Search

Aims: The prognostic impact of heart rate (HR) in acute heart failure (AHF) patients is not well known especially in atrial fibrillation (AF) patients. The aim of the study was to evaluate the impact of admission HR, discharge HR, HR difference (admission-discharge) in AHF patients with sinus rhythm (SR) or AF on long- term outcomes. Methods: We included 1398 patients consecutively admitted with AHF between October 2013 and December 2014 from a national multicentre, prospective registry. Logistic regression models were used to estimate the association between admission HR, discharge HR and HR difference and one- year all-cause mortality and HF readmission. Results: The mean age of the study population was 72 ± 12 years. Of these, 594 (42.4%) were female, 655 (77.8%) were hypertensive and 655 (46.8%) had diabetes. Among all included patients, 745 (53.2%) had sinus rhythm and 653 (46.7%) had atrial fibrillation. Only discharge HR was associated with one year all-cause mortality (Relative risk (RR) = 1.182, confidence interval (CI) 95% 1.024–1.366, p = 0.022) in SR. In AF patients discharge HR was associated with one year all cause mortality (RR = 1.276, CI 95% 1.115–1.459, p ≤ 0.001). We did not observe a prognostic effect of admission HR or HRD on long-term outcomes in both groups. This relationship is not dependent on left ventricular ejection fraction. Conclusions: In AHF patients lower discharge HR, neither the admission nor the difference, is associated with better long-term outcomes especially in AF patients. Keywords: Heart rate, Acute heart failure, Sinus rhythm, Atrial fibrillation, Mortality

Purpose: We conducted research on CDK4/6 inhibitors (CDK4/6i) simultaneously in the preclinical and clinical spaces to gain a deeper understanding of how senescence influences tumor growth in humans., Patients and Methods: We coordinated a first-in-kind phase II clinical trial of the CDK4/6i abemaciclib for patients with progressive dedifferentiated liposarcoma (DDLS) with cellular studies interrogating the molecular basis of geroconversion., Results: Thirty patients with progressing DDLS enrolled and were treated with 200 mg of abemaciclib twice daily. The median progression-free survival was 33 weeks at the time of the data lock, with 23 of 30 progression-free at 12 weeks (76.7%, two-sided 95% CI, 57.7%-90.1%). No new safety signals were identified. Concurrent preclinical work in liposarcoma cell lines identified ANGPTL4 as a necessary late regulator of geroconversion, the pathway from reversible cell-cycle exit to a stably arrested inflammation-provoking senescent cell. Using this insight, we were able to identify patients in which abemaciclib induced tumor cell senescence. Senescence correlated with increased leukocyte infiltration, primarily CD4-positive cells, within a month of therapy. However, those individuals with both senescence and increased TILs were also more likely to acquire resistance later in therapy. These suggest that combining senolytics with abemaciclib in a subset of patients may improve the duration of response., Conclusions: Abemaciclib was well tolerated and showed promising activity in DDLS. The discovery of ANGPTL4 as a late regulator of geroconversion helped to define how CDK4/6i-induced cellular senescence modulates the immune tumor microenvironment and contributes to both positive and negative clinical outcomes. See related commentary by Weiss et al., p. 649., (©2023 The Authors; Published by the American Association for Cancer Research.)

Guided bone regeneration surgeries are based on grafting a scaffold in the site to be repaired. The main focus of the scaffold is to provide mechanical support to newly formed blood vessels and cells that will colonize the grafted site, achiving bone regenertation. In this regards, the aim of this study was to characterize the anatomy, structular, surface morphologycal, chemical composition, and nanomechanical properties of ostrich and equine trabecular bone. Ostrich and equine specimens were obtained from a local abattoir and bone was obtained by blunt dissection, n = 5. Tissue bone anatomy and trabecular structure were measured using Computerized Axial Tomography (CAT). Atomic Force Microscopy (AFM) and Energy dispersion spectrometry of X-ray (EDS) were used to examine surface morphology and chemical composition of the trabecular ostrich and equine bone. Mechanical behavior was analysted by nanoindentation. Equine specimens were examined as control. CAT results suggest that in terms of anthropometry, ostrich tarsometatarsus bone is more suitable due to its length is 432.56 ± 3.12 mm vs. the highest human bone structures reported, which femur length is 533.66 ± 18.81 mm. Besides, the low radiodensity in the Hounsfield scale exhibits equine trabecular bone more brittle (Av = 1538.4 ± 0.9) than ostrich trabecular bone (Av = 462.1 ± 1.5). EDS showed a slight variation of the element Calcium (Ca 2+ ) ranging from 20% to 25.5% wt in equine bone; the Ca 2+ content variation is consistent with the ring-shaped morphology, while in ostrich bone the chemical composition is homogeneous. The elastic modulus, nanohardness (E = 5.3 ± 0.7 GPa, H = 220 ± 10 MPa) and average roughness (Ra = 207 nm) are similar to the human trabecular bone which could reduce the stress shielding, all of these findings suggest that ostrich bone can be promising for native tissue scaffolds for mechanically demanding applications. This research makes innovative contributions to science and provides a framework, which will allow us to address future biomedical tests, and rapidly identify promising organic and sustainable waste for tissue scaffold., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The hydroalcoholic extract of the steam bark of B. fagaroides var. fagaroides displayed potent cytotoxic activity against four cancer cell lines, namely KB (ED50 = 9.6 × 10(-2) μg/mL), PC-3 (ED50 = 2.5 × 10(-1) μg/mL), MCF-7 (ED50 = 6.6 μg/mL), and HF-6 (ED50 = 7.1 × 10(-3) μg/mL). This extract also showed anti-tumour activity when assayed on mice inoculated with L5178Y lymphoma cells. Bioactivity-directed isolation of this extract, afforded seven podophyllotoxin-type lignans identified as podophyllotoxin (1), β-peltatin-A-methylether (2), 5'-desmethoxy-β-peltatin-A-methylether (3), desmethoxy-yatein (4), desoxypodophyllotoxin (5), burseranin (6), and acetyl podophyllotoxin (7) by 1D and 2DNMR and FAB-MS analyses, and comparison with reported values. All the isolated compounds showed potent cytotoxic activity in the cell lines tested, especially compound 3, which exhibited greater activity than camptothecin and podophyllotoxin against PC-3 (ED50= 1.0 × 10(-5) μg/mL), and KB (ED50 = 1.0 × 10(-5) μg/mL). This is the first report of the isolation of podophyllotoxin and its acetate in a Bursera species.

Electroencephalographic (EEG) activity during both human and adult primates' sleep has been proven to be similar and consequently, it could be assessed under similar parameters. However, there is no information regarding this EEG activity in the early stages of development in non-human primates. Therefore, the aim of this study was to describe EEG sleep patterns in a 1-month-old Macaca arctoides with a non-invasive and free-movement method. Sleep stages were initially scored using the criteria of quiet sleep and active sleep. This procedure allowed us to observe graphoelements to distinguish sleep phases as described in adult macaques. Afterwards, the final score was recorded following the Slow Wave Sleep and Rapid Eye Movement Sleep criteria. The present results suggest that sleep features of this monkey are similar to those of a 2-month-old human neonate.