Marital Status and Survival in Patients Diagnosed with Melanoma.

INTRODUCTION: Previous research suggests the presence of a spouse may considerably affect melanoma detection rates through more frequent examinations, better access to healthcare, and improved social support. Yet, the role of marital status on melanoma survival is currently unknown. The aim of this study is to assess whether marital status is associated with survival following melanoma diagnosis. METHODS: We performed secondary analysis of data from all participants of the Florida Cancer Data System (FCDS) and included adult melanoma patients diagnosed between 2001 and 2009 with follow-up information available until 2015. Marital status was categorized as single, married, divorced, or widowed. The primary outcome was survival interval after melanoma diagnosis, which was assessed according to the time from the date of diagnosis to the time of death or last contact. Cox proportional hazard models were used to assess the independent association between marital status and survival. RESULTS: We assessed data from 36,578 melanoma patients. Married patients were significantly more likely to survive than single patients (Hazard ratio (HR) = 0.65; 99% Confidence Interval (CI): 0.57-0.74; P < 0.001) after adjusting for age, sex, race, ethnicity, geographic location, insurance status, tobacco use, primary site, stage, and histology. There was no evidence of effect modification by gender (P=0.189). CONCLUSIONS: Married patients, including both men and women, had a 35% reduction in the risk of death after melanoma diagnosis compared with single patients, and mechanisms independent of earlier detection, such as social support, may play a role in survival in patients with melanoma.

Use of computer simulation to teach a systems approach to metabolism.

Use of a systems approach, as embodied in the computer simulation model of metabolism of a dairy cow, Molly (Baldwin, 2005), is ideal for teaching nutrition. This approach allows the overall complexity of the comprehensive system to be broken down into smaller manageable subunits that are easier to visualize. Quantitative interactions among nutrients supplied and metabolic production processes can be observed over extended time periods. Using Molly, undergraduate animal science students are able to observe detailed effects of changing dietary inputs, altering genetic milk production potential, and exogenously manipulating metabolism on metabolism of the whole cow. This paper demonstrates how Molly is used in the classroom to teach a systems approach to nutrition using example simulations. Three simulation examples demonstrate exercises examining effects of recombinant bovine somatotropin administration, dietary protein, and amino acid supplementation and nitrogen efficiency on milk production and cow metabolism. These and similar examples have been used to teach nutrition, metabolism, and lactation to undergraduate students for the past 20 yr.

The effect of season and monensin sodium on the digestive characteristics of autumn and spring pasture fed to sheep.

The effects of season of growth and monensin treatment on ruminal digestion of fresh-cut autumn and spring pasture were measured in a single group of ruminally fistulated castrated male sheep, housed indoors in metabolism crates. Responses were assessed in terms of ruminal volatile fatty acid molar proportions, ammonia concentration, pH, apparent digestibility of the pasture, and nitrogen balance of the animals. Blood plasma concentrations of insulin, glucose, beta-hydroxybutyrate, urea, and NEFA were also evaluated. Autumn pasture contained significantly lower proportions of water-soluble carbohydrate (P < 0.05), cellulose (P < 0.05), and lignin (P < 0.05) and increased pectin (P < 0.05), hemicellulose (P < 0.05), and crude protein (P < 0.10) concentrations when compared with spring pasture. Voluntary DMI by sheep of autumn pasture was lower (P < 0.01) than that of spring pasture and was significantly (P < 0.05) reduced by monensin treatment. Monensin treatment significantly decreased the ruminal molar proportions of acetic acid (P < 0.10) and butyric acid (P < 0.001) and increased the molar proportions of propionic acid (P < 0.001) and minor VFA (P < 0.01). Nitrogen retention of the sheep was significantly (P < 0.05) reduced by monensin treatment. Plasma glucose levels were increased (P < 0.10) by monensin treatment during the fourth 5-d collection period in both seasons. Chemical analysis suggested that the composition of autumn pasture was different from that of spring pasture and that this was manifested in vivo by increased DMI and digestibility of spring vs autumn pasture. Ruminal fermentation of autumn pasture also had an increased acetate-to-propionate ratio compared with spring pasture. Monensin treatment acted consistently across seasons by increasing the proportion of propionate and decreasing the proportion of acetate in ruminal fluid.

An isotope dilution model for partitioning leucine uptake by the liver of the lactating dairy cow.

