The relative merits of quantitative coronary analysis (QCA) and intravascular ultrasound (IVUS) for the assessment of progression/regression in coronary artery disease are uncertain. To explore this ...subject further, we analyzed the angiographic and IVUS data derived from a contemporary clinical trial population.
We investigated the relationships between QCA and IVUS at single time points (n=525) and also for the changes over time (n=432). QCA and IVUS data underwent central laboratory analyses. Statistically significant correlations were observed between the QCA coronary artery score and the IVUS-derived lumen volume (r=0.65, P<0.0001) and total vessel volume (r=0.55, P<0.0001) and between the QCA cumulative coronary stenosis score and percent atheroma volume on IVUS (r=0.32, P<0.0001) at baseline for matched segments. A similar pattern of correlations was observed for global (all segments) QCA-derived and single-vessel IVUS-derived data. There were statistically significant but weak correlations between the changes over time in lumen dimensions on QCA and IVUS (P=0.005) and between the change in cumulative coronary stenosis score on QCA and percent atheroma volume on IVUS (r=0.14, P=0.01). Nevertheless, patients with and without angiographic progression had changes in plaque volume on IVUS of 9.13 and 0.20 mm3, respectively (P=0.028).
QCA- and IVUS-derived measures of lumen dimensions are correlated at single time points and for changes over time. Although the change in percent atheroma volume is only weakly correlated with QCA changes as continuous variables, disease progression on QCA is associated with significant increases in plaque volume on IVUS compared with no angiographic progression.
The chicken egg resists most environmental microbes suggesting that it potentially contains efficient antimicrobial molecules. Considering that some heparin-binding proteins in mammals are ...antibacterial, we investigated the presence and the antimicrobial activity of heparin-binding proteins from chicken egg white. Mass spectrometry analysis of the proteins recovered after heparin-affinity chromatography, revealed 20 proteins, including known antimicrobial proteins (avidin, lysozyme, TENP, ovalbumin-related protein X and avian bêta-defensin 11). The antibacterial activity of three new egg candidates (vitelline membrane outer layer protein 1, beta-microseminoprotein-like (LOC101750704) and pleiotrophin) was demonstrated against Listeria monocytogenes and/or Salmonella enterica Enteritidis. We showed that all these molecules share the property to inhibit bacterial growth through their heparin-binding domains. However, vitelline membrane outer layer 1 has additional specific structural features that can contribute to its antimicrobial potential. Moreover, we identified potential supplementary effectors of innate immunity including mucin 5B, E-selectin ligand 1, whey acidic protein 3, peptidyl prolyl isomerase B and retinoic acid receptor responder protein 2. These data support the concept of using heparin affinity combined to mass spectrometry to obtain an overview of the various effectors of innate immunity composing biological milieus, and to identify novel antimicrobial candidates of interest in the race for alternatives to antibiotics.
It remains unclear whether racial and ethnic disparities for atherosclerotic cardiovascular disease (ASCVD) persist within universal health care systems. We aimed to explore long-term ASCVD outcomes ...within a single-payer health care system with extensive drug coverage in Québec, Canada.
CARTaGENE (CaG) is a population-based prospective cohort study of individuals aged 40 to 69 years. We included only participants without previous ASCVD. The primary composite endpoint was time to the first ASCVD event (cardiovascular death, acute coronary syndrome, ischemic stroke-transient ischemic attack, or peripheral arterial vascular event).
The study cohort included 18,880 participants followed for a median of 6.6 years (2009 to 2016). The mean age was 52 years, and 52.4% were female. After further adjustment for socioeconomic and cardiovascular factors, the increase in ASCVD risk for South Asians (SAs) was attenuated (hazard ratio HR, 1.41; 95% confidence interval CI, 0.75, 2.67), whereas Black participants’ risk was lower (HR, 0.52; 95% CI, 0.29, 0.95) compared with White participants. After similar adjustments, there were no significant differences in ASCVD outcomes among the Middle Eastern, Hispanic, East-Southeast Asian, Indigenous, and mixed race-ethnicities participants and the White participants.
After adjustment for CV risk factors, the risk of ASCVD was attenuated in the SA CaG participants. Intensive risk-factor modification may mitigate the ASCVD risk of the SAs. Within a universal health care context and comprehensive drug coverage, the ASCVD risk was lower among Black compared with White CaG participants. Future studies are needed to confirm whether universal and liberal access to health care and medications can reduce the rates of ASCVD among the Black population.
