New acrylic bone cements conjugated to vitamin E: Curing parameters, properties, and biocompatibility

Acrylic bone cement formulations with antioxidant character were prepared by incorporation of a methacrylic monomer derived from vitamin E (MVE). Increasing concentrations of this monomer provided decreasing peak temperature values, ranging from 62 to 36°C, and increasing setting time with values between 17 and 25 min. Mechanical properties were evaluated by compression and tension tests. Compressive strength of the new formulations were superior to 70 MPa in all cases. The cement containing 25 wt % MVE, however, showed a significant decrease in tensile properties. Biocompatibility of the new formulations was studied in vitro. The analysis of the effect of leachables from cements into the media showed continued cell proliferation and cell viability with a significant increase for the cement containing 15 wt % MVE. This formulation also showed a significant increase in cellular proliferation over a period of 7 days as indicated by the Alamar Blue test. The cells were able to differentiate and express phenotypical markers in presence of all materials. A significant increase in alkaline phosphatase activity was observed on the cements prepared in presence of 15–25 wt % MVE compared with PMMA. Morphological assessment showed that the human osteoblast (HOB) cells were able to adhere, retain their morphology, and proliferate on all the cementsThe authors thank the help provided by M. Kayser, N. Gurav, C. Clifford, B. Annaz, M. Knight, and D. de Silva in the fulfilment of this work (Institute of Orthopaedics, United Kingdom). Financial support from the Comision Intermisterial de Cienca y Tecnologia, CICYT (MAT99-1064-CO2-01) is also gratefully acknowledged.Peer reviewe

Selective effects of the anticancer drug Yondelis (ET-743) on cell-cycle promoters

Yondelis is a potent DNA-binding anticancer drug isolated from the tunicate Ecteinascidia turbinata currently undergoing phase III clinical trials. We and others have shown selective inhibition to the transcriptional induction of several genes. We tested the hypothesis that Yondelis specifically targets cell-cycle genes. Our analysis on endogenous and transfected reporter systems revealed complex patterns of transcriptional inhibition and, surprisingly, activation. Other inducible systems-the metallothionein and the CYP3A4 promoters-were little affected. We assayed whether interference of DNA binding of the common nuclear factor Y (NF-Y) activator was responsible for the observed inhibition: in vivo chromatin immunoprecipitation analysis in NIH3T3 and HCT116 cells indicates that NF-Y binding is little affected by Yondelis addition. Finally, histone acetylation was modestly affected only on Cdc2 and cyclin B2 but not on other repressed promoters. These data prove that Yondelis is not a general inhibitor of inducible genes, and its selective effects are exerted downstream from transcription factors binding and histone acetyl transferases recruitment

NF-Y recruitment of TFIID, multiple interactions with histone fold TAF(II)s

The nuclear factor y (NF-Y) trimer and TFIID contain histone fold subunits, and their binding to the CCAAT and Initiator elements of the major histocompatibility complex class II Ea promoter is required for transcriptional activation. Using agarose-electrophoretic mobility shift assay we found that NF-Y increases the affinity of holo-TFIID for Ea in a CCAAT- and Inr-dependent manner. We began to dissect the interplay between NF-Y- and TBP-associated factors PO1II (TAF(II)s)-containing histone fold domains in protein-protein interactions and transfections. hTAF(II)20, hTAF(II)28, and hTAF(II)18-hTAF(II)28 bind to the NF-Y B-NF-YC histone fold dimer; hTAF(II)80 and hTAF(II)31-hTAF(II)80 interact with the trimer but not with the NF-YB-NF-YC dimer. The histone fold alpha2 helix of hTAF(II)80 is not required for NF-Y association, as determined by interactions with the naturally occurring splice variant hTAF(II)80delta. Expression of hTAF(II)28 and hTAF(II)18 in mouse cells significantly and specifically reduced NF-Y activation in GAL4-based experiments, whereas hTAF,120 and hTAF(II)135 increased it. These results indicate that NF-Y (i) recruits purified holo-TFIID in vitro and (ii) can associate multiple TAF(II)s, potentially accommodating different core promoter architectures

Comparing Clinical Outcomes of COVID-19 and Influenza-Induced Acute Respiratory Distress Syndrome: A Propensity-Matched Analysis

Acute respiratory distress syndrome (ARDS) is one the leading causes of mortality and morbidity in patients with COVID-19 and Influenza, with only small number of studies comparing these two viral illnesses in the setting of ARDS. Given the pathogenic differences in the two viruses, this study shows trends in national hospitalization and outcomes associated with COVID-19- and Influenza-related ARDS. To evaluate and compare the risk factors and rates of the adverse clinical outcomes in patients with COVID-19 associated ARDS (C-ARDS) relative to Influenza-related ARDS (I-ARDS), we utilized the National Inpatient Sample (NIS) database 2020. Our sample includes 106,720 patients hospitalized with either C-ARDS or I-ARDS between January and December 2020, of which 103,845 (97.3%) had C-ARDS and 2875 (2.7%) had I-ARDS. Propensity-matched analysis demonstrated a significantly higher in-hospital mortality (aOR 3.2, 95% CI 2.5–4.2, p p < 0.001), higher likelihood of requiring vasopressors (aOR 1.7, 95% CI 2.5–4.2) and invasive mechanical ventilation (IMV) (aOR 1.6, 95% CI 1.3–2.1) in C-ARDS patients. Our study shows that COVID-19-related ARDS patients had a higher rate of complications, including higher in-hospital mortality and a higher need for vasopressors and invasive mechanical ventilation relative to Influenza-related ARDS; however, it also showed an increased utilization of mechanical circulatory support and non-invasive ventilation in Influenza-related ARDS. It emphasizes the need for early detection and management of COVID-19

Impact of pneumothorax on mortality, morbidity, and hospital resource utilization in COVID-19 patients: a propensity matched analysis of nationwide inpatient sample database

Abstract Background Spontaneous pneumothorax (PTX) is more prevalent among COVID-19 patients than other critically ill patients, but studies on this are limited. This study compared clinical characteristics and in-hospital outcomes among COVID-19 patients with concomitant PTX to provide insight into how PTX affects health care utilization and complications, which informs clinical decisions and healthcare resource allocation. Methods The 2020 Nationwide Inpatient Sample was used analyze patient demographics and outcomes, including age, race, sex, insurance status, median income, length of hospital stay, mortality rate, hospitalization costs, comorbidities, mechanical ventilation, and vasopressor support. Propensity score matching was employed for additional analysis. Results Among 1,572,815 COVID-19 patients, 1.41% had PTX. These patients incurred significantly higher hospitalization costs ($435,508 vs.$96,668, p < 0.001) and longer stays (23.6 days vs. 8.6 days, p < 0.001). In-hospital mortality was substantially elevated for PTX patients (65.8% vs. 14.4%, p < 0.001), with an adjusted odds ratio of 14.3 (95% CI 12.7–16.2). Additionally, these patients were more likely to require vasopressors (16.6% vs. 3.3%), mechanical circulatory support (3.5% vs. 0.3%), hemodialysis (16.6% vs. 5.6%), invasive mechanical ventilation (76.9% vs. 15.1%), non-invasive mechanical ventilation (19.1% vs. 5.8%), tracheostomy (13.3% vs. 1.1%), and chest tube placement (59.8% vs. 0.8%). Conclusions Our findings highlight the severe impact of PTX on COVID-19 patients, characterized by higher mortality, more complications, and increased resource utilization. Also, being Hispanic, male, or obese increased the risk of developing concomitant PTX with COVID-19