An isotope dilution model for partitioning leucine uptake by the liver of the lactating dairy cow is constructed and solved in the steady state. If assumptions ae made, model solution permits calculation of the rate of leucine uptake from portal and hepatic arterial blood supply, leucine export into the hepatic vein, leucine oxidation and transamination, and synthesis and degradation of hepatic constitutive and export proteins. The model requires the measurement of plasma flow rate through the liver in combination with leucine concentrations and plateau isotopic enrichments in arterial, portal and hepatic plasma during a constant infusion of [1-13C]leucine tracer. The model can be applied to other amino acids with similar metabolic fates and will provide a means for assessing the impact of hepatic metabolism on amino acid availability to peripheral tissues. This is of particular importance when considering the dairy cow and the requirements of the mammary gland for milk protein synthesis.

Application of a mechanistic model of bovine milk protein synthesis to examine the use of isotope labeling methods.

Two types of models of bovine milk protein synthesis were used to simulate collection and analysis of data from infusion experiments involving isotope-labeled amino acids (AA). Analytical solutions to a system of ordinary differential equations that describe isotope enrichment curves of each AA pool within the mammary gland were derived and are presented. Numerical solutions from a dynamic mechanistic model suggest that normal experimental procedures can affect the shape of enrichment curves and, therefore, results derived from them. Simulation results suggest that standard methods utilizing in vivo isotope kinetics may be of limited value to characterize the metabolism of the bovine mammary gland, especially AA metabolism and milk protein synthesis and secretion. The results clearly demonstrate the flexibility of such models for the testing of many hypotheses and possible experimental protocols.

Application of a mechanistic model to study competitive inhibition of amino acid uptake by the lactating bovine mammary gland.

A mathematical model is used to describe uptake by a countertransport system and subsequent flow of three amino acids (AA), Phe, Val, and Met, from arterial blood to milk protein in the mammary gland of a lactating cow. The model suggests that total uptake of all AA is higher than net uptake and that a large proportion of the incoming AA is released from the cell directly back to blood. The model is used to predict which of the three AA is limiting the rate of milk protein synthesis and the response to increased arterial concentration of the first-limiting AA. Simulations are performed to predict possible outcomes of several experimental protocols to AA infusion, which might be used to test in vivo the responsiveness of the bovine mammary gland to an altered arterial concentration of AA. Of the three AA considered, arterial Met concentration appears to be first-limiting. The infusion profile that gives the greatest response in milk protein synthesis rate alters the arterial profile of AA such that it is identical to that of proteins originating in the mammary gland. Model construction can be simplified by acknowledging normal biological constraints.

A model to describe growth patterns of the mammary gland during pregnancy and lactation.

Extensive proliferation and death of cells in the mammary gland occur during pregnancy and lactation. In this study, a mechanistic model was developed that yielded a single equation to describe the pattern of mammary growth of mammals throughout pregnancy and lactation. The model contains a single pool, which is the cell population of the mammary gland; one influx, representing cell proliferation; and one efflux, representing cell death. The parameters of the equation lend themselves to direct physiological interpretation. The model fitted data on mammary gland DNA adequately and can be related to current knowledge on factors and inhibitors of mammary gland growth. A unique definition of the parameters of the model can be difficult because of the high degree of variation among animals, an improper number of observations, or timing, as indicated by analyses of simulated data. The model can also be applied to the study of the entire lactation curve. The widely applied gamma equation and the equation that was developed in this study were compared using weekly production data from dairy cows. The new model performed well, particularly when a sharp peak in milk production occurred. The model has the advantage of providing, for the first time, a simple biological description of the lactation curve that can be used to discriminate changes in lactational performance that are associated with experimental treatments.

Model of milk protein synthesis. A mechanistic model of milk protein synthesis in the lactating bovine mammary gland.

A model of amino acid (AA) uptake and metabolism by the mammary gland (udder) of a high producing dairy cow in mid-lactation is presented. Two cell types, milk-secreting alveolar epithelial cells, and constitutive stromal cells are represented separately. Solution of the model at steady state, with appropriate assumptions, allows calculation of amino acid (AA) pool sizes in tissue bound AA and milk protein bound AA, and concentrations of intracellular free AA. Bidirectional flux rates of amino acids between each of these pools is also estimated. The flow of two amino acids, phenylalanine (Phe) and tyrosine (Tyr), is described using uptake kinetics of the L-system AA transporter. Model results suggest that AA uptake capacity of the alveolar cells, and the amount/activity of protein translation components limit the rate of milk protein synthesis in the high-producing dairy cow. A considerable amount of experimental work is necessary to provide data, if a comprehensive quantitative understanding of milk protein synthesis is to be achieved.