Validating a behavioral economic approach to assess food demand: Effects of body mass index, dietary restraint, and impulsivity

Behavioral economic theory is a useful framework for analyzing factors influencing choice, but the majority of human behavioral economic research has focused on drug choice. The behavioral economic choice paradigm may also be valuable for understanding food-maintained behavior. Our primary objective was two-fold: (1) Validate a human laboratory model of food-appetitive behavior, and (2) Assess the contribution of individual level factors that may differentially impact food choice behavior. Two studies were conducted. In Study 1, female subjects (N=17) participated in two consecutive food choice experimental sessions, whereas in Study 2, female subjects (N=21) participated in one concurrent food choice experimental session. During consecutive choice sessions (Study 1), demand for the more palatable food (i.e., high-sugar/high-fat) was more inelastic than the less palatable (i.e., low-sugar/low-fat) option. During concurrent choice sessions, demand for the more palatable food (i.e., high-sugar/high-fat) was more inelastic for restrained vs. unrestrained eaters, and for those who were overweight vs. normal weight. Demand for both palatable and less palatable choices was more elastic for high-impulsive vs. low-impulsive subjects. These findings suggest that the behavioral economic framework can be used successfully to develop a human laboratory model of food-appetitive behavior.     

The hemochromatosis C282Y allele: a risk factor for hepatic veno-occlusive disease after hematopoietic stem cell transplantation

Hepatic veno-occlusive disease (HVOD) is a serious complication of hematopoietic stem cell transplantation (HSCT). Since the liver is a major site of iron deposition in HFE-associated hemochromatosis, and iron has oxidative toxicity, we hypothesized that HFE genotype might influence the risk of HVOD after myeloablative HSCT. We determined HFE genotypes in 166 HSCT recipients who were evaluated prospectively for HVOD. We also tested whether a common variant of the rate-limiting urea cycle enzyme, carbamyl-phosphate synthetase (CPS), previously observed to protect against HVOD in this cohort, modified the effect of HFE genotype. Risk of HVOD was significantly higher in carriers of at least one C282Y allele (RR=3.7, 95% CI 1.2-12.1) and increased progressively with C282Y allelic dose (RR=1.7, 95% CI 0.4-6.8 in heterozygotes; RR=8.6, 95% CI 1.5-48.5 in homozygotes). The CPS A allele, which encodes a more efficient urea cycle enzyme, reduced the risk of HVOD associated with HFE C282Y. We conclude that HFE C282Y is a risk factor for HVOD and that CPS polymorphisms may counteract its adverse effects. Knowledge of these genotypes and monitoring of iron stores may facilitate risk-stratification and testing of strategies to prevent HVOD, such as iron chelation and pharmacologic support of the urea cycle.     

Malignancy in Noonan syndrome and related disorders

Noonan syndrome (NS) and related disorders, such as NS with multiple lentigines (formerly called LEOPARD syndrome), cardiofaciocutaneous syndrome, and Costello syndrome, constitute an important group of developmental malformation syndromes with variable clinical and molecular features. Their underlying pathophysiologic mechanism involves dysregulation of the Ras/mitogen‐activated protein kinase signaling pathway, an essential mediator of developmental and growth processes in the prenatal and postnatal setting. Malignant tumor development is an important complication encountered in other RASopathies, such as neurofibromatosis type 1, but the neoplastic risks and incidence of malignant tumors are less clearly defined in NS and related disorders of the Noonan spectrum. Malignant tumor development remains an important complication variably seen in the RASopathies and, thus, a clear understanding of the underlying risks is essential for appropriate clinical care in this patient population. This review discusses previously published reports of malignancies in individuals with RASopathies of the Noonan spectrum.     

