A Bayesian approach to the probability of coronary heart disease subject to the -308 tumor necrosis factor-α SNP.

We study the correlation of the occurrence of coronary heart disease (CHD) with the presence of the single-nucleotide polymorphism (SNP) at the -308 position of the tumor necrosis factor alpha (TNF-α) gene. We also consider the influence of the occurrence of type 2 diabetes (t2DM). Using Bayesian inference, we first pursue a bottom-up approach to compute the working hypothesis and the probabilities derivable from the data. We then pursue a top-down approach by modelling the signal pathway that causally connects the SNP with the emergence of CHD. We compute the functional form of the probability of CHD conditional on the presence of the SNP in terms of both the statistical and biochemical properties of the system. From the probability of occurrence of a disease conditional on a given risk factor, we explore the possibility of extracting information on the pathways involved in the occurrence of the disease. This is a first study that we want to systematise into a comprehensive formalism to be applied to the inference of the mechanism connecting the risk factors to the disease.

The development and implementation of a software tool and its effect on the quality of provided clinical nutritional therapy in hospitalized patients.

The authors developed "DIET", a computerized system preparing dietary prescriptions in clinical settings. "DIET" has the ability to calculate the nutritional requirements and to produce daily menus of patients automatically. Also, it serves as an electronic medical and dietetic record and it can produce daily reports regarding portions, quantities and cost of meals. The authors also conducted a preliminary evaluation of the system by comparing the design of nutritional plans for 135 patients using "DIET" versus the customary manual methods. Its use resulted in a decrease of the error percentages, concerning appropriate food choices, data recording and calculations of daily nutrient requirements; from 12% to 1.5%. Additionally, there was a reduction by 50% of the time required to obtain and process data as well as design a patient's menu. "DIET" implementation resulted in error decrease and thus in improvement of menu planning, accuracy and recovery of data and decreased the time spent on menu planning.

Comparison of two types of TPN prescription methods in preterm neonates.

OBJECTIVE: Total parenteral nutrition is commonly used in neonates' intensive care units for nutritional support of preterm neonates. Adequacy and safety of parenteral nutrition support are amongst the major concerns of neonates' therapy. Parenteral nutrition prescription in Greek hospitals is not based on standardized protocols, thus resulting in wide diversity of formulations. In this study, the results of utilization of standardized computerized parenteral nutrition protocols and regimens for neonates are compared to the results of protocols and regimens prescribed by individual neonatologists on neonates' outcome (weight changes, adequacy of parenteral nutrition, days of hospitalization, clinical outcome). SETTING: The study took place at "Mitera" Maternity Hospital of Greece. METHOD: Two groups of 30 preterm infants (28-36 weeks) with respiratory failure were recruited for the study. They were admitted in a Greek maternity hospital and they all received total parenteral nutrition support in neonates' intensive care unit. Standardized, computer based protocols were applied for the prescription of parenteral nutrition formulations in the first group, while on the other, regimens prescribed by neonatologists were used. MAIN OUTCOME MEASURES: Macro- and micronutrients provided by the different total parenteral nutrition protocols were recorded. Body weight was measured, blood count and biochemical profile were performed at the beginning and at the end of parenteral nutrition support. The number of days of total parenteral nutrition support as well as the total number of days of hospitalization was recorded. RESULTS: Standardized protocols provided more energy (P-value: 0.05), protein (P-value: 0.023) and micronutrients than the non-standardised. Neonates that receive standardized total parenteral nutrition gained weight (+44 +/- 114 g) and had better blood count and biochemical values during total parenteral nutrition support compared to the other group, that lost weight during total parenteral nutrition support (-53 +/- 156 g). These differences were also statistically significant (P value < 0.05). Regarding the total days of hospitalization, no differences were found between the two groups. CONCLUSION: The use of standardized protocols in preterm neonates resulted in more adequate provision of nutrients, weight gain and better blood count profile compared with protocols prescribed by individual physicians.

Cholesterol ester transfer protein: a therapeutic target in atherosclerosis?

BACKGROUND: CETP has an established role in the transport of cholesterol from the peripheral tissues to the liver for elimination. The fact that CETP was recognized as a target for raising high-density lipoprotein cholesterol (HDL-C) levels has led to research on CETP inhibitors to protect against atherosclerosis. OBJECTIVE: To review the role of CETP as a pivotal target for atherosclerosis and cardiovascular diseases and the effect of its overexpression or inhibition on lipid metabolism. METHODS: A review of literature on the role of CETP in cholesterol metabolism and on recent developments on CETP inhibitors. RESULTS/CONCLUSIONS: Animal and human studies have provided evidence supporting both the pro- and antiatherogenic roles of CETP. Clinical trials with CETP inhibitors remain under serious consideration. Further studies are necessary for understanding of the role of CETP in lipid metabolism and the development of novel therapies involving a combination of strategies for treatment of atherosclerosis and cardiovascular disease.

Model for Osteosarcoma-9 as a potent factor in cell survival and resistance to apoptosis.

In this paper we use a simple model to explore the function of the gene Osteosarcoma-9 (OS-9). We are particularly interested in understanding the role of this gene as a potent anti-apoptotic factor. The theoretical description is constrained by experimental data from induction of apoptosis in cells where OS-9 is overexpressed. The data available suggest that OS-9 promotes cell viability and confers resistance to apoptosis, potentially implicating OS-9 in the survival of cancer cells. Three different apoptosis-inducing mechanisms were tested and are modeled here. A more complex and realistic model is also discussed.

Bioinformatic analysis of primary endothelial cell gene array data illustrated by the analysis of transcriptome changes in endothelial cells exposed to VEGF-A and PlGF.

We recently published a review in this journal describing the design, hybridisation and basic data processing required to use gene arrays to investigate vascular biology (Evans et al. Angiogenesis 2003; 6: 93-104). Here, we build on this review by describing a set of powerful and robust methods for the analysis and interpretation of gene array data derived from primary vascular cell cultures. First, we describe the evaluation of transcriptome heterogeneity between primary cultures derived from different individuals, and estimation of the false discovery rate introduced by this heterogeneity and by experimental noise. Then, we discuss the appropriate use of Bayesian t-tests, clustering and independent component analysis to mine the data. We illustrate these principles by analysis of a previously unpublished set of gene array data in which human umbilical vein endothelial cells (HUVEC) cultured in either rich or low-serum media were exposed to vascular endothelial growth factor (VEGF)-A165 or placental growth factor (PlGF)-1(131). We have used Affymetrix U95A gene arrays to map the effects of these factors on the HUVEC transcriptome. These experiments followed a paired design and were biologically replicated three times. In addition, one experiment was repeated using serial analysis of gene expression (SAGE). In contrast to some previous studies, we found that VEGF-A and PlGF consistently regulated only small, non-overlapping and culture media-dependant sets of HUVEC transcripts, despite causing significant cell biological changes.