Littérature scientifique sur le sujet « 791.43/75/0981 »

SummaryBoth diabetes mellitus (DM) and carriage of the CYP2C19*2 allele are associated with a reduced response to clopidogrel. The relative contributions of these factors and whether higher clopidogrel doses can overcome both factors remain unknown. The objective of this study was to test the ability of clopidogrel doses up to 300 mg daily to decrease platelet reactivity in patients with DM and/or CYP2C19*2. ELEVATE-TIMI 56 randomised 333 patients with coronary artery disease to different maintenance doses of clopidogrel in four treatment periods, each lasting approximately 14 days. On-treatment platelet reactivity was compared between patients stratified by DM, CYP2C19*2 status and clopidogrel dose. Both DM and CYP2C19*2 were independently associated with elevated on-treatment platelet reactivity with clopidogrel 75 mg daily (p<0.0001 for each). With 75 mg, mean on-treatment PRU was progressively higher (p trend <0.001) when evaluating patients: with neither DM nor CYP2C19*2 (150.7; 95 % CI 140.5–162.6), with only DM (187.2; 95 % CI, 171.3–206.9), with only CYP2C19*2 (227.9; 95 % CI, 205.1–250.8), and with both DM and CYP2C19*2 (239.9; 95 % CI, 209.7–270.1). Notably, with 75 mg, patients with only CYP2C19*2 had higher ontreatment platelet reactivity than those with only DM (p=0.0068). To achieve on-treatment platelet reactivity similar to that seen with clopidogrel 75 mg in patients with neither DM nor CYP2C19*2, the following doses were required: 150 mg with only DM, 225 mg with only CYP2C19*2, and 300 mg with both DM and CYP2C19*2. Patients with both DM and CYP2C19*2 required a four-fold increase in clopidogrel maintenance dose as compared to patients without these factors to achieve a similar antiplatelet response.

Purpose: To determine if the mathematical model used to derive critical power could be used to identify the critical resistance (CR) for the deadlift; compare predicted and actual repetitions to failure at 50%, 60%, 70%, and 80% 1-repetition maximum (1RM); and compare the CR with the estimated sustainable resistance for 30 repetitions (ESR30). Methods: Twelve subjects completed 1RM testing for the deadlift followed by 4 visits to determine the number of repetitions to failure at 50%, 60%, 70%, and 80% 1RM. The CR was calculated as the slope of the line of the total work completed (repetitions × weight [in kilograms] × distance [in meters]) vs the total distance (in meters) the barbell traveled. The actual and predicted repetitions to failure were determined from the CR model and compared using paired-samples t tests and simple linear regression. The ESR30 was determined from the power-curve analysis and compared with the CR using paired-samples t tests and simple linear regression. Results: The weight and repetitions completed at CR were 56 (11) kg and 49 (14) repetitions. The actual repetitions to failure were less than predicted at 50% 1RM (P < .001) and 80% 1RM (P < .001) and greater at 60% 1RM (P = .004), but there was no difference at 70% 1RM (P = .084). The ESR30 (75 [14] kg) was greater (P < .001) than the CR. Conclusions: The total work-vs-distance relationship can be used to identify the CR for the deadlift, which reflected a sustainable resistance that may be useful in the design of resistance-based exercise programs.

In April 2013, unthrifty rose periwinkle (Catharanthus roseus (L.) G. Don) from a residential garden in Mililani, HI, was sent to the Hawaii Department of Agriculture. Symptoms, present on all plants, included leaf chlorosis, defoliation, and premature flower drop with necrotic spots on the adaxial side of leaves corresponding to patches of grayish mildew-like growth on the abaxial side. Samples were collected and sent to USDA PPQ National Identification Services (NIS) for confirmation. At NIS, stereoscope examination of the plants revealed two distinct powdery mildews. One, on the stems and leaves, had dimorphic conidia, with lanceolate primary (54 to 72 × 14 to 22 μm) and cylindrical secondary conidia (49 to 75 × 11 to 21 μm) (n = 25 for each), both with a reticulate surface. This fungus was identified morphologically as Leveillula taurica (Lév.) G. Arnaud (1). The second powdery mildew appeared confined to the sepals and petals. The external hyphae of this fungus produced upright chains of cylindrical to ovoid conidia (up to eight per chain), which contained fibrosin bodies and measured 22 × 12 μm (n = 50) with straight foot cells averaging 43 μm long, placing this fungus in the genus Podosphaera Kunze (1). Plants containing both fungi were accessioned as BPI892677 in the US National Fungal Collection. For molecular characterization, genomic DNA of the Podosphaera was obtained by scraping conidia from a petal and extracting with Thermo Scientific's Lyse and Go PCR Reagent. DNA of the Leveillula was extracted from 5 mm2 of infected leaf using Qiagen's Plant mini kit. The ITS region of each fungus was amplified and sequenced directly with primers ITS1F and ITS4. Each consensus sequence was created from manually edited chromatograms, searched against NCBI's GenBank using MegaBLAST and phylogenetically analyzed in MEGA5.2 under maximum parsimony (MP) in context with most similar hits and representatives from phylogenetic studies (2,3). Sequences from types of these fungi are not available for comparison. The resulting Podosphaera phylogeny grouped the Podosphaera suspect (GenBank KF703448) within a clade of P. pannosa (e.g., AB525938; bootstrap = 90). The Leveillula phylogeny grouped the Leveillula suspect (KF703447) within a clade (bootstrap = 88) of L. taurica (e.g., AB044346), L. chrozophorae (AB044346), and L. elaeagni (AB048350). Although the ITS sequences of these taxa are phylogenetically indistinguishable, morphological characters differentiate each species and the suspect as L. taurica (1). L. taurica has been recorded on C. roseus in India and Korea (1). This is the first report of L. taurica on C. roseus in the United States. This is the first report of P. pannosa on C. roseus worldwide. P. pannosa is commonly known as a powdery mildew of Rosaceae hosts, and has also been reported on hosts in the Anacardaciae and Oleaceae (1). P. pannosa represents the second Podosphaera species reported on any member of the Apocynaceae, with P. sparsa reported on other Apocynaceae genera (1). The presence of two powdery mildew genera on different parts of the same plant could cause multiple forms of damage and impact the production of this popular landscape ornamental plant. References: (1) U. Braun and R. T. A. Cook. Taxonomic Manual of the Erysiphales (Powdery Mildews), CBS Biodiversity Series No. 11. CBS, Utrecht, Netherlands, 2012. (2) S. A. Khodoparast et al. Mycol. Res. 105:909, 2001. (3) S. Takamatsu et al. Persoonia 24:38, 2010.

