Phytophthora parasitica Effector PpRxLR2 Suppresses Nicotiana benthamiana Immunity.

Phytophthora species secrete several classes of effector proteins during interaction with their hosts. These proteins can have multiple functions including modulation of host physiology and immunity. The RxLR effectors have the ability to enter plant cells using the plant machinery. Some of these effectors have been characterized as immunity suppressors; however, very little is known about their functions in the interaction between Phytophthora parasitica and its hosts. Using a bioinformatics pipeline, we have identified 172 candidate RxLR effectors (CREs) in the isolate IAC 01_95 of P. parasitica. Of these 172 CREs, 93 were found to be also present in eight other genomes of P. parasitica, isolated from different hosts and continents. After transcriptomics and gene expression analysis, we have found five CREs to be up-regulated in in-vitro and in-planta samples. Subsequently, we selected three CREs for functional characterization in the model plant Nicotiana benthamiana. We show that PpRxLR2 is able to completely suppress INF-1-induced cell death, whereas PpRxLR3 and PpRxLR5 moderately suppressed N. benthamiana immunity in a less-extensive manner. Moreover, we confirmed the effector-triggered susceptibility activity of these proteins after transient transformation and infection of N. benthamiana plants. All three CREs enhanced virulence of P. parasitica during the interaction with N. benthamiana. These effectors, in particular PpRxLR2, can be targeted for the development of biotechnology-based control strategies of P. parasitica diseases.

Difficulty adhering to antidiabetic treatment: factors associated with persistence and compliance.

AIMS: This study aimed to assess the 1-year treatment persistence and compliance of new oral antidiabetic drug (OAD) users with their treatment, and to identify the factors associated with both persistence and compliance. METHODS: This population-based cohort study of new OAD users aged 18 years or above used the Quebec health insurance board databases. Those having a prescription filled for antidiabetic treatment during the period leading up to the 1-year anniversary of their first claim were considered to be persistent with their antidiabetic treatment. Of these patients, individuals with a medication possession ratio (MPR) greater or equal to 80% for OAD or insulin were deemed compliant. Also identified were the characteristics associated with both outcomes, using a multivariate logistic regression model. RESULTS: Our cohort consisted of 151,173 individuals, 119,832 (79.3%) of whom were considered persistent. Of these, 93,418 (78.0%) were also deemed compliant. Persistence and compliance were associated with older ages, living in a rural region, low socioeconomic status, having the first OAD prescribed by a general practitioner and a history of using five different drugs or more. People were less likely to be persistent and compliant if their initial OAD was a secretagogue and if they had consulted a physician eight times or more during the year prior to starting treatment. CONCLUSION: One year after OAD treatment initiation, 21% had discontinued their treatment and 22% of those still being treated were non-compliant. These results could help to tailor interventions aimed at optimizing the use of OAD treatments.

Risk of perinatal mortality associated with asthma during pregnancy.

BACKGROUND: Thirteen studies investigating the association between asthma during pregnancy and perinatal mortality reported generally no increased risk. Most of these studies should be interpreted with caution because they were limited in terms of statistical power. A study was therefore undertaken to evaluate whether maternal asthma during pregnancy increases the risk of perinatal mortality. METHODS: Through three administrative databases from Québec (Canada), a cohort of women with and without asthma who had at least one pregnancy between 1990 and 2002 was formed. Perinatal mortality was identified by diagnostic codes. The adjusted odds ratio (OR) of perinatal mortality in women with and without asthma was compared using Generalised Estimation Equation (GEE) models. The first model included all potential confounders (except small for gestational age, SGA), the second model excluded birth weight, gestational age at birth and SGA and the third model excluded birth weight, gestational age at birth but included only SGA. This analysis was also stratified for birth weight and gestational age at birth. RESULTS: The cohort was formed of 13 100 and 28 042 single pregnancies in women with and without asthma. The crude OR of perinatal mortality was 1.35 (95% CI 1.08 to 1.67), which decreased to 0.93 (95% CI 0.75 to 1.17) after adjustment for birth weight and gestational age at birth. Women with asthma had a higher rate of low birthweight babies and preterm delivery than those without asthma. CONCLUSION: The increased risk of low birthweight babies and premature delivery in women with asthma may partly explain the association between maternal asthma and the increased risk of perinatal mortality.

