Increasing donor heart use in cardiac transplantation.

ABSTRACT: A shortage of donor hearts remains a critical problem in cardiac transplantation, resulting in longer recipient wait times and increased wait list mortality. The disparity between available donor hearts and patients with end-stage heart failure who need transplant is expected to grow. The donor heart pool can be increased by using organs from expanded criteria, Public Health Service increased risk, hepatitis C, and donation after circulatory death donors.

Usp25m protease regulates ubiquitin-like processing of TUG proteins to control GLUT4 glucose transporter translocation in adipocytes.

Insulin stimulates the exocytic translocation of specialized vesicles in adipocytes, which inserts GLUT4 glucose transporters into the plasma membrane to enhance glucose uptake. Previous results support a model in which TUG (Tether containing a UBX domain for GLUT4) proteins trap these GLUT4 storage vesicles at the Golgi matrix and in which insulin triggers endoproteolytic cleavage of TUG to translocate GLUT4. Here, we identify the muscle splice form of Usp25 (Usp25m) as a protease required for insulin-stimulated TUG cleavage and GLUT4 translocation in adipocytes. Usp25m is expressed in adipocytes, binds TUG and GLUT4, dissociates from TUG-bound vesicles after insulin addition, and colocalizes with TUG and insulin-responsive cargoes in unstimulated cells. Previous results show that TUG proteolysis generates the ubiquitin-like protein, TUGUL (for TUGubiquitin-like). We now show that TUGUL modifies the kinesin motor protein, KIF5B, and that TUG proteolysis is required to load GLUT4 onto these motors. Insulin stimulates TUG proteolytic processing independently of phosphatidylinositol 3-kinase. In nonadipocytes, TUG cleavage can be reconstituted by transfection of Usp25m, but not the related Usp25a isoform, together with other proteins present on GLUT4 vesicles. In rodents with diet-induced insulin resistance, TUG proteolysis and Usp25m protein abundance are reduced in adipose tissue. These effects occur soon after dietary manipulation, prior to the attenuation of insulin signaling to Akt. Together with previous data, these results support a model whereby insulin acts through Usp25m to mediate TUG cleavage, which liberates GLUT4 storage vesicles from the Golgi matrix and activates their microtubule-based movement to the plasma membrane. This TUG proteolytic pathway for insulin action is independent of Akt and is impaired by nutritional excess.

Medical Nutrition Education, Training, and Competencies to Advance Guideline-Based Diet Counseling by Physicians: A Science Advisory From the American Heart Association.

Growing scientific evidence of the benefits of heart-healthy dietary patterns and of the massive public health and economic burdens attributed to obesity and poor diet quality have triggered national calls to increase diet counseling in outpatients with atherosclerotic cardiovascular disease or risk factors. However, despite evidence that physicians are willing to undertake this task and are viewed as credible sources of diet information, they engage patients in diet counseling at less than desirable rates and cite insufficient knowledge and training as barriers. These data align with evidence of large and persistent gaps in medical nutrition education and training in the United States. Now, major reforms in undergraduate and graduate medical education designed to incorporate advances in the science of learning and to better prepare physicians for 21st century healthcare delivery are providing a new impetus and novel ways to expand medical nutrition education and training. This science advisory reviews gaps in undergraduate and graduate medical education in nutrition in the United States, summarizes reforms that support and facilitate more robust nutrition education and training, and outlines new opportunities for accomplishing this goal via multidimensional curricula, pedagogies, technologies, and competency-based assessments. Real-world examples of efforts to improve undergraduate and graduate medical education in nutrition by integrating formal learning with practical, experiential, inquiry-driven, interprofessional, and population health management activities are provided. The authors conclude that enhancing physician education and training in nutrition, as well as increasing collaborative nutrition care delivery by 21st century health systems, will reduce the health and economic burdens from atherosclerotic cardiovascular disease to a degree not previously realized.

GLUT4 Storage Vesicles: Specialized Organelles for Regulated Trafficking.