Des doutes subsistent quant à la persistance des disparités raciales et ethniques en matière de maladies cardiovasculaires athéroscléreuses (MCVA) dans les systèmes de soins de santé universels. Nous avons voulu étudier les issues à long terme des MCVA au sein d’un système de soins de santé à payeur unique avec une couverture étendue des médicaments, en l’occurrence au Québec (Canada).
CARTaGENE (CaG) est étude de cohorte prospective menée auprès d’une population d’individus âgés de 40 à 69 ans. Seuls les participants sans MCVA antérieure ont été inclus. Le critère composé principal était le temps écoulé avant le premier événement de MCVA (décès d’origine cardiovasculaire, syndrome coronarien aigu, accident vasculaire cérébral ischémique, accident ischémique transitoire ou maladie artérielle périphérique).
La cohorte comprenait 18 880 participants suivis pendant une durée médiane de 6,6 ans (de 2009 à 2016). L’âge moyen était de 52 ans, et 52,4 % des sujets étaient des femmes. Après un ajustement supplémentaire pour tenir compte des facteurs socio-économiques et cardiovasculaires, la hausse du risque de MCVA chez les Sud-Asiatiques a été atténuée (rapport des risques instantanés RRI : 1,41; intervalle de confiance IC à 95 % : 0,75-2,67), tandis que le risque était plus faible pour les participants noirs (RRI : 0.52 ; IC à 95 % : 0,29-0,95) que pour les participants blancs. Après des ajustements similaires, aucune différence significative n’a été observée quant aux cas de MCVA entre les participants du Moyen-Orient, les Hispaniques, les Asiatiques de l’Est et du Sud-Est, les Autochtones et les participants de race mixte ou les participants blancs.
Après un ajustement pour tenir compte de facteurs de risque cardiovasculaire, le risque de MCVA était atténué chez les Sud-Asiatiques de l’étude CaG. Une modification intensive des facteurs de risque peut expliquer la baisse observée dans cette population. Dans le contexte d’un système de soins de santé universel offrant une couverture complète des médicaments, le risque de MCVA était par ailleurs plus faible chez les participants noirs que chez les participants blancs de l’étude CaG. D’autres études sont toutefois requises pour vérifier si un accès libre et universel aux soins de santé et aux médicaments peut expliquer la réduction des taux de MCVA au sein de la population noire.
In the present study a semi-artificial rearing system for the Australian ladybird Cryptolaemus montrouzieri Mulsant (Coleoptera: Coccinellidae), a specialist predator of mealybugs, was developed. In ...a first step, a rearing system using eggs of the Mediterranean flour moth Ephestia kuehniella Zeller (Lepidoptera: Pyralidae) as a food and synthetic polyester wadding as an oviposition substrate was compared with a natural rearing system using the citrus mealybug, Planococcus citri (Risso) (Hemiptera: Pseudococcidae), as to its effects on the predator’s developmental and reproductive parameters. In a second series of experiments the performance of C. montrouzieri on bee pollen or on a mixture of E. kuehniella eggs and bee pollen was assessed. E. kuehniella eggs proved to be a suitable food to support larval development of the predator. Ladybird larvae reared on flour moth eggs developed two days faster and weighed approximately 10 % more than their counterparts reared on mealybugs. Despite a prolongation of the preoviposition period with ca. eight days and a decrease in egg hatch by about 10 %, C. montrouzieri females fed moth eggs accepted the synthetic wadding as an oviposition substrate and deposited the same number of eggs their counterparts maintained on mealybugs. A mixture of E. kuehniella eggs with pollen yielded similar developmental and reproductive rates as E. kuehniella eggs alone, but a diet of bee pollen alone was not adequate for the predator. Our findings indicate the potential of a rearing system using E. kuehniella eggs as a factitious food and synthetic wadding as an artificial oviposition substrate for the mass production of C. montrouzieri.
Inhibition of the acyl coenzyme A:cholesterol acyltransferase (ACAT) enzyme may prevent excess accumulation of cholesteryl esters in macrophages. The ACAT inhibitor avasimibe was shown to reduce ...experimental atherosclerosis. This study was designed to investigate the effects of avasimibe on human coronary atherosclerosis.