ObjectiveThis report evaluates rheumatologists' stated adherence to and agreement with the 2020 American College of Rheumatology (ACR) Guideline for the Management of Gout.MethodsA 57-item questionnaire was administered to US rheumatologists. Stated adherence scores were based on several guideline recommendations reported to be followed by rheumatologists in practice, whereas stated agreement scores were based on whether respondents always followed the recommendations.ResultsAll 201 rheumatologists completed the questionnaire. The mean overall stated adherence score was 11.5 (maximum: 15), whereas the mean overall stated agreement score was 7.7 (maximum: 14). Less experienced rheumatologists (≤8 years; n=49) were likely to claim adherence to more individual ACR recommendations than those with more experience (>8 years; n=152; mean stated adherence score: 12.3 vs 11.3; P ≤ 0.05). Rheumatologists who claimed to see ≤75 patients with gout in 6 months (n=66) had a mean stated adherence score of 12.1 versus 11.2 for those who claimed to have seen >75 patients (P ≤ 0.05). Approximately 78% of rheumatologists claimed to follow the guideline for initiating urate-lowering therapy (ULT), and 89% were likely to prescribe allopurinol as a first-line ULT. Claimed adherence to recommendations for dosing was lower (febuxostat, 43%; allopurinol, 39%). Rheumatologists from academic settings were more likely to prescribe an interleukin-1 inhibitor for gout flares.ConclusionThe self-reported practice of the surveyed US rheumatologists was generally concordant with the 2020 ACR Guideline for the Management of Gout. However, there were gaps in guideline knowledge and stated adherence among rheumatologists, mainly concerning the dosing of treatment regimens.

Abstract Background Despite increased atherothrombotic risk in type 2 diabetes mellitus, (T2DM) the best preventative antithrombotic strategy remains undetermined. We defined the effects of three antiplatelet agents on functional readout and biomarker kinetics in platelet activation and coagulation in patients with T2DM. Materials and methods 56 patients with T2DM were randomised to antiplatelet monotherapy with aspirin 75 mg once daily (OD), clopidogrel 75 mg OD or prasugrel 10 mg OD during three periods of a crossover study. Platelet aggregation (PA) was determined by light-transmittance aggregometry and P-selectin expression by flow cytometry. Markers of fibrin clot dynamics, inflammation and coagulation were measured. Plasma levels of 14 miRNA were assessed by quantitative polymerase chain reactions. Results Of the 56 patients, 24 (43%) were receiving aspirin for primary prevention of ischaemic events and 32 (57%) for secondary prevention. Prasugrel was the strongest inhibitor of ADP-induced PA (mean ± SD maximum response to 20μmol/L ADP 77.6 ± 8.4% [aspirin] vs. 57.7 ± 17.6% [clopidogrel] vs. 34.1 ± 14.1% [prasugrel], p < 0.001), P-selectin expression (30 μmol/L ADP; 45.1 ± 21.4% vs. 27.1 ± 19.0% vs. 14.1 ± 14.9%, p < 0.001) and collagen-induced PA (2 μg/mL; 62.1 ± 19.4% vs. 72.3 ± 18.2% vs. 60.2 ± 18.5%, p < 0.001). Fibrin clot dynamics and levels of coagulation and inflammatory proteins were similar. Lower levels of miR-24 (p = 0.004), miR-191 (p = 0.019), miR-197 (p = 0.009) and miR-223 (p = 0.014) were demonstrated during prasugrel-therapy vs. aspirin. Circulating miR-197 was lower in those cardiovascular disease during therapy with aspirin (p = 0.039) or prasugrel (p = 0.0083). Conclusions Prasugrel monotherapy in T2DM provided potent platelet inhibition and reduced levels of a number of platelet-associated miRNAs. miR-197 is a potential marker of cardiovascular disease in this population. Clinical outcome studies investigating prasugrel monotherapy are warranted in individuals with T2DM. Trial registration EudraCT, 2009-011907-22. Registered 15 March 2010, https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-011907-22/GB.