Elderly People With Drug-Related Problems Identified in the Emergency Department : Impact of Therapeutic Complexity on Consultations to the Health System

Different scales have been validated to assess the medication regimen complexity. However, the effect of this complexity on the risk of health care center consultations in patients with drug-related problems is unknown. This study's objective is to evaluate the association between the Medication Regimen Complexity Index (MCRI) and the number of drugs prescribed and new consultations to the health care system in patients who visit an emergency service due to drug-related problems. This is a retrospective observational study. We included patients >65 years who attended in an emergency service for drug-related problems. To identify variables associated with health care center reconsultation, a multivariate analysis was performed, including demographic and comorbidity variables, number of drugs prescribed, and MCRI value. Two hundred and one patients were included. A significant association was found between the prescription of more than five drugs (odds ratio [OR] = 2.50, 95% confidence interval [CI] = [1.08, 5.79]), an MCRI > 20 (2.98 [1.46-6.09]), and an increase in the number of drugs prescribed (2.87 [1.57-5.21]) and its MCRI (2.06 [1.13-3.77]) at discharge and a new visit to the emergency department. An association was found between the prescription of more than five drugs, an MCRI > 20, an increase in the number of drugs, and in MCRI value at discharge and a new visit to any other health care center. The number of prescribed drugs and the medication complexity of patients who visit the emergency department for drug-related problems was associated with an increase in the number of revisits to the emergency department and to other health care centers

Detection of gene pathways with predictive power for breast cancer prognosis

<p>Abstract</p> <p>Background</p> <p>Prognosis is of critical interest in breast cancer research. Biomedical studies suggest that genomic measurements may have independent predictive power for prognosis. Gene profiling studies have been conducted to search for predictive genomic measurements. Genes have the inherent pathway structure, where pathways are composed of multiple genes with coordinated functions. The goal of this study is to identify gene pathways with predictive power for breast cancer prognosis. Since our goal is fundamentally different from that of existing studies, a new pathway analysis method is proposed.</p> <p>Results</p> <p>The new method advances beyond existing alternatives along the following aspects. First, it can assess the predictive power of gene pathways, whereas existing methods tend to focus on model fitting accuracy only. Second, it can account for the joint effects of multiple genes in a pathway, whereas existing methods tend to focus on the marginal effects of genes. Third, it can accommodate multiple heterogeneous datasets, whereas existing methods analyze a single dataset only. We analyze four breast cancer prognosis studies and identify 97 pathways with significant predictive power for prognosis. Important pathways missed by alternative methods are identified.</p> <p>Conclusions</p> <p>The proposed method provides a useful alternative to existing pathway analysis methods. Identified pathways can provide further insights into breast cancer prognosis.</p

The logic of the floral transition: reverse-engineering the switch controlling the identity of lateral organs

Much laboratory work has been carried out to determine the gene regulatory network (GRN) that results in plant cells becoming flowers instead of leaves. However, this also involves the spatial distribution of different cell types, and poses the question of whether alternative networks could produce the same set of observed results. This issue has been addressed here through a survey of the published intercellular distribution of expressed regulatory genes and techniques both developed and applied to Boolean network models. This has uncovered a large number of models which are compatible with the currently available data. An exhaustive exploration had some success but proved to be unfeasible due to the massive number of alternative models, so genetic programming algorithms have also been employed. This approach allows exploration on the basis of both data-fitting criteria and parsimony of the regulatory processes, ruling out biologically unrealistic mechanisms. One of the conclusions is that, despite the multiplicity of acceptable models, an overall structure dominates, with differences mostly in alternative fine-grained regulatory interactions. The overall structure confirms the known interactions, including some that were not present in the training set, showing that current data are sufficient to determine the overall structure of the GRN. The model stresses the importance of relative spatial location, through explicit references to this aspect. This approach also provides a quantitative indication of how likely some regulatory interactions might be, and can be applied to the study of other developmental transitions

Disruption of Yarrowia lipolytica TPS1 Gene Encoding Trehalose-6-P Synthase Does Not Affect Growth in Glucose but Impairs Growth at High Temperature

We have cloned the Yarrowia lipolytica TPS1 gene encoding trehalose-6-P synthase by complementation of the lack of growth in glucose of a Saccharomyces cerevisiae tps1 mutant. Disruption of YlTPS1 could only be achieved with a cassette placed in the 3′half of its coding region due to the overlap of its sequence with the promoter of the essential gene YlTFC1. The Yltps1 mutant grew in glucose although the Y. lipolytica hexokinase is extremely sensitive to inhibition by trehalose-6-P. The presence of a glucokinase, insensitive to trehalose-6-P, that constitutes about 80% of the glucose phosphorylating capacity during growth in glucose may account for the growth phenotype. Trehalose content was below 1 nmol/mg dry weight in Y. lipolytica, but it increased in strains expressing YlTPS1 under the control of the YlTEF1promoter or with a disruption of YALI0D15598 encoding a putative trehalase. mRNA levels of YlTPS1 were low and did not respond to thermal stresses, but that of YlTPS2 (YALI0D14476) and YlTPS3 (YALI0E31086) increased 4 and 6 times, repectively, by heat treatment. Disruption of YlTPS1 drastically slowed growth at 35°C. Homozygous Yltps1 diploids showed a decreased sporulation frequency that was ascribed to the low level of YALI0D20966 mRNA an homolog of the S. cerevisiae MCK1 which encodes a protein kinase that activates early meiotic gene expression

Overexpression of Hydroxynitrile Lyase in Cassava Roots Elevates Protein and Free Amino Acids while Reducing Residual Cyanogen Levels