This randomized, double-blind, placebo-controlled trial assessed the effects of avasimibe at dosages of 50, 250, and 750 mg QD on the progression of coronary atherosclerosis as assessed by intravascular ultrasound (IVUS). All patients received background lipid-lowering therapy if necessary to reach a target baseline LDL level <125 mg/dL (3.2 mmol/L). IVUS and coronary angiography were performed at baseline and repeated after up to 24 months of treatment. Approximately equal percentages of patients across groups received concurrent statin therapy (87% to 89%). The mean total plaque volume at baseline was approximately 200 mm3, and the least squares mean change at end of treatment was 0.7 mm3 for placebo and 7.7, 4.1, and 4.8 mm3 for the avasimibe 50, 250, and 750 mg groups, respectively (adjusted P=0.17 unadjusted P=0.057, 0.37, and 0.37, respectively). Percent atheroma volume increased by 0.4% with placebo and by 0.7%, 0.8%, and 1.0% in the respective avasimibe groups (P=NS). LDL cholesterol increased during the study by 1.7% with placebo but by 7.8%, 9.1%, and 10.9% in the respective avasimibe groups (P<0.05 in all groups).
Avasimibe did not favorably alter coronary atherosclerosis as assessed by IVUS. This ACAT inhibitor also caused a mild increase in LDL cholesterol.
OBJECTIVE:We evaluated recurrent intracerebral hemorrhage (ICH) risk in ICH survivors, stratified by the presence, distribution, and number of cerebral microbleeds (CMBs) on MRI (i.e., the presumed ...causal underlying small vessel disease and its severity).
METHODS:This was a meta-analysis of prospective cohorts following ICH, with blood-sensitive brain MRI soon after ICH. We estimated annualized recurrent symptomatic ICH rates for each study and compared pooled odds ratios (ORs) of recurrent ICH by CMB presence/absence and presumed etiology based on CMB distribution (strictly lobar CMBs related to probable or possible cerebral amyloid angiopathy CAA vs non-CAA) and burden (1, 2–4, 5–10, and >10 CMBs), using random effects models.
RESULTS:We pooled data from 10 studies including 1,306 patients325 with CAA-related and 981 CAA-unrelated ICH. The annual recurrent ICH risk was higher in CAA-related ICH vs CAA-unrelated ICH (7.4%, 95% confidence interval CI 3.2–12.6 vs 1.1%, 95% CI 0.5–1.7 per year, respectively; p = 0.01). In CAA-related ICH, multiple baseline CMBs (versus none) were associated with ICH recurrence during follow-up (range 1–3 years)OR 3.1 (95% CI 1.4–6.8; p = 0.006), 4.3 (95% CI 1.8–10.3; p = 0.001), and 3.4 (95% CI 1.4–8.3; p = 0.007) for 2–4, 5–10, and >10 CMBs, respectively. In CAA-unrelated ICH, only >10 CMBs (versus none) were associated with recurrent ICH (OR 5.6, 95% CI 2.1–15; p = 0.001). The presence of 1 CMB (versus none) was not associated with recurrent ICH in CAA-related or CAA-unrelated cohorts.
CONCLUSIONS:CMB burden and distribution on MRI identify subgroups of ICH survivors with higher ICH recurrence risk, which may help to predict ICH prognosis with relevance for clinical practice and treatment trials.
Following a request from the European Commission, the EFSA Panel on Plant Health (PLH) performed a quantitative analysis of the risk posed by the Flavescence dorée phytoplasma (FDp) in the EU ...territory. Three scenarios were analysed, one with current measures in place (scenario A0), one designed to improve grapevine propagation material phytosanitary status (scenario A1) and one with reinforced eradication and containment (scenario A2). The potential for entry is limited, FDp being almost non‐existent outside the EU. FDp and its major vector, Scaphoideus titanus, have already established over large parts of the EU and have the potential to establish in a large fraction of the currently unaffected EU territory. With the current measures in place (A0), spread of FDp is predicted to continue with a progression of between a few and ca 20 newly infested NUTS 2 regions during the next 10 years, illustrating the limitations of the current control measures against spread. FDp spread is predicted to be roughly similar between scenarios A1 and A2, but more restricted than under scenario A0. However, even with reinforced control scenarios, stabilisation or reduction in the number of infested NUTS 2 regions has only relatively low probability. Under scenario A0, FDp has a 0.5–1% impact on the overall EU grapes and wine production, reflecting the effectiveness of the current control measures against impact. Under both scenarios A1 and A2, FDp impact is predicted to be reduced, by approximately one‐third (A1) to two‐thirds (A2) as compared to A0, but the associated uncertainties are large. The generalised use of hot water treatment for planting material produced in infected zones has the most important contribution to FDp impact reduction in scenario A1 and has high feasibility. Both increased eradication and containment measures contribute to impact reduction under scenario A2 but the overall feasibility is lower.