Genetic variants of GSNOR and ADRB2 influence response to albuterol in African‐American children with severe asthma

African Americans are disproportionately affected by asthma. Social and economic factors play a role in this disparity, but there is evidence that genetic factors may also influence the development of asthma and response to therapy in African American children. Our hypothesis is that variations in asthma related genes contribute to the observed asthma disparities by influencing the response to asthma‐specific therapy. In order to test this hypothesis, we characterized the clinical response to asthma‐specific therapy in 107 African American children who presented to the emergency room in status asthmaticus, with a primary outcome indicator of length of time on continuous albuterol. Single locus analysis indicated that genotype variation in glutathione‐dependent S‐nitrosoglutathione reductase (GSNOR) is associated with a decreased response to asthma treatment in African American children. A post hoc multi‐locus analysis revealed that a combination of four single nucleotide polymorphisms (SNPs) within GSNOR, adrenergic receptor beta 2, and carbamoyl phosphate synthetase‐1 give a 70% predictive value for lack of response to therapy. This predictive model needs replication in other cohorts of patients with asthma, but suggests gene–gene interactions may have greater significance than that identified with single variants. Our findings also suggest that genetic variants may contribute to the observed population disparities in asthma. Pediatr Pulmonol. 2009; 44:649–654. © 2009 Wiley‐Liss, Inc.     

Rapid deployment of a telemedicine care model for genetics and metabolism during COVID‐19

The national importance of telemedicine for safe and effective patient care has been highlighted by the current COVID‐19 pandemic. Prior to the 2020 pandemic the Division of Genetics and Metabolism piloted a telemedicine program focused on initial and follow‐up visits in the patients' home. The goals were to increase access to care, decrease missed work, improve scheduling, and avoid the transport and exposure of medically fragile patients. Visits were conducted by physician medical geneticists, genetic counselors, and biochemical dietitians, together and separately. This allowed the program to develop detailed standard operating procedures. At the onset of the COVID‐19 pandemic, this pilot‐program was deployed by the full team of 22 providers in one business day. Two physicians remained on‐site for patients requiring in‐person evaluations. This model optimized patient safety and workforce preservation while providing full access to patients during a pandemic. We provide initial data on visit numbers, types of diagnoses, and no‐show rates. Experience in this implementation before and during the pandemic has confirmed the effectiveness and value of telemedicine for a highly complex medical population. This program is a model that can and will be continued well‐beyond the current crisis.     

Neonatal pulmonary hypertension--urea-cycle intermediates, nitric oxide production, and carbamoyl-phosphate synthetase function.

BACKGROUND: Endogenous production of nitric oxide is vital for the decrease in pulmonary vascular resistance that normally occurs after birth. The precursor of nitric oxide is arginine, a urea-cycle intermediate. We hypothesized that low concentrations of arginine would correlate with the presence of persistent pulmonary hypertension in newborns and that the supply of this precursor would be affected by a functional polymorphism (the substitution of asparagine for threonine at position 1405 [T1405N]) in carbamoyl-phosphate synthetase, which controls the rate-limiting step of the urea cycle. METHODS: Plasma concentrations of amino acids and genotypes of the carbamoyl-phosphate synthetase variants were determined in 65 near-term neonates with respiratory distress. Plasma nitric oxide metabolites were measured in a subgroup of 10 patients. The results in infants with pulmonary hypertension, as assessed by echocardiography, were compared with those in infants without pulmonary hypertension. The frequencies of the carbamoyl-phosphate synthetase genotypes in the study population were assessed for Hardy-Weinberg equilibrium. RESULTS: As compared with infants without pulmonary hypertension, infants with pulmonary hypertension had lower mean (+/-SD) plasma concentrations of arginine (20.2+/-8.8 vs. 39.8+/-17.0 micromol per liter, P<0.001) and nitric oxide metabolites (18.8+/-12.7 vs. 47.2+/-11.2 micromol per liter, P=0.05). As compared with the general population, the infants in the study had a significantly skewed distribution of the genotypes for the carbamoyl-phosphate synthetase variants at position 1405 (P<0.005). None of the infants with pulmonary hypertension were homozygous for the T1405N polymorphism. CONCLUSIONS: Infants with persistent pulmonary hypertension have low plasma concentrations of arginine and nitric oxide metabolites. The simultaneous presence of diminished concentrations of precursors and breakdown products suggests that inadequate production of nitric oxide is involved in the pathogenesis of neonatal pulmonary hypertension. Our preliminary observations suggest that the genetically predetermined capacity of the urea cycle--in particular, the efficiency of carbamoyl-phosphate synthetase--may contribute to the availability of precursors for nitric oxide synthesis.