Cassava is the major source of calories for more than 250 million Sub-Saharan Africans, however, it has the lowest protein-to-energy ratio of any major staple food crop in the world. A cassava-based diet provides less than 30% of the minimum daily requirement for protein. Moreover, both leaves and roots contain potentially toxic levels of cyanogenic glucosides. The major cyanogen in cassava is linamarin which is stored in the vacuole. Upon tissue disruption linamarin is deglycosylated by the apolplastic enzyme, linamarase, producing acetone cyanohydrin. Acetone cyanohydrin can spontaneously decompose at pHs >5.0 or temperatures >35°C, or is enzymatically broken down by hydroxynitrile lyase (HNL) to produce acetone and free cyanide which is then volatilized. Unlike leaves, cassava roots have little HNL activity. The lack of HNL activity in roots is associated with the accumulation of potentially toxic levels of acetone cyanohydrin in poorly processed roots. We hypothesized that the over-expression of HNL in cassava roots under the control of a root-specific, patatin promoter would not only accelerate cyanogenesis during food processing, resulting in a safer food product, but lead to increased root protein levels since HNL is sequestered in the cell wall. Transgenic lines expressing a patatin-driven HNL gene construct exhibited a 2–20 fold increase in relative HNL mRNA levels in roots when compared with wild type resulting in a threefold increase in total root protein in 7 month old plants. After food processing, HNL overexpressing lines had substantially reduced acetone cyanohydrin and cyanide levels in roots relative to wild-type roots. Furthermore, steady state linamarin levels in intact tissues were reduced by 80% in transgenic cassava roots. These results suggest that enhanced linamarin metabolism contributed to the elevated root protein levels

Patterns of Sequence Divergence and Evolution of the S1 Orthologous Regions between Asian and African Cultivated Rice Species

A strong postzygotic reproductive barrier separates the recently diverged Asian and African cultivated rice species, Oryza sativa and O. glaberrima. Recently a model of genetic incompatibilities between three adjacent loci: S1A, S1 and S1B (called together the S1 regions) interacting epistatically, was postulated to cause the allelic elimination of female gametes in interspecific hybrids. Two candidate factors for the S1 locus (including a putative F-box gene) were proposed, but candidates for S1A and S1B remained undetermined. Here, to better understand the basis of the evolution of regions involved in reproductive isolation, we studied the genic and structural changes accumulated in the S1 regions between orthologous sequences. First, we established an 813 kb genomic sequence in O. glaberrima, covering completely the S1A, S1 and the majority of the S1B regions, and compared it with the orthologous regions of O. sativa. An overall strong structural conservation was observed, with the exception of three isolated regions of disturbed collinearity: (1) a local invasion of transposable elements around a putative F-box gene within S1, (2) the multiple duplication and subsequent divergence of the same F-box gene within S1A, (3) an interspecific chromosomal inversion in S1B, which restricts recombination in our O. sativa×O. glaberrima crosses. Beside these few structural variations, a uniform conservative pattern of coding sequence divergence was found all along the S1 regions. Hence, the S1 regions have undergone no drastic variation in their recent divergence and evolution between O. sativa and O. glaberrima, suggesting that a small accumulation of genic changes, following a Bateson-Dobzhansky-Muller (BDM) model, might be involved in the establishment of the sterility barrier. In this context, genetic incompatibilities involving the duplicated F-box genes as putative candidates, and a possible strengthening step involving the chromosomal inversion might participate to the reproductive barrier between Asian and African rice species

Bioinformatics and Functional Analysis of an Entamoeba histolytica Mannosyltransferase Necessary for Parasite Complement Resistance and Hepatical Infection

The glycosylphosphatidylinositol (GPI) moiety is one of the ways by which many cell surface proteins, such as Gal/GalNAc lectin and proteophosphoglycans (PPGs) attach to the surface of Entamoeba histolytica, the agent of human amoebiasis. It is believed that these GPI-anchored molecules are involved in parasite adhesion to cells, mucus and the extracellular matrix. We identified an E. histolytica homolog of PIG-M, which is a mannosyltransferase required for synthesis of GPI. The sequence and structural analysis led to the conclusion that EhPIG-M1 is composed of one signal peptide and 11 transmembrane domains with two large intra luminal loops, one of which contains the DXD motif, involved in the enzymatic catalysis and conserved in most glycosyltransferases. Expressing a fragment of the EhPIG-M1 encoding gene in antisense orientation generated parasite lines diminished in EhPIG-M1 levels; these lines displayed reduced GPI production, were highly sensitive to complement and were dramatically inhibited for amoebic abscess formation. The data suggest a role for GPI surface anchored molecules in the survival of E. histolytica during pathogenesis

Differential Selection on Carotenoid Biosynthesis Genes as a Function of Gene Position in the Metabolic Pathway: A Study on the Carrot and Dicots

Background: Selection of genes involved in metabolic pathways could target them differently depending on the position of genes in the pathway and on their role in controlling metabolic fluxes. This hypothesis was tested in the carotenoid biosynthesis pathway using population genetics and phylogenetics. Methodology/Principal Findings: Evolutionary rates of seven genes distributed along the carotenoid biosynthesis pathway

Testing Biochemistry Revisited: How In Vivo Metabolism Can Be Understood from In Vitro Enzyme Kinetics

A decade ago, a team of biochemists including two of us, modeled yeast glycolysis and showed that one of the most studied biochemical pathways could not be quite understood in terms of the kinetic properties of the constituent enzymes as measured in cell extract. Moreover, when the same model was later applied to different experimental steady-state conditions, it often exhibited unrestrained metabolite accumulation