The prey range of Cryptolaemus montrouzieri was studied in the laboratory to investigate whether the mealybug destroyer can contribute to the suppression of other pest insects besides mealybugs and ...to assess its potential impact on non-mealybug populations as part of an environmental risk assessment for its use in biological control. Prey tested in these experiments were: tobacco aphid Myzus persicae nicotianae (Sulzer)(Hemiptera: Aphididae), pea aphid Acyrthosiphon pisum (Harris)(Hemiptera: Aphididae), tobacco whitefly Bemisia tabaci (Gennadius)(Hemiptera: Aleyrodidae), southern green stinkbug Nezara viridula (L.)(Hemiptera: Pentatomidae) eggs, western flower thrips Frankliniella occidentalis (Pergande)(Thysanoptera: Thripidae), two-spotted ladybird Adalia bipunctata (L.)(Coleoptera: Coccinellidae) eggs and eggs of the greater wax moth Galleria mellonella L. (Lepidoptera: Pyralidae). Larval survival was high to moderate when C. montrouzieri was provided with hemipteran prey and poor to zero when the ladybirds were provided with non-hemipteran prey. Females reared on M. persicae and A. pisum produced similar numbers of eggs as their counterparts fed the citrus mealybug Planococcus citri (Risso)(Hemiptera: Pseudococcidae), but fecundity was significantly lower when the ladybirds were reared on B. tabaci nymphs or on A. bipunctata eggs. Prey species that were found to be less suitable for immature development of C. montrouzieri could still be an adequate food source for reproduction and survival of adult ladybirds. For example, only 8 % of the predator larvae reached the adult stage when provided with A. bipunctata eggs, but females that had developed on eggs of the Mediterranean flour moth Ephestia kuehniella Zeller (Lepidoptera: Pyralidae) and that were supplied with A. bipunctata eggs from adult emergence on, were only 35 % less fecund than females provided with mealybugs in their adult life. The results are discussed in relation to the development of a suitable methodology for prey/host range testing in the framework of an environmental risk assessment for arthropod natural enemies.
Dalcetrapib effects on cardiovascular outcomes are determined by adenylate cyclase 9 gene polymorphisms. Our aim was to determine whether these clinical end point results are also associated with ...changes in reverse cholesterol transport and inflammation.
Participants of the dal-OUTCOMES and dal-PLAQUE-2 trials were randomly assigned to receive dalcetrapib or placebo in addition to standard care. High-sensitivity C-reactive protein was measured at baseline and at end of study in 5243 patients from dal-OUTCOMES also genotyped for the rs1967309 polymorphism in adenylate cyclase 9. Cholesterol efflux capacity of high-density lipoproteins from J774 macrophages after cAMP stimulation was determined at baseline and 12 months in 171 genotyped patients from dal-PLAQUE-2. Treatment with dalcetrapib resulted in placebo-adjusted geometric mean percent increases in high-sensitivity C-reactive protein from baseline to end of trial of 18.1% (P=0.0009) and 18.7% (P=0.00001) in participants with the GG and AG genotypes, respectively, but the change was -1.0% (P=0.89) in those with the protective AA genotype. There was an interaction between the treatment arm and the genotype groups (P=0.02). Although the mean change in cholesterol efflux was similar among study arms in patients with GG genotype (mean: 7.8% and 7.4%), increases were 22.3% and 3.5% with dalcetrapib and placebo for those with AA genotype (P=0.005). There was a significant genetic effect for change in efflux for dalcetrapib (P=0.02), but not with placebo.
Genotype-dependent effects on C-reactive protein and cholesterol efflux are supportive of dalcetrapib benefits on atherosclerotic cardiovascular outcomes in patients with the AA genotype at polymorphism rs1967309.
ClinicalTrials.gov; Unique Identifiers: NCT00658515 and NCT01059682.
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