors that classified insulin resistance across individual mice derived from three different mouse strains fed two different diets. Three inbred ILSXISS strains were fed high-fat or chow diets and subjected to metabolic phenotyping and metabolomics analysis of skeletal muscle. There was significant metabolic heterogeneity between strains, diets, and individual animals. Distinct metabolites were changed with insulin resistance, diet, and between strains. Computational analysis revealed 113 metabolites that were correlated with metabolic phenotypes. Using these 113 metabolites, combined with machine learning to segregate mice based on insulin sensitivity, we identified C22:1-CoA, C2-carnitine, and C16-ceramide as the best classifiers. Strikingly, when these three metabolites were combined into one signature, they classified mice based on insulin sensitivity more accurately than each metabolite on its own or other published metabolic signatures. Furthermore, C22:1-CoA was 2.3-fold higher in insulin-resistant mice and correlated significantly with insulin resistance. We have identified a metabolomic signature composed of three functionally unrelated metabolites that accurately predicts whole-body insulin sensitivity across three mouse strains. These data indicate the power of simultaneous analysis of individual, genetic, and environmental variance in mice for identifying novel factors that accurately predict metabolic phenotypes like whole-body insulin sensitivity.

Proteomic Analysis of GLUT4 Storage Vesicles Reveals Tumor Suppressor Candidate 5 (TUSC5) as a Novel Regulator of Insulin Action in Adipocytes.

Insulin signaling augments glucose transport by regulating glucose transporter 4 (GLUT4) trafficking from specialized intracellular compartments, termed GLUT4 storage vesicles (GSVs), to the plasma membrane. Proteomic analysis of GSVs by mass spectrometry revealed enrichment of 59 proteins in these vesicles. We measured reduced abundance of 23 of these proteins following insulin stimulation and assigned these as high confidence GSV proteins. These included established GSV proteins such as GLUT4 and insulin-responsive aminopeptidase, as well as six proteins not previously reported to be localized to GSVs. Tumor suppressor candidate 5 (TUSC5) was shown to be a novel GSV protein that underwent a 3.7-fold increase in abundance at the plasma membrane in response to insulin. siRNA-mediated knockdown of TUSC5 decreased insulin-stimulated glucose uptake, although overexpression of TUSC5 had the opposite effect, implicating TUSC5 as a positive regulator of insulin-stimulated glucose transport in adipocytes. Incubation of adipocytes with TNFα caused insulin resistance and a concomitant reduction in TUSC5. Consistent with previous studies, peroxisome proliferator-activated receptor (PPAR) γ agonism reversed TNFα-induced insulin resistance. TUSC5 expression was necessary but insufficient for PPARγ-mediated reversal of insulin resistance. These findings functionally link TUSC5 to GLUT4 trafficking, insulin action, insulin resistance, and PPARγ action in the adipocyte. Further studies are required to establish the exact role of TUSC5 in adipocytes.