Fat and muscle cells contain a specialized, intracellular organelle known as the GLUT4 storage vesicle (GSV). Insulin stimulation mobilizes GSVs, so that these vesicles fuse at the cell surface and insert GLUT4 glucose transporters into the plasma membrane. This example is likely one instance of a broader paradigm for regulated, non-secretory exocytosis, in which intracellular vesicles are translocated in response to diverse extracellular stimuli. GSVs have been studied extensively, yet these vesicles remain enigmatic. Data support the view that in unstimulated cells, GSVs are present as a pool of preformed small vesicles, which are distinct from endosomes and other membrane-bound organelles. In adipocytes, GSVs contain specific cargoes including GLUT4, IRAP, LRP1, and sortilin. They are formed by membrane budding, involving sortilin and probably CHC22 clathrin in humans, but the donor compartment from which these vesicles form remains uncertain. In unstimulated cells, GSVs are trapped by TUG proteins near the endoplasmic reticulum - Golgi intermediate compartment (ERGIC). Insulin signals through two main pathways to mobilize these vesicles. Signaling by the Akt kinase modulates Rab GTPases to target the GSVs to the cell surface. Signaling by the Rho-family GTPase TC10α stimulates Usp25m-mediated TUG cleavage to liberate the vesicles from the Golgi. Cleavage produces a ubiquitin-like protein modifier, TUGUL, that links the GSVs to KIF5B kinesin motors to promote their movement to the cell surface. In obesity, attenuation of these processes results in insulin resistance and contributes to type 2 diabetes and may simultaneously contribute to hypertension and dyslipidemia in the metabolic syndrome.

Humeral Head Ossification Predicts Peak Height Velocity Timing and Percentage of Growth Remaining in Children.

BACKGROUND: Understanding skeletal maturity is important in the management of idiopathic scoliosis. Iliac apophysis, triradiate cartilage, hand, and calcaneal ossification patterns have previously been described to assess both peak height velocity (PHV) and percent growth remaining; however, these markers may not be present on standard spine radiographs. The purpose of this study was to describe a novel maturity assessment method based on proximal humeral epiphyseal ossification patterns. METHODS: Ninety-four children were followed at least annually throughout growth with serial radiographs and physical examinations. The PHV of each child was determined by measuring the change in height observed at each visit and adjusting for the interval between visits. Percent growth remaining was determined by comparing current to final standing height. The humeral head periphyseal ossification was grouped into stages by 8 investigators ranging from medical student to attending surgeon. RESULTS: The morphologic changes involving the proximal humeral physis were categorized into 5 stages based on development of the humeral head epiphysis and fusion of the lateral margin of the physis. Our novel classification scheme was well distributed around the PHV and reliably correlated with age of peak growth and percent growth remaining with >70% nonoverlapping interquartile ranges. Furthermore, the scheme was extremely reliable with intraclass correlation coefficients of 0.96 and 0.95 for intraobserver and interobserver comparisons, respectively. CONCLUSIONS: The humeral head classification system described here was strongly correlated with age of PHV as well as percentage growth remaining. Furthermore, the staging system was extremely reliable in both interobserver and intraobserver correlations suggesting that it can be easily generalized. CLINICAL RELEVANCE: As a view of the humeral head is almost always present on standard scoliosis spine x-ray at our institution, our classification can be easily adapted by surgeons to gain additional insight into skeletal maturity of patients with scoliosis. We believe that our method will significantly improve the evaluation of the child with scoliosis without increasing radiation exposure, time, or cost.

Nutrition Education for Cardiologists: The Time Has Come.

PURPOSE OF REVIEW: Nutrition is a cornerstone of cardiovascular health, yet the training of cardiovascular specialists in nutrition has been called into question. This report summarizes the current state of nutrition education in the training of cardiovascular specialists and offers recommendations for curricular enhancements. RECENT FINDINGS: Medical students receive an average of fewer than 20 h of nutrition education, largely confined to basic sciences and discussion of vitamin deficiency states. Current guidelines for Internal Medicine residency and cardiovascular fellowship training do not contain any specific requirement for nutrition education. A recent survey showed that the vast majority of cardiologists report having received minimal nutrition training, although most cardiologists believe it is their personal responsibility to provide nutritional counseling to their patients. Cardiologists typically receive minimal training in nutrition and are not well equipped to deliver effective nutritional counseling and recognize opportunities for appropriate referral. The potential for cardiologists to become more effective team members in delivering nutritional interventions is considerable.

Controversial Dietary Patterns: A High Yield Primer for Clinicians.

In cardiology clinic visits, the discussion of optimal dietary patterns for prevention and management of cardiovascular disease is usually very limited. Herein, we explore the benefits and risks of various dietary patterns, including intermittent fasting, low carbohydrate, Paleolithic, whole food plant-based diet, and Mediterranean dietary patterns within the context of cardiovascular disease to empower clinicians with the evidence and information they need to maximally benefit their patients.

