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Frailty affects the physical, cognitive, and social domains exposing older adults to an increased risk of cardiovascular disease and death. The mechanisms linking frailty and cardiovascular outcomes are mostly unknown. Here, we studied the association of abundance (flow cytometry) and gene expression profile (RNAseq) of stem/progenitor cells (HSPCs) and molecular markers of inflammaging (ELISA) with the cardiorespiratory phenotype and prospective adverse events of individuals classified according to levels of frailty. Two cohorts of older adults were enrolled in the study. In a cohort of pre-frail 35 individuals (average age: 75 years), a physical frailty score above the median identified subjects with initial alterations in cardiorespiratory function. RNA sequencing revealed S100A8/A9 upregulation in HSPCs from the bone marrow (>10-fold) and peripheral blood (>200-fold) of individuals with greater physical frailty. Moreover higher frailty was associated with increased alarmins S100A8/A9 and inflammatory cytokines in peripheral blood. We then studied a cohort of 104 more frail individuals (average age: 81 years) with multidomain health deficits. Reduced levels of circulating HSPCs and increased S100A8/A9 concentrations were independently associated with the frailty index. Remarkably, low HSPCs and high S100A8/A9 simultaneously predicted major adverse cardiovascular events at 1-year follow-up after adjustment for age and frailty index. In conclusion, inflammaging characterized by alarmin and pro-inflammatory cytokines in pre-frail individuals is mirrored by the pauperization of HSPCs in frail older people with comorbidities. S100A8/A9 is upregulated within HSPCs, identifying a phenotype that associates with poor cardiovascular outcomes., (© 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Background Elderly patients have high ischemic and bleeding rates after acute coronary syndrome; however, the occurrence of these complications over time has never been studied. This study sought to characterize average daily ischemic rates ( ADIRs ) and average daily bleeding rates ( ADBRs ) over 1 year in patients aged >74 years with acute coronary syndrome undergoing percutaneous coronary intervention who were randomized in the Elderly ACS 2 trial, comparing low-dose prasugrel (5 mg daily) with clopidogrel (75 mg daily). Methods and Results ADIRs and ADBRs were calculated as the total number of events, including recurrent events, divided by the number of patient-days of follow-up and assessed within different clinical phases: acute (0-3 days), subacute (4-30 days), and late (31-365 days). Generalized estimating equations were used to test the least squares mean differences for the pairwise comparisons of ADIRs and ADBRs and the pairwise comparison of clopidogrel versus prasugrel effects. Globally, ADIRs were 2.6 times (95% CI, 2.4-2.9) higher than ADBRs . ADIRs were significantly higher in the clopidogrel arm than in the low-dose prasugrel arm in the subacute phase ( P adj <0.001) without a difference in ADBRs ( P adj =0.35). In the late phase, ADIRs remained significantly higher with clopidogrel ( P adj <0.001), whereas ADBRs were significantly higher with low-dose prasugrel ( P adj <0.001). Conclusions Ischemic burden was greater than bleeding burden in all clinical phases of 1-year follow-up of elderly patients with acute coronary syndrome treated with percutaneous coronary intervention. Low-dose prasugrel reduced ischemic events in the subacute and chronic phases compared with clopidogrel, whereas bleeding burden was lower with clopidogrel in the late phase. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01777503.

Background: Age- and sex-specific differences exist in the treatment and outcome of ST-elevation myocardial infarction (STEMI). We sought to describe age- and sex-matched contemporary trends of in-hospital management and outcome of patients with STEMI., Methods and Results: We analyzed data from 5 Italian nationwide prospective registries, conducted between 2001 and 2014, including consecutive patients with STEMI. All the analyses were age- and sex-matched, considering 4 age classes: <55, 55 to 64, 65 to 74, and ≥75 years. A total of 13 235 patients were classified as having STEMI (72.1% men and 27.9% women). A progressive shift from thrombolysis to primary percutaneous coronary intervention occurred over time, with a concomitant increase in overall reperfusion rates (P for trend <0.0001), which was consistent across sex and age classes. The crude rates of in-hospital death were 3.2% in men and 8.4% in women (P<0.0001), with a significant increase over age classes for both sexes and a significant decrease over time for both sexes (all P for trend <0.01). On multivariable analysis, age (odds ratio 1.09, 95% CI 1.07-1.10, P<0.0001) and female sex (odds ratio 1.44, 95% CI 1.07-1.93, P=0.009) were found to be significantly associated with in-hospital mortality after adjustment for other risk factors, but no significant interaction between these 2 variables was observed (P for interaction=0.61)., Conclusions: Despite a nationwide shift from thrombolytic therapy to primary percutaneous coronary intervention for STEMI affecting both sexes and all ages, women continue to experience higher in-hospital mortality than men, irrespective of age., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

In the title compound, C(13)H(9)N(3)S(2), the thio-phene and phenyl rings are oriented at dihedral angles of 8.00 (7) and 6.31 (7)°, respectively, with respect to the central thia-diazole ring. No significant C-H⋯S and π-π inter-actions exist in the crystal structure.

The title compounds, 1,3-dibenzoylimidazolidine-2-thione, C17H14N2O2S, (I), and 1,3-dibenzoyl-3,4,5,6-tetrahydropyrimidine-2(1H)-thione, C18H16N2O2S, (II), were obtained from the reactions of imidazolidine-2-thione and 1,4,5,6-tetrahydropyrimidine-2-thiol, respectively, with benzoyl chloride. Compounds (I) and (II) contain, respectively, imidazolidinethione [C=S = 1.6509 (14) A] and pyrimidinethione [C=S = 1.6918 (19) A] moieties bonded to two benzoyl rings. The molecules of (I) exhibit C2 symmetry, the C=S bond lying along the twofold rotation axis, while the molecules of (II) have mirror symmetry (Cs). The imidazolidine ring in (I) is essentially planar, while the pyrimidine ring in (II) adopts a boat conformation. Molecules of (I) are linked by weak intermolecular C-H...O interactions, while molecules of (II) are held together by van der Waals interactions.

Crystals of purified phospholipase D (E.C. 3.1.4.4) from Streptomyces sp. strain PMF have been grown under two different crystallization conditions using vapour diffusion. Both conditions gave monoclinic crystals in space group P2(1). The unit-cell parameters were a = 57.28, b = 57.42, c = 68.70 A, beta = 93.17 degrees. The crystals diffract at 110 K to a resolution beyond 1.4 A using synchrotron radiation.