Stability of an empirical psychosocial taxonomy across type of diabetes and treatment.

AIMS: The aims of the study were (i) to examine whether an empirical psychosocial taxonomy, based on key diabetes-related variables, is independent of type of diabetes and treatment, and (ii) to further establish the external validation of the taxonomy. METHODS: In a cross-sectional study, 82 patients with Type 1 and 86 patients with Type 2 diabetes mellitus were assigned to one of three psychosocial patient profiles based on their Multidimensional Diabetes Questionnaire (MDQ) scores. General psychological and diabetes-specific measures were obtained through self-report and HbA(1c) was measured. RESULTS: Equal proportions of Type 1 and Type 2 patients, and of patients using insulin and oral medication/diet only were classified within each of the three psychosocial profiles. External validation confirmed the validity and distinctiveness of the patients' profiles. The patient profiles were independent of demographic variables, body mass index, duration of diabetes, complexity of treatment, number of complications, social desirability, and major stress levels. CONCLUSIONS: The Psychosocial Taxonomy for Patients with Diabetes provides a new way to categorize individuals who may have more in common than just their type of diabetes and/or its treatment and can help target interventions to individual patients' needs.

Development and initial validation of a new preference-based disease-specific health-related quality of life instrument for erectile function.

UNLABELLED: Health-related quality of life instruments may be generic or specific. In general, only generic instruments use preference-based scoring. We report on a novel approach to combine in one instrument the strengths of the specific approach, greater disease relevance and responsiveness, with those of preference-based scoring, generalizability through utilities. OBJECTIVES: The primary objective was to develop a self-administered, preference-based instrument capable of measuring utilities in the disease-specific context of erectile dysfunction (ED). METHODS: Content derivation/validation began with a literature review. Eight attributes (domains) were selected to provide clinical experts structure for focus group discussion. Four levels describing a continuum of dysfunction-function were defined for each domain. Each domain, including functional levels, was reviewed and modified until consensus was achieved regarding content. This content was then integrated into a preference based scoring instrument using two visual analogue scales (VAS) with which patients rated three 'marker' health states (representing mild, moderate and severe ED), their self-state and a previously validated external marker state. The instrument was pilot tested, and implemented in a clinical trial. Initial validation analyses have been performed. RESULTS: A self-administered, preference-based, VAS instrument was developed for use in the ED population, and the instrument was feasible to complete, was reliable beyond the threshold of acceptability established a priori and demonstrated good validity. Evidence of these properties accumulates over time and this study begins that process with this instrument. Responsiveness is being assessed in the context of a clinical trial.

The Canadian SCORE questionnaire: optimizing the use of technology for low bone density assessment. Simple Calculated Osteoporosis Risk Estimate.

The Simple Calculated Osteoporosis Risk Estimation (SCORE) questionnaire is a tool to assist physicians to identify women who might require bone densitometry. The purpose of this study was to develop a Canadian SCORE and to assess validity and reliability. Twenty sites enrolled 307 postmenopausal women ages 50-70 yr. SCORE results were compared to hip and lumbar spine bone density assessed by dual X-ray absorptiometry. Sensitivity and specificity of a range of SCORE cut-points were assessed in a receiver operating characteristics analysis to determine the optimal cut-point for SCORE. With low bone density defined as a T-score < or = -2.0, a SCORE cut-point of 6 in women ages 50-59 yr displayed a sensitivity of 0. 96, 95% confidence interval (CI) (0.89, 1.00), a specificity of 0.51, 95% CI (0.43, 0.58). In women ages 60-70 yr, a SCORE cut-point of 8 displayed a sensitivity of 0.90, 95% CI (0.80, 0.97) and a specificity of 0.20, 95% CI (0.11, 0.29). The test-retest reliability (intraclass correlation coefficient) was 0.95. SCORE performed better in women in their fifties than women in ther sixties. Older women require higher SCORE cut-points. The use of SCORE as an initial measure for identifying those at risk for osteoporosis may reduce costs by limiting unnecessary tests.