Trending Nutrition Controversies #3: Top Controversies in 2021.

Each year, patients are bombarded with diverging and even contradictory reports concerning the impact of certain additives, foods, and nutrients on cardiovascular health and its risk factors. Accordingly, this third review of nutrition controversies examines the impact of artificial sweeteners, cacao, soy, plant-based meats, nitrates, and meats from grass compared to grain-fed animals on cardiovascular and other health outcomes with the goal of optimizing clinician-led diet counseling.

Insulin-stimulated endoproteolytic TUG cleavage links energy expenditure with glucose uptake.

TUG tethering proteins bind and sequester GLUT4 glucose transporters intracellularly, and insulin stimulates TUG cleavage to translocate GLUT4 to the cell surface and increase glucose uptake. This effect of insulin is independent of phosphatidylinositol 3-kinase, and its physiological relevance remains uncertain. Here we show that this TUG cleavage pathway regulates both insulin-stimulated glucose uptake in muscle and organism-level energy expenditure. Using mice with muscle-specific Tug (Aspscr1)-knockout and muscle-specific constitutive TUG cleavage, we show that, after GLUT4 release, the TUG C-terminal cleavage product enters the nucleus, binds peroxisome proliferator-activated receptor (PPAR)γ and its coactivator PGC-1α and regulates gene expression to promote lipid oxidation and thermogenesis. This pathway acts in muscle and adipose cells to upregulate sarcolipin and uncoupling protein 1 (UCP1), respectively. The PPARγ2 Pro12Ala polymorphism, which reduces diabetes risk, enhances TUG binding. The ATE1 arginyltransferase, which mediates a specific protein degradation pathway and controls thermogenesis, regulates the stability of the TUG product. We conclude that insulin-stimulated TUG cleavage coordinates whole-body energy expenditure with glucose uptake, that this mechanism might contribute to the thermic effect of food and that its attenuation could promote obesity.

Impact of an Online Nutrition Course to Address a Gap in Medical Education: A Feasibility Study.

BACKGROUND AND OBJECTIVES: Nutrition is a foundation of health, yet there is a deficiency of nutrition training in graduate medical education. The purpose of this feasibility study was to assess the impact of a brief online clinical nutrition course on medical residents' knowledge and attitudes related to the role of nutrition in clinical practice. METHODS: Medical residents from two institutions took a 3-hour, online, self-paced and interactive clinical nutrition course that reviewed macronutrients, evidence-based dietary patterns, a rapid nutrition assessment, and motivational interviewing. We administered surveys of nutrition knowledge and attitudes at three time points: (1) just prior to taking the online course, (2) immediately following, and (3) 3 months after course completion. RESULTS: Seventy-six residents enrolled in the study and 47 (62%) completed the online course and postcourse surveys. For residents who completed the study, the summated nutrition knowledge scores assessed both immediately after taking the course and 3 months later showed significant improvement (P<.001). Three months after completing the course, residents were more likely to believe it was their role to personally provide detailed nutrition information to patients (P=.045) and to endorse the view that a healthy diet is important for self-care (P<.001). The estimated time residents spent counseling patients on nutrition did not change after the intervention. CONCLUSION: This feasibility study demonstrated the potential of a 3-hour, online, self-paced nutrition course administered to medical residents to result in a significant and sustained increase in nutrition knowledge and positive attitudes about the role of nutrition in clinical practice.

The Proximal Humeral Ossification System Improves Assessment of Maturity in Patients with Scoliosis.

BACKGROUND: We recently developed a classification system to assess skeletal maturity by scoring proximal humeral ossification in a similar way to the canonical Risser sign. The purpose of the present study was to determine whether our system can be used to reliably assess radiographs of the spine for modern patients with idiopathic scoliosis, whether it can be used in combination with the Sanders hand system, and whether the consideration of patient factors such as age, sex, and standing height improves the accuracy of predictions. METHODS: We retrospectively reviewed 414 randomized radiographs from 216 modern patients with scoliosis and measured reliability with use of the intraclass correlation coefficient (ICC). We then analyzed 606 proximal humeral radiographs for 70 children from a historical collection to determine the value of integrating multiple classification systems. The age of peak height velocity (PHV) was predicted with use of linear regression models, and performance was evaluated with use of tenfold cross-validation. RESULTS: The proximal humeral ossification system demonstrated excellent reliability in modern patients with scoliosis, with an ICC of 0.97 and 0.92 for intraobserver and interobserver comparisons, respectively. The use of our system in combination with the Sanders hand system yielded 7 categories prior to PHV and demonstrated better results compared with either system alone. Linear regression algorithms showed that integration of the proximal part of the humerus, patient factors, and other classification systems outperformed models based on canonical Risser and triradiate-closure methods. CONCLUSIONS: Humeral head ossification can be reliably assessed in modern patients with scoliosis. Furthermore, the system described here can be used in combination with other parameters such as the Sanders hand system, age, sex, and height to predict PHV and percent growth remaining with high accuracy. CLINICAL RELEVANCE: The proximal humeral ossification system can improve the prediction of PHV in patients with scoliosis on the basis of a standard spine radiograph without a hand radiograph for the determination of bone age. This increased accuracy for predicting maturity will allow physicians to better assess patient maturity relative to PHV and therefore can help to guide treatment decision-making without increasing radiation exposure, time, or cost. The present study demonstrates that assessment of the proximal humeral physis is a viable and valuable aid in the determination of skeletal maturity as obtained from radiographs of the spine that happen to include the shoulder in adolescent patients with idiopathic scoliosis.

The Deficit of Nutrition Education of Physicians.

Globally, death rates from cardiovascular disease are increasing, rising 41% between 1990 and 2013, and are often attributed, at least in part, to poor diet quality. With urbanization, economic development, and mass marketing, global dietary patterns have become more Westernized to include more sugar-sweetened beverages, highly processed foods, animal-based foods, and fewer fruits and vegetables, which has contributed to increasing cardiovascular disease globally. In this paper, we will examine the trends occurring globally in the realm of nutrition and cardiovascular disease prevention and also present new data that international nutrition knowledge amongst cardiovascular disease providers is limited. In turn, this lack of knowledge has resulted in less patient education and counseling, which is having profound effects on cardiovascular disease prevention efforts worldwide.

A Clinician's Guide for Trending Cardiovascular Nutrition Controversies: Part II.

The potential cardiovascular (CV) benefits of many trending foods and dietary patterns are still incompletely understood, and scientific inquiry continues to evolve. In the meantime, however, a number of controversial dietary patterns, foods, and nutrients have received significant media attention and are mired by "hype." This second review addresses some of the more recent popular foods and dietary patterns that are recommended for CV health to provide clinicians with current information for patient discussions in the clinical setting. Specifically, this paper delves into dairy products, added sugars, legumes, coffee, tea, alcoholic beverages, energy drinks, mushrooms, fermented foods, seaweed, plant and marine-derived omega-3-fatty acids, and vitamin B12.

Trending Cardiovascular Nutrition Controversies.

The potential cardiovascular benefits of several trending foods and dietary patterns are still incompletely understood, and nutritional science continues to evolve. However, in the meantime, a number of controversial dietary patterns, foods, and nutrients have received significant media exposure and are mired by hype. This review addresses some of the more popular foods and dietary patterns that are promoted for cardiovascular health to provide clinicians with accurate information for patient discussions in the clinical setting.

A Deficiency of Nutrition Education and Practice in Cardiology.

BACKGROUND: Nutrition is one of the foundations of cardiovascular guidelines for risk reduction and treatment. However, little is known about whether cardiologists, cardiology fellows-in-training, and cardiovascular team members have the nutrition education and knowledge necessary to implement these guidelines. The aim of this study was to describe the educational experiences, attitudes, and practices relating to nutrition among cardiovascular professionals. METHODS: Surveys completed by cardiologists, fellows-in-training, and cardiovascular team members inquired about their personal dietary habits, history of nutrition education, and attitudes regarding nutrition interventions. RESULTS: A total of 930 surveys were completed. Among cardiologists, 90% reported receiving no or minimal nutrition education during fellowship training, 59% reported no nutrition education during internal medicine training, and 31% reported receiving no nutrition education in medical school. Among cardiologists, 8% described themselves as having "expert" nutrition knowledge. Nevertheless, fully 95% of cardiologists believe that their role includes personally providing patients with at least basic nutrition information. The percentage of respondents who ate ≥5 servings of vegetables and fruits per day was: 20% (cardiologists), 21% (fellows-in-training), and 26% (cardiovascular team members). CONCLUSIONS: A large proportion of cardiovascular specialists have received minimal medical education and training in nutrition, and current trainees continue to experience significant education and training gaps.